mercaptopurine and Leukemia

Topics: Female; Genotype; Humans; Leukemia; Male; Mercaptopurine; Methyltransferases; Pyrophosphatases; Thioguanine

Thiopurines are the cornerstone of treatment for a wide variety of medical disorders, ranging from pediatric leukemia to inflammatory bowel disease. Because of their complex metabolism and potential toxicities, the use of biomarkers to predict risk and response is paramount. Thiopurine S-methyltransferase and thiopurine metabolite levels have emerged as companion diagnostics with crucial roles in facilitating safe and effective treatment. This review serves to update the reader on how these tools are being developed and implemented in clinical practice. A useful paradigm in thiopurine therapeutic strategy is presented, along with fresh insights into the mechanisms underlying these approaches. We elaborate on potential future developments in the optimization of thiopurine therapy.

Topics: Allopurinol; Biomarkers; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Leukemia; Mercaptopurine; Methyltransferases

This chapter introduces some fundamental results in survival analysis. We first describe what is censored failure time data and how to interpret the failure time distribution. Two nonparametric methods for estimating the survival curve, the life table estimator and the Kaplan-Meier estimator, are demonstrated. We then discuss the two-sample problem and the usage of the log-rank test for comparing survival distributions between groups. Lastly, we discuss in some detail the proportional hazards model, which is a semiparametric regression model specifically developed for censored data. All methods are illustrated with artificial or real data sets.

Topics: Antimetabolites, Antineoplastic; Clinical Trials as Topic; Humans; Leukemia; Life Tables; Lung Neoplasms; Mercaptopurine; Proportional Hazards Models; Recurrence; Survival Analysis

The thiopurine drugs, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG) are commonly used cytotoxic agents. A derivative of 6-MP, azathioprine, is commonly used as an immunosuppressant. A prominent route for the metabolism of these agents is mediated by the enzyme thiopurine methyltransferase (TPMT). This enzyme exhibits considerable inter-individual variation in activity, partly due to the presence of common genetic polymorphisms, which influence cytotoxicity of the thiopurine drugs. Variations in the number of tandem repeats in the 5' promoter region have also been shown to influence TPMT expression in vitro. In this article, we review the impact of variations in TPMT activity on sensitivity to the thiopurine drugs in vitro and also in vivo in terms of their clinical efficacy and toxicity. A possible relationship between TPMT and secondary malignancies is also reviewed.

Topics: Animals; Antimetabolites, Antineoplastic; Azathioprine; Cell Line, Tumor; Guanine Nucleotides; Humans; Immunosuppressive Agents; Leukemia; Mercaptopurine; Methyltransferases; Polymorphism, Genetic; Thioguanine; Thionucleotides

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Child; Chromosomes, Human, Pair 6; Humans; Leukemia; Mercaptopurine; Methotrexate; Methyltransferases; Polymorphism, Genetic; Thioguanine

Topics: Antimetabolites, Antineoplastic; Humans; Leukemia; Mercaptopurine; Methyltransferases; Polymorphism, Genetic

Topics: Animals; Antimetabolites, Antineoplastic; Cell Survival; DNA, Neoplasm; Humans; Leukemia; Mercaptopurine; Nucleotides; Purines; RNA, Neoplasm; Sulfhydryl Compounds

For a disease like leukemia with an annual incidence of 3 to 4 per a 100,000 population, a multicenter cooperative study is essential to develop better therapeutic regimens. Our Japan Adult Leukemia Study Group (JALSG) started its first multicenter cooperative study in 1987. In the AML 87 study, response-oriented individualized induction therapy produced 78% complete remissions in 252 consecutive adult AML, a higher remission rate than that of any multicenter studies in the U.S.A. and Europe. For further development of clinical study for cancer in Japan, financial support to highly qualified clinical study groups by the government is urgently needed.

Topics: Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Cytarabine; Daunorubicin; Humans; Japan; Leukemia; Mercaptopurine; Middle Aged; Multicenter Studies as Topic; Prednisolone; Remission Induction; Survival Rate

This review is intended to provide a concise portrayal of the background, rationale, and current use of intravenous infusions of mercaptopurine (6MP) in patients with acute leukemia.. After a brief description of the mode of action of 6MP and the formulation, pharmacokinetics, and history of its intravenous administration, the rationale for current use of intravenous 6MP infusion is explained. Subsequently, the review summarizes and discusses clinical experience with intravenous 6MP alone and in combination with intravenous methotrexate (Mtx) and cytarabine (Ara-C).. Although still an investigative drug, intravenous 6MP has been used for 40 years and currently is being administered extensively to children with previously untreated acute lymphoid leukemia (ALL) in frontline protocol studies. The reasons are the better and more consistent bioavailability of intravenous versus oral MP, higher blood and CSF levels, compliance, and preliminary evidence suggesting superior remission experience for intravenous Mtx and 6MP than for Mtx alone. The apparent lack of late adverse sequelae with 6MP as compared with other antileukemia drugs adds to this interest.. The new life of intravenous 6MP at age 40 years illustrates the need for continued investigation of significant anticancer drugs as insights and technology progress.

Topics: Acute Disease; Animals; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Humans; Infusions, Intravenous; Leukemia; Mercaptopurine; Methotrexate

The blood-brain barrier provides a pharmacologic sanctuary for leukemic cells within the central nervous system (CNS), protecting them from the cytotoxic effects of systemic antileukemic therapy. Attempts to overcome this problem have included specific CNS-directed treatment in the form of direct intrathecal drug injection, cranial irradiation, and alteration in the dose and schedule of systemic agents to enhance their CNS penetration. Use of these treatments and strategies has led to the effective prevention and control of meningeal leukemia. Intrathecal therapy, primarily with methotrexate or cytosine arabinoside, is a form of regional chemotherapy that can achieve very high drug concentrations at the target site [i.e., in the meninges and cerebrospinal fluid (CSF)] with a low total dose. Therefore, there is minimal systemic toxicity. The dose and schedules, clinical pharmacology, and toxicities of the commonly used intrathecal agents are discussed in detail in this article. Another approach to overcoming the limited penetration of antileukemic drugs into the CNS has been the use of high-dose systemic therapy. Methotrexate and cytosine arabinoside in high doses have produced favorable clinical responses in patients with overt meningeal disease, and pharmacokinetic studies have documented cytotoxic concentrations of these drugs within the cerebrospinal fluid. A clear understanding of the CNS pharmacology of the antileukemic drugs is required in order to use these agents in the safest and most efficacious manner for the treatment of meningeal leukemia.

Topics: Antineoplastic Agents; Central Nervous System; Child; Cytarabine; Humans; Leukemia; Mercaptopurine; Methotrexate; Thiotepa

This article focuses on the chemotherapeutic agents which alter purine metabolism as a means to achieve selective killing of leukemic cells. We present an overview of purine metabolism in order to highlight enzymatic steps which are targeted by antileukemic drugs. Purine antimetabolites used in the treatment of leukemia can be grouped into three classes: (1) structural analogs of normal purines (6-mercaptopurine and 6-thioguanine); (2) inhibitors of de novo purine biosynthesis (methotrexate and hydroxyurea); and (3) inhibitors of purine salvage (2'-deoxycoformycin). In addition, a number of investigational drugs (trimetrexate, fludarabine and 2'-chlorodeoxyadenosine) have been recently introduced and show promise in early clinical trials. Purine antimetabolites are active in a variety of lymphoid and myeloid leukemias and represent an important component of the therapy of these disorders. Several of the drugs have been developed with the specific intent of perturbing enzymes involved in purine metabolism. Refinements in our understanding of purine biochemistry in normal and leukemic cells may aid future efforts to design more effective drugs.

Topics: Antineoplastic Agents; Drugs, Investigational; Humans; Hydroxyurea; Leukemia; Mercaptopurine; Methotrexate; Pentostatin; Purines; Thioguanine

Topics: Aminoacridines; Amsacrine; Animals; Antineoplastic Combined Chemotherapy Protocols; Arabinofuranosylcytosine Triphosphate; Cisplatin; Cyclophosphamide; Cytarabine; Daunorubicin; DNA; DNA Repair; Doxorubicin; Drug Interactions; Drug Resistance; Humans; Interphase; Leukemia; Mercaptopurine; Phosphorylation; Thioguanine; Thymidine; Time Factors

Topics: Acquired Immunodeficiency Syndrome; Animals; Antibody Formation; Autoimmune Diseases; Cyclophosphamide; Herpesviridae Infections; Humans; Immunization, Passive; Immunoglobulin Idiotypes; Immunosuppression Therapy; Immunosuppressive Agents; Leukemia; Lymphoma; Mercaptopurine; Sarcoma, Kaposi; T-Lymphocytes; Transplantation Immunology

Topics: Adolescent; Adult; Asparaginase; B-Lymphocytes; Bacterial Infections; Child; Child, Preschool; Chromosome Aberrations; Chromosome Disorders; Diagnosis, Differential; Drug Therapy, Combination; Female; Humans; Infant; Leukemia; Leukemia, Lymphoid; Leukocyte Count; Male; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Prednisolone; T-Lymphocytes; Testicular Neoplasms; Vincristine

Topics: Allopurinol; Drug Interactions; Drug Resistance; Humans; Leukemia; Mercaptopurine; Neoplasms; Purines; Thioguanine

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Prednisone; Prognosis; Remission, Spontaneous; Vincristine

Topics: Age Factors; Breast Neoplasms; Cell Movement; Clinical Enzyme Tests; Colonic Neoplasms; Cytarabine; Diagnosis, Differential; Doxorubicin; Drug Combinations; Drug Evaluation; Drug Evaluation, Preclinical; Fluorouracil; Humans; Kinetics; Leukemia; Mercaptopurine; Methods; Methotrexate; Models, Chemical; Neoplasms; Prognosis; Sarcoma; Testosterone; Thioguanine

Topics: Adrenal Cortex Hormones; Alkylating Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Cytarabine; Drug Synergism; Drug Therapy, Combination; Fluorouracil; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Mitosis; Neoplasm Metastasis; Thymine Nucleotides

Topics: Acute Disease; Adrenal Cortex Hormones; Antineoplastic Agents; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Infection Control; Injections, Intramuscular; Injections, Intravenous; Leukemia; Mercaptopurine; Methods; Methotrexate; Mitosis; Prednisolone; Remission, Spontaneous; Time Factors; Vincristine

Topics: Acute Disease; Adult; Age Factors; Antineoplastic Agents; Asparaginase; Child; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methods; Methotrexate; Prednisolone; Recurrence; Remission, Spontaneous; Vincristine

Topics: Acute Disease; Antineoplastic Agents; Chlorambucil; Chlorine; Chronic Disease; Daunorubicin; Dimethoate; Drug Therapy, Combination; Ethylamines; Glucocorticoids; Humans; Immunoglobulins; Immunosuppression Therapy; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocyte Count; Lymphocytosis; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous

Topics: Acute Disease; Adult; Aged; Antineoplastic Agents; Blood Coagulation Disorders; Cell Transformation, Neoplastic; Daunorubicin; Humans; Immunotherapy; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Middle Aged; Mitosis; Prednisolone; Prednisone; Remission, Spontaneous; Vincristine

Topics: Asparaginase; Blood Transfusion; Cytarabine; Daunorubicin; Humans; Immunotherapy; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocytes; Meninges; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous

Topics: Antineoplastic Agents; Child; Fluorouracil; Forecasting; Humans; Leukemia; Mercaptopurine; Methotrexate; Neoplasms; Prognosis

Topics: Adrenal Cortex Hormones; Aminopterin; Antineoplastic Agents; Asparaginase; Child; Child, Preschool; Chlorambucil; Cyclophosphamide; Cytarabine; Daunorubicin; Fluorouracil; Humans; Leukemia; Lymphoma; Mercaptopurine; Methotrexate; Nitrogen Mustard Compounds; Procarbazine; Sarcoma; Vinblastine; Vincristine

Topics: Acute Disease; Age Factors; Child; Diagnostic Errors; Drug Synergism; Family Practice; Follow-Up Studies; Humans; Leukemia; Mercaptopurine; Methotrexate; Referral and Consultation; Remission, Spontaneous; Time Factors

Topics: Acute Disease; Administration, Oral; Adult; Age Factors; Body Weight; Burkitt Lymphoma; Carcinoma, Squamous Cell; Child; Choriocarcinoma; Drug Combinations; Female; Folic Acid Antagonists; Humans; Injections, Intramuscular; Injections, Intravenous; Leukemia; Mercaptopurine; Methotrexate; Prednisone; Pregnancy; Time Factors; Vincristine

Topics: Allopurinol; Animals; Antimetabolites; Azathioprine; Cell Division; Chemical Phenomena; Chemistry; Cytarabine; DNA, Neoplasm; Fluorouracil; Folic Acid Antagonists; Humans; Leukemia; Mercaptopurine; Methotrexate; Neoplasms; Pyrimidines; Thioguanine

Topics: Antineoplastic Agents; Asparaginase; Daunorubicin; Humans; Leucovorin; Leukemia; Lymphatic Diseases; Mercaptopurine; Methotrexate; Prednisolone; Vincristine

Topics: Adrenal Cortex Hormones; Alkylating Agents; Antineoplastic Agents; Asparaginase; Busulfan; Chlorambucil; Cyclophosphamide; Cytarabine; Daunorubicin; Leukemia; Mannomustine; Mercaptopurine; Methotrexate; Vincristine

Topics: Busulfan; Cytarabine; Dexamethasone; DNA; DNA, Neoplasm; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Mercaptopurine; Nucleic Acids; Prednisolone; Pyrimidines; RNA; RNA, Neoplasm

Topics: Acute Disease; Adrenal Cortex Hormones; Antineoplastic Agents; Asparaginase; Blood Transfusion; Cyclophosphamide; Diagnosis, Differential; Humans; Immunization; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Nitroso Compounds; Prednisolone; Vincristine

Topics: Alkaloids; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Cell Nucleus; Cell Transformation, Neoplastic; Colchicine; Colchicum; DNA; Drug Synergism; Glutamine; Glycolysis; Humans; Leukemia; Mercaptopurine; Methotrexate; Mitosis; Neoplasms; Plant Extracts; Plants, Medicinal; Plants, Toxic; Podophyllum; Prednisone; Purines; Pyrimidines; RNA; Steroids; Vincristine

Topics: Adrenal Cortex Hormones; Antimetabolites; Asparaginase; Humans; Leukemia; Mercaptopurine; Methotrexate; Prednisone

Topics: Anilides; Animals; Cell Division; Cyclophosphamide; Cytarabine; DNA, Neoplasm; Fluorouracil; Humans; Hydroxyurea; In Vitro Techniques; Leukemia; Leukemia L1210; Leukemia, Lymphoid; Mechlorethamine; Mercaptopurine; Methotrexate; Mice; Mitosis; Nitroso Compounds; Prednisone; Thymidine; Time Factors; Tritium; Vinblastine; Vincristine

Topics: Acute Disease; Animals; Asparaginase; Burkitt Lymphoma; Child; Cyclophosphamide; Cytarabine; Dactinomycin; Daunorubicin; Fluorouracil; Humans; Leukemia; Melphalan; Mercaptopurine; Methotrexate; Mice; Oncogenic Viruses; Prednisolone; Prednisone; Vincristine

Topics: Adrenal Cortex Hormones; Age Factors; Anti-Bacterial Agents; Asparaginase; Blood Platelets; Blood Transfusion; Bone Marrow Cells; Cyclophosphamide; Cytarabine; Folic Acid Antagonists; Humans; Leukemia; Mercaptopurine; Metals; Methotrexate; Prognosis; Radioisotopes; Radiotherapy; Staphylococcal Infections; Steroids; Vincristine

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Chloroquine; Cyclophosphamide; Cytarabine; Drug Synergism; Fluorouracil; Humans; Japan; Leukemia; Lymphoma; Mercaptopurine; Mitomycins; Neoplasms; Podophyllin; Prednisolone; Thiotepa; Vincristine; Vitamin K 1

Topics: Asphyxia; Blood Transfusion, Intrauterine; Child; Cyclophosphamide; Erythroblastosis, Fetal; Female; Fetal Death; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Infant, Newborn, Diseases; Leukemia; Medical Records; Mercaptopurine; Methotrexate; Prednisolone; Pregnancy; Transposition of Great Vessels; Vincristine

Topics: Acute Disease; Age Factors; Antineoplastic Agents; Child; Cyclophosphamide; Glucocorticoids; Humans; Leukemia; Mercaptopurine; Methotrexate; Prognosis; Time Factors; Vincristine

Topics: Adult; Allopurinol; Amidohydrolases; Antimetabolites; Cytarabine; Enzyme Inhibitors; Female; Fluorouracil; Folic Acid Antagonists; Humans; Leukemia; Ligases; Male; Mercaptopurine; Middle Aged; Thymidine Kinase; Xanthine Oxidase

Topics: Acute Disease; Adrenal Cortex Hormones; Chronic Disease; Humans; Leukemia; Mercaptopurine; Methotrexate; Vincristine

Topics: Adrenal Cortex Hormones; Folic Acid Antagonists; Humans; Leukemia; Mercaptopurine

Topics: Acid Phosphatase; Alkaline Phosphatase; Biochemical Phenomena; Biochemistry; Carbohydrate Metabolism; DNA; Folic Acid Antagonists; Glutathione; Heparin; Histamine; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Lipid Metabolism; Lymphocytes; Mercaptopurine; Metabolism; Pathology; Peroxidases; Phagocytosis; Plasminogen; Pyrimidines; RNA; Thymidine; Trace Elements

Topics: Allopurinol; Antineoplastic Agents; Blood Transfusion; Cyclophosphamide; Humans; Injections, Intravenous; Leukemia; Mercaptopurine; Methotrexate; Prednisone; Time Factors; Vincristine

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Antineoplastic Agents; Busulfan; Cyclophosphamide; Folic Acid Antagonists; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine

The purpose of this study was to determine the effectiveness of intravenous ondansetron in preventing vomiting after the administration of intrathecal chemotherapy in children.. Twenty-six children (ages 18 mo to 15 y) receiving intrathecal chemotherapy with either methotrexate or the combination of methotrexate, hydrocortisone, and Ara-C for the prophylactic treatment of central nervous system leukemia were randomly assigned to receive an infusion of normal saline or ondansetron at one of two doses (0.15 or 0.45 mg/kg) 30 minutes before undergoing the procedure. One hundred forty-six infusions were administered (51 placebo, 47 at the lower ondansetron dose, and 48 at the higher dose). Each patient acted as his or her own control, and each patient was studied at least three times.. Twenty-three of 26 patients (88.5%) had postprocedural vomiting on at least one occasion. At least one episode of vomiting occurred during the 24 hours after the procedure in fifty-two of the procedures (35.6%). The incidence of vomiting was significantly greater after infusion of placebo than after either low-dose or high-dose ondansetron. The likelihood of severe vomiting was even more significantly reduced by the preadministration of ondansetron. Almost all of the intrathecal treatments associated with severe vomiting occurred after the infusion of placebo.. Vomiting induced by intrathecal chemotherapy can be greatly reduced by the intravenous administration of ondansetron before the procedure, and severe vomiting can be virtually eliminated.

Topics: Adolescent; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cross-Over Studies; Cytarabine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Headache; Humans; Hydrocortisone; Injections, Intravenous; Leukemia; Male; Mercaptopurine; Methotrexate; Nausea; Ondansetron; Risk; Serotonin Antagonists; Treatment Outcome; Vincristine; Vomiting

Ten per cent of children entered into the national leukaemia study UKALL VIII were under 2 years at diagnosis. The 6 year event-free survival of this cohort was 39%. Specific adverse features were age under 1 year, high initial white cell count and null cell ALL. Those with common ALL, WBC 10-50 x 10(9) 1-1 and especially those aged 18 months or older did not have an adverse prognosis compared with the whole trial entrants. Overall, however there was a doubling of CNS relapse rate and of both induction and remission deaths. Those with a WBC under 10 x 10(9) 1-1 had a high haematological relapse rate. The type of leukaemia and method of management rather than specifically the age appeared to be the predictor for poor outcome.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bone Marrow Transplantation; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Infant; Leukemia; Male; Mercaptopurine; Methotrexate; Prednisone; Radiotherapy Dosage; Time Factors; Treatment Outcome; United Kingdom; Vincristine

For over 30 years, oral 6-mercaptopurine (6-MP) has been a mainstay of systemic maintenance therapy for acute lymphoblastic leukemia. Despite its efficacy as an antileukemic agent, 6-MP has not been previously administered by the intrathecal (IT) route. In anticipation of a clinical trial of IT 6-MP, preclinical cytotoxicity and pharmacology studies were performed to define a safe, effective dose. The optimal concentration (greater than 1 microM) and duration of exposure (greater than 12 h) to 6-MP required for cytotoxicity were determined in vitro using human leukemia cell lines. The dose required to achieve the desired cerebrospinal fluid concentrations in humans was derived from pharmacokinetic parameters determined in rhesus monkeys. A phase I/II study was then performed in pediatric patients with refractory meningeal leukemia. Nine patients (aged 3.5 to 16 years) with chronic meningeal leukemia (2 to 6 central nervous system relapses) were entered onto the study. All had previously failed, at a minimum, IT methotrexate, IT cytarabine, and cranial (+/- spinal) radiation. A 10-mg IT dose of 6-MP (calculated to produce cytotoxic cerebrospinal fluid levels for 12 h) was administered twice weekly for 4 weeks. There were four complete responses and three partial responses. The duration of complete responses ranged from 7 to 22 weeks. Observed toxicities were not dose limiting and included mild headache (three patients) and minimal nausea (two patients). Pharmacokinetic studies performed in patients confirmed that cerebrospinal fluid concentrations of 6-MP were greater than 1 microM for 12 h. These results indicate that the IT administration of 6-MP is feasible, is not associated with significant toxicity, and has definite activity in patients with refractory meningeal leukemia.

Topics: Adolescent; Animals; Child; Child, Preschool; Drug Evaluation; Female; Humans; Injections, Spinal; Leukemia; Lymphoma, Non-Hodgkin; Macaca mulatta; Male; Meningeal Neoplasms; Mercaptopurine; Tumor Cells, Cultured

BHAC-MMP therapy, a combination of behenoyl-ara-C, mitoxantrone, 6-mercaptopurine and prednisolone, was applied to 49 patients with acute leukemia for remission induction. Complete remission was obtained in 6 out of 11 previously untreated patients (55%), and in 16 of 38 pretreated patients (42%). Median duration of complete remission was 41 weeks in previously treated patients, while 67% of untreated patients were still in complete remission. Most frequent side effects other than hematological toxicities were gastrointestinal disturbances, and GPT elevation etc., although most of these were not severe. In conclusion, BHAC-MMP therapy seems to be very promising for remission induction or for possible intensification treatment for acute leukemia.

Topics: Acute Disease; Adolescent; Adult; Aged; Anthraquinones; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Cytarabine; Female; Humans; Leukemia; Leukemia, Lymphoid; Male; Mercaptopurine; Middle Aged; Mitoxantrone; Prednisolone

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Clinical Trials as Topic; Cytarabine; Female; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Mitoxantrone; Prednisolone; Vincristine

We have recently performed a prognostic investigation of a randomized controlled trial with bestatin for acute non-lymphocytic leukemia in adults. Out of 115 patients registered in this study, 101 patients (48 in a bestatin group and 53 in a control group) were evaluated as eligible. The 50% remission duration was 20.4 months for the bestatin group compared with 11.3 months for the control group. Long-term remission rate at 4 years was 36.5% for the bestatin group compared with 24.1% for the control group, and their respective 50% survival time were 33.0 and 18.1 months, while the long-term survival rate at 4 years was 46.0% for the bestatin group compared with 25.5% for the control group. The bestatin group had a longer remission duration and survival time than the control group. The remission duration and survival time in patients under 49 years of age were not different between the groups. However, in patients over 50 years of age, the bestatin group had a significantly longer remission duration and survival time than the control group. Side effects of bestatin were mild and transient. These data suggest the usefulness of bestatin for the treatment of adult acute nonlymphocytic leukemia.

Topics: Aclarubicin; Acute Disease; Adjuvants, Immunologic; Adolescent; Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Follow-Up Studies; Humans; Leucine; Leukemia; Mercaptopurine; Middle Aged; Naphthacenes; Prednisolone; Prognosis; Random Allocation

From 1976 until 1978, 136 adult patients with acute leukemia were treated in four hospitals in Berlin. A complete remission was achieved in 47 patients (35%). Twenty-six patients with non-lymphocytic acute leukemia, who had achieved a complete remission with induction chemotherapy consisting of daunorubicin (45 mg/m2/day, day 1, 2 and 3) and cytosine-arabinoside (100 mg/m2/day, continuous infusion, day 1 to day 7) were entered into a randomized trial. Thirteen patients were treated with an intermittent combination chemotherapy at 4-week intervals; the other group of patients received in addition a specific immunotherapy consisting of neuraminidase-modified allogeneic blast cells. The results revealed that the addition of this kind of immunotherapy did not increase the duration of first remission or survival.

Topics: Adolescent; Adult; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Humans; Immunotherapy; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Thioguanine; Vincristine

Topics: Acute Disease; Adolescent; Adult; Aged; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Inosine; Leukemia; Male; Mercaptopurine; Methylthioinosine; Middle Aged; Time Factors

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone

The urinary excretion of 4-aminimidazole-5-carboxamide (AIC) as been reported to be increased in children with acute leukemia and has been correlated with disease status. Using a modification of the method of Skibba et al [5], determinations were made on urine from 26 children with acute leukemia. The urine from ten normal children served as controls. The effect of chemotherapy on urinary AIC was studied comparing patients on vincristine and prednisone (V+P) with those on 6-mercaptopurine, methotrexate, and cyclophosphamide (Triple Rx). Patients in remission on Triple Rx had lower levels of urinary AIC than did patients on Triple Rx in relapse or patients on V+P in either remission or relapse. Twenty patients had sequential measurements. Values for individual patients were not predictive of disease status. One such patient is described. This study demonstrates that chemotherapy, as well as disease status, affects the urinary excretion of AIC in children with acute leukemia.

Topics: Acute Disease; Adolescent; Aminoimidazole Carboxamide; Antineoplastic Agents; Child; Child, Preschool; Clinical Trials as Topic; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Imidazoles; Infant; Leukemia; Male; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

This study was designed to determine if resistance to a standard drug during the second remission of children with acute leukemia was reduced by discontinuation of therapy during the initial remission. The initial maintenance therapy was either 6-mercaptopurine (6-MP), methotrexate (MTX), or cyclophosphamide (CYC) given continuously to relapse or discontinued (at random) at 2 or 6 months. Following the initial relapse and after induction of a second complete remission, 72 evaluable patients received (continuously to relapse) either 6-MP (53 patients) or CYC (19 patients) for the second remission maintenance. Resistance of 6-MP occurred during the second maintenance, regardless of the drug used during the initial maintenance, in that the length of second remissions was significantly shorter than the length of first remissions. However, this resistance was most pronounced in patients who initially relapsed while on continuous 6-MP maintenance (medium duration of remission [MDR] of 9 weeks). Patients whose initial relapse occurred after the discontinuation of 6-MP had a MDR of 23 weeks and patients whose second remission was maintained with CYC (after relapse from initial continuous remission on 6-MP) had a MDR of 25 weeks.

Topics: Acute Disease; Antineoplastic Agents; Child; Clinical Trials as Topic; Cyclophosphamide; Drug Resistance; Follow-Up Studies; Humans; Leukemia; Mercaptopurine; Methotrexate; Neoplasm Recurrence, Local; Remission, Spontaneous

Of 41 adults with a diagnosis of acute leukemia that were randomized for induction therapy in combination with methotrexate, 6-MP, vincristine and prednisone (POMP) versus a combination of cytosine arabinoside, cytoxan, vincristine and prednisone (COAP), 23 (56%) patients achieved a complete remission. During remission, patients received consolidation therapy with the three courses of remission induction regimen that they had not received initially. They then received daunomycin (three courses) and L-asparaginase and were then maintained for two years with their induction therapy. The median duration of survival for all patients was 40 weeks; the median duration of survival of those patients that responded to chemotherapy was 80 weeks. There was no significant difference between the two induction regimens with regard to complete remission more than four and one half years from diagnosis and two and one half years from discontinuation of all therapy.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Agents; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Drug Administration Schedule; Female; Humans; Infant; Infant, Newborn; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Remission, Spontaneous; Vincristine

Remission induction therapy with 6MP and adriamycin in combination was administered to 19 adult leukemic patients refractory to previous therapy. Eight patients also received vincristine and prednisone. Thirteen patients had acute myelogenous leukemia, 3 undifferentiated leukemia, and 3 blastic transformation of chronic myelogenous leukemia. Four patients achieved remission but in only 2 were the remissions complete. Eleven patients failed to respond. Ten of the 19 patients developed unexpected severe liver toxicity manifested by a clinical picture of cholestasis (in the majority) or ascending cholangitis (in 2 patients). In the postmortem examination of 8 patients there was cholestasis and mild to severe hepatocellular damage in all.

Topics: Acute Disease; Adult; Blood Cell Count; Clinical Trials as Topic; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leukemia; Male; Mercaptopurine; Remission, Spontaneous; Time Factors

In 67 patients with acute leukemia 76 treatment-series were performed which were analyzed to evaluate whether chemotherapy has brought some progress during the past years. With 67 sufficient treatments a total of 26 remissions were achieved. VIDaP-scheme with 43 p.c. and cytosinarabinosid with 46 p.c. were significantly superior to the older scheme methotrexat-purinethol-prednisone with only 29 p.c. remissions. A remarkable deterioration of prognosis with increasing age rises the question whether treatment with cytotoxic drugs should be tried in patients more than 60 years old. Remission rate in patients below 20 was especially high with 71 p.c. so that the well-known good prognosis of juvenile leukemia can be extended with some limitations until age 20.

Topics: Acute Disease; Adolescent; Adult; Age Factors; Aged; Aminosalicylic Acids; Antineoplastic Agents; Cytarabine; Drug Combinations; Esterases; Histocytochemistry; Humans; Leukemia; Mercaptopurine; Methotrexate; Middle Aged; Peroxidases; Prednisone; Prognosis; Remission, Spontaneous; Vincristine

A total of 313 patients with childhood acute leukemia received a combination of vincristine (2 mg/m2/week) and prednisone (60 mg/m2/day); 86% of 276 evaluable patients achieved a complete bone marrow remission in a median of 35 days. When a complete bone marrow remission was achieved, patients were randomized to one of three oral maintenance therapies: 6-mercaptopurine (6MP) (75 mg/m2/day), methotrexate (MTX) (25 mg/m2/twice weekly), or cyclophosphamide (CYC) (100 mg/m2/day). Patients receiving maintenance therapy were further randomized at 2 and 6 months after the start of maintenance either to continue or discontinue therapy. tthe median lengths of subsequent bone marrow remission for patients randomized at 2 months to continue vs. discontinue therapy were: 37 vs. 19 weeks for 6-MP patients; 25 vs. 14 weeks for MTX patients; and 29 vs. 13 weeks for CYC patients. The median lengths of subsequent marrow remissions for patients receiving maintenance therapy for 6 months and randomized to continue vs. discontinue were: 57 vs. 17 weeks for 6-MP patients; 60 vs. 40 weeks for MTX patients; and 23 vs. 10 weeks for CYC patients. Results indicate a significant advantage for continuing maintenance therapy at 2 and 6 months after the start of complete bone marrow remission.

Topics: Acute Disease; Adolescent; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Infant; Infant, Newborn; Leukemia; Male; Mercaptopurine; Methotrexate; Prednisone; Pregnancy; Vincristine

A total of 180 children with acute leukemia was randomized to one of two induction regimens: vincristine plus prednisone, or 6-mercaptopurine plus prednisone. Of 170 patients evaluable for induction therapy, a hematologic remission was achieved in 83% (72/87) on vincristine plus prednisone, and in 93% (77/83) on 6-mercaptopurine plus prednisone. When hematologic remission was achieved, patients were randomized to one of three maintenance schedules: 6-mercaptopurine alone, 6-mercaptopurine plus prednisone for 4 weeks every 3 months, or 6-mercaptopurine plus prednisone plus vincristine for 4 weeks every 3 months. The durations of hematologic remission were compared from the achievement of hematologic remission to bone marrow relapse. The survival data were presented as an overview of the effect of this initial therapy on duration of survival. There was no statistical difference between the two induction regimens. The most important finding in the comparison of the three maintenance schedules was that reinforcement of 6-mercaptopurine maintenance therapy with either prednisone or prednisone plus vincristine resulted in significantly longer durations of remission. Vincristine added to prednisone for reinforcement after induction of remission by vincristine plus prednisone did not increase the duration of hematologic remission or survival over prednisone reinforcement alone.

Topics: Acute Disease; Adolescent; Child; Drug Therapy, Combination; Humans; Leukemia; Mercaptopurine; Prednisone; Remission, Spontaneous; Time Factors; Vincristine

This was designed to compare vincristine-prednisone (VP) vs. prednisolone, vincristine, methotrexate, and 6-mercaptopurine (POMP) with respect to response rates and toxicity for induction therapy in acute leukemia. Children with acute lymphoblastic, acute undifferentiated, or acute stem cell leukemia were stratified on the basis of initial leukocyte count and age, then randomly assigned to POMP or VP induction therapy. On the POMP regime, 19/34 (56%) achieved complete remission (CR), 7 achieved partial remission (PR), and 5 did not respond (NR). Three died prior to day 25 of the study. On the VP regime, 37/39 (95%) had CR, and 2 NR. On the VP regime neither sepsis nor toxicity were significant problems. The POMP regime had a higher incidence of sepsis and other toxicities frequently causing therapy interruption, but not enequivocally causing the poor response rate. Several other factors were evaluated as possible causes for the lack of response to POMP therapy.

Topics: Acute Disease; Adolescent; Child; Child, Preschool; Drug Therapy, Combination; Humans; Infant; Leukemia; Mercaptopurine; Methotrexate; Prednisolone; Prednisone; Vincristine

Topics: Adolescent; Antibiotics, Antineoplastic; Child; Child, Preschool; Clinical Trials as Topic; Colonic Neoplasms; Cyclophosphamide; Drug Combinations; Evaluation Studies as Topic; Female; Fluorouracil; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

Topics: Acute Disease; Bone Marrow Examination; Child; Cyclophosphamide; Humans; Leukemia; Mercaptopurine; Methotrexate; Prednisone

Topics: Alopecia; Antibody Formation; Bone Marrow; Bone Marrow Cells; Child; Child, Preschool; Chromosome Aberrations; Daunorubicin; Drug Hypersensitivity; Heart; Humans; Immunosuppressive Agents; Inflammation; Intestinal Mucosa; Leukemia; Leukocytes; Leukopenia; Lymphocyte Activation; Mercaptopurine

Topics: Adolescent; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Infant; Leukemia; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Vincristine

Topics: Adult; Azathioprine; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lung Diseases; Male; Mercaptopurine; Radiography, Thoracic; Vincristine

Topics: Adolescent; Australia; Child; Child, Preschool; Clinical Trials as Topic; Cyclophosphamide; Female; Humans; Infant; Leukemia; Male; Mercaptopurine; Methotrexate; Vincristine

Topics: Adolescent; Adult; Drug Synergism; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Prednisone

Topics: Adolescent; Adult; Aged; Blood; Clinical Trials as Topic; Humans; In Vitro Techniques; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Middle Aged; Prednisone; Prognosis; Statistics as Topic

Topics: Adolescent; Alopecia; Child; Child, Preschool; Cyclophosphamide; Cystitis; Drug Synergism; Female; Humans; Leukemia; Male; Mercaptopurine; Prednisone

Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone

It has been suggested that childhood asthma lowers the risk of childhood leukaemia. Studies have found an inverse association between these conditions. However, most studies on this relationship are based on questionnaires and telephone interviews, introducing recall bias. Therefore, we conducted a matched case-control study based on drug prescription data to assess the relationship between both conditions.. In a large database, covering more than one million individuals, we identified cases of children who had been prescribed 6-mercaptopurine (6-MP). This drug is used in the outpatient maintenance therapy of childhood leukaemia. We matched every child with leukaemia on sex and age (±6 months) to children without leukaemia (controls). The variable of having had asthma was defined as receiving at least two prescriptions for an inhaled corticosteroid within 12 months.. We identified 59 children aged 2-18 who had been prescribed 6-MP (cases), and they were matched to 21,918 controls. Of the children with childhood leukaemia, three (5%) had childhood asthma, whereas in the control group 4889 (22%) had childhood asthma (odds ratio [OR] 0.19; 95% confidence interval 0.06-0.60).. In this study on the relationship between childhood asthma and childhood leukaemia, we found a strong inverse association.

Topics: Adrenal Cortex Hormones; Asthma; Case-Control Studies; Child; Humans; Leukemia; Mercaptopurine; Netherlands

Topics: Apoptosis; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Line; Humans; Jurkat Cells; Leukemia; Mercaptopurine; Molecular Docking Simulation; Multidrug Resistance-Associated Proteins

This pilot study explored the feasibility and acceptability of implementing text-based assessments of oral chemotherapy adherence in adolescents and young adults (AYA) with leukemia.. AYA prescribed maintenance 6-mercaptopurine (6MP) received daily text message surveys and utilized an electronic pill bottle for 28 days. Text surveys assessed 6MP adherence and contextual associates (eg, mood). Feasibility was defined by recruitment/retention rates, survey completion rates, cost, and technical issues. After the 28-day period, AYA completed an acceptability survey. Secondary analyses compared text survey and electronic pill bottle adherence rates, and explored the daily associations between contextual factors and 6MP nonadherence.. Eighteen AYA enrolled (M age = 18, range 15-22) and completed study procedures (100% recruitment and retention rates). Adherence survey completion rates were high (M = 88.9%), the technology cost was $204.00, and there were few technical issues. AYA reported high satisfaction with the surveys and perceived them as a helpful medication reminder. While not significantly correlated, survey and electronic pill bottle adherence data converged on the majority of days (>90%). Exploratory analyses showed that AYA were more likely to miss a dose of 6MP on weekends (OR = 2.33, P = .048) and on days when their adherence motivation (OR = 0.28, P = .047) and negative affect (OR = 3.92, P = .02) worsened from their own typical functioning.. For AYA with leukemia, daily text-based surveys are a feasible and acceptable method for delivering medication adherence assessments, and may operate as a short-term intervention. To develop personalized mobile health interventions, findings also highlighted the need to study time-varying predictors of 6MP nonadherence.

Topics: Adolescent; Antimetabolites, Antineoplastic; Female; Humans; Leukemia; Male; Medication Adherence; Mercaptopurine; Motivation; Pilot Projects; Reminder Systems; Surveys and Questionnaires; Text Messaging; Young Adult

As a first-line drug widely used in the treatment of leukemia, 6-MP has obvious effects on leukemia. However, 6-MP disadvantages such as poor solubility in water, easy binding with serum proteins, short circulation time, and large toxic and side effects greatly limit the application of 6-MP. For this reason, various 6-MP nano drug-loading systems have been designed to increase the water solubility of 6-MP, extend the circulation time, and increase the bioavailability of 6-MP to a certain extent, reducing its toxic and side effects. However, its therapeutic effect

Topics: Cell Line, Tumor; Drug Liberation; Humans; Hyaluronan Receptors; Hyaluronic Acid; Leukemia; Mercaptopurine; Nanomedicine; Nanoparticles; Prodrugs

Thiopurines are widely used as antileukemia agents and immunosuppressants. Recent large-scale clinical studies revealed a strong association between the NUDT15 p.Arg139Cys (NUDT15

Topics: Animals; DNA Repair; Female; Flow Cytometry; Gene Knock-In Techniques; Genotype; Hematopoietic Stem Cells; Humans; Leukemia; Leukopenia; Male; Mercaptopurine; Mice; Mice, Inbred C57BL; Mice, Transgenic; Polymorphism, Genetic; Pyrophosphatases

In this work, a nanohybrid-based imprinted polymer consisting of N-doped hollow carbon nanospheres and palladium is reported for the electroanalysis of ultratrace level of anticancer drug, 6-mercaptopurine, used in the treatment of leukemia. For this, N-doped carbon nanospheres decorated with palladium were first developed, and subsequently, a molecular imprinted polymer layer was grown onto their surfaces. The so-produced silica-embedded nanocomposite was made hollow by etching silica moieties with hydrofluoric acid. Finally, the whole system was doped on an ionic-liquid-modified pencil graphite electrode. The underlying synergistic effect of hollow carbon nanosphere-supported palladium nanoparticles inculcated electrocatalytic action. Notably, all rebinding sites in solid core-shells were confined within the shell, which hampers the effective diffusion of template. However, in this work, an effective diffusion of template across the hollow structure of inner and outer surfaces was observed. Consequently, this rendered approximately 2-fold heterogeneous rate constant as compared to the solid core-shell-based sensor. Differential pulse voltammetric transduction was used for ultratrace detection of 6-mercaptopurine through anodic stripping method. The hollow imprinted sensor revealed a linear dependence of current with concentration range 0.80-70.748 ng mL

Topics: Antineoplastic Agents; Carbon; Electrochemical Techniques; Electrodes; Humans; Leukemia; Limit of Detection; Mercaptopurine; Molecular Imprinting; Nanocomposites; Nanospheres; Nitrogen; Palladium; Pharmaceutical Preparations; Polymers; Reproducibility of Results

Thiopurines (eg, 6-mercaptopurine [MP]) are highly efficacious antileukemic agents, but they are also associated with dose-limiting toxicities. Recent studies by us and others have identified inherited

Topics: Animals; Antimetabolites, Antineoplastic; Child; CRISPR-Cas Systems; Drug Dosage Calculations; Drug Evaluation, Preclinical; Gene Deletion; Gene Editing; Genotype; Humans; Leukemia; Mercaptopurine; Mice; Mice, Knockout; Phosphoric Diester Hydrolases; Pyrophosphatases

Improving medication adherence among children with B-cell precursor acute lymphoblastic leukemia (B-ALL) has the potential to reduce relapse rates but requires an investment in resources. An economic evaluation is needed to understand the potential costs and benefits of delivering adherence-promotion interventions (APIs) as part of standard clinical care.. A Markov decision analytic model was used to simulate the potential incremental cost-effectiveness per quality-adjusted life year (QALY) to be gained from an API for children with B-ALL in first continuous remission compared with treatment as usual (TAU, no intervention). Model parameter estimates were informed by previously published studies. The primary outcome was incremental cost (2015 US$) per QALY gained for API compared with TAU.. The model predicts the API to result in superior health outcomes (4.87 vs. 4.86 QALYs) and cost savings ($43,540.73 vs. $46,675.71) as compared with TAU, and simulations indicate that, across a range of plausible parameter estimates, there is a 95% chance that the API is more effective and less costly than TAU. The API was estimated to remain more effective and less costly than TAU in situations where the prevalence of nonadherence exceeds 32% and when API improves baseline adherence in at least 3% of patients.. Providing APIs to children with B-ALL may improve health outcomes and save costs over a 6-year period.

Topics: Adolescent; Adult; Antimetabolites, Antineoplastic; Child; Child, Preschool; Cost Savings; Cost-Benefit Analysis; Humans; Infant; Leukemia; Markov Chains; Medication Adherence; Mercaptopurine; Quality-Adjusted Life Years; Young Adult

For enhanced intracellular accumulation of 6-mercaptopurine (6-MP) in leukemia, a folate receptor-targeted and glutathione (GSH)-responsive polymeric prodrug nanoparticle was made. The nanoparticles were prepared by conjugating 6-MP to carboxymethyl chitosan via a GSH-sensitive carbonyl vinyl sulfide linkage, ultrasonic self-assembly and surface decoration with folate. The TEM graphs shows that the as-synthesized nanoparticles are spherical with a particle size of 170~220 nm. In vitro drug release of nanoparticles demonstrated acceptable stability in PBS containing 20 μM GSH at pH 7.4. However, the cumulative drug release rate of the samples containing 20 mM and 10 mM GSH medium reached 78.9% and 64.8%, respectively, in pH 5.0 at 20 h. This indicated that this nano-sized system is highly sensitive to GSH. The inhibition ratio of folate-modified nanoparticles compared to unmodified nanoparticles was higher in cancer cells (human promyelocytic leukemia cells, HL-60) while their cytotoxicity was lower in normal cells (mouse fibroblast cell lines, L929). Furthermore, in vitro cancer cell incubation studies confirmed that folate-modified nanoparticles therapeutics were significantly more effective than unmodified nanoparticles therapeutics. Our results suggest that folate receptor-targeting and GSH-stimulation can significantly elevate tumour intracellular drug release. Therefore, folate-modified nanoparticles containing chemoradiotherapy is a potential treatment for leukemia therapy.

Topics: Animals; Antimetabolites, Antineoplastic; Chemoradiotherapy; Drug Carriers; Drug Liberation; Drug Screening Assays, Antitumor; Drug Stability; Fibroblasts; Folate Receptors, GPI-Anchored; Folic Acid; Glutathione; HL-60 Cells; Humans; Leukemia; Mercaptopurine; Mice; Microscopy, Electron, Transmission; Nanoparticles

Drug repositioning is the application of the existing drugs to new uses and has the potential to reduce the time and cost required for the typical drug discovery process. In this study, we repositioned thiopurine drugs used for the treatment of acute leukaemia as new tyrosinase inhibitors. Tyrosinase catalyses two successive oxidations in melanin biosynthesis: the conversions of tyrosine to dihydroxyphenylalanine (DOPA) and DOPA to dopaquinone. Continuous efforts are underway to discover small molecule inhibitors of tyrosinase for therapeutic and cosmetic purposes. Structure-based virtual screening predicted inhibitor candidates from the US Food and Drug Administration (FDA)-approved drugs. Enzyme assays confirmed the thiopurine leukaemia drug, thioguanine, as a tyrosinase inhibitor with the inhibitory constant of 52 μM. Two other thiopurine drugs, mercaptopurine and azathioprine, were also evaluated for their tyrosinase inhibition; mercaptopurine caused stronger inhibition than thioguanine did, whereas azathioprine was a poor inhibitor. The inhibitory constant of mercaptopurine (16 μM) was comparable to that of the well-known inhibitor kojic acid (13 μM). The cell-based assay using B16F10 melanoma cells confirmed that the compounds inhibit mammalian tyrosinase. Particularly, 50 μM thioguanine reduced the melanin content by 57%, without apparent cytotoxicity. Cheminformatics showed that the thiopurine drugs shared little chemical similarity with the known tyrosinase inhibitors.

Topics: Acute Disease; Antimetabolites, Antineoplastic; Azathioprine; Catalytic Domain; Drug Repositioning; Enzyme Assays; Enzyme Inhibitors; Humans; Leukemia; Melanins; Melanoma, Experimental; Mercaptopurine; Molecular Docking Simulation; Monophenol Monooxygenase; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Structure-Activity Relationship; Thioguanine; Tumor Cells, Cultured

We performed a genomewide association study (GWAS) of primary erythrocyte thiopurine S-methyltransferase (TPMT) activity in children with leukemia (n = 1,026). Adjusting for age and ancestry, TPMT was the only gene that reached genomewide significance (top hit rs1142345 or 719A>G; P = 8.6 × 10

Topics: Antimetabolites, Antineoplastic; Child; Dose-Response Relationship, Drug; Female; Genome-Wide Association Study; Genotype; Humans; Leukemia; Male; Mercaptopurine; Methyltransferases; Pharmacogenetics; Polymorphism, Single Nucleotide

Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Child; History, 20th Century; Humans; Leukemia; Mercaptopurine; Methotrexate; Prednisone; Remission Induction

The pharmacokinetics and pharmacodynamics of therapeutic drugs can greatly vary among individuals. For example, it is sometimes necessary to alter the treatment of childhood acute lymphoblastic leukemia from the standard protocol. Genetic variation is one important factor, which can exert a wide range of effects on sensitivities and responses to therapeutic agents. Thiopurine S-methyl transferase (TPMT) is a useful test for predicting 6-mercaptopurine (6-MP) sensitivity in Caucasians. However, it is not effective for predicting the 6-MP therapeutic responses of Japanese patients because the frequency of TPMT deficiency is lower in the Japanese population (approximately 1% versus approximately 10% in Caucasians). Recently, NUDT15 polymorphisms have been reported to be predictive factors contributing to responsiveness to thiopurine therapy in Asians. The associations between genetic variants and therapeutic responses have been reported in Western countries. However, questions remain about whether results studying other races are applicable to Japanese due to differences in genetic variant frequencies among races. To provide personalized therapy based on genetic factors, we need to ascertain the relationships between genetic variants and therapeutic responses in Japanese childhood acute lymphoblastic leukemia cases.

Topics: Antimetabolites, Antineoplastic; Humans; Leukemia; Mercaptopurine; Methotrexate; Pharmacogenetics; Polymorphism, Genetic

The coating of an active drug, 6-mercaptopurine, into the iron oxide nanoparticles-polyethylene glycol (FNPs-PEG) in order to form a new nanocomposite, FPEGMP-2, was accomplished using coprecipitation technique. The resulting nanosized with a narrow size distribution magnetic polymeric particles show the superparamagnetic properties with 38.6 emu/g saturation magnetization at room temperature. Fourier transform infrared spectroscopy and the thermal analysis study supported the formation of the nanocomposite and the enhancement of thermal stability in the resulting nanocomposite comparing with its counterpart in free state. The loading of 6-mercaptopurine (MP) in the FPEGMP-2 nanocomposite was estimated to be about 5.6% and the kinetic experimental data properly correlated with the pseudo-second order model. Also, the release of MP from the FPEGMP-2 nanocomposite shows the sustained release manner which is remarkably lower in phosphate buffered solution at pH 7.4 than pH 4.8, due to different release mechanism. The maximum percentage release of MP from the nanocomposite reached about 60% and 97% within about 92 and 74 hours when exposed to pH 7.4 and 4.8, respectively.

Topics: Animals; Cell Line, Tumor; Cell Survival; Drug Delivery Systems; Leukemia; Magnetite Nanoparticles; Mercaptopurine; Mice; Particle Size; Polyethylene Glycols

Thiopurine efficacy is partly reflected by the genetic polymorphism of the thiopurine methyltransferase (TPMT) enzyme, which is responsible for variation in the metabolism, toxicity and therapeutic efficacy of the thiopurines azathioprine (AZA), 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). Determination of TPMT activity before administration of thiopurines is thus crucial for individualized dosing in order to prevent toxicity in TPMT deficient individuals. These individuals must be treated with markedly lower (eg, 5-10% of the standard) doses of the prescribed medications. This paper describes a comparison of three different methods for the quantification of TPMT activity in red blood cells (RBC) and cultured human cell lines. We succeeded to perform the measurement of TPMT activity in a minimum amount of 1×10(6) cultured cells with an HPLC-UV system modified and optimized in our laboratory. The TPMT activity was linearly correlated with the cell concentration of the cultured cell line in a range of 1-10×10(6) cells. A significant correlation of determination of TPMT activity in RBC between radiometric detection by HPLC, classic radiochemical detection and UV detection by HPLC, was observed, correlation coefficient (r) were 0.72 and 0.73, respectively. The within-day and day-to-day coefficients of variation of the HPLC-UV-based method were 8% and 16%, respectively. The evaluation of the methods was demonstrated by studying the TPMT activity in RBC isolated from 198 patients, as well as in MOLT4 leukemic cell line and its sub-cell lines with acquired resistance to 6-MP and 6-TG.

Topics: Cell Line, Tumor; Chromatography, High Pressure Liquid; Enzyme Assays; Humans; Leukemia; Mercaptopurine; Methyltransferases; Reproducibility of Results

We propose a Bayesian approach for estimating the hazard functions under the constraint of a monotone hazard ratio. We construct a model for the monotone hazard ratio utilizing the Cox's proportional hazards model with a monotone time-dependent coefficient. To reduce computational complexity, we use a signed gamma process prior for the time-dependent coefficient and the Bayesian bootstrap prior for the baseline hazard function. We develop an efficient MCMC algorithm and illustrate the proposed method on simulated and real data sets.

Topics: Algorithms; Bayes Theorem; Computer Simulation; Female; Humans; Leukemia; Markov Chains; Mercaptopurine; Monte Carlo Method; Ovarian Neoplasms; Proportional Hazards Models; Stochastic Processes

We describe a pediatric patient with acute leukemia who developed an uncommon but significant metabolic consequence of pegaspargase therapy-severe hypertriglyceridemia (hyperTG). We also relate our experience with continuous insulin infusion treatment for pegaspargase-induced hyperTG. This treatment approach led to a decrease in triglycerides from 4640 mg/dL on admission to 522 mg/dL at discharge 9 days later. Genetic testing revealed that our patient was an apolipoprotein E 3/4 heterozygote. Our review of the literature suggests that apolipoprotein E polymorphism may influence the development of hyperlipidemia in acute lymphoblastic leukemia patients receiving asparaginase therapy and may identify patients at high risk for developing asparaginase-induced hyperTG.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Cyclophosphamide; Cytarabine; Humans; Hypertriglyceridemia; Infusions, Intravenous; Insulin; Leukemia; Male; Mercaptopurine; Polyethylene Glycols

The CD33 antigen is expressed on leukemia cells in most patients with acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL), and in 20% of patients with acute lymphoblastic leukemia (ALL), while it is absent from pluripotent hematopoietic stem cells and nonhematopoietic cells. Gemtuzumab ozogamicin (GO) is an immunoconjugate of an anti-CD33 antibody linked to calicheamicin, which is a potent cytotoxic agent that causes double-strand DNA breaks, resulting in cell death. GO was developed against CD33 antigen-positive leukemias. The aim of this study was to investigate the cytotoxic effects of this agent in combination with conventional antileukemic agents.. The cytotoxic effects of GO in combination with antileukemic agents were studied against human CD33 antigen-positive leukemia HL-60, U937, TCC-S and NALM20 cells. The leukemia cells were exposed simultaneously to GO and to the other agents for 4 days. Cell growth inhibition was determined using a MTT reduction assay. The isobologram method was used to evaluate the cytotoxic interaction.. GO produced synergistic effects with mitoxantrone, additive effects with cytarabine, daunorubicin, idarubicin, doxorubicin, etoposide and 6-mercaptopurine, and antagonistic effects with methotrexate and vincristine.. Our findings suggest that the simultaneous administration of GO with most agents studied would be advantageous for antileukemic activity. The simultaneous administration of GO with methotrexate or vincristine would have little cytotoxic effect, and this combination may be inappropriate. These findings may be useful in clinical trials of combination chemotherapy including GO or other monoclonal antibodies linked to calicheamicin.

Topics: Aminoglycosides; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Cytarabine; Daunorubicin; Dose-Response Relationship, Drug; Doxorubicin; Drug Synergism; Etoposide; Gemtuzumab; HL-60 Cells; Humans; Idarubicin; Immunotoxins; Leukemia; Mercaptopurine; Methotrexate; Mitoxantrone; Sialic Acid Binding Ig-like Lectin 3; U937 Cells; Vincristine

To investigate the mechanism of cellular resistance to 6-MP, we established a 6-MP resistant cell line (CEM-MP5) by stepwise selection of the human T-lymphoblastic leukemia cell line (CEM). CEM-MP5 cells were about 100-fold resistant to 6-MP compared with parental CEM cells. Western blot analysis demonstrated that multidrug resistant protein 4 (MRP4) was increased in CEM-MP5 cells, whereas the levels of the nucleoside transporters hENT1, hCNT2 and hCNT3 were decreased compared with those of parental CEM cells. Consistent with the operation of an efflux pump, accumulation of [14C]6-MP and/or its metabolites was reduced, and ATP-dependent efflux was increased in CEM-MP5 cells. Taken together these results showed that up-regulation of MRP4 and down-regulation of influx transporters played a major role in 6-MP resistance of CEM-MP5 cells.

Topics: Antimetabolites, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Cell Line; Drug Resistance, Neoplasm; Equilibrative Nucleoside Transporter 1; Equilibrative-Nucleoside Transporter 2; Humans; Hypoxanthine Phosphoribosyltransferase; Leukemia; Membrane Transport Proteins; Mercaptopurine; Methyltransferases; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; Nucleoside Transport Proteins; Up-Regulation

6-mercaptopurine and its riboside derivatives are some of the most widely utilized anti-leukemic and anti-inflammatory drugs. Their short biological half-life and severe side effects limit their use. A new delivery method for these drugs based on 4-5 nm gold nanoparticles can potentially resolve these issues. We have found substantial enhancement of the antiproliferative effect against K-562 leukemia cells of Au nanoparticles bearing 6-mercaptopurine-9-beta-d-ribofuranoside compared to the same drug in typically administered free form. The improvement was attributed to enhanced intracellular transport followed by the subsequent release in lysosomes. Enhanced activity and nanoparticle carriers will make possible the reduction of the overall concentration of the drug, renal clearance, and, thus, side effects. The nanoparticles with mercaptopurine also showed excellent stability over 1 year without loss of inhibitory activity.

Topics: Antineoplastic Agents; Flow Cytometry; Gold; Humans; Leukemia; Mercaptopurine; Metal Nanoparticles; Microscopy, Atomic Force; Microscopy, Electron, Transmission

FK228 is a novel antitumor depsipeptide that inhibits histone deacetylases and restores the expression of genes aberrantly suppressed in cancer cells. This agent was shown to have broad antitumor activity in preclinical studies, and is currently under phase I/II evaluations. Because of its wide spectrum of actions, it is reasonable to consider the combination with other anticancer drugs in clinical application. We studied the cytotoxic interaction of FK228 in combination with conventional antileukemic agents using human promyelocytic leukemia HL60, Philadelphia chromosome-positive (Ph(+)) chronic myelogenous leukemia KU-812, T-cell lymphoblastic leukemia MOLT3 and Burkitt's lymphoma Raji cell lines. For the combination of FK228 and imatinib, Ph(+) leukemia KU812, K562 and TCC-S cell lines were used. The cells were exposed simultaneously to FK228 and other agents for 4 days. Cell growth inhibition was determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. We used the isobologram method of Steel and Peckham to evaluate the cytotoxic interaction at the concentration of drugs that produced 80% cell growth inhibition (IC(80)). FK228 showed an additive effect with cytarabine, carboplatin, doxorubicin, etoposide, 4-hydroperoxy-cyclophosphamide, 6-mercaptopurine and SN-38 (active metabolite of irinotecan) in all cell lines studied. FK228 with methotrexate and vincristine showed an antagonistic effect in three and one of the four cell lines, respectively. FK228 was additive with imatinib in all three Ph(+) leukemia cells. Our findings suggest that FK228 is a promising candidate for combining with most anticancer agents except for methotrexate and vincristine, which produce suboptimal effects.

Topics: Antineoplastic Agents; Apoptosis; Benzamides; Camptothecin; Carboplatin; Cell Line, Tumor; Cell Survival; Cyclophosphamide; Cytarabine; Depsipeptides; Dose-Response Relationship, Drug; Doxorubicin; Drug Synergism; Etoposide; Histone Deacetylase Inhibitors; HL-60 Cells; Humans; Imatinib Mesylate; Irinotecan; K562 Cells; Leukemia; Lymphoma; Mercaptopurine; Piperazines; Pyrimidines; Time Factors

6-mercaptopurine (6-MP) is a purine analogue used in childhood leukemia. Because of the oral bioavailability of 6-MP is low and highly variable, the aim of this study was to develop a new parenteral formulation that can prolong the biological half-life of the drug, improve its therapeutic efficacy, and its associated reduce side effects. Conventional and stealth 6-MP liposomes were prepared by a thin film hydration technique followed by a high-pressure homogenization process and characterized for percent entrapment efficiency (%EE), particle size, and stability in human plasma. Pharmacokinetic, tissue distribution, and biochemical analysis were performed after intravenous (IV) administration of all formulations of 6-MP on rats. The conventional liposomes were found less stable than stealth liposomes in human plasma at 37 degrees C. Stealth liposomes exhibited high peak plasma concentration (C(max)), and long circulating capacity in blood and biological half-life. The uptake of stealth liposomes by the liver and spleen and accumulation in the kidney were significantly less than that of conventional liposomes and the free drug. Serum urea, creatinine, GOT (Glutamic Oxaloacetic Transaminase), and GPT (Glutamic Pyruvic Transaminase) increased significantly in rats given an IV injection of conventional liposomes and the free drug, but not in those administered with the same dose of stealth liposomes. Stealth liposomes may help to increase therapeutic efficacy of 6-MP and to reduce total amount of dose as well as frequency of the dose. It also may reduce the possibility of the risk of toxicity to the liver and kidney generally associated with free 6-MP.

Topics: Animals; Antimetabolites, Antineoplastic; Female; Kidney; Leukemia; Liposomes; Liver; Male; Mercaptopurine; Rats; Rats, Inbred Strains; Tissue Distribution

A coefficient of explained randomness, analogous to explained variation but for non-linear models, was presented by Kent. The construct hinges upon the notion of Kullback-Leibler information gain. Kent and O'Quigley developed these ideas, obtaining simple, multiple and partial coefficients for the situation of proportional hazards regression. Their approach was based upon the idea of transforming a general proportional hazards model to a specific one of Weibull form. Xu and O'Quigley developed a more direct approach, more in harmony with the semi-parametric nature of the proportional hazards model thereby simplifying inference and allowing, for instance, the use of time dependent covariates. A potential drawback to the coefficient of Xu and O'Quigley is its interpretation as explained randomness in the covariate given time. An investigator might feel that the interpretation of the Kent and O'Quigley coefficient, as a proportion of explained randomness of time given the covariate, is preferable. One purpose of this note is to indicate that, under an independent censoring assumption, the two population coefficients coincide. Thus the simpler inferential setting for Xu and O'Quigley can also be applied to the coefficient of Kent and O'Quigley. Our second purpose is to point out that a sample-based coefficient in common use in the SAS statistical package can be interpreted as an estimate of explained randomness when there is no censoring. When there is censoring the SAS coefficient would not seem satisfactory in that its population counterpart depends on an independent censoring mechanism. However there is a quick fix and we argue in favour of its use.

Topics: Antimetabolites, Antineoplastic; Humans; Leukemia; Mercaptopurine; Proportional Hazards Models; Remission Induction; Survival Analysis

In this paper, we propose a hybrid variance estimator for the Kaplan-Meier survival function. This new estimator approximates the true variance by a Binomial variance formula, where the proportion parameter is a piecewise non-increasing function of the Kaplan-Meier survival function and its upper bound, as described below. Also, the effective sample size equals the number of subjects not censored prior to that time. In addition, we consider an adjusted hybrid variance estimator that modifies the regular estimator for small sample sizes. We present a simulation study to compare the performance of the regular and adjusted hybrid variance estimators to the Greenwood and Peto variance estimators for small sample sizes. We show that on average these hybrid variance estimators give closer variance estimates to the true values than the traditional variance estimators, and hence confidence intervals constructed with these hybrid variance estimators have more nominal coverage rates. Indeed, the Greenwood and Peto variance estimators can substantially underestimate the true variance in the left and right tails of the survival distribution, even with moderately censored data. Finally, we illustrate the use of these hybrid and traditional variance estimators on a data set from a leukaemia clinical trial.

Topics: Analysis of Variance; Antimetabolites, Antineoplastic; Computer Simulation; Confidence Intervals; Data Interpretation, Statistical; Humans; Leukemia; Mercaptopurine; Randomized Controlled Trials as Topic; Remission Induction; Sample Size; Survival Analysis

Topics: Antimetabolites, Antineoplastic; Chemistry, Pharmaceutical; Drug Design; History, 20th Century; Humans; Leukemia; Mercaptopurine; Nobel Prize; Purines; United States

Methotrexate (MTX) followed by 6-mercaptopurine (6MP) is one of the best known combinations for the treatment of childhood acute lymphoblastic leukaemia. Tiazofurin (TF) and 6-thioguanine (TG) are also used as chemotherapy agents in the treatment of malignancies. We have examined the induction of apoptosis by combinations of these drugs to gain more insights into their efficacy in the treatment of malignancies.. The induction of apoptosis was examined in Molt-4, a human malignant acute lymphoblastic T-cell line. The cells were exposed to increasing drug concentrations at various exposure times. Annexin V/FITC and propidium iodide (PI) were used as markers for apoptosis and cell death. Annexin V/FITC positive and PI positive cells were detected by flow-cytometric analysis.. Sequential 24-h exposure with MTX (0.005-0.02 micro mol) followed by 6MP (1-10 micro mol) and 24-h exposure with TF (5-20 micro mol) followed by TG (0.5-2 micro mol) showed a more than additive induction of apoptosis compared with single-drug exposure. Simultaneous administration of the drugs does not show an additive effect on apoptosis.. The results of this study indicate that sequential administration of MTX before 6MP and of TF before TG may be essential for therapeutic success in the treatment of leukaemia.

Topics: Annexin A5; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cell Survival; Child; Coloring Agents; Humans; Leukemia; Mercaptopurine; Methotrexate; Models, Biological; Purines; Ribavirin; Thioguanine; Time Factors; Tumor Cells, Cultured

High-dose methotrexate (HDM) given concurrently with oral 6-mercaptopurine (6 MP) may be followed by myelotoxicity, which may necessitate treatment interruption and thus interfere with the efficacy of the treatment of childhood acute lymphoblastic leukemia (ALL). Through inhibition of purine de novo synthesis and enhancement of the bioavailability, HDM may increase the incorporation into DNA of 6-thioguanine nucleotides, the cytotoxic metabolites of 6 MP.A total of 26 children diagnosed 3/1996-4/2001 with ALL received five courses of HDM (5 g/m(2)/24 h with leucovorin rescue) at 8 weeks intervals during their first year of maintenance therapy with oral methotrexate (20 mg/m(2)/week) and 6MP (75 mg/m(2)/day). The dose of oral 6MP was reduced to a median of 51% (75% range: 39-62%, maximum 74%) of the standard dose from 2 weeks prior to until 2 weeks after HDM, because the previous HDM had led to a thrombocyte nadir < or =60 x 10(9)/l and/or a neutrophil nadir < or =0.7 x 10(9)/l. The 6MP dose reductions raised the median thrombocyte nadir following HDM from 46 x 10(9)/l (range: 6-214) to 133 x 10(9)/l (range: 21-305; P<0.001) and the median neutrophil nadir from 0.5 x 10(9)/l (range: 0.0-1.4) to 0.9 x 10(9)/l (range: 0.2-3.2; P<0.001). The effect of 6MP dose reductions was not significantly related to risk group, gender, age, or thiopurine methyltransferase genotype. With 6MP dose reductions, the median duration of treatment interruption following HDM was reduced from 8 to 0 days (P < 0.001). The reduction of 6MP dosage during HDM can significantly reduce the risk of severe myelotoxicity and prevent treatment interruptions.

Topics: Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Bone Marrow Cells; Cell Count; Child; Cohort Studies; Dose-Response Relationship, Drug; Female; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Neutrophils

For the purpose of clarifying the influence of thiopurine methyltransferase (TPMT) gene single nucleotide polymorphisms (SNPs) on the efficacy of thiopurines and risk for its toxicity and therefore improving the safety and efficacy of thiopurines, the authors investigated TPMT genotype in acute leukemia in children who were intolerant to the treatment with 6-mercap topurine (6-MP).. TPMT genotype was determined in an unrelated population of 250 Chinese healthy blood donors and 280 children with acute leukemia. TPMT genotyping assay was based on polymerase chain reaction (PCR), restriction digestion of PCR products, denaturing high-performance liquid chromatography (DHPLC) and direct DNA sequencing in the TPMT * 2 (G238C), TPMT * 3A (G460A, A719G) and TPMT * 3C (A719G).. There were 10 TPMT * 1/TPMT * 3C heterozygotes in 280 children. The frequency of the polymorphism was 3.6%. All the involved alleles were TPMT * 3C. Of the 160 children acute leukemia evaluated, 45 (26%) were intolerant to 6-MP. Presentations included hepatotoxicity and hematological toxicity. Six out of 45 children were heterozygous, while the other 39 were wild type homozygous. Before dosage adjustments for thiopurine, the hematologic toxicity and hepatotoxicity in TPMT heterozygous individuals occurred more frequently than in homozygous. Therefore, cases of TPMT heterozygotes experienced more missed doses of 6-MP.. TPMT genotype is associated with tolerance in acute leukemia in children. The heterozygote individuals have low TPMT activity. Therefore the frequencies of hemtopoietic toxicity and hepatoxicity are high after using 6-MP. Detection of SNPs in the TPMT genes is useful in identifying children before administration of 6-MP.

Topics: Acute Disease; Adolescent; Antimetabolites, Antineoplastic; Child; Child, Preschool; Chromatography, Liquid; Drug Resistance, Neoplasm; Exons; Female; Gene Frequency; Genotype; Humans; Infant; Leukemia; Male; Mercaptopurine; Methyltransferases; Polymerase Chain Reaction; Polymorphism, Single Nucleotide

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; History, 20th Century; Humans; Japan; Leukemia; Mercaptopurine; Prednisolone; Vincristine

The efficiency and toxicity of treatment regimens for nonintensive cytoreduction in 57 outpatients with refractory acute leukemia (mean age 56 years, 51 AML, six ALL/AUL) were retrospectively studied. Seventeen patients received one treatment regimen, 19 patients two treatment regimens, and 21 patients three or more treatment regimens. The treatment regimens analyzed were 6-thioguanine p.o. (daily) (T), 6-thioguanine p.o. (4-7 days/week) + cytarabine s.c./i.v. (once a week) (T+C), 6-mercaptopurine p.o. (daily) (MP), 6-mercaptopurine p.o. (daily) + methotrexate p.o./i.v. (once a week) (MP+MTX), etoposide p.o. (daily) (E), and mitoxantrone i.v. (M). The median leukocyte count was higher for M (73 x 10(9)/l) than for the other treatment regimens (T: 27 x 10(9)/l, T+ C: 37 x 10(9)/l, MP: 24 x 10(9)/l, MP + MTX: 30 x 10(9)/l, E: 31 x 10(9)/l). A cytoreduction >50% in the peripheral blood was achieved by T in 11/19, by T+C in 7/11, by MP in 5/8, by MP+MTX in 3/6, by E in 3/4, and by M in 16/22 patients. The period of cytoreduction was regarded as the duration of response - T: median 53 days, range 5-98; T+C: median 61 days, range 14-226; MP: median 37 days, range 4-192; MP + MTX: median 58 days, range 36-59; E: median 121 days, range 26-159; M: median 39 days, range 8-78. T and T + C were well tolerated by all but three patients (stomatitis, diarrhea, WHO grade 2). MP was accompanied by a rise of transaminases (WHO 1-3) in 5/6 patients. E led to stomatitis (WHO 1,2) in 4/5 and M to nausea/vomiting (WHO 1,2) in 5/22 and to stomatitis (WHO 2) in 4/22 cases. The mean survival time after start of palliative cytoreduction was 16 weeks (2-65). In summary, 6-thioguanine +/- cytarabine was best tolerated with effective but in oral monotherapy - often protracted cytoreduction in 60% of patients. Mitoxantrone showed tolerable side effects and potent cytoreduction in 73% of patients even after ineffective palliative pretreatment. Palliative cytoreductive therapy does not reduce the quality of life and can prevent complications of significant leukocytosis in refractory acute leukemia.

Topics: Acute Disease; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Diarrhea; Female; Humans; Injections, Intravenous; Injections, Subcutaneous; Leukemia; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Middle Aged; Nausea; Palliative Care; Retrospective Studies; Stomatitis; Thioguanine

Low entrapment of drugs into liposomes is a serious challenge in their commercial application. 6-Mercaptopurine (6-MP), an antineoplastic agent, is such a drug with low entrapment efficiency (EE). We devised their lipophilic derivatization as a means of enhancing EE by covalently coupling 6-MP with glyceryl monostearate (GMS) via a succinic anhydride spacer. This prodrug had an improved partition coefficient value of 25.16 compared to 1.22 for free drug, confirming higher lipophilicity. A hydrolysis rate study of prodrug indicated 2.90%, 12.5%, 24.1%, and 25.1% hydrolysis in phosphate buffered saline (PBS) (pH 7.4) and 10%, 20%, and 30% serum, respectively. Liposomes of phosphatidylcholine (PC)/sphingomyelin, cholesterol, and dicetyl phosphate bearing drug or prodrug were prepared by shaking by hand and sonication methods. The EE was found to increase from 1.92% for free drug to 91.8% for drug-conjugate. An in vitro cell line toxicity study on L1210 leukemia cells showed improved performance of liposome-encapsulated drug-conjugate compared to free drug. The plasma drug level profile following administration of free drug and the liposomal formulation containing prodrug (HE liposome) manifested a higher sustained level of the latter, which was further improved in case of sphingomyelin-containing liposomes (STHE liposome). The pharmacokinetic parameters revealed an increase in half-life, from 61 min to 120 min for the HE liposomes and 296 min for the STHE liposomes. Therefore, increased entrapment was made possible through lipophilic derivatization, and it was subsequently tested in vivo.

Topics: Animals; Antimetabolites, Antineoplastic; Cholesterol; Female; Half-Life; Leukemia; Liposomes; Male; Mercaptopurine; Organophosphates; Phosphatidylcholines; Prodrugs; Rats; Sphingomyelins; Tumor Cells, Cultured

Most complications of 6-mercaptopurine (6MP) used in the treatment of inflammatory bowel disease (IBD) occur early, whereas neoplasms occur late in the course. Concern persists that the risk is increased when 6MP is used. We report our experience with malignant tumors developing over 27 yr of treating IBD patients with 6MP.. A total of 591 patients with IBD treated with 6MP between 1969 and 1997 were followed or traced until present to identify all malignant tumors and blood dyscrasias that had developed to determine the type, distribution, and duration of the IBD, the dose and duration of 6MP therapy, the concurrent versus previous use of 6MP, the incidence and probable relationship of 6MP to specific neoplasms, and whether the 6MP had been effective in treatment.. A total of 550 patients (93%) fulfilled the criteria for follow-up; these included 380 with Crohn's disease (CD) and 170 with ulcerative colitis (UC). Twenty-five patients had developed neoplasms (16 of 380 CD and nine of 170 UC) (p = 0.66). In half of the cases, the goal of therapy had been achieved with 6MP. In 10 patients, the neoplasm was diagnosed while the patients were taking 6MP (40%) and in 15, many years after the 6MP had been terminated (60%). The incidence of neoplasms (25 of 550) was 2.7/1000 patient-years of follow-up. The most common neoplasms were found in the bowel (eight of 550, 1.6%; five CD, and three UC), and breast (three, 0.5%; two CD, and one UC). Non-Hodgkins lymphomas occurred in two patients with CD; one was cerebral and the other abdominal. One patient with CD developed leukemia. The duration of 6MP therapy ranged from 5 months to 22 yr, with a mean of 5 yr. The dose of 6MP ranged from a quarter of a tablet/day (12.5 mg) to 100 mg/day, with the majority in a range from 50 to 75 mg/day.. In no instance could a neoplasm be attributed to the use of 6MP. The incidence of colon cancer is not greater than that with long standing colitis. Suspicion of a relationship between 6MP and leukemia/lymphoma persists, but the incidence is low. This must be weighed against the improved quality of life due to 6MP for patients with IBD.

Topics: Abdominal Neoplasms; Adult; Aged; Aged, 80 and over; Brain Neoplasms; Breast Neoplasms; Colitis, Ulcerative; Crohn Disease; Drug Administration Schedule; Female; Follow-Up Studies; Hematologic Diseases; Humans; Immunosuppressive Agents; Incidence; Inflammatory Bowel Diseases; Intestinal Neoplasms; Leukemia; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Middle Aged; Neoplasms; Risk Factors; Time Factors

The level of expression of the enzyme thiopurine methyltransferase (TPMT) is an important determinant of the metabolism of thiopurines used in the treatment of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Studies in red blood cells (RBC) have shown that TPMT expression displays genetic polymorphism with 11% of individuals having intermediate and one in 300 undetectable levels. The genetic basis for this polymorphism has now been elucidated and polymerase chain reaction (PCR)-based assays described for the most common mutations accounting for reduced activity. In previous studies, genotype has been correlated with red blood cell activity. In this report, we describe the relationship between genotype and TPMT activity measured directly in the target of drug action, the leukemic cell. We have demonstrated that the TPMT activity in lymphoblasts from 38 children and adults found by PCR to be homozygotes (*1/*1) was significantly higher than that in the five heterozygotes (*1/*3) detected (median, 0.25 v 0.08, P < .002, Mann-Whitney U). Similar results were obtained when results from children were analyzed separately. However, comparison of activity in blasts from AML and ALL showed a higher level in the former (0.35 v 0.22 nU/mg, P < .002, n = 17, 35), suggesting that factors other than genotype may also influence expression.

Topics: Acute Disease; Adolescent; Adult; Aged; Antimetabolites, Antineoplastic; Child; Child, Preschool; Drug Resistance, Neoplasm; Enzyme Induction; Female; Genotype; Humans; Hypoxanthine Phosphoribosyltransferase; Infant; Leukemia; Male; Mercaptopurine; Methyltransferases; Middle Aged; Neoplasm Proteins; Polymorphism, Genetic; Prodrugs; Xanthine Oxidase

The Cox proportional hazards model is the most popular model for the analysis of survival data. The use of cubic spline functions allows investigation of non-linear effects of continuous covariates and flexible assessment of time-by-covariate interactions. Two main advantages are provided--no particular functional form has to be specified and standard computer software packages like SAS or BMDP can be used. A SAS macro which implements the method is presented.

Topics: Antimetabolites, Antineoplastic; Clinical Trials as Topic; Data Interpretation, Statistical; Humans; Leukemia; Mathematical Computing; Mercaptopurine; Proportional Hazards Models; Software; Software Design

Topics: Aclarubicin; Acute Disease; Adult; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cohort Studies; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Etoposide; Female; Finland; Humans; Immunocompromised Host; Incidence; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Mitoxantrone; Pneumonia, Pneumocystis; Prednisone; Premedication; Retrospective Studies; Thioguanine; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

Forty-four adults with AML (n = 18) or ALL (n = 26) beyond first remission underwent unpurged (n = 39) or purged (n = 5) autografting after 110-140 mg/m2 melphalan and 1050 cGy TBI. ALL patients were eligible to receive maintenance chemotherapy with 6-mercaptopurine and methotrexate for 2 years after hematologic recovery. The duration of first remission was 1-167 months (median 11). The median time to 50 x 10(9)/I platelets was 76 days, and that to 0.5 x 10(9)/I neutrophils 31 days. Eight patients died of transplant-related toxicity; seven within 1 year. Twenty-two patients relapsed at 1-20 months (median 2.5 months). The 3-year probabilities (95% CI) of relapse and disease-free survival are 58% (43-75%) and 31% (17-45%), respectively. The duration of the first remission (< 1 year vs > or = 1 year) and the stage of transplant (second remission vs other) had no effect on relapse or disease-free survival. There was a trend towards higher relapse rates (76 vs 34%) and poorer disease-free survival (19 vs 49%) among ALL patients compared with AML which did not reach significant levels due to small patient numbers. We conclude that melphalan-TBI is a suitable conditioning regimen for autografting in advanced leukemia. The outcome of AML patients is comparable to standard regimens, but the outcome of ALL patients is poor and measures to enhance the anti-leukemic efficacy are necessary.

Topics: Acute Disease; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Purging; Bone Marrow Transplantation; Combined Modality Therapy; Disease-Free Survival; Female; Humans; Leukemia; Leukemia, Myeloid; Male; Melphalan; Mercaptopurine; Methotrexate; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Salvage Therapy; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Whole-Body Irradiation

The formation of intracellular thionucleotides are a prerequisite for mercaptopurine (MP) cytotoxicity, and interindividual variations in the inherited level of thiopurine methyltransferase (TPMT) activity regulate their formation. Measurement of pretreatment TPMT activities can identify the TPMT "deficient" patient and, conversely, the individual with very high enzyme activities. The former are at higher risk of acute toxicity and potentially fatal bone marrow failure and the latter of suboptimal treatment. Leukaemic children taking MP therapy who form inadequate amounts of thioguanine nucleotides (TGNs) do not experience drug toxicity and are at an increased risk of disease relapse. When low TGNs are due to very high TPMT activities, thioguanine may be a more appropriate thiopurine. Another cause of inadequate TGN concentrations is partial or noncompliance with oral chemotherapy. Compliance problems can be identified by the measurement of both TGNs and methylated drug metabolites.

Topics: Antimetabolites, Antineoplastic; Azathioprine; Humans; Leukemia; Mercaptopurine; Methyltransferases; Patient Compliance; Polymorphism, Genetic; Thioguanine

In this note we use the Buckley-James method for censored regression in the p sample problem where the samples are subject to right-censoring. The samples are reconstructed so as to remove the effect of censoring, and graphical procedures based on quantiles (such as boxplots) may then be used as a standard data-analytic tool to describe the variable being measured.

Topics: Antimetabolites, Antineoplastic; Biometry; Controlled Clinical Trials as Topic; Humans; Least-Squares Analysis; Leukemia; Mathematics; Mercaptopurine; Models, Statistical; Placebos; Regression Analysis; Remission Induction; Research Design; Survival Rate; Time Factors

Selective combinations of purine and pyrimidine analogs increase remission rates in pediatric patients with relapsed leukemias. The combination of 6-mercaptopurine (6-MP) and cytosine arabinoside (ara-C) may exhibit synergism similar to that observed for fludarabine and ara-C and may diminish the potential for development of resistance since the two drugs are activated by separate enzymatic pathways. To determine the efficacy of the combination against human leukemia cells, we investigated the time-concentration relationships of the drugs given alone or in combination to the resultant cytotoxicity. To determine whether the combination leads to enhanced activity of deoxycytidine kinase (dCk), the rate-limiting enzyme in ara-C activation, we characterized the cellular dCk in CCRF/CEM/0, CCRF/CEM/ara-C/7A, and CCRF/CEM/ara-C/3A monoclonal cells before and after treatment with 6-MP. CCRF/CEM/0 (wild type), CCRF/CEM/ara-C/7A (approximately 50% ara-C-resistant as determined by ara-C sensitivity assay and dCk characterization), and CCRF/CEM/ara-C/3A (approximately 90% resistant to ara-C) human leukemia cells were incubated with various concentrations of 6-MP and ara-C given alone or in combination. Cell survival, inhibition of DNA synthetic capacity (DSC), ara-CTP anabolism, and dCk enzymatic characteristics were studied. Incubation of CEM/0 cells with 6-MP for 24 h, followed by ara-C for 48 h, increased cell-growth inhibition by approximately 0.5-1 log10, corresponding to 5- to 10-fold synergism, as compared with ara-C alone after identical drug incubation in all cell lines. Simultaneous administration showed no synergism, whereas reversal of the sequence produced an antagonistic effect. The ara-CTP levels were 2- to 3.5-fold and 3- to 5-fold higher in CEM/0 and CEM/ara-C/7A cells, respectively, in cells exposed to 6-MP followed by ara-C than in those exposed to ara-C alone at the same concentrations. Furthermore, a progressive increase in ara-CTP levels was noted in CEM/0 cells exposed to increasing concentrations of 6-MP followed by 10 or 20 microM ara-C. A significant decrease in DSC was observed upon treatment of wild-type and ara-C-resistant cells with 6-MP and ara-C. The combination of 6-MP and ara-C exhibits significant sequence-specific synergism in both wild-type and partially ara-C-resistant leukemia cell lines. The combination also exerts collateral sensitivity in the ara-C-resistant cell lines. 6-MP pretreatment may play a role in enhancing ara-C ac

Topics: Arabinofuranosylcytosine Triphosphate; Cell Division; Cell Survival; Cytarabine; Deoxycytidine Kinase; DNA, Neoplasm; Dose-Response Relationship, Drug; Drug Resistance; Drug Synergism; Humans; Kinetics; Leukemia; Mercaptopurine; Tumor Cells, Cultured

1. Red blood cells from four children with lymphoblastic leukemia were age fractionated on Percoll density gradients into 'young', 'middle-aged' and 'old' cells. 2. The rates of accumulation of the mercaptopurine (MP) metabolites thioguanine nucleotides (TGNs) and methylmercaptopurine nucleotides (MeMPs) were measured in the cell fractions from the start of MP continuing chemotherapy. 3. TGNs and MeMP metabolites were present in all the red cell fractions after 3 days oral MP. There was no significant difference between the metabolite concentrations measured in either young, middle-aged or old cells (Mann-Whitney P = 1.0 to 0.12). 4. These observations suggest that MP metabolites do not enter red cells at the stem cell level at the start of therapy. 5. With respect to the monitoring of therapy, these results suggest that the concentration of TGNs after 7 to 10 days MP could be used to predict eventual steady-state concentrations using a simple model.

Topics: Cell Count; Child; Child, Preschool; Drug Therapy; Erythrocyte Aging; Erythrocytes; Female; Humans; Leukemia; Male; Mercaptopurine; Time Factors

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Cytarabine; Daunorubicin; Granulocyte Colony-Stimulating Factor; Hematologic Tests; Humans; L-Lactate Dehydrogenase; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mercaptopurine; Prednisolone; Remission Induction

A case of congenital leukemia with monosomy 7 is reported. Immunological study of the blast cells using monoclonal antibodies was suggestive of both myelomegakaryocytic and T-lymphoblastic leukemia. Chromosomal analysis of the bone marrow cells showed monosomy 7. Chemotherapy was initiated with a combination of adriamycin, cytosine arabinoside, 6-mercaptopurine, and prednisolone. The patient obtained complete remission, which has been maintained for 4 years and 1 month. He receives no chemotherapy now. Our case shows that monosomy 7 in congenital leukemia is rare, but the presence of monosomy 7 in congenital leukemia does not necessarily indicate a poor prognosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chromosomes, Human, Pair 7; Cytarabine; Doxorubicin; Humans; Infant, Newborn; Karyotyping; Leukemia; Leukemia-Lymphoma, Adult T-Cell; Leukemia, Megakaryoblastic, Acute; Male; Mercaptopurine; Monosomy; Prednisolone; Remission Induction

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Cytarabine; Daunorubicin; Humans; Leukemia; Mercaptopurine; Prednisolone

Topics: Cytarabine; Deoxycytidine; DNA Topoisomerases, Type I; Etoposide; Gemcitabine; Humans; Leukemia; Mercaptopurine; Methotrexate; Purines; Pyrimidines; Thioguanine; Topoisomerase I Inhibitors

The meninges are a unique site of recurrence for certain malignancies because of the limited penetration of systemically administered cytotoxic drugs across the blood-brain barrier. While this phenomenon was first recognized in children with acute lymphoblastic leukemia, a similar pattern is also occurring in breast cancer, ovarian cancer, and small cell lung cancer. Recognition of the limitations of standard systemic antileukemic therapy for the treatment of meningeal disease led to the development of new therapeutic strategies targeted directly at the CNS. These include intralumbar therapy using methotrexate or cytarabine, intraventricular chemotherapy, and high-dose systemic drug administration. New agents showing promise are intrathecal diaziquone, 6-mercaptopurine, and mafosfamide.

Topics: Adolescent; Adult; Antineoplastic Agents; Aziridines; Benzoquinones; Blood-Brain Barrier; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Humans; Infant; Infant, Newborn; Leukemia; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Thiotepa

The number of circulating hematopoietic progenitor cells was determined during 47 courses of chemotherapy in 23 patients with hematopoietic malignancies. rhG-CSF was given subcutaneously to 14 patients to rescue chemotherapy-induced neutropenia following 22 courses of chemotherapy. The mean numbers of CFU-GM in patients with malignant lymphoma (ML), acute leukemia (AL) and myeloma (MM) were 56.0 +/- 58.8 (mean +/- SD), 46.7 +/- 66.0 and 11.0 +/- 11.1 CFU-GM/ml, respectively. The number of CFU-GM in MM was significantly less than in normal subjects (51.2 +/- 30.6 CFU-GM/ml). The number of CFU-GM in PB in all patients began to rise between 2 days before and 8 days after nadir of WBC count, and then reached the peak at the subsequent 5 days. The peak values of CFU-GM in ML, AL and MM were 711.3 +/- 974.7, 660.0 +/- 374.7 and 403.6 +/- 232.5 CFU-GM/ml, respectively, but there was no statistical difference among them. When ML patients were treated with rhG-CSF, the CFU-GM peak values increased as much as 5.5-folds compared with those following chemotherapy only. However, neither the period from nadir to start of increase in the CFU-GM count nor the time of the CFU-GM peak showed any significant change. These results indicate that the administration of rhG-CSF makes it possible to increase the number of circulating progenitor cells. It appears possible in most of the patients with hematopoietic malignancies to harvest the sufficient number of progenitor cells which are necessary for autologous blood stem cell transplantation.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cell Cycle; Colony-Stimulating Factors; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; Leukemia; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Middle Aged; Multiple Myeloma; Prednisolone; Prednisone; Vincristine

Topics: Azathioprine; Cells, Cultured; Electrochemistry; Electrodes; Leukemia; Mercaptopurine; Pharmaceutical Preparations; Polarography; Purines; Tablets

Methotrexate (MTX) causes an inhibition of purine de novo synthesis (PDNS), resulting in increased intracellular availability of 5-phosphoribosyl-1-pyrophosphate (PRPP) in human malignant lymphoblasts with an active PDNS. Normal bone marrow cells and peripheral blood lymphocytes lack this capacity. The increased levels of PRPP can be used for enhanced incorporation of 6-mercaptopurine (6MP), indicating a potential time-, sequence- and dose-dependent synergism of both drugs. The effects of 0.02 microM and 0.2 microM MTX on the PDNS of MOLT-4 (T-), RAJI (B-) and KM-3 (non-B-non-T-) human malignant lymphoblasts were studied with respect to PRPP levels, aminoimidazolecarboxamide ribonucleosidemonophosphate (AICAR) levels and the incorporation of labeled glycine into purine metabolites. These results were correlated with the activity of the PDNS (labeled glycine incorporation) and the purine salvage pathway (labeled hypoxanthine incorporation) in untreated cells. Inhibition of PDNS by 0.02 microM MTX was complete in KM-3 cells with a moderately active PDNS and salvage pathway. RAJI cells, with a relatively low PDNS and high salvage pathway, demonstrated an incomplete, but increasing inhibition of PDNS, whereas inhibition of PDNS in MOLT-4 cells with both pathways active was minimal and recovered in time. Treatment with 0.2 microM MTX resulted in a complete inhibition of PDNS in all cell lines. After treatment with MTX an enhanced incorporation of labeled hypoxanthine and 6MP was noticed, confirming the potential rescue from MTX cytotoxicity by hypoxanthine and a potential synergism of MTX and 6MP on cytotoxicity. The enhanced incorporation of 6MP was more obvious in RAJI and KM-3 cells in comparison with MOLT-4 cells. These data demonstrate the important role of both the activities of the PDNS and the purine salvage pathway in malignant lymphoblasts of different subclasses with respect to the synergism of MTX and 6MP.

Topics: Aminoimidazole Carboxamide; Drug Synergism; Glycine; Humans; Hypoxanthine; Hypoxanthines; Leukemia; Lymphocytes; Mercaptopurine; Methotrexate; Phosphoribosyl Pyrophosphate; Purines; Ribonucleotides; Tumor Cells, Cultured

Topics: Adolescent; Child; Child, Preschool; Chromatography, High Pressure Liquid; Female; Humans; Leukemia; Male; Mercaptopurine; Monitoring, Physiologic; Patient Compliance

A highly sensitive reversed-phase high-performance liquid chromatographic assay, with ultraviolet detection, for 6-thioinosinic acid and the 6-thioguanine nucleotides (6TGNs) was developed. The 6TGNs are major red blood cell metabolites of the immunosuppressive agent azathioprine and the cytotoxic drugs 6-thioguanine and 6-mercaptopurine. The assay is based on the specific extraction, via phenyl mercury adduct formation, of the thiopurine released on acid hydrolysis of the thionucleotide metabolite. Red blood cell 6TGN concentrations in eighteen leukaemic children receiving chronic 6-mercaptopurine chemotherapy were measured and compared to a previously published spectrophotofluorometric assay. Linear regression analysis gave r = 0.991; P less than 0.001; y = 40 + 0.94x.

Topics: Chromatography, High Pressure Liquid; Drug Stability; Erythrocytes; Humans; Inosine Monophosphate; Inosine Nucleotides; Leukemia; Mercaptopurine; Nucleotides; Spectrometry, Fluorescence; Thioguanine; Thionucleotides

Three cases of secondary leukemia developing after chemotherapy and/or radiotherapy for myeloma, mycosis fungoides, and non-Hodgkin's lymphoma are reported. The first case was a 51-year-old man with IgG-lambda myeloma, treated with melphalan and prednisolone, who developed acute myelomonocytic leukemia 54 months after the diagnosis of myeloma. The second case was a 54-year-old woman with mycosis fungoides treated with radiation, predonine, and cyclophosphamide, who developed acute megakaryoblastic leukemia 298 months after the diagnosis of mycosis fungoides. The third case was a 35-year-old woman with stage IV non-Hodgkin's lymphoma treated with VEMP who developed acute myelogenous leukemia 26 months after the diagnosis of malignant lymphoma. All cases showed pancytopenia and two of three cases had morphologic abnormality in several hemopoietic cell lineages in the leukemic stage. There is a possibility that second malignancies are an increasingly recognized complication in the patients treated with a large amount of chemo-radiotherapy.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Humans; Leukemia; Leukemia, Megakaryoblastic, Acute; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Lymphoma, Non-Hodgkin; Male; Melphalan; Mercaptopurine; Middle Aged; Multiple Myeloma; Mycosis Fungoides; Pancytopenia; Prednisolone; Vincristine

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Hemorrhage; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Mucous Membrane; Naphthacenes; Prednisolone; Urinary Bladder Diseases

Topics: History, 20th Century; Humans; Immunosuppressive Agents; Leukemia; Mercaptopurine

The concentrations of 6-mercaptopurine were studied in plasma and red blood cells from 10 children with acute leukaemia or non-Hodgkin lymphoma receiving oral maintenance therapy. The doses varied between 25 and 79 mg/m2 body surface once daily. Large interindividual differences were found in the concentrations both in plasma and in red blood cells. There was no clear relationship between the dose administered and the concentrations obtained. However, in each patient the concentrations in plasma and in red blood cells were very similar. In most patients, the peak concentrations were reached 1-2 hours after dose intake and the concentrations then declined with half-lives less than 1 hour. Further studies are necessary to evaluate the potential value of drug level monitoring in optimizing treatment with oral 6-mercaptopurine.

Topics: Acute Disease; Administration, Oral; Adolescent; Child; Child, Preschool; Erythrocytes; Female; Humans; Kinetics; Leukemia; Lymphoma; Male; Mercaptopurine

Topics: Acute Disease; Cytarabine; Erythrocytes; Humans; Kinetics; Leukemia; Mercaptopurine

The accumulation, metabolism, and retention of mercaptopurine (MP) was studied in four human neoplastic cell lines (three acute leukemia lines Molt-4, CCRF-CEM, and HL-60; and one Burkitt's lymphoma line, Wilson), each of which was sensitive to MP. Two cell lines resistant to MP (WilsonR and CCRF-CEMR) were also studied. The cell lines were incubated for 3 h in 10 microM [14C]MP and then placed in drug-free media for an additional 3 h. Cell samples were obtained at regular intervals, and the intracellular MP metabolites were measured in the acid-soluble fractions by anion-exchange high-pressure liquid chromatography. MP accumulated progressively within cells during the 3-h drug exposure period and declined rapidly when the cells were placed in drug-free media. Over 80% of the intracellular MP was present in the form of three nucleotide metabolites, MP ribose monophosphate, thioxanthosine monophosphate, and thioguanosine monophosphate. MP ribose monophosphate was found in greatest amount, accounting for 59-85% of the intracellular metabolite pool. Thioxanthosine monophosphate thioguanosine monophosphate were detected in lesser amounts. Study of leukemic cells obtained from patients demonstrated a similar pattern of MP accumulation, metabolism, and retention, although the overall amounts of the various metabolites formed were less. In contrast, there was essentially no MP nucleotide metabolite formation in the two MP-resistant cell lines. A more complete understanding of the cellular pharmacokinetics of MP in human neoplastic cells is likely to lead to a more rational use of the drug in the clinical setting.

Topics: Adenosine Triphosphate; Cell Line; Chromatography, High Pressure Liquid; Guanosine Triphosphate; Humans; Kinetics; Leukemia; Mercaptopurine; Neoplasms; Nucleotides; Phosphoribosyl Pyrophosphate

Between 1964 and 1982, 862 patients with acute leukemia who were collected from medical institutions throughout the country had a survival of 5 years or longer. Their remission has been achieved mainly with a combination therapy of vincristine and prednisone in childhood acute leukemia and daunomycin, cytosine arabinoside, 6-mercaptopurine, prednisone (DCMP) regimen in adult acute leukemia. Among 320 relapsed patients, 88 (38.8%) of 227 children had a primary relapse in the marrow, 85 in the central nervous system (CNS), 37 in the testis/ovary, and 13 in a combined site. The large majority of adult relapsed patients relapsed in the marrow. Ninety-three patients who experienced only one relapse had a much longer prolongation of survival, not yet reaching a median over 14 years after diagnosis, compared to those experiencing two or more relapses. Survival curves in five groups of patients divided by length of maintained remission were investigated by the life table method. In children as well as adults, survival duration in patients on 5 or more years maintained remission was significantly longer than that in the other maintained groups. With respect to relation between frequency of CNS relapse and type of CNS prophylaxis, there was no statistically significant difference between patients who received CNS prophylaxis and patients who did not. However, a better survival was observed in patients who received CNS prophylaxis with cranial radiation plus intrathecal methotrexate. Thus, long-term clinical follow-up might provide important information for the therapeutic strategy against acute leukemia.

Topics: Actuarial Analysis; Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Child; Child, Preschool; Cytarabine; Daunorubicin; Female; Health Surveys; Humans; Infant; Japan; Leukemia; Leukemia, Lymphoid; Male; Mercaptopurine; Middle Aged; Nervous System Neoplasms; Prednisolone; Recurrence; Testicular Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Cyclophosphamide; Daunorubicin; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Risk; Thioguanine; Vincristine

Topics: Aclarubicin; Acute Disease; Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Digestive System; Female; Gastrointestinal Diseases; Humans; Leukemia; Male; Mercaptopurine; Naphthacenes; Prednisolone

Controlled clinical trials of therapy for childhood acute leukemia are reviewed in the Children's Cancer & Leukemia Group Studies 1972-1981. The mortality of acute lymphocytic leukemia in children has been reduced about one-half in the past 10 years. Continued progress depends on maintaining our objective of curing all children and in conceiving and testing new ideas that might contribute to cure. Nowadays, the end result of most importance is long-term leukemia-free survival, i.e., the freedom from relapse after off therapy. Advances in the childhood leukemia have paved the way for encouraging progress in the management of the much more common malignancies that affects adults.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Child; Drug Administration Schedule; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisolone; Prognosis; Vincristine

A highly sensitive and rapid assay for the detection of 6-mercaptopurine metabolites in the red blood cells of leukemic patients receiving the drug has been developed. The method employs a batch-chromatographic procedure using a mercurial cellulose resin to selectively absorb thiol compounds combined with separation by high-performance liquid chromatography using a Partisil-SAX column and uv detection. This method permits detection of 6-thioinosine monophosphate, 6-thiouric acid, and 6-thioguanosine mono-, di-, and triphosphates in patient samples with a sensitivity of 5-10 pmol. No 6-thioinosine di- or triphosphates were detected in patient samples. The results of our study indicate that 6-thioguanosine triphosphate is the major metabolite of 6-mercaptopurine retained by red blood cells after oral or iv administration of the drug.

Topics: Biotransformation; Cellulose; Chromatography, High Pressure Liquid; Erythrocytes; Humans; Leukemia; Mercaptoethanol; Mercaptopurine; Methylthioinosine; Organomercury Compounds; Thioguanine

Topics: Acute Disease; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Humans; Leukemia; Male; Mercaptopurine; Prednisolone; Vincristine

Topics: Acute Disease; Adolescent; Adult; Aged; Ancitabine; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine Monophosphate; Doxorubicin; Female; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Recurrence

While the combination of L1210 murine leukemia cell vaccine (L1210 vaccine) with 6-mercaptopurine (6-MP) or 6-thioguanine produces a therapeutic response greater than that induced by either of these agents alone, its combination with cyclophosphamide, N4-behenoyl-1-beta-D-arabinofuranosylcytosine, or 5-fluorouracil does not produce such a response. The administration of cyclophosphamide, N4-behenoyl-1-beta-D-arabinofuranosylcytosine, or 5-fluorouracil alone resulted in a response as great as, or greater than, that induced by 6-MP alone. This and the finding that the 6-MP-induced response was more pronounced upon its delayed rather than its early administration indicate that 6-MP-induced reduction of the tumor burden does not explain this augmentation. The combination of 6-MP and L1210 vaccine was not effective in mice bearing 6-MP-resistant L1210 leukemia; however, an augmented response occurred when the tumor burden was reduced by N4-behenoyl-1-beta-D-arabinofuranosylcytosine, indicating that reduction of the tumor burden by 6-MP was only partially associated with augmentation of the therapeutic response. Augmentation was associated with vaccine-induced antitumor immunity because it was induced by the combination of 6-MP and concanavalin A-bound, but not concanavalin A-free L1210 vaccine. This augmentation was dependent on the timing of the L1210 vaccine administration. The combination was not effective in mice bearing P388 leukemia, indicating the tumor specificity of the augmentation. These results show that 6-MP not only reduced the tumor burden but also potentiated the vaccine-dependent antitumor immunity, resulting in the induction of an augmented therapeutic response.

Topics: Animals; Concanavalin A; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Synergism; Immunotherapy; Leukemia; Leukemia L1210; Leukemia P388; Leukemia, Experimental; Male; Mercaptopurine; Mice; Thioguanine

Topics: Adult; Child, Preschool; Cytarabine; DNA, Neoplasm; Humans; Leukemia; Mercaptopurine; Middle Aged

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Deoxycytidine Monophosphate; Humans; Leukemia; Mercaptopurine; Prednisolone

Topics: Acute Disease; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cell Division; Cytarabine; Daunorubicin; Female; Humans; Kinetics; Leukemia; Male; Mercaptopurine; Middle Aged; Neoplastic Stem Cells; Prednisolone; Prognosis

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Daunorubicin; Drug Evaluation; Humans; Leukemia; Mercaptopurine; Middle Aged; Prednisolone

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Female; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Naphthacenes; Pancreatitis; Prednisolone

We analysed the effects of three different regimens for first induction therapy with 50 cases of acute nonlymphocytic leukemia in adults and reported the results of combination therapy including aclacinomycin for reinduction therapy. Results obtained were as follows: The regimens of DCMP 2 step and Cc, P were superior to DCMP in remission rate (78%, 78% and 41%), median duration of CR (8.3 months, 5.0 months and 3.5 months) and survival time (6.5 months, 11.5 months and 2 months). Cc, P regimens obtained favorable CR rate in elderly patients over 50 years of age. (Cc, P: 100%, others: 40-50%) No significant difference in survival time was observed in patients who attained CR by three different regimens. In patients treated with combination therapy including aclacinomycin, the CR rate was 89% in the 9 previously treated patients (5 relapse cases and 4 refractory leukemias): All of these patients had previously been treated with DCMP 2 step or BHAC-DMP. Daunomycin (D), Cytosine Arabinoside (C), 6-Mercaptopurine (M) and Prednisolone (P) (DCMP), DCMP 2 step and Cyclocytidine (Cc) P.

Topics: Aclarubicin; Acute Disease; Adult; Age Factors; Ancitabine; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Naphthacenes; Prednisolone

31 adults suffering from acute leukemia were followed for a period of more than 5 years after achieving complete remission. Maintenance chemotherapy consisted of antimetabolite treatment (mercaptopurine + methotrexate) as well as COAP reinduction every 3 months. Chemotherapy was stopped if the first complete remission lasted for 3 years ("long term remission"). This was the case in 8 out of 31 remission patients (26%). Analysis of hematological parameters at diagnose for long term remission patients revealed that the initial leukocyte count was of prognostic significance.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Female; Follow-Up Studies; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Time Factors; Vincristine

Bone marrow cells from adult patients with acute leukemia were serially cultured using an in vitro agar culture method. Four categories of growth pattern were recognized according to growth characteristics in vitro in previously untreated patients with leukemia. Detailed cytological investigation was performed for the determination of cell morphology and the origin of colonies. In vitro agar culture may be useful for monitoring the remission-relapse status in acute leukemia.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Colony-Forming Units Assay; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Prednisolone; Prognosis

Methotrexate (MTX) and 6-mercaptopurine (6MP), the two drugs most commonly used for maintenance treatment of childhood leukemia, are both potent hepatotoxins. In order to assess MTX-6MP-induced damage, we obtained biopsies from 11 children with acute lymphocytic leukemia (ALL) for light microscopic and transmission electron microscopic study. Prednisone, vincristine, and L-asparaginase were used for induction of remission in all patients. Although light microscopic findings were minimal, we found significant ultrastructural abnormalities in all patients. Changes included nuclear abnormalities, disruption of rough and smooth endoplasmic reticulum, a variety of mitochondrial changes, steatosis, fibrosis, and changes in peroxisomes and lysosomes. These abnormalities could not have been predicted from liver function tests or histopathology. Three of the eleven patients studied had also received cyclophosphamide and cytosine arabinoside during maintenance therapy. The ultrastructural abnormalities in this group were not distinguishable from those observed in the group that did not receive these additional chemotherapeutic agents. The long-term clinical significance of these findings is not known.

Topics: Adolescent; Cell Nucleus; Child; Child, Preschool; Endoplasmic Reticulum; Humans; Infant; Leukemia; Liver; Mercaptopurine; Methotrexate

In this study the duration of complete remission by daunomycin, cytosine arabinoside (Ara-C), 6MP and prednisolone (DCMP) therapy using a large dose of Ara-C (200 mg) (protocol 2M-80) was compared with that of DCMP therapy with a low dose of Ara-C (80-160 mg) in acute non-lymphocytic leukemia (ANLL). In protocol 2M-80, the chemotherapy was continued until leukemic blasts in marrow were attained below 3%. Complete remission was induced in about 80% of ANLL patients in both chemotherapies. However, the duration of remission in protocol 2M-80 appeared to be much longer than that of DCMP therapy with a low, dose of Ara-C. This difference was dependent not on the consolidation and maintenance therapy, but on the total dose of Ara-C used and leukemic blasts left in marrow at the end of chemotherapy. This suggests that it is important to reduce leukemic blasts in marrow as low as possible by induction chemotherapy to obtain a long-term remission in ANLL.

Topics: Acute Disease; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cytarabine; Daunorubicin; Drug Administration Schedule; Drug Therapy, Combination; Humans; Leukemia; Mercaptopurine; Middle Aged; Prednisolone

A four-drug regimen, based on cell kinetic principles, induced complete remissions in 68 of 95 children (72%) with acute nonlymphocytic leukemia (ANLL). Patients entered remission after 2-5 weekly cycles of vincristine-daunorubicin (day 1) followed by sequential cytosine arabinoside and 6-azauridine (days 4-7). With continuation therapy of monthly vincristine-doxorubicin-cyclophosphamide, weekly cytosine arabinoside, and daily 6-mercaptopurine, the median duration of complete remission was 10 mo and the median survival time 21 mo. Portal triaditis, evident in 11 of 23 patients with liver biopsies, was associated with long remissions. A larger spleen size (greater than 5 cm) and a higher myeloblast labeling index (greater than 10%) at diagnosis were clearly related to shorter durations of remission. Splenectomy within 1 mo of remission had no statistically significant effect on the frequency of relapse or length of remission. Patients without central nervous system (CNS) leukemia at diagnosis, all treated prophylactically with intrathecal methotrexate, had a low frequency of initial CNS relapse (3/56, 5%). The 2-yr disease-free survival rate is 29% (20 of 68 patients attaining complete remission). fifteen patients have completed 2.5 yr of therapy, and each remains in continuous complete remission, off treatment, for 1+ -36+ mo. This induction chemotherapy was as effective as more intensive regimens, with the advantage of less toxicity and shorter periods of hospitalization.

Topics: Acute Disease; Adolescent; Asparaginase; Brain Neoplasms; Child; Cyclophosphamide; Cytarabine; Doxorubicin; Humans; Injections, Spinal; Leukemia; Mercaptopurine; Methotrexate; Prednisone; Splenectomy; Vincristine

Topics: Aclarubicin; Adult; Cytarabine; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Naphthacenes; Prednisolone

The authors observed 70 patients with acute leukemia treated by polychemotherapy. In 2 patients the signs of severe liver damage were found. The occurrence, course and results of laboratory tests suggested Purinethol predominantly as the cause of development of these alterations. The complication did not occur frequently in our patients. The changes regressed in a satisfactory way after the withdrawal of the hepatotoxic cytostatic from the therapy.

Topics: Acute Disease; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Humans; Leukemia; Mercaptopurine; Methotrexate; Vincristine

Cytogenetic studies of chronic myelogenous leukemia (CML) have shown that the majority of hemopoietic cells originate from pluripotential stem cells affected in this disease. Evidence that lymphocytes are also progeny of these stem cells, however, has been indirect. Philadelphia-chromosome-positive leukemic blasts from a 4 10/12-yr-old boy with CML in blast crisis had features characteristic of pre-B leukemic cells, including expression of cytoplasmic IgM and absence of surface immunoglobulin. Additional immunologic, enzymatic, and pharmacologic characterization of these cells supported their pre-B-cell phenotype. Together, these features provide direct evidence for CML stem cell ancestry to lymphocytes of the B-cell lineage.

Topics: B-Lymphocytes; Cell Transformation, Neoplastic; Child; Chromosomes, Human, 21-22 and Y; Humans; Hydroxyurea; Leukemia; Leukemia, Myeloid; Male; Mercaptopurine; Methotrexate; Phenotype; Prednisone; Time Factors; Vincristine

Thirty adult patients suffering from acute nonlymphocytic leukemia (ANLL) were treated according to a modified COAP regimen. Vincristine, cyclophosphamide, and prednisone were given by push injection, while cytosine arabinoside was infused over periods of 8 h. Nineteen patients (63%) achieved complete remission. Remission maintenance therapy consisted of 6-mercaptopurine daily and methotrexate twice weekly. Later in the study, COAP consolidation and reinduction was added, which improved the median duration of complete remission from 7 to 24 months. Comparison of the results with the literature shows that the modified COAP regimen is one of the most effective treatment schedules for adult ANLL.

Topics: Acute Disease; Adolescent; Adult; Aged; Cyclophosphamide; Cytarabine; Female; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Time Factors; Vincristine

Topics: Acute Disease; Adult; Aged; Bloodletting; Busulfan; Evaluation Studies as Topic; Female; Humans; Leukemia; Leukemia, Radiation-Induced; Male; Mercaptopurine; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Thromboembolism; Veins

Report on a case of acute childhood leukemia, who presents with the following exceptional features: During complete remission early bilateral leukemic infiltrations of the testes, followed--after an intervall of several months--by a serve, general relapse with ascites. New induction therapy resulted in a second complete remission, persisting for the next 8 years with 6MP as well as after cessation of therapy until up to more than 17 years. Comparable courses are not as yet on record.

Topics: Acute Disease; Adolescent; Adult; Blood Transfusion; Child; Child, Preschool; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Splenomegaly; Testicular Neoplasms

Topics: Allopurinol; Anaphylaxis; Anemia; Antibiotics, Antineoplastic; Bicarbonates; Blood Transfusion; Child; Child, Preschool; Cystitis; Disseminated Intravascular Coagulation; Erythrocytes; Female; Furosemide; Heart Arrest; Heparin; Humans; Hydrogen-Ion Concentration; Kidney; Leukemia; Lung Diseases; Male; Mercaptopurine; Mutation; Neoplasms; Phospholipids; Renal Dialysis; Thrombocytopenia; Uric Acid

391 children received complex chemotherapy according to uniform treatment schedules, proposed by the Hungarian Study Group for Childhood Leukaemia, which was established in 1971. Survival among the patients showed an increasing tendency: more than 50% of patients with ALL are stille alive 3 years after the beginning of treatment. One patient is in complete remission 9 3/4 years after the establishment of the diagnosis. Two types of maintenance therapy were investigated among the patients entered for this study in 1974. "Pulses" with Vincristine-Prednisolone every second month were found to be more optimal than monthly "pulses".

Topics: Age Factors; Child; Cytarabine; Daunorubicin; Humans; Hungary; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Thioguanine; Vincristine

For the purpose of preventing a relapse of acute leukemia which is currently the major problem in the successful treatment of the disease, repeated consolidation or intensification therapy during the first year following remission is important. To evaluate these therapies, we investigated the serial changes in CFU-C's of the marrow cells from 12 patients with acute nonlymphocytic leukemia in remission and tried to estimate the relationship between the intensity of consolidation or intensification therapy and the duration of remission, utilizing the degree of reduction in CFU-C's seven days after these treatments as an indicator. As a result, after 21 out of 22 courses of therapy where CFU-C's were reduced significantly after the therapy, the patients were still in remission at the time of the next intensificiation therapy (at most for about 100 days). On the other hand, after five out of ten courses where CFU-C's were not reduced significantly, the patients were in relapse at the time of the next intensification therapy. From these results, it may be inferred that cases whose CFU-C's are not reduced significantly should be treated intensively again within a short period.

Topics: Acute Disease; Adult; Child; Colony-Forming Units Assay; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Remission, Spontaneous

Topics: Central Nervous System Diseases; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Immunotherapy; Injections, Spinal; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous; Vincristine

Topics: Acute Disease; Adolescent; Child; Child, Preschool; Cytarabine; Daunorubicin; Humans; Immune Adherence Reaction; Immunity, Cellular; Infant; Leukemia; Mercaptopurine; Prednisolone; Vincristine

Leukocytes from patients with leukemia and L1210 cells from mice were examined for the rate of formation and cellular concentration of phosphoribosylpyrophosphate, the rate of thioinosinic acid formation, and a number of selected enzymes involved in purine nucleotide synthesis. The amount of thioinosinic acid formed in L1210 cells was much higher than that in human leukemic leukocytes. In cell extracts, the synthesis of thioinosinic acid was similar in both cell types, and the amount of purine phosphoribosyltransferase was not rate limiting in either case. Much higher concentrations and rates of formation of phosphoribosylpyrophosphate were found in L1210 cells than in human leukemic leukocytes. The difference in response to 6-mercaptopurine between L1210 cells and human leukemic leukocytes might be attributed to their difference in supply of phosphoribosylpyrophosphate. Phosphoribosylpyrophosphate-amidotransferase was found to be high in L1210 cells, but was not detected in human leukemic leukocytes.

Topics: Animals; Erythrocytes; Humans; In Vitro Techniques; Leukemia; Leukemia L1210; Leukocytes; Mercaptopurine; Mice; Phosphoribosyl Pyrophosphate; Thioinosine

For the purpose of evaluating the efficiency of an unspecific immunostimulation in acute leukaemias the results of treatment obtained from two groups of patients (a total of 55 children) were compiled. In the first group an unspecific immunostimulation with vaccination (BCG, diphtheria-tetanus-pertussis, measles) could be observed after the induction of remission during a cytostatic maintenance therapy. In the second group a polychemical therapy and the CNS-irradiation was applied according to the treatment scheme developed by the working team of Donald Pinkel. The group of patients treated with unspecific immunostimulation involved a high percentage of surviving children. In total there was no essential difference between the treatment results of both schemes of therapy during our period of observation. As before, the treatment of hyperleukocytic forms of leukaemias will cause particular difficulties.

Topics: Acute Disease; BCG Vaccine; Brain Neoplasms; Child; Cyclophosphamide; Diphtheria Toxoid; Drug Therapy, Combination; Gold Radioisotopes; Humans; Injections, Spinal; Leukemia; Mercaptopurine; Methotrexate; Pertussis Vaccine; Prednisone; Tetanus Toxoid; Vincristine

Topics: Acute Disease; Adolescent; Adult; Aminobiphenyl Compounds; Antineoplastic Agents; Asparaginase; Bone Marrow; Cell Survival; Child; Child, Preschool; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukocyte Count; Male; Mercaptopurine; Mesylates; Methotrexate; Middle Aged; Neutrophils; Prednisolone; Time Factors; Zinostatin

The PRPP concentrations, PRPP formation, and phosphorylation of 6-mercaptopurine in leukocyte suspensions and homogenates prepared from leukemic patients were studied...

Topics: Amidophosphoribosyltransferase; Animals; Humans; Hypoxanthine Phosphoribosyltransferase; Hypoxanthines; In Vitro Techniques; Inosine; Inosine Monophosphate; Leukemia; Leukemia L1210; Leukemia, Myeloid, Acute; Leukocytes; Mercaptopurine; Phosphoribosyl Pyrophosphate; Purine-Nucleoside Phosphorylase

Topics: Asparaginase; Cytarabine; Daunorubicin; Doxorubicin; Humans; Leukemia; Mercaptopurine; Methotrexate; Prednisolone; Thioguanine; Vincristine

In 87 cases of acute leukemia, leukemic and normal hematopoietic cell count in the bone marrow was serially observed, and the findings were used for evaluating the effectiveness of antileukemic agents and also for determining the grade of decrease in the marrow leukemic cell count required to start the proliferation of normal hematopoietic cells and to obtain complete remission of acute leukemia in adults.

Topics: Bone Marrow; Bone Marrow Cells; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Remission, Spontaneous; Vincristine

A regime of treatment of acute non-lymphoblastic leukemia in adult, employing DMCP protocol, especially two step method consisting of daunorubicin, cytosine arabinoside, 6-mercaptopurine and prednisolone is described. Out of 32 adult patients with ANLL treated with DCMP regime 26 (81.3%) achieved complete remission. The median durations of complete remission and survival were 53 weeks and 54 weeks, respectively. The longest duration of complete remission was more than 220 weeks, and 3 cases are still maintaining initial complete remission more than 3 years.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Remission, Spontaneous

Topics: Acute Disease; Adolescent; Adult; Cells, Cultured; Chromosome Aberrations; Chromosomes; DNA Replication; Female; Humans; Karyotyping; Leukemia; Lymphocytes; Male; Mercaptopurine; Middle Aged; Mitosis

In three patients with malignant disease HBsAg was detected in the serum at least 6 months before the development of acute hepatitis type B, which in each case followed a fulminant course to death. It is suggested that suppression of the normal immunological responses to hepatitis-B viral antigens by cytotoxic drug therapy permitted widespread infection of hepatocytes. Subsequently, upon withdrawal of these drugs, recovery of immunocompetence resulted in rapid destruction of all infected hepatocytes and massive liver damage. Screening for HBsAg before cytotoxic drug therapy, careful monitoring of liver function during its withdrawal, and prompt treatment with corticosteroids should abnormalities occur may prevent this unfortunate sequence of events.

Topics: Adult; Antineoplastic Agents; Chlorambucil; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Female; Hepatitis B; Hepatitis B Antigens; Humans; Immunosuppression Therapy; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Mercaptopurine; Methotrexate; Prednisolone; Pregnancy; Substance Withdrawal Syndrome; Vincristine

The in vitro sensitivity of leukemic cells to cytotoxic drugs was assessed in 61 cases of acute leukemia in adults, 49 of them were of the no lymphoblastic type and in the first phase of the disease. The depression of the incorporation of 14-C-thymidine and 3-H-uridine after a two hours incubation with the various cytotoxic drugs was compared with the clinical result obtained with two of them There is a significant correlation between the in vitro depression of the incorporation of 14-C-thymidine and the clinical effect of the drugs. This method, which may be utilized also in solid tumors, allows to predict with some accuracy the effect of chemotherapy, and to select between the various cytotoxic drugs. However the failure of a chemotherapy is generally related to an in vitro insensitivity of the malignant cells to almost all drugs.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Agents; Asparaginase; Carbon Radioisotopes; Cells, Cultured; Cyclophosphamide; Cytarabine; Daunorubicin; Depression, Chemical; Humans; In Vitro Techniques; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Middle Aged; Monomethylhydrazine; Prednisolone; Remission, Spontaneous; Thymidine; Tritium; Uridine; Vincristine

Topics: Acute Disease; Antineoplastic Agents; Asparaginase; Carmustine; Cyclophosphamide; Cytarabine; Dacarbazine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia; Mercaptopurine; Thioguanine

Topics: Acute Disease; Adult; Aged; Cytarabine; Doxorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Prednisolone

Topics: Acute Disease; Adult; Child; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia; Mercaptopurine; Middle Aged; Prednisolone

Topics: Antimetabolites, Antineoplastic; Bone Marrow; Bone Marrow Cells; Cytarabine; Evaluation Studies as Topic; Humans; Leukemia; Mercaptopurine; Methotrexate; Mitosis; Prednisolone; Time Factors; Vincristine

Topics: Amidophosphoribosyltransferase; Animals; Humans; Leukemia; Leukemia L1210; Leukocytes; Mercaptopurine; Pentosyltransferases

Topics: Acute Disease; Adult; Female; Humans; Leukemia; Leukocytes; Male; Mercaptopurine; Middle Aged; Pentosephosphates; Phosphoribosyl Pyrophosphate

Topics: Allopurinol; Drug Synergism; Humans; Leukemia; Lymphoma; Mercaptopurine; Thiouridine

Topics: Bone Marrow Examination; Child; Child, Preschool; Daunorubicin; Drug Therapy, Combination; Evaluation Studies as Topic; Hematopoietic Stem Cells; Histocytochemistry; Humans; Infant; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Periodic Acid; Peroxidases; Prednisone; Prognosis; Remission, Spontaneous; Retrospective Studies; Staining and Labeling; Vincristine

Topics: Blood Cell Count; Blood Platelets; Child; Child, Preschool; Clot Retraction; Cyclophosphamide; Humans; Immunosuppressive Agents; Leukemia; Mercaptopurine; Methotrexate; Nephrotic Syndrome; Platelet Adhesiveness; Platelet Aggregation; Thrombelastography; Vincristine

Topics: Bence Jones Protein; Bone Marrow Cells; Child; Chromatography, Gel; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Electrophoresis; Fluorescent Antibody Technique; Humans; Immune Sera; Immunoelectrophoresis; Immunoglobulin Fab Fragments; Immunoglobulin Fc Fragments; Injections, Spinal; Leukemia; Male; Mercaptopurine; Methotrexate; Microscopy, Electron; Prednisone; Vincristine; Waldenstrom Macroglobulinemia

Topics: Adolescent; Bone Marrow; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Female; Humans; Immunodiffusion; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infant; Leukemia; Leukemia, Myeloid; Lymphocytes; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Brain Neoplasms; Child; Child, Preschool; Cyclophosphamide; Cystitis; Drug Therapy, Combination; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Infant; Infections; Leukemia; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Pneumonia, Viral; Prednisone; Remission, Spontaneous; Skin Diseases; Vincristine; Viral Vaccines; Virus Diseases

Topics: Age Factors; Asparaginase; Chickenpox; Child, Preschool; Counseling; Cyclophosphamide; Cytarabine; Cytomegalovirus Infections; Daunorubicin; Drug-Related Side Effects and Adverse Reactions; Humans; Injections, Spinal; Leukemia; Mercaptopurine; Methotrexate; Patient Care Planning; Pediatrics; Physician-Patient Relations; Prednisone; Prognosis; Sex Factors; Vincristine

Topics: Acute Disease; Adolescent; Adult; Antineoplastic Agents; Asparaginase; Biphenyl Compounds; Daunorubicin; Female; Humans; Leukemia; Leukocyte Count; Male; Mercaptopurine; Mesylates; Methotrexate; Prednisolone

Topics: Acute Disease; Adult; Age Factors; Aged; Drug Therapy, Combination; Female; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Remission, Spontaneous; Time Factors; Vincristine

Topics: Acute Disease; Adolescent; Adult; Female; Follow-Up Studies; Humans; Leukemia; Mercaptopurine; Prednisone; Remission, Spontaneous; Time Factors

Topics: Acute Disease; Adolescent; Adult; Antineoplastic Agents; Asparaginase; Cytarabine; Drug Therapy, Combination; Female; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Prednisolone; Vincristine

Topics: Carbon Radioisotopes; Cells, Cultured; Humans; Leukemia; Leukocytes; Mercaptopurine; Oxidative Phosphorylation

Topics: Acute Disease; Adult; Animals; Child; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia; Leukemia L1210; Mercaptopurine; Prednisolone; Time Factors

Topics: Adenine; Alkaline Phosphatase; Drug Resistance; Guanine; Humans; Hypoxanthines; Leukemia; Leukemia, Lymphoid; Lymphocytes; Mercaptopurine; Pentosyltransferases; Thioguanine

Topics: Adult; Eye Manifestations; Humans; Iris; Leukemia; Leukemia, Lymphoid; Male; Meninges; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

Topics: Brain Neoplasms; Child; Child, Preschool; Cross Infection; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Infant; Injections, Intravenous; Leukemia; Leukemia, Lymphoid; Male; Measles; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous; Spinal Neoplasms; Vincristine

Topics: Acute Disease; Animals; Antilymphocyte Serum; Humans; Immunosuppression Therapy; L Forms; Leukemia; Leukocyte Count; Mercaptopurine; Mice; Muramidase; Penicillins; Pneumonia; Prednisolone

Topics: Acute Disease; Adult; Antineoplastic Agents; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia; Mercaptopurine; Middle Aged; Prednisone; Remission, Spontaneous; Retrospective Studies; Vincristine

Topics: Adolescent; Adult; Aged; Busulfan; Histocytochemistry; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Mercaptopurine; Methotrexate; Middle Aged; Tetrahydrofolate Dehydrogenase

Topics: Acute Disease; Adult; Antineoplastic Agents; Asparaginase; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Humans; Infection Control; Leukemia; Life Expectancy; Male; Mercaptopurine; Methotrexate; Middle Aged; Patient Isolators; Prednisolone; Thioguanine; Time Factors; Vincristine

Topics: Animals; Benzyl Compounds; Brain; DDT; Electron Spin Resonance Spectroscopy; Free Radicals; Humans; Kinetics; Leukemia; Liver; Lung Neoplasms; Lymphocytes; Mathematics; Melphalan; Mercaptopurine; Mice; Neoplasm Metastasis; Neoplasms; Neoplasms, Experimental; Nitrosourea Compounds; Rats; Thiotepa; Time Factors

Topics: Adolescent; Appendicitis; Child; Child, Preschool; Gastrointestinal Diseases; Humans; Hypersplenism; Infant; Intestinal Obstruction; Intussusception; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Pancreatitis; Postoperative Complications; Prednisone; Thrombocytopenia; Time Factors

Topics: Acute Disease; Adolescent; Adult; Age Factors; Biopsy, Needle; Breast Neoplasms; Child; Cytarabine; Daunorubicin; Diagnosis, Differential; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Menarche; Mercaptopurine; Methotrexate; Prednisolone; Sulfates; Vincristine

Topics: Acute Disease; Adult; Child; Cyclophosphamide; Cytarabine; Humans; Hydroxyurea; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisolone; Thioguanine; Vincristine

Topics: Acute Disease; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

Topics: Adenine; Adolescent; Adult; Aged; Antimetabolites; Drug Resistance; Female; Guanine; Humans; Hypoxanthines; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Male; Mercaptopurine; Mutation; Pentosyltransferases; Remission, Spontaneous; Thioguanine

Topics: Acute Disease; Adult; Child; Female; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Prednisolone; Recurrence; Remission, Spontaneous

Topics: Acute Disease; Adolescent; Adult; Blood Cells; Chromosome Aberrations; Chromosome Disorders; Chromosomes; Female; Humans; Karyotyping; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphatic Diseases; Male; Mercaptopurine; Middle Aged

Topics: Antineoplastic Agents; Autopsy; Busulfan; Child; Female; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Pneumonia; Vincristine

Topics: Adenine; Allopurinol; Bone Marrow; Bone Marrow Cells; Carbon Radioisotopes; Cell-Free System; Chromatography, Paper; Formates; Guanine Nucleotides; Humans; Hypoxanthines; Kinetics; Leucovorin; Leukemia; Leukemia, Myeloid, Acute; Leukocytes; Ligases; Mercaptopurine; Pentosephosphates; Pentosyltransferases; Spectrophotometry, Ultraviolet; Tetrahydrofolates

Topics: Cytarabine; Cytological Techniques; DNA, Neoplasm; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Phosphorus

Topics: Adult; Asparaginase; Breast Neoplasms; Cecal Diseases; Child; Cytarabine; Daunorubicin; Female; Fluorouracil; Humans; Intestinal Perforation; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Necrosis; Prednisone; Thioguanine; Vincristine

Topics: Acute Disease; Adolescent; Ambulatory Care; Antineoplastic Agents; Asparaginase; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Humans; Immunotherapy; Leukemia; Mercaptopurine; Methotrexate; Prednisolone; Vincristine

Topics: Autopsy; Brain Neoplasms; Child; Child, Preschool; Daunorubicin; Humans; Leukemia; Male; Mercaptopurine; Neoplasm Metastasis; Prednisone; Time Factors; Vincristine

Topics: Adjuvants, Immunologic; Animals; Antibody-Producing Cells; Antigens, Neoplasm; Asparaginase; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Immunotherapy; Leukemia; Mercaptopurine; Methotrexate; Mice; Poly I-C; Prednisone; Vincristine

Topics: Antineoplastic Agents; Asparaginase; Cell Division; Chemistry; Culture Techniques; Cytarabine; Daunorubicin; Depression, Chemical; DNA; Drug Combinations; Drug Resistance; Germ-Free Life; Half-Life; History, 20th Century; Hodgkin Disease; Humans; Leukemia; Lymphatic Diseases; Mercaptopurine; Remission, Spontaneous; Stimulation, Chemical; Thioguanine

Topics: Antigens, Neoplasm; Bone Marrow; Bone Marrow Cells; Cell Membrane; Chromium Isotopes; Cytotoxicity Tests, Immunologic; Humans; Immunity, Cellular; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphocyte Culture Test, Mixed; Mercaptopurine; Methotrexate; Prednisone; Skin Tests; Thymidine; Tritium; Vincristine

Topics: Adolescent; Adult; Asparaginase; Child; Child, Preschool; Cytarabine; Evaluation Studies as Topic; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Remission, Spontaneous; Vincristine

Topics: Antibiotics, Antineoplastic; Bone Marrow; Bone Marrow Cells; Carbon Isotopes; Cell Differentiation; Cells, Cultured; DNA Nucleotidyltransferases; DNA, Neoplasm; Humans; Hydroxyurea; Kinetics; Leukemia; Leukocytes; Lymphocytes; Mercaptopurine; Methotrexate; Rifampin; RNA, Neoplasm; Thymidine; Tritium; Uridine

Topics: Adrenal Cortex Hormones; Bone Marrow; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Mercaptopurine; Methotrexate; Prognosis; Remission, Spontaneous; Time Factors

Topics: Acute Disease; Chickenpox; Child, Preschool; Female; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate

Topics: Adjuvants, Immunologic; Asparaginase; Bacterial Vaccines; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Synergism; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Mycobacterium bovis; Prednisone; Remission, Spontaneous; Thioguanine; Vincristine

Topics: Adolescent; Adult; Aged; Animals; Antilymphocyte Serum; Bone Marrow Transplantation; Child; Child, Preschool; Cyclophosphamide; Cytotoxicity Tests, Immunologic; Humans; Immunity, Active; Immunization; Leukemia; Leukemia L1210; Leukemia, Experimental; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Mice; Middle Aged; Mycobacterium bovis; Poly I-C

Topics: Acute Disease; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Combinations; Drug Interactions; Drug Synergism; Humans; Leukemia; Mercaptopurine; Prednisone; Thioguanine

Topics: Adolescent; Asparaginase; Diabetic Ketoacidosis; Humans; Hyperglycemia; Leukemia; Leukopenia; Male; Mercaptopurine; Prednisone; Remission, Spontaneous

Topics: Acute Disease; Adolescent; Adult; Antibiotics, Antineoplastic; Humans; Leukemia; Male; Mercaptopurine; Prednisolone; Recurrence; Remission, Spontaneous

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Cytarabine; Daunorubicin; Humans; Injections, Intravenous; Leukemia; Mercaptopurine; Middle Aged; Prednisolone

Topics: Adrenal Cortex Hormones; Adult; Cytarabine; Humans; Leukemia; Male; Mercaptopurine; Vincristine

Topics: Adolescent; Adult; Aged; Allopurinol; Drug Synergism; Female; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Time Factors

Topics: Acute Disease; Adolescent; Age Factors; Antineoplastic Agents; Asparaginase; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Glucocorticoids; Humans; Leukemia; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Acute Disease; Child; Crystallization; Hematuria; Humans; Injections, Intravenous; Kidney; Leukemia; Mercaptopurine; Remission, Spontaneous; Urine

Topics: Adult; Aged; Child; Child, Preschool; Cyclophosphamide; DNA; DNA, Neoplasm; Female; Humans; In Vitro Techniques; Lectins; Leukemia; Leukocytes; Lymphocyte Activation; Male; Mercaptopurine; Ouabain; Prednisone; Thymidine; Tritium

Topics: Adolescent; Adult; Child; Child, Preschool; Drug Synergism; Female; Follow-Up Studies; Humans; Injections, Spinal; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisone; Time Factors; Vincristine

Topics: Acute Disease; Adrenal Cortex Hormones; Blood Transfusion; Chickenpox; Child; Female; gamma-Globulins; Humans; Leukemia; Mercaptopurine; Prednisolone; Purpura, Thrombocytopenic

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aminoisobutyric Acids; Asparagine; Child; Female; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Thymine; Vinblastine

Topics: Adolescent; Agranulocytosis; Candida; Child; Child, Preschool; Enterocolitis, Pseudomembranous; Escherichia coli; Female; Fever; Humans; Infant; Infections; Leukemia; Male; Mercaptopurine; Methotrexate; Mycoses; Pneumonia; Prednisone; Pseudomonas aeruginosa; Remission, Spontaneous; Sepsis; Staphylococcus; Time Factors; Vincristine

Topics: Acute Disease; Autoradiography; Child; Child, Preschool; Female; Humans; Lectins; Leukemia; Lymphocyte Activation; Lymphocytes; Mercaptopurine; Methotrexate; Remission, Spontaneous; RNA; Tritium; Uridine

Topics: Azathioprine; Bone Marrow; Bone Marrow Cells; Humans; In Vitro Techniques; Leukemia; Mercaptopurine; Mitosis

Topics: Adolescent; Child; Child, Preschool; Cobalt Isotopes; Cyclophosphamide; Head and Neck Neoplasms; Humans; Leukemia; Lymphoma, Non-Hodgkin; Mediastinal Neoplasms; Mercaptopurine; Methotrexate; Peritoneal Neoplasms; Prednisone; Radioisotope Teletherapy; Remission, Spontaneous; Time Factors; Vincristine

Topics: Acute Disease; Adolescent; Agammaglobulinemia; Antibody Formation; Antineoplastic Agents; Blood Transfusion; Child; Child, Preschool; Cyclophosphamide; Daunorubicin; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulins; Immunosuppressive Agents; Infant; Infections; Leukemia; Male; Mercaptopurine; Methotrexate; Prednisone; Serum Albumin

Topics: Adult; Aged; Cytarabine; DNA; Evaluation Studies as Topic; Female; Humans; Infant; Leukemia; Leukocytes; Male; Mercaptopurine; Middle Aged; Quinacrine; RNA; Thymidine; Tritium; Uridine

Topics: Animals; Breast Neoplasms; Carcinoma; Cell Transformation, Neoplastic; Cyclophosphamide; Disease Models, Animal; DNA Replication; Female; Humans; Leukemia; Lymph Nodes; Mercaptopurine; Mice; Neoplasm Metastasis; Sarcoma

Topics: Acute Disease; Anti-Bacterial Agents; Blood Transfusion; Glucocorticoids; Humans; Leukemia; Mercaptopurine; Phagocytosis; Ribonucleases; Vitamins

Topics: Acute Disease; Antibiotics, Antineoplastic; Antineoplastic Agents; Child; Cyclophosphamide; Cytarabine; Humans; Leukemia; Mercaptopurine; Methotrexate; Prednisolone; Vinblastine; Vincristine

Topics: Betamethasone; Bone Marrow Examination; Candidiasis; Daunorubicin; Humans; Leukemia; Leukemia, Myeloid, Acute; Male; Meninges; Meningitis; Mercaptopurine; Methotrexate; Middle Aged; Remission, Spontaneous

Topics: Antineoplastic Agents; Bronchial Neoplasms; Carcinoma, Bronchogenic; Drug Tolerance; Glycine; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Purines; Sulfides; Valerates

Topics: Antineoplastic Agents; Bone Marrow; Child; Child, Preschool; Cytidine; Drug Tolerance; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Leukocytes; Mercaptopurine; Prednisone; Remission, Spontaneous; Thiazines; Vincristine

Topics: Acute Disease; Adolescent; Adrenal Cortex Hormones; Adult; Age Factors; Aged; Asparaginase; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Remission, Spontaneous; Vincristine

Topics: Adolescent; Adult; Aged; Agranulocytosis; Allopurinol; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Blood Transfusion; Cytarabine; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Muramidase; Nausea; Prednisolone; Thrombocytopenia; Vincristine

Topics: Adolescent; Adult; Age Factors; Aged; Antineoplastic Agents; Asparaginase; Cyclophosphamide; Cytosine Nucleotides; Female; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Vincristine

Topics: Antineoplastic Agents; Cell Membrane Permeability; Child; Cyclophosphamide; Cytarabine; Drug Combinations; Drug Resistance; Follow-Up Studies; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Nucleotides; Prednisone; Prognosis; Vincristine

Topics: Adolescent; Age Factors; Asparaginase; Blood Platelets; Blood Transfusion; Child; Child, Preschool; Cyclophosphamide; Humans; Infant; Leukemia; Leukocytes; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Bone Marrow; Busulfan; Child; Cyclophosphamide; Female; Hematopoietic System; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Mononuclear Phagocyte System

Topics: Adenocarcinoma; Aged; Bone Marrow Diseases; Erythrocytes; Humans; Leukemia; Lung Neoplasms; Male; Megakaryocytes; Mercaptopurine; Middle Aged; Thiotepa; Thrombocythemia, Essential

Topics: Acute Disease; Adolescent; Adult; Age Factors; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Blood Cell Count; Bone Marrow Examination; DNA, Neoplasm; Drug Synergism; Esterases; Evaluation Studies as Topic; Female; Genetics, Medical; Histocytochemistry; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Peroxidases; Photometry; Polyploidy; Prednisone; Remission, Spontaneous; Staining and Labeling; Time Factors; Vincristine

Topics: Child, Preschool; gamma-Globulins; Humans; Immunoglobulin G; Immunoglobulin M; Infant; Leukemia; Mercaptopurine; Methotrexate

A patient with atypical acute leukaemia is described. This patient has, in addition, monoclonal IgG hyperglobulinaemia without myelomatous lesions and is living and well three years after diagnosis. The cell types found in the blood and in the bone marrow are atypical, and the histochemical findings are discussed. The relationship between monoclonal hypergammaglobulinaemia and malignant blood diseases is also discussed, and the literature on the subject reviewed.

Topics: Blood Platelets; Blood Protein Disorders; Blood Protein Electrophoresis; Bone Marrow Examination; Chronic Disease; gamma-Globulins; Humans; Hypergammaglobulinemia; Immunoelectrophoresis; Immunoglobulin G; Leukemia; Leukocyte Count; Male; Mercaptopurine; Middle Aged; Prednisolone

Topics: ABO Blood-Group System; Absorption; Adenocarcinoma; Antineoplastic Agents; Blood Platelets; Breast Neoplasms; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Dysgerminoma; Erythrocytes; Female; Hemagglutination Tests; Humans; Immune Sera; Isoantigens; Leukemia; Leukocytes; Male; Mercaptopurine; Methotrexate; Nitrogen Mustard Compounds; Pregnancy; Uracil Mustard

Topics: Acute Disease; Asparaginase; BCG Vaccine; Bone Marrow Transplantation; Daunorubicin; Drug Synergism; Humans; Immunity, Cellular; Immunization, Passive; Leukemia; Mercaptopurine; Methotrexate; Prednisone; Vincristine

The clinical findings in 12 patients with an unusual type of leukemia have been reviewed. The leukemic cell cannot be identified with any of the normal hematopoietic cells or with any of the lymphomas and may best be referred to by the descriptive term "hairy cell", which describes its appearance, most clearly seen on phase contrast microscopy. The patients were all males and the major clinical features were enlargement of the liver and spleen, with little lymph node enlargement. Hematologic findings in most patients have been anemia and thrombocytopenia with the characteristic abnormal cells present in the peripheral blood and bone marrow. The disease most often runs an indolent course and has shown little or no response to a variety of forms of treatment.

Topics: Adult; Aged; Blood Cell Count; Blood Platelets; Bone Marrow Cells; Cyclophosphamide; Hepatomegaly; Humans; Leukemia; Leukocyte Count; Leukocytes; Lymph Nodes; Lymphocytes; Lymphoma, Large B-Cell, Diffuse; Male; Mercaptopurine; Middle Aged; Prednisone; Reticulocytes; Sex Factors; Splenomegaly; Vincristine

Topics: Acute Disease; Blood Platelets; Child; Child, Preschool; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Long-Term Care; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adult; Aged; Bone Marrow Examination; Chlorambucil; Female; Hemoglobinometry; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Mercaptopurine; Prednisone; Radiation Effects; Radiography

Topics: Central Nervous System Diseases; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Injections, Spinal; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocyte Count; Leukocytes; Male; Mercaptopurine; Methotrexate; Prednisone; Spinal Puncture; Vincristine

Topics: Adolescent; Brain Neoplasms; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Infant; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Neurologic Manifestations; Prednisone; Prognosis; Vincristine

Topics: Acute Disease; Adolescent; Adult; Antibiotics, Antineoplastic; Antilymphocyte Serum; Antineoplastic Agents; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Drug Synergism; Female; Humans; Immunotherapy; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Acute Disease; Antibiotics, Antineoplastic; Bone Marrow Examination; Child; Cytarabine; Humans; Leukemia; Leukemia, Lymphoid; Leukocytosis; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Recurrence; Vincristine

Topics: Allopurinol; Aneuploidy; Blood Cell Count; Bone Marrow Examination; Chromosome Aberrations; Clone Cells; Cytogenetics; Humans; Karyotyping; Leukemia; Male; Mercaptopurine; Middle Aged; Mitosis; Prednisone; Vincristine

Topics: Acute Disease; Asparaginase; Child; Cyclophosphamide; Humans; Leukemia; Mercaptopurine; Methotrexate; Vincristine

Topics: Acute Disease; Adult; Blood Cell Count; Female; Humans; Leukemia; Mercaptopurine; Methotrexate; Pericarditis; Pericardium

Topics: Adolescent; Allopurinol; Child; Child, Preschool; Female; Humans; Leukemia; Male; Mercaptopurine; Prednisone; Uric Acid; Vincristine

Topics: Adolescent; Child; Child, Preschool; Female; Humans; Leukemia; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Vincristine

Topics: Aminopterin; Child; Child, Preschool; Diagnosis, Differential; Haptoglobins; Hematologic Diseases; Humans; Infant; Infections; Leukemia; Lymphoma; Mercaptopurine; Neuroblastoma; Prednisone

Topics: Animals; Cytosine; Leukemia; Leukemia, Experimental; Leukemia, Lymphoid; Mercaptopurine; Mice; Thymine

Topics: Acute Disease; Adult; Antineoplastic Agents; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Nitroso Compounds; Prednisone; Urea; Vincristine

Topics: Acute Disease; Adult; Asparaginase; Blood Platelets; Blood Transfusion; Cyclophosphamide; Cytarabine; Humans; Leukemia; Leukocytes; Mercaptopurine; Prednisolone; Sweden

Topics: Adolescent; Adult; Aged; Alkaloids; Aminopterin; BCG Vaccine; Female; Humans; Leukemia; Mercaptopurine; Middle Aged; Prednisolone

Topics: Animals; Antineoplastic Agents; Asparaginase; Cyclophosphamide; Humans; Leukemia; Mercaptopurine; Methotrexate; Mice; Vincristine

Topics: Acute Disease; Aminopterin; Antineoplastic Agents; Asparaginase; Child; Cortisone; Cyclophosphamide; Cytarabine; Daunorubicin; Evaluation Studies as Topic; Humans; Leukemia; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Animals; Autopsy; Child, Preschool; Drug Combinations; Female; Humans; Leukemia; Liver Cirrhosis; Liver Regeneration; Male; Mercaptopurine; Methotrexate; Mice; Mice, Inbred Strains; Remission, Spontaneous

Topics: Acute Disease; Child; Child, Preschool; Humans; Infant; Leukemia; Mercaptopurine; Prednisolone

Topics: Carbon Isotopes; Humans; Leukemia; Mercaptopurine; Nucleosides; Nucleotides; Purines; Pyrazoles; Pyrimidines; Sulfides

Topics: Acute Disease; Adolescent; Adult; Aged; Cyclophosphamide; Cytarabine; Drug Resistance, Microbial; Female; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Vincristine

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Infant; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone; Prognosis

Topics: Adolescent; Adult; Aftercare; Aged; Antineoplastic Agents; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone

Topics: Antineoplastic Agents; Bone Marrow; Bone Marrow Cells; Bone Marrow Diseases; Bone Marrow Examination; Busulfan; Chlorambucil; Cortisone; Daunorubicin; Etiocholanolone; Female; Hematologic Diseases; Hodgkin Disease; Humans; Leukemia; Leukocyte Count; Male; Mercaptopurine; Radiation Effects; Vinblastine

Topics: Chronic Disease; Cyclophosphamide; Deoxyuridine; DNA; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Leukocytes; Ligases; Mercaptopurine; Methotrexate; Nucleosides; Nucleotides; Phosphotransferases; Tetrahydrofolate Dehydrogenase; Thymidine Kinase

Topics: Adolescent; Adult; Bone Diseases; Bone Marrow; Bone Marrow Cells; Child; Female; Gallbladder Diseases; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Myocardium; Pancreatic Diseases; Pericardial Effusion; Prednisone; Splenic Diseases; Time Factors; Vincristine

Topics: Animals; Antineoplastic Agents; Burkitt Lymphoma; Culture Techniques; Humans; Leukemia; Leukemia L1210; Leukemia, Experimental; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Mercaptopurine; Methotrexate; Mice; Prednisolone; Vincristine

Topics: Acute Disease; Adolescent; Adult; Aged; Blood; Extracorporeal Circulation; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Mercaptopurine; Middle Aged; Radiation Effects; Strontium Isotopes

Topics: Adolescent; Antineoplastic Agents; Central Nervous System Diseases; Child; Dactinomycin; Humans; Leukemia; Mechlorethamine; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adolescent; Antineoplastic Agents; Asparaginase; Central Nervous System Diseases; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Humans; Injections, Intravenous; Leukemia; Male; Meninges; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adolescent; Adrenal Cortex Hormones; Body Height; Body Weight; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adult; Female; Glucocorticoids; Humans; Leukemia; Lymphatic Diseases; Mercaptopurine

Topics: Acute Disease; Adolescent; Child; Child, Preschool; Female; Humans; Infant; Leukemia; Male; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Vincristine

Topics: Abortion, Therapeutic; Adolescent; Adult; Female; Humans; Leukemia; Mercaptopurine; Middle Aged; Pregnancy; Pregnancy Complications, Hematologic; Steroids

Topics: Acute Disease; Adult; Female; Humans; Leukemia; Male; Mercaptopurine; Prednisolone; Vincristine

Topics: Acute Disease; Autoradiography; Cytosine; Humans; Leukemia; Leukocytes; Mercaptopurine; Nucleic Acids; Steroids

Topics: Cyclophosphamide; Leukemia; Mercaptopurine; Methotrexate; Steroids; Vincristine

Topics: Animals; Biological Assay; Bone Marrow; Culture Techniques; Humans; Leukemia; Leukemia L1210; Leukocytes; Lymphocytes; Mercaptopurine; Mice

Topics: Allopurinol; Child; Humans; Leukemia; Mercaptopurine; Prednisone

Topics: Acute Disease; Child; Cyclophosphamide; Humans; Leukemia; Mercaptopurine

Topics: Acute Disease; Child; Cyclophosphamide; Humans; Leukemia; Mercaptopurine

Topics: Acute Disease; Child; Chronic Disease; Cyclophosphamide; Diagnosis, Differential; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged

Topics: Achilles Tendon; Action Potentials; Adult; Child; Child, Preschool; Cranial Nerves; Drug Synergism; Electrodiagnosis; Gait; Gastrointestinal Diseases; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Motor Neurons; Nervous System Diseases; Neural Conduction; Pain; Paralysis; Prednisolone; Reflex, Abnormal; Sensation; Time Factors; Vincristine

Topics: Acute Disease; Autoimmune Diseases; Blood Protein Disorders; Blood Protein Electrophoresis; Bone Marrow; Bone Marrow Cells; Child; gamma-Globulins; Humans; Leukemia; Male; Mercaptopurine; Pyoderma

Topics: Antineoplastic Agents; Busulfan; Carcinoma, Squamous Cell; Child; Chlorambucil; Choriocarcinoma; Dactinomycin; Female; Fluorouracil; Gonadal Steroid Hormones; Hodgkin Disease; Humans; Hydrazines; Leukemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Mesenchymoma; Methotrexate; Multiple Myeloma; Nitrogen Mustard Compounds; Ovarian Neoplasms; Pregnancy; Prostatic Neoplasms; Steroids; Testicular Neoplasms; Urethane; Vinblastine; Vincristine; Wilms Tumor

Topics: Adolescent; Adult; Aged; Bone Marrow Examination; Chromosome Aberrations; Female; Humans; Karyotyping; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Mosaicism; Nitrogen Mustard Compounds; Penicillins; Prednisolone; Streptomycin; Vitamins

Topics: Antineoplastic Agents; Hematologic Diseases; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Multiple Myeloma; Polycythemia Vera; Prednisone; Vincristine; Waldenstrom Macroglobulinemia

Topics: Blood Cell Count; Child; Child, Preschool; Chlorambucil; Cyclophosphamide; Female; Humans; Leukemia; Leukemia, Lymphoid; Liver; Male; Mercaptopurine; Methotrexate; Organ Size; Prednisone; Prognosis; Spleen; Triethylenemelamine; Vincristine

Topics: Bone Marrow; Bone Marrow Cells; Carbon Isotopes; Chromatography, Paper; Folic Acid; Formates; Humans; Leukemia; Leukocytes; Ligases; Mercaptopurine; Nucleosides; Nucleotides; Oxidoreductases; Purines; Tetrahydrofolate Dehydrogenase

Topics: Asparaginase; Busulfan; Chlorambucil; Cyclophosphamide; Cytarabine; Humans; Hydroxyurea; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Pipobroman; Prednisolone; Vincristine

Topics: Age Factors; Antineoplastic Agents; Cyclophosphamide; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Paramethasone; Prognosis; Sex Factors; Vincristine

Topics: Biopsy; Blood Cell Count; Blood Cells; Bone Marrow; Bone Marrow Cells; Chromosome Aberrations; Chromosome Disorders; Cytogenetics; Female; Humans; Infant, Newborn; Karyotyping; Leukemia; Leukemia, Lymphoid; Liver; Mercaptopurine; Prednisone; Vincristine

Topics: Acute Disease; Child; Child, Preschool; Cyclophosphamide; Humans; Leukemia; Mercaptopurine; Methotrexate; Prednisone; Time Factors; Vincristine

Topics: Acute Disease; Adult; Aged; Female; Humans; Leukemia; Male; Mercaptopurine; Methylation; Middle Aged; Neoplasm Metastasis; Ribose

Topics: Adult; Chemical and Drug Induced Liver Injury; Cholestasis; Female; Glomerulonephritis; Humans; Leukemia; Liver Function Tests; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Middle Aged

Topics: Humans; Leukemia; Mercaptopurine; Methotrexate; Vincristine

Topics: Adult; Aged; Humans; Leukemia; Mercaptopurine; Middle Aged; Primary Myelofibrosis; Vincristine

Topics: Acute Disease; Adolescent; Child; Child, Preschool; Drug Therapy; Humans; Leukemia; Mercaptopurine; Prednisone

Topics: Adolescent; Adult; Aged; Anemia, Hemolytic, Autoimmune; Autoimmune Diseases; Azathioprine; Colitis, Ulcerative; Female; Humans; Lectins; Leukemia; Male; Mercaptopurine; Middle Aged; Nephrotic Syndrome; Purpura, Thrombotic Thrombocytopenic

Topics: Adaptation, Psychological; Blood Transfusion; Child; Cyclophosphamide; Humans; Leukemia; Mercaptopurine; Methotrexate; Physician-Patient Relations; Prednisone; Vincristine

Topics: Acute Disease; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Animals; Asparaginase; Child, Preschool; Cyclophosphamide; Female; Humans; In Vitro Techniques; Leukemia; Male; Mercaptopurine; Mice; Middle Aged; Rabbits

Topics: Allopurinol; Humans; Leukemia; Mercaptopurine; Uric Acid

Topics: Acute Disease; Adult; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Prednisolone; Suppuration

Topics: Animals; Antibodies; Antigens; Autoradiography; Chickens; Hemagglutination Tests; Humans; Immune Sera; Infant; Iodine Isotopes; Leukemia; Liver; Mercaptopurine; Spleen

Topics: Adenine; Carbon Isotopes; Guanine; Humans; Hypoxanthines; Leukemia; Leukocytes; Mercaptopurine; Nucleic Acids; Purines

Topics: Anemia, Hemolytic; Culture Techniques; Cyclophosphamide; Cytarabine; Humans; Immune Tolerance; Lectins; Leukemia; Lymphocytes; Mercaptopurine; Methotrexate; Neoplasms; Prednisolone; Smallpox Vaccine; Uveitis; Vincristine

Topics: Animals; Cricetinae; Cyclophosphamide; Humans; Leukemia; Leukemia L1210; Mercaptopurine; Methotrexate; Mice; Neoplasms, Experimental; Plasmacytoma; Prednisone; Vincristine

Topics: Adrenal Cortex Hormones; Adult; Cardiac Tamponade; Humans; Leukemia; Male; Mercaptopurine; Pericardial Effusion

Topics: Adenine; Animals; Body Weight; Cytarabine; Drug Antagonism; Drug Synergism; Fluorouracil; Guanine; Leukemia; Leukemia L1210; Mercaptopurine; Methotrexate; Mice; Nucleosides; Phosphotransferases; Purines; Vincristine

Topics: Bone Marrow Cells; Cell Division; Humans; Leukemia; Leukocyte Count; Mercaptopurine; Methotrexate; Vincristine

Topics: Child; Cyclophosphamide; Humans; Leukemia; Mercaptopurine; Methotrexate; Patient Care Planning; Vincristine

Topics: Cyclophosphamide; Humans; Leukemia; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Child; Cytarabine; Humans; Leukemia; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Acetylesterase; Acid Phosphatase; Adolescent; Adult; Aged; Alkaline Phosphatase; Cell Differentiation; Histocytochemistry; Humans; Leukemia; Leukocytes; Mercaptopurine; Methotrexate; Middle Aged; Peroxidases; Staining and Labeling; Steroids

Topics: Age Factors; Aminopterin; Animals; Antineoplastic Agents; Busulfan; Chlorambucil; Cyclophosphamide; Dactinomycin; Drug Tolerance; Graft vs Host Disease; Immunosuppressive Agents; Leukemia; Melphalan; Mercaptopurine; Methotrexate; Mice; Plants, Medicinal; Plants, Toxic; Podophyllin; Podophyllum; Skin Transplantation; Thioguanine; Transplantation, Homologous

Topics: Anti-Bacterial Agents; Child; Cytomegalovirus Infections; Female; Humans; Leukemia; Male; Mercaptopurine; Pneumonia, Viral

Topics: Adolescent; Child; Child, Preschool; Cyclophosphamide; Dactinomycin; Female; Humans; Infant; Leukemia; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Paraplegia; Prednisolone; Retroperitoneal Neoplasms; Sarcoma, Ewing; Spinal Cord Neoplasms; Vinblastine; Vincristine; Wilms Tumor

Topics: Acute Disease; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Agranulocytosis; Aspergillosis; Candidiasis; Cytarabine; Female; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Mucormycosis; Nocardia Infections; Prednisone; Proteus Infections; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Strongyloidiasis; Uracil; Vinblastine

Topics: Adult; Aged; Alkylating Agents; Diagnosis, Differential; Emotions; Female; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Prednisone

Topics: Adolescent; Bone Marrow Examination; Child; Child, Preschool; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Prednisone

Topics: Blood Cell Count; Cytarabine; DNA; Humans; In Vitro Techniques; Injections, Intravenous; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Mercaptopurine; Multiple Myeloma; Prednisone; RNA; Tritium; Uridine; Vincristine

Topics: Acute Disease; Adrenal Cortex Hormones; Adult; Antineoplastic Agents; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Thrombocythemia, Essential; Vincristine

Topics: Antineoplastic Agents; Asparaginase; Burkitt Lymphoma; Cyclophosphamide; Cytarabine; Daunorubicin; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Nitroso Compounds; Prednisone; Urea; Vincristine

Topics: Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisolone

Topics: Adrenal Cortex Hormones; Blood Transfusion; Child; Child, Preschool; Diagnosis, Differential; Humans; Leukemia; Mercaptopurine

Topics: Androgens; Anti-Bacterial Agents; Antineoplastic Agents; Busulfan; Chlorambucil; Cyclophosphamide; Estrogens; Glucocorticoids; Humans; Leukemia; Mercaptopurine; Neoplasms; Plant Extracts; Plants; Triaziquone; Triethylenemelamine; Vincristine

Topics: Blood Cells; Bone Marrow Cells; Child; Folic Acid Antagonists; Humans; Leukemia; Mercaptopurine; Methotrexate; Prognosis

Topics: Child; Humans; Leukemia; Mercaptopurine; Methotrexate; Prednisolone

Topics: Adult; Child; Cyclophosphamide; Female; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisolone

Topics: Acute Disease; Aged; Antineoplastic Agents; Female; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Vincristine

Topics: Cell Transformation, Neoplastic; Culture Media; Humans; Leukemia; Leukocytes; Mercaptopurine

Topics: Adolescent; Age Factors; Child; Child, Preschool; Female; Glucocorticoids; Humans; Infant; Leukemia; Male; Mercaptopurine; Prognosis; Sex Factors

Topics: Busulfan; Cell Nucleus; Humans; Leukemia; Leukocytes; Mercaptopurine; Mouth Mucosa; Sex Chromatin

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Biopsy; Blood Protein Electrophoresis; Blood Sedimentation; Blood Transfusion; Busulfan; Congo; Female; gamma-Globulins; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Male; Mercaptopurine; Middle Aged; Prednisone

Topics: Acetazolamide; Adolescent; Amphotericin B; Candidiasis; Humans; Infectious Mononucleosis; Kidney Diseases; Leukemia; Male; Mercaptopurine; Methotrexate; Nystatin; Penicillins; Peripheral Nervous System Diseases; Prednisone; Rolitetracycline; Sepsis; Uric Acid

Topics: Adolescent; Adrenocorticotropic Hormone; Female; Humans; Leukemia; Mercaptopurine; Potassium Chloride; Prednisone

Topics: Aminopterin; Antineoplastic Agents; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Leukemia; Male; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Prednisone; Radiography; Vincristine; Wilms Tumor

Topics: Adrenal Cortex Hormones; Leukemia; Mercaptopurine

Topics: Antineoplastic Agents; Busulfan; Cyclophosphamide; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Adrenal Cortex Hormones; Adult; Antimetabolites; Antineoplastic Agents; Blood Transfusion; Child; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Plasmacytoma; Prednisone; Vincristine

Topics: Child, Preschool; Complement Fixation Tests; Cortisone; Female; Humans; Leukemia; Lung; Mercaptopurine; Pneumonia, Pneumocystis

Topics: Adrenal Cortex Hormones; Bone Marrow Transplantation; Cyclophosphamide; Folic Acid Antagonists; Humans; Leukemia; Mercaptopurine; Vincristine

Topics: Adult; Antineoplastic Agents; Child; Cyclophosphamide; Humans; Leukemia; Mercaptopurine; Methotrexate; Prednisolone; Vincristine

Topics: Antimetabolites; Humans; Inflammation; Leukemia; Mercaptopurine; Methotrexate; Neoplasms; Uveitis

Topics: Child; Child, Preschool; Cyclophosphamide; Humans; Leukemia; Mercaptopurine; Methotrexate; Methylprednisolone; Vincristine

Topics: Adolescent; Child; Child, Preschool; Diet Therapy; Dietary Proteins; Female; Humans; Leukemia; Male; Mercaptopurine; Prednisone; Vitamins

Topics: Adolescent; Adult; Folic Acid Antagonists; Follow-Up Studies; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Mortality; Steroids

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Antineoplastic Agents; Blood Transfusion; Busulfan; Child; Humans; Leukemia; Mercaptopurine; Vincristine

Topics: Aminopterin; Antimetabolites; Azaserine; Child; Child, Preschool; Choriocarcinoma; Diazooxonorleucine; Female; Fluorouracil; Folic Acid Antagonists; Humans; Leukemia; Mercaptopurine; Methotrexate; Pregnancy; Pyrimethamine; Toxoplasmosis; Vitamin K; Vitamins

Topics: Adult; Anti-Bacterial Agents; Culture Media; Cyclophosphamide; Fluorouracil; Germ-Free Life; Humans; Leukemia; Leukopenia; Male; Mercaptopurine; Methotrexate; Prednisolone; Teratoma; Vincristine

Topics: Bone Marrow Cells; Drug Therapy; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Prognosis; Statistics as Topic; Toxicology

Topics: Adrenal Cortex Hormones; Alkylating Agents; Child; Cyclophosphamide; Drug Therapy; Herpes Zoster; Hodgkin Disease; Leukemia; Lymphoma; Mechlorethamine; Mercaptopurine; Methotrexate; Neoplasms; Prednisolone; Surgical Procedures, Operative; Thrombocytopenia

Topics: Antineoplastic Agents; Child; Chlorambucil; Cyclophosphamide; Drug Therapy; Ganglioneuroma; Gastrointestinal Diseases; Hodgkin Disease; Leukemia; Leukemia, Myeloid; Liver Neoplasms; Lymphoma; Mechlorethamine; Mercaptopurine; Methotrexate; Neoplasms; Pathology; Radiation Injuries; Stomach; Toxicology; Vinblastine; Vincristine; Wilms Tumor

Topics: Antineoplastic Agents; Child; Chloramphenicol; Clinical Enzyme Tests; Dactinomycin; Drug Therapy; Glucose-6-Phosphatase; Humans; Leukemia; Liver; Mercaptopurine; Methotrexate; Penicillins; Prednisone; Toxicology; Vincristine

Topics: Antineoplastic Agents; Central Nervous System Diseases; Child; Clinical Laboratory Techniques; Drug Therapy; Headache; Humans; Intracranial Pressure; Leukemia; Mercaptopurine; Methotrexate; Neoplasms; Papilledema; Prednisone; Vomiting

Topics: Adolescent; Adrenal Cortex Hormones; Deafness; Drug Therapy; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Topics: Adolescent; Antimetabolites; Child; Drug Therapy; Humans; Infant; Leukemia; Mercaptopurine; Prednisone

Topics: Biomedical Research; Biometry; Blood Cell Count; Leukemia; Leukemia, Lymphoid; Lymphocytes; Mathematics; Mercaptopurine; Methotrexate; Neoplasms; Therapeutics

Topics: Acute Disease; Drug Therapy; Humans; Leukemia; Mercaptopurine; Methotrexate

Topics: Alkylating Agents; Aminopterin; Busulfan; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mechlorethamine; Mercaptopurine; Methotrexate; Multiple Myeloma; Neoplasms; Pathology; Primary Myelofibrosis; Sarcoma; Triethylenemelamine; Tuberculosis; Tuberculosis, Pulmonary; Urethane

Topics: Child; Drug Therapy; Leukemia; Mercaptopurine; Methotrexate; Neoplasms; Remission Induction

Topics: Animals; Estradiol; Friends; Leukemia; Leukemia Virus, Murine; Leukemia, Experimental; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Methylcellulose; Mice; Mitomycin; Mitomycins; Neoplasm Transplantation; Neoplasms; Pharmacology; Research; Sarcoma; Triethylenemelamine; Urethane

Topics: Adolescent; Adrenal Cortex Hormones; Child; Drug Therapy; Geriatrics; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphocytes; Mercaptopurine; Microscopy, Electron, Scanning Transmission

Topics: Antineoplastic Agents; Bone Marrow Cells; Drug Therapy; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Pathology; Prednisone; Toxicology; Vincristine

Topics: Drug Therapy; Guanidines; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Mitoguazone; Pyruvaldehyde; Toxicology

Topics: Adolescent; Black People; Bone Marrow Examination; Busulfan; Child; Chromosome Aberrations; Cyclophosphamide; Drug Therapy; Genetics, Medical; Humans; Infant; Leukemia; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Mortality; Pathology; Psychotherapy; Social Conditions; Statistics as Topic; Steroids; United Kingdom; Vincristine; Virus Diseases; White People

Topics: Acute Disease; Adolescent; Adult; Aging; Cortisone; Drug Therapy; Humans; Leukemia; Mercaptopurine; Methotrexate; Penicillins; Prednisone; Statistics as Topic; Streptomycin

Topics: Acute Disease; Adolescent; Aminopterin; Child; Humans; Leukemia; Mercaptopurine; Neoplasms; Prednisone; Thymectomy

Topics: Acute Disease; Adrenal Cortex Hormones; Androgens; Cyclophosphamide; Humans; Leukemia; Mercaptopurine; Methotrexate; Neoplasms; Prednisone; Vincristine

Topics: Adolescent; Bone Marrow; Bone Marrow Examination; Child; Humans; Intestines; Kidney; Leukemia; Liver; Lung; Male; Mercaptopurine; Methotrexate; Neoplasms; Pathology; Testis

Topics: Adolescent; Antineoplastic Agents; Busulfan; Child; Cyclophosphamide; Drug Therapy; Humans; Infant; Leukemia; Leukemia, Myeloid; Melphalan; Mercaptopurine; Multiple Myeloma; Neoplasms; Phosphorus Isotopes; Prednisone

Topics: Acute Disease; Drug Therapy; Humans; Leukemia; Mercaptopurine; Methotrexate

Topics: Adult; Child; Cyclophosphamide; Humans; Leukemia; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Animals; Dactinomycin; Floxuridine; Leukemia; Melphalan; Mercaptopurine; Methotrexate; Mitomycins; Neoplasm Metastasis; Pyrimidines; Sarcoma, Experimental; Thiotepa

Topics: ABO Blood-Group System; Adolescent; Adrenocorticotropic Hormone; Adult; Blood Transfusion; Erythrocytes; Hemagglutination; Humans; Leukemia; Mercaptopurine; Prednisone

Topics: Adolescent; Appendicitis; Child; Child, Preschool; Escherichia coli Infections; Female; Humans; Leukemia; Male; Mercaptopurine; Mortality; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Antineoplastic Agents; Humans; Leukemia; Mercaptopurine; Middle Aged; Prednisone; Prognosis

Topics: Adolescent; Adrenal Cortex Hormones; Child; Child, Preschool; Female; Folic Acid Antagonists; Humans; Infant; Leukemia; Male; Mercaptopurine; Switzerland

Topics: Antibodies; Antigens; Antimetabolites; Antineoplastic Agents; Humans; Immunosuppressive Agents; Leukemia; Mercaptopurine; Methotrexate; Neoplasms; Prednisone; Uveitis; Vincristine

Topics: Antineoplastic Agents; Chemistry, Clinical; Cyclophosphamide; Drug Synergism; Hemorrhagic Disorders; Humans; Leukemia; Mercaptopurine; Mitomycins; Paramethasone; Prednisolone

Topics: Antimetabolites; Blood Cell Count; Child; Child, Preschool; Chromosome Aberrations; Chromosome Disorders; Cyclophosphamide; Humans; Leukemia; Mercaptopurine; Methotrexate; Mutation; Prognosis; Steroids

Topics: Aminohippuric Acids; Antipyrine; Blood-Brain Barrier; Child; Humans; Hydrocortisone; Leukemia; Male; Mercaptopurine; Methotrexate; Perfusion; Sulfadiazine; Vincristine

Topics: Adolescent; Aminopterin; Animals; Azaserine; Child; Female; Humans; In Vitro Techniques; Leukemia; Leukemia, Lymphoid; Male; Mercaptopurine; Mice; Microscopy, Electron; Prednisolone; Rats; Retroviridae

Topics: Adolescent; Child; Child, Preschool; Humans; Leukemia; Liver; Mercaptopurine; Prednisolone; Prothrombin

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Azo Compounds; Child; Child, Preschool; Female; Humans; In Vitro Techniques; Infant; Infant, Newborn; Leukemia; Male; Mercaptopurine; Middle Aged; Mitomycins; Pyrimidines

Topics: Adult; Aged; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Blood Transfusion; Female; Hemorrhage; Humans; Leukemia; Male; Mercaptopurine; Middle Aged; Thrombocythemia, Essential

Topics: Acute Kidney Injury; Adolescent; Blood; Dialysis; Humans; Kidney Diseases; Leukemia; Mercaptopurine; Metabolism; Methotrexate; Peritoneal Dialysis; Renal Dialysis; Renal Insufficiency; Toxicology; Uric Acid; Urine

Topics: Antineoplastic Agents; Busulfan; Chlorambucil; Cyclophosphamide; Leukemia; Mercaptopurine; Methotrexate; Neoplasms; Prednisone; Prognosis; Triamcinolone

Topics: Aneuploidy; Bone Marrow Examination; Child; Chromosome Aberrations; Chromosome Disorders; Chromosomes; Cyclophosphamide; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Microscopy, Electron, Scanning Transmission; Neoplasms; Pathology; Prednisone

Topics: Adolescent; Antineoplastic Agents; Blood; Child; Complement System Proteins; Cyclophosphamide; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Serologic Tests; Spectrophotometry; Thioguanine

Topics: Acute Disease; Female; Geriatrics; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic

Topics: Clinical Enzyme Tests; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocyte Count; Mercaptopurine; Metabolism; Phosphotransferases; Pyrophosphatases

Topics: Antineoplastic Agents; Bone Marrow Examination; Erythrocyte Count; Hemorrhage; Humans; Leukemia; Leukocyte Count; Leukopenia; Mercaptopurine; Nucleosides; Thioinosine; Toxicology

Topics: Adrenal Cortex Hormones; Chlorambucil; Cyclophosphamide; Dermatitis, Exfoliative; Genetic Diseases, X-Linked; Geriatrics; Hodgkin Disease; Leukemia; Leukemia, Hairy Cell; Leukemia, Lymphoid; Lymphatic Diseases; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Mycosis Fungoides; Neoplasms; Pathology; Peptide Nucleic Acids; Physiology; Sarcoma; Severe Combined Immunodeficiency

Topics: Guanidines; Humans; Leukemia; Leukemia, Myeloid; Mercaptopurine; Mitoguazone; Pyruvaldehyde; Toxicology

Topics: Antineoplastic Agents; Blood Platelets; Busulfan; Chlorambucil; Factor Analysis, Statistical; Hemoglobinometry; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukocyte Count; Mercaptopurine; Phosphorus Isotopes; Toxicology; Triethylenemelamine

Topics: Blood Chemical Analysis; Blood Platelets; Busulfan; Child; Chromosome Aberrations; Erythrocyte Count; Hematocrit; Humans; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukocyte Count; Male; Mercaptopurine; Neoplasms; Pathology; Priapism; Splenomegaly

Topics: Anemia, Sickle Cell; Eosinophilia; Erythrocytes; Humans; Kwashiorkor; Leukemia; Leukemia, Lymphoid; Leukocytes; Mercaptopurine; Methotrexate; Oxidation-Reduction; Polycythemia Vera; Prednisolone; Purpura; Purpura, Thrombocytopenic; Reticulocytes; Thalassemia

Topics: Anemia; Anemia, Hemolytic; Betamethasone; Chlorambucil; Dexamethasone; Geriatrics; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Lymphoma, Non-Hodgkin; Mechlorethamine; Mercaptopurine; Methylprednisolone; Pharmacology; Prednisone; Radiotherapy; Thrombocytopenia; Triamcinolone

Topics: Adolescent; Arthritis; Arthritis, Juvenile; Attention; Diagnosis, Differential; Humans; Leukemia; Mercaptopurine; Prednisone

Topics: Adolescent; Busulfan; Cyclophosphamide; Geriatrics; Leukemia; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Mercaptopurine; Nitrogen Mustard Compounds; Phenothiazines; Toxicology; Uracil Mustard

Topics: Adolescent; Black People; Child; Chlorambucil; Cyclophosphamide; Dactinomycin; Geriatrics; Leukemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mechlorethamine; Mercaptopurine; Neoplasms; Phagocytosis; Sarcoma; Steroids; Triethylenemelamine

Topics: Blood Transfusion; Chemical and Drug Induced Liver Injury; Child; Hepatitis; Hepatitis B virus; Leukemia; Mercaptopurine; Pathology; Prednisone; Statistics as Topic; Toxicology

Topics: Adrenal Cortex Hormones; Blood Cell Count; Blood Transfusion; Bone Marrow Examination; Eosinophils; Hemostatics; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Pathology; Tetracycline; Thrombin; Vitamin B Complex

Topics: Adrenal Cortex Hormones; Antimetabolites; Antineoplastic Agents; Child; Hodgkin Disease; Humans; Infant; Leukemia; Lymphatic Metastasis; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Neoplasms; Neuroblastoma; Nitrogen Mustard Compounds; Toxicology; Vincristine

Topics: Aminopterin; Animals; Antineoplastic Agents; Busulfan; Chlorambucil; Cyclophosphamide; Geriatrics; Histological Techniques; Hydrocortisone; Leukemia; Leukemia, Lymphoid; Leukocytosis; Mercaptopurine; Methotrexate; Mice; Polycythemia Vera; Purines; Research; Tissue Culture Techniques

Topics: Blood Transfusion; Child; Humans; Hydrocortisone; Leukemia; Mercaptopurine; Penicillins; Streptomycin; Time Factors

Topics: Autopsy; Bone Marrow Examination; Busulfan; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Humans; Leukemia; Leukemia, Myeloid; Mercaptopurine; Polyuria; Prednisone; Vasopressins

Topics: Adolescent; Antineoplastic Agents; Child; Leukemia; Mercaptopurine; Nucleosides; Prednisone; Uracil

Topics: Brain Diseases; Carbohydrates; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Cranial Nerves; Folic Acid Antagonists; Headache; Hematocrit; Humans; Injections; Injections, Spinal; Leukemia; Leukocyte Count; Mercaptopurine; Methotrexate; Prednisone; Seizures; Toxicology

Topics: Adrenal Cortex Hormones; Cyclophosphamide; Leukemia; Mercaptopurine; Neoplasms; Pathology; Prognosis; Vinblastine

Topics: Adolescent; Anti-Bacterial Agents; Antibiotics, Antitubercular; Antitubercular Agents; Blood Transfusion; Bone Marrow Examination; Central Nervous System Diseases; Child; Dextrans; Hematoma; Hematoma, Subdural; Humans; Isoniazid; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Norepinephrine; Oleandomycin; Paraplegia; Prednisone; Streptomycin; Tetracycline

Topics: Black People; Blood Cell Count; Bone Marrow Examination; Child; Cyclophosphamide; Drug Therapy; Humans; Leukemia; Leukemia, Myeloid; Mercaptopurine; Methylprednisolone; Prednisone; Sarcoma, Myeloid; Vincristine

Topics: Alkaline Phosphatase; Erythromycin; Female; Fluorescence; Humans; Leukemia; Leukemia, Myeloid; Leukocytes; Maternal-Fetal Exchange; Mercaptopurine; Microscopy; Microscopy, Fluorescence; Oxytetracycline; Placenta; Prednisone; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Quinacrine

Topics: Adolescent; Alpha-Globulins; Beta-Globulins; Blood Protein Disorders; Blood Protein Electrophoresis; Child; Drug Therapy; gamma-Globulins; Infant; Leukemia; Mercaptopurine; Prednisolone; Serum; Serum Albumin; Serum Globulins

Topics: Animals; Antineoplastic Agents; Antioxidants; Carbon Isotopes; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Leukemia; Leukemia, Experimental; Liver Neoplasms; Mercaptopurine; Neoplasm Proteins; Neoplasms, Experimental; Pharmacology; Proteins; Rats; Research

Topics: Animals; Antineoplastic Agents; Cyclophosphamide; Fluorouracil; Leukemia; Leukemia, Experimental; Melphalan; Mercaptopurine; Mice; Neoplasms; Neoplasms, Experimental; Oncogenic Viruses; Pharmacology; Research; Triethylenemelamine

Topics: Aziridines; Blood Platelets; Bone Marrow; Busulfan; Cell Division; Colchicine; Erythropoiesis; Hematopoiesis; Hodgkin Disease; Leukemia; Leukemia, Myeloid; Mercaptopurine; Pharmacology; Rats; Research; Reticulocytes; Vinblastine

Topics: Aldehydes; Anilides; Animals; Antineoplastic Agents; Cyclophosphamide; Humans; Leukemia; Leukemia L1210; Leukemia, Experimental; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Mice; Neoplasms; Neoplasms, Experimental; Pharmacology; Research; Vincristine

Topics: Animals; Bone Marrow Transplantation; Hematopoietic System; Leukemia; Leukemia, Experimental; Leukemia, Myeloid; Lymphoma; Mercaptopurine; Mice; Neoplasms; Neoplasms, Experimental; Organotherapy; Pharmacology; Research

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Busulfan; Carcinoma, Ehrlich Tumor; Leukemia; Leukemia, Myeloid; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Olivomycins; Pharmacology; Research; Sarcoma 180; Thiotepa; Toxicology

Topics: Animals; Antineoplastic Agents; Chlorambucil; Fluorouracil; Leukemia; Leukemia, Experimental; Mercaptopurine; Methotrexate; Mice; Pharmacology; Pyrimidines; Research; Stilbamidines; Triparanol

Topics: Busulfan; Drug Therapy; Helminthiasis; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine

Topics: Carbon Isotopes; Chromatography; Glucosyltransferases; Humans; Leukemia; Leukemia, Lymphoid; Liver; Mercaptopurine; Metabolism; Nucleosides; Oxidoreductases; Rats; Research; Spectrophotometry; Xanthines

Topics: Antineoplastic Agents; Bone Neoplasms; Dactinomycin; Female; Floxuridine; Fluorouracil; Genital Neoplasms, Female; Humans; In Vitro Techniques; Intestinal Neoplasms; Leukemia; Mechlorethamine; Melanoma; Mercaptopurine; Methotrexate; Neoplasms; Pharyngeal Neoplasms; Respiratory Tract Neoplasms; Stomach Neoplasms; Thiotepa

Topics: 2-Aminopurine; Aminopterin; Animals; Aspartic Acid; Azaguanine; Biological Products; Colchicine; Cortisone; Glutamates; Leukemia; Leukemia L1210; Leukemia, Experimental; Mercaptopurine; Methotrexate; Mice; Pharmacology; Purines; Research; Tryptophan; Vinblastine

Topics: Adolescent; Aminopterin; Anti-Bacterial Agents; Blood Transfusion; Child; Cortisone; Dermatologic Agents; Humans; Infant; Intracranial Pressure; Leukemia; Mercaptopurine; Methotrexate; Neurologic Manifestations; Norway; Prednisone; Toxicology

Topics: Afibrinogenemia; Blood Cell Count; Bone Marrow Examination; Drug Therapy; Factor V Deficiency; Fibrinogen; Humans; Hypoprothrombinemias; Leukemia; Leukemia, Myeloid; Leukemia, Promyelocytic, Acute; Mercaptopurine; Pathology; Statistics as Topic; Thrombocytopenia

Topics: Biopsy; Bone Marrow; Cell Division; Chromosome Aberrations; Chromosome Disorders; Drug Therapy; Histological Techniques; Humans; Leukemia; Leukocytes; Mercaptopurine; Skin; Toxicology

Topics: Adolescent; Blood; Calcium; Calcium, Dietary; Creatine; Creatinine; Humans; Hypercalcemia; Leukemia; Leukemia, Myeloid; Mercaptopurine; Potassium; Prednisone; Urea

Topics: Antineoplastic Agents; Busulfan; Child; Cyclophosphamide; Dactinomycin; Humans; Hydroxyurea; Leukemia; Leukemia, Lymphoid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Neoplasms; Neuroblastoma; Sarcoma; Urea

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Alkylating Agents; Anemia; Anemia, Hemolytic, Autoimmune; Busulfan; Chlorambucil; Cyclophosphamide; Folic Acid Antagonists; Hemorrhage; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Neoplasms; Nitrogen Mustard Compounds; Phosphorus Isotopes; Splenectomy; Thioguanine; Triethylenemelamine

Topics: Adrenal Cortex Hormones; Antineoplastic Agents; Asian People; Busulfan; DNA; DNA, Neoplasm; Epidemiology; Formates; Geriatrics; Humans; Infant; Japan; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Mitomycin; Neoplasms; Prednisolone; RNA; RNA, Neoplasm

Topics: Child; Drug Therapy; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Pathology; Prednisolone

Topics: Antineoplastic Agents; Cortisone; Cyclophosphamide; Folic Acid Antagonists; Hemostasis; Infections; Leukemia; Leukemia, Experimental; Lymphoma; Mercaptopurine; Mice; Penicillins; Rats; Research

Topics: Animals; Bone Marrow Examination; Hemagglutination Inhibition Tests; Interferons; Leukemia; Leukemia, Myeloid; Lymph Nodes; Mercaptopurine; Neoplasms; Neutralization Tests; Newcastle disease virus; Orthomyxoviridae; Spleen; Tissue Culture Techniques; Vertebrates; Viruses

Topics: Humans; Hyperthyroidism; Iodine; Iodine Isotopes; Leukemia; Leukemia, Radiation-Induced; Mercaptopurine; Prednisolone; Radiation; Radioisotopes

Topics: Blood Cell Count; Blood Protein Electrophoresis; Cell Division; Chromosome Aberrations; Chromosome Disorders; Chromosomes; Endoreduplication; Hematocrit; Humans; Leukemia; Mercaptopurine; Plant Lectins; Prednisone

Topics: Adenine Nucleotides; Bone Marrow; Cyclophosphamide; DNA; Formates; Guanine Nucleotides; Humans; In Vitro Techniques; Leukemia; Leukemia, Myeloid; Leukocytes; Mercaptopurine; Metabolism; Mitomycin; Mitomycins; Pharmacology; Prednisolone; Rabbits; Research; RNA; Thymine

Topics: Adolescent; Child; Humans; Infant; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Neoplasms; Prednisone; Prognosis

Topics: Adrenal Cortex Hormones; Busulfan; Chlorambucil; Cortisone; Cyclophosphamide; Hodgkin Disease; Humans; Leukemia; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mechlorethamine; Mercaptopurine; Methotrexate; Neoplasms; Palliative Care; Sarcoma; Vinblastine

Topics: Bone Marrow Examination; Child; Drug Therapy; Genetic Diseases, X-Linked; Leukemia; Leukemia, Hairy Cell; Lymphatic Diseases; Mercaptopurine; Severe Combined Immunodeficiency

Topics: Adolescent; Anti-Bacterial Agents; Antibiotics, Antitubercular; Blood; Blood Transfusion; Bone Marrow Examination; Child; Drug Therapy; Humans; Leukemia; Mercaptopurine; Properdin; Vitamin K; Vitamins

Topics: Abnormal Karyotype; Blood Cell Count; Bone Marrow Examination; Busulfan; Chromosome Aberrations; Chromosome Disorders; Geriatrics; Gout; Hemoglobinometry; Humans; Kidney Calculi; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Mercaptopurine; Nephrectomy; Prednisone

Topics: Abnormalities, Drug-Induced; Blood Transfusion; Dental Enamel; Female; Humans; Infant; Infant, Newborn; Leukemia; Leukemia, Myeloid; Mercaptopurine; Prednisone; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Tetracycline; Tooth Discoloration; Tooth, Deciduous; Toxicology

Topics: Bone Marrow Examination; Brain Neoplasms; Cerebrospinal Fluid Proteins; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Meninges; Mercaptopurine; Methotrexate; Neoplasms; Prednisone

Topics: Busulfan; Chlorambucil; Cyclophosphamide; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Mustard Plant; Neoplasms; Splenomegaly; Steroids; Uracil

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Glutaminase; Leukemia; Leukemia, Experimental; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Neoplasms; Neoplasms, Experimental; Pharmacology; Research; Sarcoma 180; Toxicology

Topics: Adolescent; Blood Cell Count; Blood Platelets; Bone Marrow; Bone Marrow Transplantation; Erythrocytes; Erythrocytes, Abnormal; Erythropoiesis; Hemoglobins; Humans; Leukemia; Leukemia, Lymphoid; Leukocyte Count; Mercaptopurine; Prednisolone; Reticulocytes; Tissue Banks; Transplantation, Autologous

Topics: Animals; Leukemia; Leukemia, Experimental; Mercaptopurine; Mice; Pharmacology; Research; Urethane

Topics: Adolescent; Child; Hematoma; Hematoma, Epidural, Cranial; Hematoma, Subdural; Humans; Hydrocephalus; Leucovorin; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Meninges; Mercaptopurine; Methotrexate; Pathology; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Radiography; Subarachnoid Hemorrhage; Vinblastine

Topics: Adrenal Cortex Hormones; Azaserine; Busulfan; Diagnosis, Differential; Drug Therapy; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid; Liver; Lymph Nodes; Mercaptopurine; Neoplasms; Pathology; Spleen

Topics: Blood Transfusion; Bone Marrow Cells; Bone Marrow Examination; Child; Diabetes Mellitus; Glucagon; Humans; Leukemia; Mercaptopurine; Methotrexate; Prednisolone; Prognosis; Toxicology; Triamcinolone

Topics: Child; Diagnosis; Electrocardiography; Heart; Heart Failure; Humans; Leukemia; Mercaptopurine; Methyltestosterone; Pathology; Prednisone; Radiography, Thoracic; Radiotherapy

Topics: Chickenpox; Child; Drug Therapy; Leukemia; Mercaptopurine; Methotrexate; Prednisone; Prognosis

Topics: Enzyme Activation; Enzyme Activators; Enzyme Inhibitors; Formates; Kinetics; Leukemia; Leukemia, Myeloid; Ligases; Liver; Mercaptopurine; Metabolism; Rats; Research; Transferases

Topics: Adrenal Cortex Hormones; Alkaline Phosphatase; Blood Cell Count; Bone Marrow Examination; Busulfan; Child; Chromosome Aberrations; Drug Therapy; Hemoglobins; Humans; Infant; Leukemia; Leukemia, Myeloid; Mercaptopurine; Splenomegaly; Thrombocytopenia

Topics: Adolescent; Aneuploidy; Antineoplastic Agents; Bone Marrow Cells; Child; Chromosome Aberrations; Chromosome Disorders; Cyclophosphamide; Genetics, Medical; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Research; Vincristine

Topics: Cerebral Hemorrhage; Geriatrics; Leukemia; Leukemia, Myeloid; Mercaptopurine; Neurologic Manifestations; Pathology

Topics: Busulfan; Chromosome Aberrations; Chromosome Disorders; Eosinophilia; Humans; Hypereosinophilic Syndrome; Leukemia; Leukemia, Myeloid; Mercaptopurine; Methylprednisolone; Prednisone

Topics: Biopsy; Bone Marrow Cells; Carcinoma; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Lymphoma; Mercaptopurine; Multiple Myeloma; Myositis; Neoplasms; Polymyositis; Prednisone; Sarcoma

Topics: Adenine; Antineoplastic Agents; Drug Therapy; Fever; Hematocrit; Leukemia; Leukocyte Count; Mercaptopurine; Purines; Thioguanine; Toxicology

Topics: Adolescent; Adrenal Cortex Hormones; Child; Drug Therapy; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Neoplasms; Prednisone

Topics: Child; Drug Therapy; Humans; Hydrocortisone; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Periodicity; Prednisone; Prognosis; Statistics as Topic; Stem Cells

Topics: Child; Drug Therapy; Encephalitis; Humans; Leukemia; Leukemia, Lymphoid; Lymphocytes; Mercaptopurine; Prednisone

Topics: Acute Disease; Adrenal Cortex Hormones; Drug Therapy; Folic Acid Antagonists; Humans; Leukemia; Mercaptopurine

Topics: Antineoplastic Agents; Drug Therapy; Humans; Leukemia; Leukemia, Myeloid; Mercaptopurine; Prognosis; Purines

Topics: Adrenal Cortex Hormones; Female; Leukemia; Leukemia, Myeloid; Mercaptopurine; Pregnancy; Pregnancy Complications, Hematologic

Topics: Blood Cell Count; Bone Marrow Examination; Candidiasis; Erythema Nodosum; Female; Gastrointestinal Hemorrhage; Humans; Leukemia; Mercaptopurine; Middle Aged; Prednisone; Sepsis

Topics: Adolescent; Alkylating Agents; Antimetabolites; Antineoplastic Agents; Blood Cell Count; Female; Glucocorticoids; Humans; Leukemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Multiple Myeloma; Polycythemia Vera

Topics: Antineoplastic Agents; Glyoxal; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine

Topics: Busulfan; Humans; Leukemia; Leukemia, Myeloid; Mercaptopurine; Prednisone

Topics: Allografts; Antineoplastic Agents; Leukemia; Leukemia, Experimental; Melphalan; Mercaptopurine; Radiation; Spleen; Transplantation; Transplantation, Homologous; Triethylenemelamine

Topics: Dexamethasone; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphocytes; Mercaptopurine; Methylprednisolone; Prednisolone; Prednisone

Topics: Leukemia; Leukemia, Basophilic, Acute; Mercaptopurine; Prednisone; Triamcinolone

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Acute Disease; Humans; Leukemia; Mercaptopurine

Topics: Busulfan; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mercaptopurine; Neoplasms; Radiotherapy

Topics: Adolescent; Alanine; Antineoplastic Agents; Child; Dexamethasone; Humans; Leukemia; Mechlorethamine; Mercaptopurine; Neoplasms; Pathology; Radiotherapy; Sarcoma, Myeloid

Topics: Animals; Antimetabolites; Cell Respiration; Leukemia; Leukemia, Experimental; Mercaptopurine; Metabolism; Methotrexate; Mice; Research

Topics: Adrenal Cortex Hormones; Agammaglobulinemia; Anemia; Anemia, Hemolytic; Autoimmune Diseases; Blood Protein Disorders; gamma-Globulins; Humans; Leukemia; Lymphoma; Mercaptopurine; Nitrogen Mustard Compounds; Waldenstrom Macroglobulinemia

Topics: Humans; Infant; Intestinal Perforation; Leukemia; Mercaptopurine; Methotrexate; Pathology; Stomach; Toxicology; Triamcinolone

Topics: Busulfan; Child; Cyclophosphamide; Disease Management; Leukemia; Mercaptopurine; Methotrexate; Prednisolone; Prognosis

Topics: Busulfan; Chlorambucil; Cyclophosphamide; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Prednisone; Triamcinolone

Topics: Blood Platelet Disorders; Busulfan; Child; Humans; Leukemia; Leukemia, Myeloid; Leukocytosis; Lymph Nodes; Mercaptopurine; Prednisone; Primary Myelofibrosis; Radiotherapy; Thrombocytopenia; Triamcinolone

Topics: Cause of Death; Child; Death, Sudden; Folic Acid; Humans; Intussusception; Leukemia; Leukemia, Lymphoid; Lymphocytes; Lymphoma, Non-Hodgkin; Mercaptopurine; Steroids

Topics: Busulfan; Hodgkin Disease; Inflammation; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocyte Count; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Nitrogen Mustard Compounds; Skin Tests; Skin Window Technique

Topics: Adrenocorticotropic Hormone; Gangrene; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Mercaptopurine; Penicillins; Prednisolone; Skin

Topics: Antimetabolites; Gout; Humans; Leukemia; Mercaptopurine; Pharmacology; Psoriasis; Purines; Pyrazoles; Pyrimidines

Topics: Adolescent; Black People; Colchicine; Gout; Humans; Leukemia; Leukemia, Lymphoid; Lymphocytes; Mercaptopurine; Prednisone; Toxicology

Topics: Aminopterin; Antineoplastic Agents; Azaguanine; Carbohydrate Metabolism; In Vitro Techniques; Lactates; Leukemia; Leukocytes; Mechlorethamine; Mercaptopurine; Metabolism; Neoplasms; Prednisone; Research; Thiotepa; Vinblastine

Topics: Adrenal Cortex Hormones; Alkaloids; Antineoplastic Agents; Child; Cyclophosphamide; Humans; Injections, Intravenous; Leukemia; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Prognosis; Toxicology; Vincristine

Topics: Alkylating Agents; Blood Chemical Analysis; Busulfan; Deoxyribonuclease I; DNA; Humans; Leukemia; Leukemia, Myeloid; Leukocyte Count; Mechlorethamine; Mercaptopurine; Neoplasms; Ribose

Topics: Animals; Antineoplastic Agents; Body Weight; Chlorprothixene; Leukemia; Leukemia, Experimental; Leukocyte Count; Liver; Mercaptopurine; Mice; Research; Spleen

Topics: Adrenocorticotropic Hormone; Antineoplastic Agents; Blood Cells; Busulfan; Electrons; Geriatrics; Leukemia; Leukemia, Myeloid; Mercaptopurine; Microscopy; Microscopy, Electron; Prednisone

Topics: Aminocaproates; Aminocaproic Acid; Anemia; Antineoplastic Agents; Blood Transfusion; Busulfan; Central Nervous System; Fever; Hemorrhage; Humans; Leukemia; Mechlorethamine; Mercaptopurine; Nervous System; Physiology; Prednisolone; Thiotepa; Vitamin K 1

Topics: Animals; Antineoplastic Agents; Antiviral Agents; Cyclophosphamide; Fluorouracil; Leukemia; Leukemia, Experimental; Leukemia, Lymphoid; Melphalan; Mercaptopurine; Mice; Oncogenic Viruses; Pathology; Pharmacology; Rauscher Virus; Research; Splenomegaly; Thiosemicarbazones; Vincristine

Topics: Adrenal Cortex Hormones; Antineoplastic Agents; Busulfan; Folic Acid Antagonists; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Neoplasms; Nitrogen Mustard Compounds

Topics: Busulfan; Child; Chlorambucil; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Neoplasms; Phosphorus Isotopes; Prednisolone; Prednisone; Urethane

Topics: Blood Cells; Folic Acid; Humans; Isomerases; Leucovorin; Leukemia; Mercaptopurine; Metabolism; Methotrexate; Oxidoreductases

Topics: Adolescent; Adrenal Cortex Hormones; Anti-Bacterial Agents; Antimetabolites; Antineoplastic Agents; Blood Transfusion; Cerebral Hemorrhage; Child; Hemorrhagic Disorders; Humans; Infant; Leukemia; Leukemia, Myeloid; Mercaptopurine; Neoplasms; Photomicrography; Sepsis; Toxicology; Vitamins

Topics: Adolescent; Child; Dexamethasone; Humans; Infant; Leukemia; Mercaptopurine; Prednisone; Triamcinolone

Topics: Child; Diagnosis; Hepatomegaly; Humans; Infant; Leukemia; Leukocyte Disorders; Leukocytosis; Liver Diseases; Lymphadenitis; Mercaptopurine; Prednisolone; Prednisone; Splenomegaly

Topics: Adolescent; Adrenal Cortex Hormones; Antineoplastic Agents; Child; Cyclophosphamide; Humans; Leukemia; Mercaptopurine; Methotrexate; Prednisolone; Vincristine

Topics: Animals; Blood Protein Electrophoresis; Busulfan; Complement System Proteins; Erythrocytes; Guinea Pigs; Hydrazines; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukocyte Count; Mercaptopurine; Prednisolone; Sheep

Topics: Blood Transfusion; Busulfan; Cortisone; Erythrocyte Count; Hemoglobinometry; Humans; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukocyte Count; Mercaptopurine; Nitrogen Mustard Compounds; Prednisolone; Prednisone; Uracil Mustard

Topics: Dermatology; Diagnosis; Geriatrics; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Mercaptopurine; Prednisolone

Topics: Acute Disease; Blood Transfusion; Child; Humans; Leukemia; Lymphocytes; Mercaptopurine; Prednisone; RNA; Surgical Procedures, Operative; Thymectomy; Thymus Gland

Topics: Acute Disease; Adrenal Cortex Hormones; Leukemia; Mercaptopurine

Topics: Antimetabolites; Child; Humans; Infant; Leukemia; Mercaptopurine; Thioinosine

Topics: Antineoplastic Agents; Child; Infant; Leukemia; Mercaptopurine

Topics: Health Services; Humans; Imidazoles; Leukemia; Mercaptopurine; Purine Nucleosides; Sulfur Compounds

Topics: Busulfan; Disease Management; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Mercaptopurine

Topics: Leukemia; Mercaptopurine; Pregnancy; Pregnancy Complications

Topics: Acute Disease; Antineoplastic Agents; Child; Humans; Infant; Leukemia; Mercaptopurine

Topics: Acute Disease; Antineoplastic Agents; Biomedical Research; Child; Humans; Infant; Leucine; Leukemia; Mercaptopurine

Topics: Acute Disease; Adrenocorticotropic Hormone; Biomedical Research; Child; Humans; Hydrocortisone; Infant; Leukemia; Mercaptopurine

Topics: Acute Disease; Folic Acid Antagonists; Leukemia; Mercaptopurine; Prednisone

Topics: Acute Disease; Blood Cells; Leukemia; Mercaptopurine; Steroids

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Blood Transfusion; Dermatologic Agents; Humans; Leukemia; Mercaptopurine; Prednisone

Topics: Adrenal Cortex Hormones; Aged; Bone Marrow; Busulfan; Chlorambucil; Cyclophosphamide; Hodgkin Disease; Humans; Leukemia; Lymphoid Tissue; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Multiple Myeloma; Neoplasms; Sarcoma

Topics: 17-Ketosteroids; Adrenal Cortex Hormones; Anti-Bacterial Agents; Antibiotics, Antitubercular; Blood Transfusion; Child; Humans; Leukemia; Mercaptopurine; Vitamins

Topics: Acute Disease; Adrenocorticotropic Hormone; Child; Humans; Hydrocortisone; Leukemia; Mercaptopurine

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Antimetabolites; Child; Folic Acid Antagonists; Humans; Leukemia; Mercaptopurine; Steroids

Topics: Leukemia; Mercaptopurine

Topics: Leukemia; Leukemia, Myeloid; Mercaptopurine

Topics: Humans; Leukemia; Leukemia, Myeloid; Mercaptopurine

Topics: Acute Disease; Antineoplastic Agents; Drug Therapy, Combination; Leukemia; Mercaptopurine

Topics: Leukemia; Mercaptopurine; Neoplasms

Topics: Leukemia; Mercaptopurine

Topics: Antigens; Erythrocytes; Hemagglutination; Hemagglutination Tests; Humans; Leukemia; Leukocytes; Mercaptopurine; Prednisone

Topics: Amino Acids; Humans; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukocytes; Mercaptopurine

Topics: Antimetabolites; Child; Humans; Infant; Leukemia; Mercaptopurine; Purines; Thioinosine

Topics: Adrenal Cortex Hormones; Child; Drug Therapy, Combination; Folic Acid Antagonists; Glucocorticoids; Humans; Infant; Leukemia; Mercaptopurine

Topics: Acetylation; Animals; Coenzymes; Humans; Leukemia; Mercaptopurine; Triethylenemelamine

Topics: Anemia; Anemia, Aplastic; Bone Marrow; Humans; Leukemia; Mercaptopurine

Topics: Humans; In Vitro Techniques; Leukemia; Mercaptopurine; Nucleic Acids

Topics: Acute Disease; Humans; Leukemia; Mercaptopurine; Thioguanine

Topics: Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mercaptopurine

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Animals; Leukemia; Leukemia, Experimental; Mercaptopurine; Purines

Topics: Acute Disease; Antineoplastic Agents; Azaserine; Biomedical Research; Leukemia; Mercaptopurine

Topics: Hepatitis; Humans; Leukemia; Mercaptopurine; Viral Vaccines

Topics: Busulfan; Hematinics; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Mercaptopurine; Vitamin B 12

Topics: Acute Disease; Child; Humans; Infant; Leukemia; Mercaptopurine; Prednisone; Purines

Topics: Humans; Leukemia; Leukemia, Myeloid; Mercaptopurine

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Acute Disease; Adrenal Cortex Hormones; Leukemia; Leukemia, Myeloid; Mercaptopurine

Topics: Blood Transfusion; Leukemia; Mercaptopurine; Platelet Transfusion

Topics: Acute Disease; Humans; Leukemia; Mercaptopurine

Topics: Leukemia; Mercaptopurine; Purines

Topics: Humans; Leukemia; Mercaptopurine; Steroids

Topics: Busulfan; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Mercaptopurine

Topics: Acute Disease; Drug Therapy, Combination; Folic Acid Antagonists; Humans; Leukemia; Mercaptopurine

Topics: Adrenal Cortex Hormones; Aminopterin; Child; Humans; Infant; Leukemia; Leukemia, Lymphoid; Mercaptopurine

Topics: Acute Disease; Humans; Leukemia; Medicine; Mercaptopurine; Prednisone

Topics: Acute Disease; Adult; Humans; Leukemia; Mercaptopurine

Topics: Acute Disease; Child; Cortisone; Folic Acid Antagonists; Humans; Infant; Leukemia; Mercaptopurine

Topics: Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Mercaptopurine; Monocytes

Topics: Acute Disease; Cortisone; Leukemia; Mercaptopurine

Topics: Disease Management; Humans; Leukemia; Mercaptopurine; Neoplasms

Topics: Humans; Leukemia; Mercaptopurine; Polycythemia Vera; Vitamin B 12

Topics: Child; Humans; Infant; Leukemia; Leukemia, Lymphoid; Lymphatic Vessels; Mercaptopurine

Topics: Acute Disease; Female; Humans; Leukemia; Leukemia, Myeloid; Mercaptopurine; Pregnancy

Topics: Humans; Leukemia; Mercaptopurine

Topics: Cortisone; Leukemia; Mercaptopurine

Current trends in the search for chemical compounds having an inhibitory action on the growth of malignant cells are reviewed in this article. Several agents are sufficiently promising that clinical trials with them are in progress. One of these, an aromatic nitrogen mustard (C.B. 1348), appears to be useful as an adjunctive therapeutic measure in patients with malignant lymphoma, chronic lymphocytic leukemia, and mycosis fungoides who have become refractory to other methods of treatment. The introduction of certain purine antagonists, of which 6-mercaptopurine has been given the most extensive clinical trial, has opened up a new field of experimental and clinical investigation. 6-mercaptopurine and related compounds appear to be particularly useful in the treatment of acute leukemia in adults, but they are also useful, together with the folic acid antagonists and the steroid hormones, in the management of acute leukemia in children. While at present chemotherapeutic agents currently under investigation rarely cause significant regression of inoperable primary or metastatic solid tumors, the possibility of eventual more effective control in many types of malignant disease is not as dismal as it was a decade ago.

Topics: Adult; Antineoplastic Agents; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma; Mercaptopurine; Mycosis Fungoides; Neoplasms

Topics: Cortisone; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Mercaptopurine; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purines

Topics: Acute Disease; Adrenocorticotropic Hormone; Cortisone; Leukemia; Mercaptopurine; Purines

Topics: Cortisone; Leukemia; Mercaptopurine; Neoplasms; Purines

Topics: Humans; Leukemia; Leukemia, Myeloid; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Mononuclear Phagocyte System; Neoplasms; Purines

Topics: Humans; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Mercaptopurine

Topics: Animals; Combined Modality Therapy; Folic Acid Antagonists; Leukemia; Leukemia, Experimental; Mercaptopurine; Methotrexate; Mice

Topics: Acute Disease; Female; Humans; Leukemia; Mercaptopurine; Pregnancy

Topics: Antimitotic Agents; Cell Respiration; Glucose; Glycolysis; Humans; Leukemia; Leukocytes; Mercaptopurine; Physiological Phenomena; Prednisone

Topics: Animals; Leukemia; Leukemia, Experimental; Mercaptopurine; Phosphorus; Purines; Rats; Thiotepa

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Antineoplastic Agents; Leukemia; Mercaptopurine; Purines

Topics: Aminopterin; Child; Cortisone; Humans; Infant; Leukemia; Mercaptopurine; Purines

Topics: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Purines

Topics: Child; Humans; Infant; Leukemia; Mercaptopurine; Purines

Topics: Humans; Leukemia; Mercaptopurine; Purines

Topics: Arylsulfonates; Leukemia; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Acute Disease; Child; Humans; Infant; Leukemia; Mercaptopurine; Purines

Topics: Animals; Leukemia; Leukemia, Experimental; Mercaptopurine; Mitosis; Neoplasms, Experimental; Phosphoramides; Poisons; Purines; Triethylenemelamine; Triethylenephosphoramide

Topics: Leukemia; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Acute Disease; Humans; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Neoplasms; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Child; Humans; Infant; Leukemia; Mercaptopurine; Purines

Topics: Arylsulfonates; Leukemia; Mercaptopurine; Neoplasms; Purines

Topics: Leukemia; Mercaptopurine; Neoplasms; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Neoplasms; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Humans; Leukemia; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Child; Humans; Infant; Leukemia; Mercaptopurine; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Biomedical Research; Leukemia; Mercaptopurine; Neoplasms; Purines

Topics: Leukemia; Mercaptopurine; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Antimetabolites; Leukemia; Mercaptopurine; Purines

Topics: Antimetabolites; Leukemia; Mercaptopurine; Purines

Topics: Busulfan; Cortisone; Cysteamine; Ethylamines; Leukemia; Mercaptopurine; Phosphoramides; Phosphorus; Phosphorus, Dietary; Purines; Triethylenephosphoramide

Topics: Leukemia; Mercaptopurine; Purines