mercaptopurine and Acute-Disease

Crohn's disease and ulcerative colitis, together popularly known as inflammatory bowel disease (IBD), are characterized by a number of extraintestinal manifestations. Although infrequent, acute pancreatitis, and less often chronic pancreatitis, may occur as a result of the disease itself or secondary to the medications used in the treatment. The increased incidence of acute pancreatitis in Crohn's disease can be explained based on the high predisposition to cholesterol as well as pigment stones as a result of ileal disease, anatomic abnormalities of the duodenum, immunologic disturbances associated with IBD, and, above all, to the side effects of many medications used in the treatment. Sulfasalazine, 5-aminosalicylic acid, azathioprine, and 6-mercaptopurine are well known to cause acute pancreatitis as a result of a possible idiosyncratic mechanism. Crohn's disease and ulcerative colitis share many clinical manifestations and treatment modalities. Nonspecific elevations of serum pancreatic enzymes in IBD make it difficult to avoid over diagnosis of acute pancreatitis, particularly in patients with Crohn's disease who suffer from abdominal pain often. The IBD-pancreas association is further reflected in many reports of exocrine as well as endocrine pancreatic insufficiency.

Topics: Acute Disease; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Colitis, Ulcerative; Crohn Disease; Humans; Immunosuppressive Agents; Incidence; Inflammatory Bowel Diseases; Mercaptopurine; Mesalamine; Pancreatitis; Sulfasalazine

In Crohn's disease therapeutic concepts are according to distinct conditions. Course of the disease, the individual disease pattern and the aim of treatment are of particular significance. Care of patients with Crohn's disease requires interdisciplinary cooperation between gastroenterologists and surgeons. Primary therapy in mild to moderate disease comprises aminosalicylates and budesonide. Treatment of refractory or severe cases are corticosteroids. Immunosuppressive therapy is indicated in all kinds of complicated disease. First line immunosuppressants are Azathioprine and 6-Mercaptopurine while Methotrexate, Infliximab, Mycophenolatmofetil and other compounds represent alternative or rescue medications. Maintenance of remission should not be done on a regular basis but rather regarding the individual patients' situation. Risks have to be carefully balanced with possible benefits. The most important aim of treatment is quality of life.

Topics: Acute Disease; Adrenal Cortex Hormones; Adult; Algorithms; Aminosalicylic Acids; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Azathioprine; Budesonide; Child; Crohn Disease; Drug Therapy, Combination; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Infliximab; Mercaptopurine; Methotrexate; Mycophenolic Acid; Practice Guidelines as Topic; Prognosis; Remission Induction; Risk Factors; Time Factors

In the past years there have been many exciting developments in IBD management. New therapies and concepts of remission induction and of maintenance have been developed. This paper is intending to bring together the basic topics in patient-management in the various medical fields that represent the most accepted ways of therapies. The introduction deals with the most common aspects of Crohn's disease and that of the ulcerative colitis. It describes the treatment of ulcerative colitis according to the different groups of patients and the degree of activity. First it analyses the possible ways leading to the remission, then the prevention of relapse, lastly the other therapeutic options which have not been given any evidence of so far. The main standards of Crohn's disease therapy are presented on the bases of the small bowel Crohn's disease. After discussing the essential principles in treating the complications it carries on the treating of the large bowel Crohn's disease and then it is completed with the consideration of prevention of the relapse and the supportive therapeutic possibilities.

Topics: Acute Disease; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Chronic Disease; Colitis, Ulcerative; Crohn Disease; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mercaptopurine; Mesalamine; Prednisolone; Recurrence; Risk Factors; Severity of Illness Index; Sulfasalazine

The patient was a 62-year-old man. His hematological data in April 2000 had shown no abnormalities, but he was referred to our hospital because of a fever and leukocytosis in June 2000. The peripheral blood showed 29.8 x 10(9)/L white blood cells, with 68.0% blasts. A bone marrow aspirate showed hypercellularity with a proliferation of large leukemic blasts. The leukemic cells were positive for CD13 (91%), CD33 (54.8%), CD34 (94.5%), and HLA-DR (97.9%). Some leukemic cells (15.6%) also expressed CD14. Cytogenetic analysis revealed 92,XXYY,t(9;22)(q34;q11)x2 in all 20 metaphase cells. Reverse transcriptase polymerase chain reaction analysis detected the minor BCR/ABL messenger RNA (mRNA) but failed to detect the major BCR/ABL mRNA. The patient achieved complete remission after induction chemotherapy, with no evidence of Philadelphia chromosome (Ph) or minor BCR/ABL mRNA. Ph-positive acute myeloid leukemia (Ph-AML) has rarely been reported. Herein, we report a case of Ph-AML with tetraploidy and review the previously reported Ph-AML cases.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cytarabine; Daunorubicin; Fusion Proteins, bcr-abl; Humans; Karyotyping; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Mercaptopurine; Middle Aged; Mitoxantrone; Polyploidy; Prednisolone; Remission Induction; RNA, Messenger; RNA, Neoplasm

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

We report two additional patients with acute myeloid leukemia (AML) and a translocation between chromosomes 7 and 11: t(7;11)(p15;p15). One patient was diagnosed as having AML-M2 and the other as AML with myelofibrosis. Both patients had low-level neutrophil alkaline phosphatase (NAP) scores. In the literature, only 15 AML patients with t(7;11)(p15;p15) have been reported; nine of them had an AML-M2 morphology, and all had a decreased NAP score. Moreover, mean survival of the reported AML patients with t(7;11)(p15;p15) was 15 months, although 85% of them obtained complete remission, indicating that this type of leukemia frequently tends to relapse. These findings indicate a strong association between the chromosome abnormality and hematologic manifestations of this disease.

Topics: Acute Disease; Adult; Alkaline Phosphatase; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 7; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Neutrophils; Prednisolone; Primary Myelofibrosis; Remission Induction; Translocation, Genetic

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

Topics: Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Pericarditis

Topics: Acute Disease; Allopurinol; Antineoplastic Agents; Child; Humans; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Prednisone; Uric Acid; Xanthine Oxidase

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: 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: Acute Disease; Age Factors; Alcoholism; Azathioprine; Chemical and Drug Induced Liver Injury; Chronic Disease; Cortisone; Diet Therapy; Exchange Transfusion, Whole Blood; Halothane; Hepatic Encephalopathy; Hepatitis; Hepatitis A; Hepatitis B; Hepatitis B Antigens; Hospitalization; Humans; Liver Diseases; Liver Function Tests; Malabsorption Syndromes; Mercaptopurine; Prednisone; Prognosis; Pruritus

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: 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: Acute Disease; Glucocorticoids; Hepatitis; Humans; Immunosuppressive Agents; Liver; Liver Cirrhosis; Liver Diseases; Mercaptopurine; Prednisolone; Prednisone

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

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

In ulcerative colitis (UC) gut bacteria drive inflammation. Bacterial recognition and T-cell responses are shaped by intestinal dendritic cells (DCs); therapeutic effects of probiotic bacteria may relate to modulation of intestinal DC. The probiotic mixture, VSL#3, increases interleukin (IL)-10 and downregulates IL-12p40 production by DC in vitro. We evaluated in vivo effects of oral VSL#3 and steroids on colonic DC in patients with acute UC.. Rectal biopsies were obtained from patients with active UC before and after treatment with VSL#3, corticosteroids, or placebo, and from healthy controls. Myeloid colonic DC were studied from freshly isolated lamina propria cells using multicolor flow cytometry. Surface expression of activation markers, CD40, CD86, pattern recognition receptors, Toll-like receptor (TLR)-2 and TLR-4 were assessed. Changed function was measured from ongoing intracellular IL-10, IL-12p40, IL-6, and IL-13 production.. Acute UC colonic myeloid DC were producing more IL-10 and IL-12p40 than control DC (P = 0.01). In VSL#3-treated patients DC TLR-2 expression decreased (P < 0.05), IL-10 production increased and IL-12p40 production decreased (P < 0.005); 10/14 patients on VSL#3 showed a clinical response. Corticosteroids also resulted in increased IL-10 and reduced IL-12p40 production by DC. Conversely, in patients on placebo, TLR-2 expression and intensity of staining for IL-12p40 and IL-6 increased (all P < 0.05); 5/14 patients on placebo showed a clinical response (P = NS).. Despite small numbers of human colonic DC available, we showed that treatment of UC patients with probiotic VSL#3 and corticosteroids induced "favorable" intestinal DC function in vivo, increasing regulatory cytokines and lowering proinflammatory cytokines and TLR expression. These effects may contribute to therapeutic benefit.

Topics: Acute Disease; Adrenal Cortex Hormones; Adult; Aged; Azathioprine; B7-2 Antigen; CD40 Antigens; Colitis, Ulcerative; Colon; Dendritic Cells; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Interleukin-10; Interleukin-12 Subunit p40; Interleukin-13; Interleukin-6; Male; Mercaptopurine; Mesalamine; Middle Aged; Probiotics; Receptors, Pattern Recognition; Young Adult

To determine whether, after very intensive induction and consolidation therapy in childhood AML, further maintenance therapy (MT) confers any advantage.. Three hundred-nine children with previously untreated AML were registered in the LAME 89/91 protocol. This three-cycle intensive regimen included an induction phase (mitoxantrone plus cytarabine) and, for non-allografted patients, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine. In the LAME 89 study, patients were given an additional MT consisting of mercaptopurine and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to be given or not MT after consolidation therapy.. Out of 309 patients, 276 (90%) achieved a complete remission. The overall survival (OS) and event-free survival at 6 years for all patients were 60% +/- 6% and 48% +/- 6%, respectively. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no further treatment than in patients randomized for MT (81% +/- 13% vs 58% +/- 15%; p = 0.04) whilst the 5-year disease-free survival was not significantly different (60% +/- 19% vs 50% +/- 15%; p = 0.25). The improvement of OS in MT-patients appeared to be related to a higher salvage rate after relapse.. Over 50% of patients can be cured of AML in childhood. In the context of a very short and drug-intensive regimen, low-dose MT, owing to the lack of improvement in disease control and the worsening of survival, should not be recommended. Over the past 20 years, the outcome of acute myeloid leukemia (AML) in children has improved substantially. In the eighties, complete remission (CR) was achieved in nearly 90% of patients but event-free survival (EFS) was poor. Myeloablative therapy followed by allogenic bone-marrow transplantation (allo BMT) from an HLA-identical sibling was demonstrated, in our experience, to be the treatment of choice for improving DFS in children with AML in first remission. The major issue was how best to maintain complete remission for patients without an HLA sibling donor. Whereas several groups continued to include low-dose MT and others decided to omit it, in 1991, our group undertook a prospective randomized trial (LAME 91 protocol), the main aim of which was to assess the efficacy of MT in addition to an intensive induction and consolidation chemotherapy. The main results have been published previously and are now updated and described in a higher number of patients.

Topics: Acute Disease; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bone Marrow Transplantation; Child; Chromosome Aberrations; Cytarabine; Disease-Free Survival; Humans; Leukemia, Myeloid; Mercaptopurine; Mitoxantrone; Prognosis; Survival Analysis; Time Factors

In acute myeloid leukemia (AML), p53 mutations are reportedly infrequent but associated with a poor prognosis. The majority of mutations are missense mutations, which generally lead to accumulation of nuclear p53 protein. However, the prognostic significance of the accumulation remains unknown in AML. In this study, we compared the prognostic value of p53 mutations versus accumulation of the product. p53 mutations were found in 9 (4.5%) of 200 patients with de novo AML. The p53 mutation detectable (mutation+) group had a worse prognosis (p = 0.0009) than the mutation not detectable (mutation-) group. Multivariate analysis showed that the p53 mutation was an independent factor (p = 0.005) for short overall survival as well as 60 yr or older (p = 0.001) and unfavorable karyotypes (p = 0.001). In 79 of the 200 patients, the expression of p53 was studied by immunocytochemistry (ICC) using anti-p53 monoclonal antibody (DO-7). All samples carrying missense mutations (N = 6) were positive for ICC in over 15% of nuclei of each sample, chosen as the optimized cutoff value of p53 accumulation. Accumulation was thus found in 14 of the 79 patients. However, there was no prognostic difference according to the accumulation, because the mutation-/accumulation+ group (N = 8) tended to have a good prognosis. These findings indicate that molecular detection of p53 mutations yields better prognostic information than ICC. In a subset of AML, p53 protein might be accumulated without mutation presumably due to upstream signals of p53.

Topics: Acute Disease; Adult; Aged; Amino Acid Substitution; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; DNA Mutational Analysis; Etoposide; Female; Gene Deletion; Genes, p53; Humans; Japan; Leukemia, Myeloid; Life Tables; Male; Mercaptopurine; Middle Aged; Mutation; Mutation, Missense; Neoplasm Proteins; Prednisolone; Prognosis; Regulatory Sequences, Nucleic Acid; Single-Blind Method; Survival Analysis; Tumor Suppressor Protein p53; Vincristine

To assess the efficacy of etoposide added to the standard remission induction therapy for acute myeloid leukemia (AML), newly diagnosed adult AML patients were randomized to receive either daunorubicin (40 mg/m2/day x 4 or more), behenoyl cytarabine (200 mg/m2/day x 10 or more), and 6-mercaptopurine (70 mg/m2/day x 10 or more) (BHAC-DM), or the same three drugs plus etoposide (100 mg/m2/day x 5) (BHAC-EDM) for response-oriented individualized induction therapy. The patients achieving complete remission (CR) received the same 3 courses of consolidation therapy followed by 6 courses of maintenance/intensification therapy. M3 patients were excluded because all-trans retinoic acid was used. Of 667 patients registered, 655 were evaluable. The median age was 49 (range 15 to 85). CR rates were 77% in the BHAC-DM group and 75% in the BHAC-EDM group. In 173 M4 patients, CR rates were 86% and 69% (P = 0.009), and in 32 M5 patients, 80% and 77% (P = 0.810) in the BHAC-DM and the BHAC-EDM groups, respectively. The predicted 6-year overall survival rates were 30% and 38% (P = 0.925) for the BHAC-DM and BHAC-EDM groups, and the disease-free survival rates of CR patients were 25% and 35% (P = 0.352), respectively. Nonhematological toxicities after the first course of induction therapy were almost equal among the two groups, with the exception of a greater loss of hair (P = 0.024) and more frequent diarrhea (P = 0.013) in the BHAC-EDM group. We concluded that in the present study, the addition of etoposide to the standard individualized induction therapy showed no advantage in adult AML, even among M4 and M5 patients.

Topics: Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Etoposide; Female; Humans; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Prospective Studies; Remission Induction; Survival Analysis

The cure rate of acute myeloid leukemia might increase if G-CSF were given concurrently with repeated postremission chemotherapy. However, this therapy might cause severe complications, including depletion of normal hematopoietic progenitors as a long-term toxicity. Thus, we conducted a pilot study of this strategy. Twenty-six acute myeloid leukemia patients in a first complete remission (CR) were treated with two courses of consolidation chemotherapy (10-day BHAC-DMP, consisting of behenoyl cytosine arabinoside, daunorubicin, 6-mercaptopurine and prednisolone) and repeated maintenance-intensification therapy including eight cycles of six-day BHAC-DMP. G-CSF (filgrastim) was administered concurrently with these BHAC-DMP therapies. Toxicity during the therapeutic period was not significant in the study group compared with the historical control, treated with the same regimen without G-CSF. Neutrophil recovery after the consolidation therapy was more rapid in the study group than in the historical control (p = 0.066 and 0.024 for the first and second consolidation courses, respectively). Long-term toxicity, such as cytopenia, has not been seen in eight patients who have remained in CR for a long period (range: 39-58 months). At a median follow-up of 39 months, the predicted rate of 42-month CR duration for these 26 patients was 50% (95% confidence limits: 30% to 71%). We conclude that G-CSF-combined repeated BHAC-DMP postremission therapy is feasible. Full elucidation of the clinical benefit of this strategy will require further study.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Pilot Projects; Prednisolone; Recombinant Proteins; Time Factors; Vincristine

High-dose, continuous infusion of intravenous mercaptopurine (HD 6MP) followed by intermediate-dose continuous cytarabine (ID Ara-C) has been shown to produce remissions in children with relapsed acute myeloid leukemia (AML). The purpose of this pilot study was to explore the feasibility of using this drug regimen as a component of treatment during the first remission of AML. Of 17 children with newly diagnosed AML registered in the study, 14 developed complete remission on conventional induction therapy and subsequently received the HD 6MP and ID Ara-C combination. The dosages of HD 6MP were escalated from 500 mg/m2 to 1250 mg/m2 in 24-hr infusions. The initial dosages of ID Ara-C were escalated from 250 mg/m2 to 650 mg/m2/24 hr and from 1 day to 4 days. Conventional treatment for AML was administered simultaneously. Seven of the 14 children remain in initial complete remission for 15 to 46 months and have completed treatment. Severe pancytopenia was observed in all patients, but there were no toxic deaths and no deaths during remission. The inclusion of HD 6MP and ID Ara-C in the treatment of AML in first remission appears to be feasible. Evaluation of its efficacy will require a comparative clinical trial.

Topics: Acute Disease; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Dose-Response Relationship, Drug; Female; Humans; Infant; Leukemia, Myeloid; Male; Mercaptopurine; Treatment Outcome

We analyzed complete remission (CR), disease-free survival (DFS), and event-free survival (EFS) rates in two groups of patients treated with either N4-behenoyl-1-beta-D-arabinosylcytosine (BHAC) or cytarabine, and analyzed DFS with or without ubenimex, a biologic response modifier.. Newly diagnosed patients with acute myeloid leukemia (AML) were randomized to receive either BHAC or cytarabine as remission-induction combination chemotherapy and two courses of consolidation therapy. After maintenance/intensification therapy, patients in CR were randomized to receive either ubenimex and no drug.. Of 341 patients registered, 326 were assessable. The age of assessable patients ranged from 15 to 82 years (median, 48). The overall CR rate was 77%: 72% in the BHAC group and 81% in the cytarabine group, and there was a significant difference between the two groups (P = .035, chi 2 test). The predicted 55-month EFS rate of all patients was 30%: 23% in the BHAC group and 35% in the cytarabine group, with a significant difference between groups (P = .0253). The predicted 55-month DFS rate of all CR patients was 38% and that of CR patients less than 50 years of age was 47%. There was no significant difference in DFS between the ubenimex group and the group that did not receive ubenimex.. Analyses of our clinical trial showed that the use of BHAC in remission-induction therapy and in consolidation therapy resulted in poorer CR and EFS rates in adult AML patients compared with the use of cytarabine at the doses and schedules tested. Immunotherapy with ubenimex after the end of all chemotherapy did not improve DFS.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chi-Square Distribution; Cytarabine; Daunorubicin; Disease-Free Survival; Female; Follow-Up Studies; Humans; Leucine; Leukemia, Myeloid; Logistic Models; Male; Mercaptopurine; Middle Aged; Multivariate Analysis; Prednisolone; Prospective Studies; Remission Induction; Survival Rate; Treatment Outcome

The overall cure rate of adults with newly-diagnosed acute myelogenous leukemia (AML) treated with continuous infusion high-dose cytarabine (CIHDAC) is comparable to that with standard-dose ara-C plus anthracycline or amsacrine (AMSA). We tested whether the addition of AMSA to CIH-DAC improves the outcome of adults with untreated AML. 75 patients with untreated AML were treated with AMSA (75 mg/m2/day x 4) plus CIHDAC (1.5 g/m2/day x 4) for induction and, if in complete remission (CR), early and late intensification. Results were compared to those in 129 patients treated on a previous study with CIHDAC alone. The principal comparison in both groups was between those 117 patients (AMSA/CIHDAC n = 52, CIHDAC n = 65) who met the initial eligibility criteria for the AMSA/CIHDAC study (risk of early mortality < or = 1) and who were treated at a time when relatively few eligible patients were excluded (19% in the AMSA/CIHDAC group, 34% in the CIHDAC group). There was no difference between regimens in CR rate, remission duration, or survival in this cohort. When attention was turned to all 204 patients, outcome was superior with AMSA/CIHDAC very largely as a result of outcome in patients with APL. Aside from these patients, addition of amsacrine to CIHDAC did not appear to be productive.

Topics: Acute Disease; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid; Leukemia, Promyelocytic, Acute; Life Tables; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Remission Induction; Survival Analysis; Treatment Outcome; Vincristine

Topics: Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Daunorubicin; Disease-Free Survival; Etoposide; Female; Humans; Leukemia, Myeloid; Male; Mercaptopurine; Remission Induction; Russia; Survival Analysis; Time Factors

The risk for induction of epipodophyllotoxin-related acute myeloid leukemia (AML) depends largely on the schedule of drug administration and, to a lesser degree, the cumulative dose. Concomitant use of other genotoxic drugs, such as alkylating agents and cisplatin, can increase the hazard further. We have treated 154 consecutive higher-risk cases of acute lymphoblastic leukemia in our recent Total Therapy Study XIII with an intensive post-remission regimen of chemotherapy that included etoposide given every other week or less often-a schedule associated with a relatively low cumulative incidence of secondary AML in our Study XI. Unexpectedly, four patients have developed secondary AML at 12 to 23 months from the start of treatment (median, 16 months). The 2-year cumulative risk estimate significantly exceeds that for 185 historical controls in Study XI whose continuation regimen included epipodophyllotoxins every other week: 5.4% (95% confidence interval, 0-11%) compared with 1.1% (0-2.6%), P = 0.046. Compared to patients treated in Study XI, those enrolled in Study XIII receive fewer scheduled doses of epipodophyllotoxin (48 (all etoposide) vs 63 (30 etoposide, 33 teniposide)) but 16 to 19 additional doses of L-asparaginase and eight additional doses of high-dose methotrexate, all within the week preceding etoposide treatment. We attribute the apparently increased rate of secondary AML in Study XIII to the use of L-asparaginase immediately before etoposide administration. On this schedule, the enzyme could increase systemic exposure to etoposide or its catechol metabolites and reduce the ability of cells to repair DNA damage.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Synergism; Etoposide; Humans; Infant; Karyotyping; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Neoplasms, Second Primary; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone

This phase I/II study was designed to explore the feasibility, toxicity, and potential efficacy of administering high-dose continuous intravenous mercaptopurine (6MP) followed by intermediate-dose continuous intravenous cytarabine (Ara-C) to children with relapsed or unresponsive acute leukemia.. Twenty-three children with relapsed or unresponsive acute leukemia (13 myeloid, 10 lymphoid) were entered onto the study. After initial hydration and alkalinization, 1,000 or 1,250 mg/m2 of 6MP was administered by continuous intravenous infusion over 24 hours. Following another period of hydration, 500 mg/m2 of Ara-C was administered by continuous intravenous infusion daily for 4 days. In 17 children, plasma concentrations of 6MP were measured at hours 4, 24, and 27 of the 6MP infusions. Plasma concentrations of Ara-C were measured at hours 8, 24, 48, 72, and 96 of the Ara-C infusions. Intracellular Ara-C triphosphate (Ara-CTP) concentrations were measured in peripheral-blood leukemia cells of the five patients with sufficient cells for measurement. Children who developed remission received repeated courses of this regimen every 3 to 4 weeks until relapse or completion of 12 courses.. Of 13 children with acute myeloid leukemia (AML), six developed complete remissions (CRs) lasting 7 months to nearly 4 years. Two children remain in CR with normal growth, development, and health 3 years after cessation of treatment. Of 10 children with acute lymphoid leukemia (ALL), one had a CR of 2 months' duration. Dose-limiting toxicity consisted of severe hematosuppression with fever, neutropenia, and serious infection. There were two toxic deaths. The mean steady-state plasma concentrations of 6MP were approximately 4 mumol/L and of Ara-C approximately 3 mumol/L. The median Ara-CTP concentration in peripheral-blood leukemia cells was 308 mumol/L at hour 8 of the Ara-C infusion.. High-dose continuous intravenous 6MP followed by intermediate-dose intravenous Ara-C produced CRs of longer than 6 months in approximately half of children with relapsed or unresponsive AML. Further study of this drug regimen is justified.

Topics: Acute Disease; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Drug Administration Schedule; Feasibility Studies; Female; Humans; Infusions, Intravenous; Leukemia, Myeloid; Male; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Treatment Outcome

Aclarubicin was evaluated in combination chemotherapy for adult acute myeloid leukemia in a randomized trial involving 58 institutions throughout Japan. Behenoyl cytosine arabinoside (BH-AC).daunorubicin, 6-mercaptopurine, and prednisolone (DMP) was compared with BH-AC.aclarubicin, 6-mercaptopurine, and prednisolone (AMP). In the 360 evaluable cases among the 433 cases enrolled, complete remission (CR) rates were 63.7% (116/182) for BH-AC.DMP and 53.9% (96/178) for BH-AC.AMP (P = 0.0587). Median survival periods and 7-year survival rates were 15.8 months and 19.3% for BH-AC.DMP and 9.5 months and 20.2% for BH-AC.AMP (P = 0.0091 according to the generalized Wilcoxon test [GW], P = 0.196 according the log-rank test [LR]). Median disease-free survival periods were 15.4 months for BH-AC.DMP and 14.1 months for BH-AC.AMP (P = 0.851 by GW, P = 0.439 by LR). Among the 346 cases of extramurally confirmed FAB subtypes, CR rates were 67.9% (19/28) with BH-AC.DMP and 31.8% (7/22) with BH-AC.AMP for subtype M3 (P = 0.011) and 63.3% (93/147) with BH-AC.DMP and 56.8% (84/148) with BH-AC.AMP (P = 0.254) for subtypes M1, M2, M4, and M5. Diarrhea, ileus, pneumonia, and renal failure were more frequent with BH-AC.AMP than with BH-AC.DMP. The results indicate, at least on the basis of the long-term outcome, that BH-AC.AMP has antileukemic effects on subtypes M1, M2, M4, and M5 that are comparable with those of BH-AC.DMP.

Topics: Aclarubicin; Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Prednisolone; Prospective Studies; Survival Analysis

Topics: Acute Disease; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Communicable Diseases; Cytarabine; Daunorubicin; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid; Mercaptopurine; Prednisolone; Recombinant Proteins; Recurrence; Remission Induction; Survival Analysis; Time Factors; Vincristine

It was assessed whether addition of vincristine (VCR) to remission induction therapy would increase the complete remission (CR) rate, and, secondarily, whether 12 courses of maintenance-intensification therapy would produce longer survival than 4 courses in adult acute myeloid leukemia (AML).. A randomized comparison of individualized induction therapy was conducted between daunorubicin, behenoyl cytarabine, 6-mercaptopurine, and prednisolone with or without VCR. After 3 courses of intensive consolidation therapy, maintenance-intensification therapy was randomized to 4 or 12 courses given every 6 weeks.. Of 265 patients registered, 252 were evaluable. CR was obtained in 78%; 80% in 205 patients of age younger than 60 years, and 65% in 47 of age 60 years or older. Addition of VCR reduced the CR rate significantly (84% to 70%, P = 0.007). Predicted 4-year survival, continuing CR, and disease-free survival (DFS) rates of 196 CR patients are 45%, 41%, and 35%, respectively. Patients receiving 12 courses of maintenance-intensification showed better DFS. By multivariate analyses, significant factors for achievement of CR were performance status 0 to 2, age younger than 60 years, and no VCR; and those for longer DFS were achievement of CR by one course, age younger than 50 years, and French-American-British (FAB) classification M3 or M5. Among 131 patients randomized to the maintenance, the administration of 12 courses was the most important factor (P = 0.0040) for longer DFS, followed by FAB M3 or M5, and by achievement of CR by one course.. Addition of VCR in remission induction therapy was harmful, and longer intensive maintenance therapy prolonged DFS in adult AML.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Prednisolone; Prospective Studies; Remission Induction; Survival Rate; Time Factors; Vincristine

Topics: Acute Disease; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Resistance; Female; Humans; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Remission Induction; Time Factors

We asked 2 questions in this study. First was the additional effect of VCR in induction therapy, and the second was the duration of maintenance therapy. Adult AML were treated by an individualized response-oriented induction therapy with behenoyl Ara-C 200 mg/m2 daily + 6MP 70 mg/m2 daily + prednisolone 40 mg/m2 on days 1-4 + DNA 40 mg/m2 on days 1-3 and additionally on days 7, 8, 11, 12 (for M3, DNR 50 mg/m2 daily) (BHAC-DMP) until bone marrow became severely hypoplastic with less than 5% of blasts. Patients were randomized to BHAC-DMP or BHAC-DMP + VCR 0.35 mg/m2 on days 1-4. After obtaining CR, 3 courses of intensive consolidation therapy were given together with I.T. MTX+Ara-C+PSL. Maintenance intensification therapy was randomized to either 4 or 12 courses given every 2 months. Patients of age greater than or equal to 60 received about 2/3 reduced doses. From June 1987 to Sept. 1989, 265 consecutive adult AML were registered from 19 institutions and 258 were evaluable. Age ranged from 15 to 79 (med., 48). Out of 258, 200 (77.5%) achieved CR (80% in 209 of age less than 60 and 65% in 49 of age greater than or equal to 60). Unexpectedly, addition of VCR reduced the high CR rate of BHAC-DMP significantly (84% to 70%, p = 0.007). At the median follow-up of 37 mo., overall survival is 37%, and event-free survival (EVS) 27%. Survival, continuing CR and disease-free survival (DFS) rates of 200 CR cases are 45%, 40% and 35%, respectively. Patients received 12 courses of maintenance therapy showed better DFS (P = 0.0555). The VCR group had significantly worse EFS. By multivariate analysis, significant prognostic factors for the achievement of CR were age less than 60, PS 0-2 and no addition of VCR. Significant factors for longer DFS were induction of CR by one course, FAB M3 or M5 and age less than 50. The present multi-institutional study confirmed the high CR rates of the response-oriented individualized therapy reported from several centers in Japan, but failed to support an additional effect of VCR reported from one center.

Topics: Acute Disease; Adolescent; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Administration Schedule; Female; Humans; Japan; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Prednisolone; Remission Induction; Vincristine

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

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

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

Topics: Acute Disease; Age Factors; Animals; Antineoplastic Agents; Asparaginase; Central Nervous System Diseases; Child; Child, Preschool; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Infant; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; 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

Consecutive adult patients admitted to St. Bartholomew's Hospital with acute myelogenous leukaemia have been treated with a remission induction drug schedule consisting of daunorubicin and cytosine arabinoside. Intermittent five-day courses were used in 72 patients, and a complete remission was obtained in 39 patients (54%). An alternative drug schedule in 22 patients resulted in fewer remissions but this may have been due to age differences in the two groups. Age and initial platelet count were found to be important factors in determining the success of remission induction therapy; the older patients and those with low platelet counts responded less well.A series of 23 patients who achieved remissions was divided into two groups; one received intermittent combination chemotherapy as the only form of maintenance, and the other was given weekly immunotherapy in addition to the chemotherapy. The immunotherapy consisted of irradiated allogeneic leukaemic cells and B.C.G. Eight of the 10 patients on chemotherapy alone have already relapsed compared with five out of 13 patients in the immunotherapy group. It is hoped that these promising initial results with this form of maintenance will be confirmed as more patients enter the maintenance trials.

Topics: Acute Disease; Adolescent; Adult; Age Factors; Aged; Antineoplastic Agents; BCG Vaccine; Blood Cell Count; Blood Platelets; Child; Cytarabine; Daunorubicin; Humans; Immunotherapy; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Remission, Spontaneous; Thioguanine

Topics: Acute Disease; Adult; Antineoplastic Agents; Clinical Trials as Topic; Daunorubicin; Female; Humans; Leukemia, Myeloid; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prospective Studies; Remission, Spontaneous; Time Factors; Vincristine

One hundred and ninety-one cases of acute lymphoblastic leukaemia were entered in a trial in which, for five months, all received cytotoxic therapy with prednisolone, vincristine, mercaptopurine, L-asparaginase, and methotrexate (the latter in high dosage followed by folinic acid). Patients were then randomized to receive immunotherapy (B.C.G.), twice-weekly methotrexate, or no further treatment.One hundred and seventy-seven patients (93%) achieved full remission and at the time of analysis, 26 months from the beginning of the trial, 143 were still alive, including 70 in their first remission. Median "post-intensive" remission lengths were 17 weeks (no treatment), 27 weeks (B.C.G.), and 52 weeks (methotrexate). The prolongation of remission by methotrexate was most evident in those patients with low initial white cell counts. B.C.G. seemed to cause lymphocytosis but was without other conspicuous effect. The incidence of toxic reactions is reported, including an unusually low rate of anaphylaxis with L-asparaginase.These preliminary results are discussed and compared with those of similar trials.

Topics: Acute Disease; Adolescent; Adult; Anaphylaxis; Asparaginase; BCG Vaccine; Child; Child, Preschool; Clinical Trials as Topic; Humans; Infant; Leucovorin; Leukemia, Lymphoid; Leukocyte Count; Lymphocytes; Lymphocytosis; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous; Skin Tests; Tuberculin Test; Vincristine

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

Active non-specific immunotherapy has been used to prolong remissions in acute lymphoblastic leukaemia. The series reported here used Bordetella pertussis vaccine in a controlle trial after intensive chemotherapy. Possibly immunotherapy delayed the onset of relapse in the treated patients, but no long-term remissions were obtained. Further work is needed to establish the role of immunotherapy in general, and the use of B. pertussis vaccine in particular, in the treatment of acute leukaemia.

Topics: Acute Disease; Clinical Trials as Topic; Female; Humans; Immunotherapy; Leukemia, Lymphoid; Male; Mercaptopurine; Pertussis Vaccine; Prednisolone; Vincristine

Topics: Acute Disease; Antimetabolites, Antineoplastic; Factor V Deficiency; Humans; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Topics: Acute Disease; Burkitt Lymphoma; Chemical and Drug Induced Liver Injury; COVID-19; COVID-19 Drug Treatment; Humans; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; SARS-CoV-2

Hypoglycemia has been observed in children receiving acute lymphoblastic leukemia (ALL) therapy, and it can negatively affect patient outcomes. We documented a 4%-6% prevalence of hypoglycemia among patients in the two clinics in this study. We aim to reduce morning hypoglycemia in children on chemotherapy for ALL at two community pediatric oncology clinics (A and B) by 50% in 9 months.. We used the Institute for Healthcare Improvement (IHI) Model for Improvement as the framework. Prolonged hours of fasting for procedural sedation, gaps in the caregivers' knowledge of hypoglycemia risk, and a lack of awareness of the new mercaptopurine administration guidelines were the most likely contributing factors for hypoglycemia. We developed a hypoglycemia prevention educational program for staff and caregivers followed by a knowledge assessment tool.. Each month, the average number of patients seen in both clinics was 43. The monthly average of blood glucose tests in these patients was 94. After implementing the intervention, the percentage of caregivers who received hypoglycemia education reached 88%. Of those, 78% scored ≥ 75% in the knowledge reassessment resurvey. The combined average hypoglycemic episodes in the two clinics decreased by 46%. A higher reduction in hypoglycemic episodes was observed in clinic A (75%) compared with clinic B (17%).. Implementing hypoglycemia education led to a significant drop in hypoglycemic episodes among children on ALL therapy. Despite using a similar approach, one of the two clinics showed a more than fourfold improvement compared with the other.

Topics: Acute Disease; Child; Fasting; Humans; Hypoglycemia; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Diffuse alveolar hemorrhage is an uncommon and often fatal condition in children that is characterized by distinct histopathological etiologies. Herein, we discuss the case of an 11-year-old girl who presented with acute worsening of hypoxia and left-sided chest pain. The patient had lung biopsy-proven idiopathic pulmonary capillaritis and was being treated with prednisolone every alternate day, azathioprine, and hydroxychloroquine. A contrast-computed tomography (CT) scan of the chest showed an acute left lower-lobe pulmonary embolism. Negative results were obtained on a test for thrombophilia. In children, pulmonary embolism with anti-neutrophil cytoplasmic antibody-negative idiopathic pulmonary capillaritis is a rare clinical condition. The exact cause of thrombus formation in this case is unknown; however, obesity, immobility, and chronic systemic corticosteroid therapy probably played a role.

Topics: Acute Disease; Antibodies, Antineutrophil Cytoplasmic; Capillaries; Chest Pain; Child; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Hydroxychloroquine; Hypoxia; Lung; Lung Diseases; Mercaptopurine; Prednisolone; Pulmonary Alveoli; Pulmonary Embolism; Treatment Outcome; Vasculitis

Topics: Acute Disease; Adult; Azathioprine; Budesonide; Crohn Disease; Drug Substitution; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Sialadenitis; Submandibular Gland; Ultrasonography

We report a rare case of hypercalcemia and acute pancreatitis in a subject with acute promyelocytic leukemia (APL) and pulmonary tuberculosis, during all-trans-retinoic acid (ATRA) treatment. Both associated complications were potentially due to several causes. A careful monitoring and exclusion of all causative factors must be addressed. Further research is necessary to improve our understanding of risk factors for these complications in patients with (APL). Studying these patterns may help us to improve outcomes for all children and young adults with hematologic malignancies.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Causality; Febrile Neutropenia; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Models, Biological; Pancreatitis; Pleural Effusion; Prednisone; Pulmonary Aspergillosis; Risk Factors; Tretinoin; Tuberculosis, Pulmonary; Vincristine

Topics: Acute Disease; Allopurinol; Child; DNA, Neoplasm; History, 20th Century; Humans; Hyperuricemia; Mercaptopurine; Pediatrics; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tumor Lysis Syndrome; Uric Acid

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

Thiopurine drugs have been widely used in the treatment of inflammatory bowel disease. However, their use is limited by adverse effect that can lead to cessation of therapy. We report 2 cases of thiopurine-induced acute pancreatitis in patients with inflammatory bowel disease. Both patients complained of abdominal pain, showed elevated pancreatic enzymes, and swollen pancreases on computed tomography. The patients' signs and symptoms resolved uneventfully after withdrawal of the thiopurine drugs. Although the mechanism of thiopurine-induced pancreatitis remains unclear, close monitoring and early recognition of acute pancreatitis is important in the management of new thiopurine users.

Topics: Acute Disease; Adolescent; Adult; Azathioprine; Humans; Inflammatory Bowel Diseases; Male; Mercaptopurine; Pancreatitis

Topics: Acute Disease; Adolescent; Adult; Aged; Antibodies, Monoclonal; Colectomy; Colitis, Ulcerative; Cyclosporine; Drug Therapy, Combination; Female; Hospitalization; Humans; Immunosuppressive Agents; Infliximab; Length of Stay; Male; Mercaptopurine; Middle Aged; Salvage Therapy; Severity of Illness Index; Time Factors; Young Adult

Topics: Acute Disease; Azathioprine; Chemical and Drug Induced Liver Injury; Colitis, Ulcerative; Drug Hypersensitivity; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Mesalamine; Methyltransferases; Middle Aged; Prednisolone; Treatment Outcome

Several reports suggest an increased rate of adverse reactions to azathioprine in patients with Crohn's disease.. To compare the incidence of thiopurine-induced acute pancreatitis in patients with inflammatory bowel disease (IBD) with that in patients with vasculitis.. This retrospective analysis was performed using data collected in three databases by two university hospitals (241 patients with IBD and 108 patients with vasculitis) and one general district hospital (72 patients with IBD).. The cumulative incidence of thiopurine-induced acute pancreatitis in Crohn's disease equalled that of ulcerative colitis (UC) (2.6% vs. 3.7%) and this did not differ from vasculitis patients (2.6% vs.1.9%). In addition, the cumulative incidence of thiopurine-induced acute pancreatitis in UC patients was not different from that in vasculitis patients. In the IBD group, 100% of thiopurine-induced acute pancreatitis patients were women, whereas in the vasculitis group the two observed thiopurine-induced acute pancreatitis cases (n = 2 of 2) concerned were men (P = 0.012).. In this study, the alleged higher cumulative incidence of thiopurine-induced acute pancreatitis in Crohn's disease compared with vasculitis or UC patients was not confirmed. Female gender appears to be a risk factor for developing thiopurine-induced acute pancreatitis in IBD patients.

Topics: Acute Disease; Adolescent; Adult; Aged; Antimetabolites; Azathioprine; Crohn Disease; Female; Humans; Male; Mercaptopurine; Middle Aged; Pancreatitis; Retrospective Studies; Statistics as Topic; Young Adult

Disease-stabilizing therapy with the histone deacetylase inhibitor valproic acid and all-trans retinoic acid (ATRA) has been investigated in acute myelogenous leukemia (AML) in a number of trials. Experimental studies suggest that valproic acid induces a broad chemoresistant phenotype in human AML cells; however, clinical observations combining valproic acid with conventional therapy in a disease-stabilizing setting have not been reported that would confirm this as a clinical issue. We describe five patients receiving oral treatment with low-dose oral 6-mercaptopurin and/or hydroxyurea together with ATRA+valproric acid+theophylline. Hyperleukocytosis was controlled by low doses of the cytotoxic drugs, no unexpected toxicity appeared and the increases in normal peripheral blood cell counts induced by ATRA+valproic acid+theophylline were maintained during therapy. In two patients increasing blast counts later occurred during chemotherapy; a change to the alternative cytotoxic drug was then effective in controlling hyperleukocytosis. We conclude that valproic acid+ATRA+theophylline combined with 6-mercaptopurin or hydroxyurea can be safe and effective in palliative treatment of human AML.

Topics: Acute Disease; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Female; Histone Deacetylase Inhibitors; Humans; Hydroxyurea; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Treatment Outcome; Valproic Acid

We present the unusual case of a 16-year-old girl with T-cell acute lymphoblastic leukemia (ALL) with an early thymocyte immunophenotype without myeloid markers, who after 13 months of complete hematological remission relapsed as acute myelogenous leukemia (AML) with minimal differentiation and died of her disease. Whether the AML represented a relapse with lineage switch of the original immature T-cell clone or a new secondary malignancy, could not be proven due to the absence of molecular or clonal markers. This report suggests that a subset of CD7+ T-cell leukemias without mature T-cell antigens (CD4-, CD8-) are minimally differentiated and can relapse as AML.

Topics: Acute Disease; Adolescent; Antigens, CD7; Antigens, Differentiation, T-Lymphocyte; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bone Marrow; Cell Differentiation; Cell Lineage; Core Binding Factor Alpha 2 Subunit; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Diagnosis, Differential; Doxorubicin; Etoposide; Fatal Outcome; Female; Gene Dosage; Histone-Lysine N-Methyltransferase; Humans; Immunophenotyping; Karyotyping; Leukemia-Lymphoma, Adult T-Cell; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Myeloid-Lymphoid Leukemia Protein; Neoplasms, Second Primary; Neoplastic Stem Cells; Proto-Oncogenes; Recurrence; T-Lymphocyte Subsets; Vincristine

The introduction of the United Kingdom Medical Research Council's 10th AML trial (MRC AML 10) protocol incorporating high-dose anthracycline therapy has improved outcome of children with acute myeloid leukemia (AML). In this study, we review the results of childhood AML therapy in a Singapore university hospital over the last 17 years emphasizing toxicity and outcome.. Retrospective analysis revealed 34 children with AML between 1988 and 2003. Prior to September 1996, therapy consisted of: POG-8498 (n = 10), others (n = 9). From September 1996, all but one of 15 children received MRC AML 10 treatment.. At the time of analysis, 17 had died from disease, and 17 patients were alive among whom 2 had relapsed. MRC AML 10-treated patients (n = 14) had significantly better 3-year overall, event-free, and disease-free survival (74% vs. 35%, 77% vs. 20%, 83% vs. 31%; P = 0.019, P = 0.002, and P = 0.010, respectively) and were likelier to achieve complete remission (CR) than non-MRC AML 10 patients (P = 0.102). Among patients who achieved CR, MRC AML 10-treated patients were significantly more likely to achieve CR after only one cycle of chemotherapy (P = 0.016). Hematologic toxicity was similar among the different regimens (P = 0.9).. These findings suggest that MRC AML 10 treatment results in significantly superior survival, without excess toxicity. Future studies should attempt to elucidate the relative importance of individual MRC AML 10 components and reduce the high cumulative anthracycline dose without compromising outcome.

Topics: Acute Disease; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Cytarabine; Daunorubicin; Developing Countries; Disease-Free Survival; Drug Evaluation; Etoposide; Female; Gastrointestinal Diseases; Heart Diseases; Hematologic Diseases; Humans; Infant; Infections; Kaplan-Meier Estimate; Leukemia, Myeloid; Male; Mercaptopurine; Methotrexate; Mitoxantrone; Prednisone; Remission Induction; Retrospective Studies; Singapore; Survival Analysis; Thioguanine; Treatment Outcome; Vincristine

Acute cryptogenic hepatitis may represent both a self-limited disease as well as the onset of chronic hepatitis. The aim of this analysis was to evaluate the effect of steroid treatment in patients with acute cryptogenic hepatitis.. We retrospectively analyzed four patients with acute cryptogenic hepatitis. Histories were negative for alcohol and hepatotoxic drug intake. Markers of metabolic liver disease, liver-related autoantibodies, and viral markers were negative in all patients. Gamma globulins were in the normal range. ALT rose above 1000 U/L in all patients and bilirubin levels were elevated to more than 400 micromol/L. Histopathological assessment revealed minimal infiltration with plasma cells, eosinophils and bile duct lesions. Using the international scoring system for the diagnosis of autoimmune hepatitis, all patients were classified as 'probable disease' in the absence of specific markers.. We started immunosuppressive treatment with prednisolone because of persisting high aminotransferases and impaired liver function. All patients responded to steroids with normalization of liver function and a rapid decrease of aminotransferases. In one patient, additional treatment with azathioprine was necessary due to rebounding aminotransferases during steroid tapering.. Steroids have to be taken into account in the therapy for severe acute cryptogenic hepatitis. The response to steroid treatment could be indicative for an autoimmune genesis of the disease.

Topics: Acute Disease; Adult; Female; Hepatitis, Chronic; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Middle Aged; Prednisolone; Steroids; Treatment Outcome

Topics: Acute Disease; Adult; Age Factors; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Budesonide; Child; Controlled Clinical Trials as Topic; Crohn Disease; Drug Therapy, Combination; Follow-Up Studies; Humans; Immunosuppressive Agents; Mercaptopurine; Mesalamine; Meta-Analysis as Topic; Nutritional Physiological Phenomena; Prednisolone; Time Factors

Low-dose methotrexate (MTX) is used as disease-modifying therapy in severe rheumatoid arthritis and as maintenance treatment in patients with complete remission of acute lymphoblastic leukemia (ALL). It is generally well tolerated, but in 27% of patients acute pneumonitis leads to discontinuation of treatment. We describe a 56-year-old female patient with newly diagnosed pre-B-ALL. She was treated with induction chemotherapy in July 1999 which lead to complete remission. Maintenance treatment with low-dose MTX and 6-mercaptopurine (6-MP) was started in December 1999. In April 2000 she was hospitalized because of fever, cough, and rapidly progressive dyspnea. No pathogens could be cultured from blood or bronchoalveolar lavage fluid. Computed tomography of the lungs revealed interstitial infiltration and ground-glass opacities. Acute pneumonitis was diagnosed, and MTX was stopped. Prednisone therapy lead to rapid clinical amelioration of dyspnea and hypoxemia. Since for this patient there was no alternative leukemia therapy, MTX was successfully reintroduced in August 2000 without reappearance of any respiratory symptoms. We discuss risk profile, clinical and histological presentation, and therapy of MTX-induced pneumonitis. To our knowledge, this is the first patient with ALL in whom successful reintroduction of MTX after severe pneumonitis has been reported.

Topics: Acute Disease; Female; Humans; Mercaptopurine; Methotrexate; Middle Aged; Pneumonia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Remission Induction; Tomography, X-Ray Computed

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

We describe a 69-year-old Japanese male with acute leukemia with a CD7+ and CD56+ immunophenotype presenting with multiple lymphadenopathy. He was treated with idarubicin and cytosine arabinoside. Although the leukemia showed partial response, the patient did not achieve complete remission. He died of sepsis due to severe neutropenia after the third course of chemotherapy. His autopsy revealed blast infiltration in the lymph nodes, liver, spleen and vertebral bone marrow. Recently, CD7+ and CD56+ myeloid/natural killer precursor acute leukemia has been associated with a poor prognosis. Our case illustrates that myeloid/natural killer cell precursor acute leukemia shows some response to intensive chemotherapy for acute myeloid leukemia, but such therapy is insufficient to effect a cure. To overcome the resistance of this disease to chemotherapy, further studies should explore other treatment strategies.

Topics: Acute Disease; Aged; Antigens, CD; Antigens, CD7; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; CD56 Antigen; Cytarabine; Daunorubicin; Diagnosis, Differential; Etoposide; Fatal Outcome; Humans; Idarubicin; Killer Cells, Natural; Leukemia, Myeloid; Leukemic Infiltration; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Mitoxantrone; Myeloid Cells; Neoplastic Stem Cells; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sarcoma, Myeloid; Sialic Acid Binding Ig-like Lectin 3

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

Topics: Acute Disease; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mercaptopurine; Pancreatitis

Topics: Acute Disease; Adolescent; Antimetabolites, Antineoplastic; Child; Female; Humans; Male; Mercaptopurine; Pancreatitis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence

We retrospectively analyzed 126 acute myelogenous leukemia (AML) patients aged > or =60 years who had all been referred to the same hematological department between 1989 and 1999. In 76 de novo AML cases, 53 patients (median age, 72 years) were treated with combination chemotherapy (CT) for remission induction. Complete remission (CR) rate was 57.1%. The median overall survival (OS) was 16 months, and the rate of 3-year OS was 28%. The favorable prognostic factors were performance status < or =2, cholinesterase > or =100 IU, and intermediate or favorable karyotype (P < .01). Seventeen patients (median age, 78 years) with hypocellular bone marrow or poor general condition were treated with low-dose cytosine arabinoside (LDAraC). In these patients, the CR rate was 50% and the median OS was 11 months, with an OS estimate at 3 years of 14%. All patients with hypocellular bone marrow who received LDAraC for 21 days achieved CR. In 50 patients who developed AML following a myelodysplastic syndrome (MDS/AML), 22 patients (median age, 74 years) were treated with CT, and 14 (median age, 74 years) patients were treated with LDAraC. The CR rates were 22.7% and 21.4%, respectively, and the median OS durations were 8 months and 11 months, respectively. There were no significant factors that would indicate a good prognosis in MDS/AML patients.

Topics: Acute Disease; Age Factors; Aged; Allopurinol; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cholinesterases; Cytarabine; Daunorubicin; Disease Progression; Female; Humans; Japan; Karyotyping; Leukemia, Myeloid; Life Tables; Male; Mercaptopurine; Middle Aged; Myelodysplastic Syndromes; Neoplasm Proteins; Prognosis; Remission Induction; Risk Factors; Survival Analysis; Survival Rate

To clarify the characteristics of de novo acute myeloid leukemia (AML) among the elderly, we reviewed 112 patients over 60 years old (median age 72 years) who were treated at hospitals in Nagasaki Prefecture with a population of 1.5 million between 1987 and 1994. Reclassification of morphological diagnosis revealed that the proportion of M3 was lower but that of M6 and the incidence of cases with trilineage dysplasia (TLD), known as poor prognostic features, were higher in the elderly than in patients less than 60 years old. Similarly, chromosomal data showed a lower frequency of favorable karyotypes such as t(8;21) and t(15;17) in the elderly. The overall survival of all 112 patients was 10.3% at 5 years. Multivariate analysis indicated that good performance status (PS), low WBC at diagnosis, standard dose multi-drug chemotherapy and all-trans retinoic acid (ATRA) treatment for M3 patients, and morphological findings without TLD were significantly correlated with longer survival. Most of the long-term survivors were found among those who received standard dose therapy in this series, although no consensus has been established how to treat elderly AML patients. We propose that a prospective controlled trial is necessary to confirm the role of standard dose chemotherapy for elderly patients with de novo AML.

Topics: Acute Disease; Aged; Aged, 80 and over; Aging; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Humans; Karyotyping; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Prognosis; Treatment Outcome; Tretinoin

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

We describe a patient with leukocytosis with all the stages of neutrophilic series, peripheral dominant myeloblast proliferation, marked dysplasia of myeloid and erythroid series, and extramedullary hematopoiesis of the lymph nodes. A cytogenetic study of the bone marrow cells showed normal karyotype, and molecular analysis of the leukemic cells showed negative for BCR-ABL by RT-PCR. After chemotherapy, the patient went into complete remission with a normal blood and bone marrow profile with no dysplasia. On relapse, the hematological findings showed a typical bone marrow dominant acute myeloid leukemia, with the leukemic cells having a chromosomal abnormality. The patient exhibited the combined features of myeloproliferative disorder, myelodysplastic syndrome, peripheral dominant myeloblast proliferation (so-called peripheral leukemia) and typical acute myeloid leukemia throughout the clinical course. This is thought to be a rare overlapping disease involving these distinct hematological conditions that do not usually occur in the same patient.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cytarabine; Daunorubicin; Disease Progression; Hematopoiesis, Extramedullary; Humans; Leukemia, Myeloid; Male; Mercaptopurine; Middle Aged; Myelodysplastic Syndromes; Myeloproliferative Disorders; Prednisolone; Preleukemia; Remission Induction

Bone marrow aspirates from 60 patients with acute myeloid leukemia (AML) were investigated using 95% ethanol fixation Papanicolaou stained preparations. The blasts were grouped into those with a clear halo around nucleoli (BCHN) and those without a clear halo. The patients were classified into three groups according to the degree of persistent BCHN at the end of induction therapy: group 1, no BCHN; group 2, less than 1% BCHN; and group 3, 1% or more BCHN. All patients in groups 1 (17 cases) and 2 (12 cases), and 12 of 31 cases in group 3 achieved complete remission (CR). Of 17 patients in group 1, two underwent bone marrow transplantation and two died from infection. Of the 37 patients who achieved CR, relapse was observed in two of 13 patients in group 1, and in all patients in groups 2 and 3. As to the patients treated with N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine + daunorubicin + 6-mercaptopurine + prednisolone (BHAC-DMP) protocol, the percentages and number of BCHN at the diagnosis of AML in group 1 were significantly lower than those of groups 2 and 3. The percentage and number of BCHN at the diagnosis of AML were significant factors for the achievement of CR and for the prediction of long-term outcome. The reduction of BCHN to less than 1% at the end of induction therapy is a good indicator for the achievement of CR, and the disappearance of BCHN is a useful target for a long-lasting first CR; conversely, the persistence of BCHN is a major adverse factor for relapse.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Cells; Cell Nucleolus; Child; Child, Preschool; Cytarabine; Daunorubicin; Disease-Free Survival; Humans; Immunoenzyme Techniques; Ki-67 Antigen; Leukemia, Myeloid; Mercaptopurine; Middle Aged; Neoplasm Recurrence, Local; Prednisolone; Remission Induction; Retrospective Studies; Vincristine

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

A 67 year old male developed a therapy related myelodysplastic process culminating in acute myeloid leukemia 16 years following initial treatment for a large cell lymphoma. A second relapse of this leukemia showed 12% blasts including numerous giant blasts. The presence of giant blasts suggested the possibility of relapsed malignant lymphoma, however, flow cytometry and immunohistochemistry identified them as myeloid and chromosomal analysis revealed a near-tetraploid cell line. No evidence of lymphoma was seen. Although remission was induced with chemotherapy he subsequently relapsed with marrow and/or CNS involvement and was maintained on palliative therapy until he developed sepsis and died, 13 months following the observation of tetraploidy and 33 months following the onset of acute leukemia.

Topics: Acute Disease; Aged; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Chromosome Aberrations; Combined Modality Therapy; Cyclophosphamide; Fatal Outcome; Humans; Immunophenotyping; Karyotyping; Leukemia, Myeloid; Leukemia, Radiation-Induced; Lymphoma, Large B-Cell, Diffuse; Male; Mercaptopurine; Methotrexate; Neoplasms, Second Primary; Neoplastic Stem Cells; Palliative Care; Polyploidy; Prednisone; Procarbazine; Recurrence; Vincristine

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

A 62 year old male patient was previously admitted to another hospital in February 1989 because of palpitation. Peripheral blood examination revealed pancytopenia. Although the number of nucleated cells in the bone marrow aspirate was in the normal range. It contained 2.2% of blastic cells and dysplastic cells. He was diagnosed to be myelodysplastic syndrome with refractory anemia. He subsequently received repeated blood transfusions and other symptomatic treatments as an outpatient until 1990. When he was admitted to our hospital because of severe pancytopenia. The numbers of WBC, RBC, and platelets were 2,000/microliters, 134 x 10(4)/microliters, 2.9 x 10(4)/microliters respectively. Bone marrow aspiration resulted in dry tap, and biopsy at the iliac bone showed remarkable fibrosis with marked decrease of normal hematopoietic cells. Chromosome analysis revealed multiple aberrations such as 47XY, +8, 13q-, 14p+, 48XY, +8, +9, 13q+. The patient was treated with BHAC-AMP combination chemotherapy. After 3 cycles of the therapy, pancytopenia was improved and chromosomal aberration disappeared. This case was considered to be an acute myelofibrosis developed from myelodysplastic syndrome and worth to reporting with a review of literature, because drastic combination chemotherapy was extremely effective.

Topics: Aclarubicin; Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Chromosome Aberrations; Cytarabine; Humans; Male; Mercaptopurine; Middle Aged; Myelodysplastic Syndromes; Prednisolone; Primary Myelofibrosis

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

The treatment of acute myeloid leukemia (AML) in children with Down's syndrome (DS) has engendered considerable controversy. Because of the concerns for toxicity and increased rate of infections, treatment approaches varied considerably in the past with mixed results. However, experience on the recently completed Pediatric Oncology Group (POG) 8498 AML study suggests that DS children with AML constitute a distinct subgroup that responds well to therapy. Twelve of 285 children on POG 8498 (protocol for newly diagnosed AML) had DS. Children with DS and AML were predominantly male (9 of 12) and were quite younger at diagnosis (< 24 months in 10). The white blood cell count was less than 50 x 10(3)/microL in all 12 and French-American-British types M6 and M7 were frequent (5 of 12). An abnormal cytogenetic marker, in addition to constitutional trisomy 21, was present in 9 of 12 and involved chromosome 8 in 4 of 9. All cases studied (n = 5) were positive for myeloid cell surface markers (CD33, CD13, or CD11b) and, interestingly, were also positive for the CD7 antigen. Chemotherapy included daunorubicin, cytarabine (Ara-C), and 6-thioguanine for remission induction and featured high-dose Ara-C (3 g/m2 per dose) with or without L-asparaginase early in remission. Compared with children without DS, children with DS had a superior event-free survival (EFS at 4 years 100% v 28% +/- 6.2%; P = .003). The EFS remained superior even when compared with non-DS children less than 2 years of age with a white blood cell count less than 10 x 100,000/microL (100% v 48% +/- 17.3%; P = .01).

Topics: Acute Disease; Adolescent; Adult; Antigens, CD; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Azacitidine; Child; Chromosome Aberrations; Chromosome Disorders; Cytarabine; Daunorubicin; Down Syndrome; Etoposide; Female; Follow-Up Studies; Humans; Leukemia, Myeloid; Male; Mercaptopurine; Methotrexate; Prednisone; Remission Induction; Thioguanine; Vincristine

Forty-one consecutive adult patients with acute myeloid leukemia (AML) were treated with an intensive individualized induction therapy of behenoyl cytarabine, daunorubicin, and 6-mercaptopurine, 29 patients (71%) achieved complete remission (CR). Patients then received three courses of intensive consolidation therapy, including intermediate-dose continuous cytarabine (400 mg/m2, for 5 days) and non-cross resistant drugs such as mitoxantron, etoposide and vincristine. During the course of the consolidation therapy, three patients died of infections and one died of myocardial infarction. Four patients underwent allogeneic bone marrow transplantation. The patients then received six courses of moderately intensive maintenance therapy for 1 year. The predicted 5-year continuing CR and disease-free survival rates of the CR patients were 62% (95% confidence limit, 41% to 83%) and 53% (33% to 73%), respectively. Although the number of patients in this study is small, the present study indicated that it may be possible to cure a fairly large proportion of AML patients by chemotherapy alone, if intensive induction therapy is followed by intensive consolidation therapy.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Etoposide; Female; Humans; Leukemia, Myeloid; Male; Mercaptopurine; Mitoxantrone; Vinca Alkaloids

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: Acute Disease; Adult; Humans; Male; Mercaptopurine; Pancreatitis

Topics: Aclarubicin; Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Naphthacenes; Pancreatitis; Vincristine

Topics: Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cytarabine; Daunorubicin; Female; Graft vs Host Disease; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Platelet Transfusion; Prednisolone; Transfusion Reaction

Chlorambucil is useful in patients with rheumatoid arthritis (RA) refractory to other agents but there is concern about the risk of haematological malignancy with this agent. A retrospective survey was performed to assess the incidence of all types of malignancy in 39 patients treated with chlorambucil (mean daily dose 4.25 mg, mean duration of treatment 25 months). These patients were compared with 30 patients with RA who received contemporaneously, the purine analogues azathioprine or 6-mercaptopurine (mean dose 100 mg, mean duration of treatment 24 months). Eight patients treated with chlorambucil and one patient receiving purine analogues developed cutaneous malignancy (p = 0.03). In the chlorambucil-treated patients these were mostly multiple and recurrent. Three patients treated with chlorambucil developed myeloid leukaemia or a preleukaemic state, whilst no patient treated with purine analogues developed this complication. The use of chlorambucil in RA is associated with an increased risk of cutaneous as well as haematological oncogenesis.

Topics: Acute Disease; Arthritis, Rheumatoid; Azathioprine; Carcinogens; Chlorambucil; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Pancytopenia; Time Factors

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

Fifty-one consecutive previously untreated adult patients with acute myelogenous leukemia (AML) were treated with BHAC-DMP (N4-behenoyl-I-beta-D-arabinofuranosyl-cytosine, daunorubicin, 6-mercaptopurine, and prednisolone) therapy. Forty-two patients (82.4%) achieved complete remission (CR). The Kaplan-Meier analysis revealed a probability for remaining in remission of 14% and for survival of 23% at 6 years. Pretreatment factors related to the achievement of CR, such as age, French-American-British (FAB) classification and WBC at the start of treatment, were not identified. Factors related to the CR duration and survival time of the patients who had achieved CR were first analyzed by a univariate analysis with the generalized Wilcoxon test. WBC count at the start of treatment, percent of blasts in the marrow at 1 and 2 weeks after the initiation of therapy, days required until CR, number of courses of induction therapy required until CR, and days required for the disappearance of circulating blasts were identified as statistically significant prognostic factors. When these characteristics were further analyzed by the Cox multivariate regression model, the percent of blasts in the bone marrow at 2 weeks was the most important prognostic factor with a statistical significance, and WBC count at the start of treatment and days required until CR (or number of courses required to achieve CR) were also important factors, with borderline significance.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisone; Prognosis; Statistics as Topic

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

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: 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

Complex clinical, neurological and psychological examination was carried out in 23 children with acute lymphoblastic leukemia (ALL), being in complete initial remission from 5 to 12 years and without medication following the successful intensive therapy according to the protocol 0171 from 2 1/2 to 9 years. Somatic deficiency was observed in 2 children. Slightly hypoplastic bone marrow haemopoesis was found in 2 children. All children had normal haemogram. In 7 children lowered values of E-rosettes and in 3 children lowered levels of serum IgA were detected. Two children were HBsAg positive, in one of them with mild fibrosis was found at biopsy. Pathological neurological findings occurred in 7 children; pathological electromyogram (EMG) and electroencephalogram (EEG) in 8 and 5 children, respectively. Deviations of intellectual development were observed in 13 children. Deviations found can be connected in particular with long-term antileukemic therapy, especially with neurotoxic effects of some components of therapeutic regimen used (methotrexate, brain irradiation).

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; BCG Vaccine; Child; Child, Preschool; Combined Modality Therapy; Cytarabine; Female; Humans; Leukemia, Lymphoid; Male; Mental Disorders; Mercaptopurine; Methotrexate; Nervous System Diseases; Prednisone; Time Factors; Vincristine

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

Two patients with inflammatory bowel disease who developed acute pancreatitis within 21 days of commencing treatment with 6-mercaptopurine are presented. Both were inadvertently reexposed to the drug and developed recurrent pancreatitis within 3 hr of a single dose.

Topics: Acute Disease; Adult; Colitis, Ulcerative; Crohn Disease; Female; Follow-Up Studies; Humans; Male; Mercaptopurine; Pancreatitis; Recurrence

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

Topics: Acute Disease; Azathioprine; Colitis, Ulcerative; Crohn Disease; Humans; Mercaptopurine; Methylprednisolone; Metronidazole; Parenteral Nutrition; Sulfasalazine

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

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

We describe two adolescent girls with acute lymphoblastic leukemia (ALL) whose leukemia cells were near-haploid. Their lymphoblasts stained in a block pattern with periodic acid Schiff and had "common ALL" surface markers confirmed by indirect immunofluorescence. Each patient had two populations of blasts, one near-haploid and one hyperdiploid, which was an exact doubling of the near-haploid karyotype. The first patient had a predominant population of cells with 26 chromosomes and a few with 52, while the second had a predominance of cells with 56 and a minority with 28. Flow cytometric analysis of DNA content initially detected the minor near-haploid population in the second patient, which was confirmed later by cytogenetic review of the marrow sample. In addition to our two patients, only four patients have been reported with near-haploid ALL. Of these six, five were girls, five were adolescents, and five had short survivals (median, 10 mo). All six had disomy of chromosome 21 with or without disomy for chromosomes 10, 14, 18, or X (four patients each). Thus, near-haploid ALL may represent a unique subgroup of ALL with a poor prognosis. To detect these and other possible subgroups, we have included cytogenetic analysis and flow cytometric analysis of DNA content in our initial evaluation of patients with ALL.

Topics: Acute Disease; Adolescent; Bone Marrow Examination; Brain Neoplasms; Child; Daunorubicin; Female; Haploidy; Humans; Injections, Spinal; Karyotyping; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Prednisone; Prognosis; Vincristine

Topics: Acute Disease; Child, Preschool; Histiocytosis, Langerhans-Cell; Humans; Infant; Male; Mercaptopurine; Methotrexate; Prednisolone; Vinblastine

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

On the basis of five observations of adult patients with the clinical feature of mature cellular leukaemia which proved to be therapy-refractory and which was characterized by a rapid course is referred to the necessity of the differentiation of such cases from the classical myeloic leukaemia. The cardinal symptoms of this type of disease, which probably is identified with the cases described in literature as atypical chronic myelosis, as paraneutrophil leukaemia or as acute myelofibrosis, and also shows common features with the juvenile chronic myelosis, are, apart from the mature cellular differential blood picture a short life expectancy (less than 1 year), an initial thrombocytopenia, a normal or increased activity of the alkaline granulocyte phosphatase, the lack of Ph1-chromosome as well as the bad therapeutic reaction to busulfan. The observation of the simultaneously existing fibroses of the bone marrow as well as of the final increase of immature blasts induced the classification of the clinical picture as a special form of the myeloproliferative syndrome.

Topics: Acute Disease; Adult; Azathioprine; Bone Marrow Examination; Fetal Hemoglobin; Hematopoietic Stem Cells; Humans; Leukemia, Myeloid; Mercaptopurine; Myeloproliferative Disorders; Primary Myelofibrosis

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

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

Possibility and necessity of the immunosuppressive treatment is considerably determined by the underlying pathologo-anatomical substrate. The uncertainty concerning the chances of the success of such a therapy for the individual patient at least still at present allows a latitude of estimation. From this results the demand for a particularly intensive conscience of the responsibility taken on by us in finding the decision.

Topics: Acute Disease; Antilymphocyte Serum; Azathioprine; Chlorambucil; Chronic Disease; Cyclophosphamide; Dactinomycin; Glomerulonephritis; Humans; Immunosuppressive Agents; Kidney Glomerulus; Mercaptopurine; Methotrexate

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

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

In accordance with the recommendations of Pinkel, 147 children with acute lymphoblastic leukemia were treated by a combined cytostatic and radiation therapy during a joint study between May 1971 and Jan. 1, 1974. After a primary cytostatical treatment which brought about a remission of 94% of the patients within four to six weeks, the cranial irradiation was performed, depending on age, with a focal dose of 1500 up to 2400 rd in the course of three or four weeks. Simultaneously, the patients were given methotrexate intrathecally which was followed, later on, by a long-term therapy with cytostatics. By means of this combined treatment, a three-year survival was obtained in 50% (8 of 16) and a complete remission in 44% (7 of 16). The prognosis is the same for boys as for girls. A less favorable prognosis concerns the patients with an initial leukocytosisf more than 50 000 leukocytes/mm3 of blood, an age of more than ten years, and leukemic cells already demonstrable in the cerebrospinal fluid.

Topics: Acute Disease; Adolescent; Age Factors; Alopecia; Brain Neoplasms; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Premedication; Prognosis; Radiotherapy; Radiotherapy Dosage; Remission, Spontaneous; Skull; Vincristine

Survival and response to chemotherapy were evaluated in 84 adults with granulocytic leukemia (AGL) and 22 with acute lymphocytic leukemia (ALL). Twenty-two of the 84 patients with AGL reveived no chemotherapy (untreated group). The median survival for patients with AGL who achieved complete remission (CR) was 17.1 months, compared to 6.5 months for those who achieved partial remission (PR (p less than 0.05), 2.8 months for those who failed chemotherapy (p less than 0.01), and 2.1 months for the untreated group (p less than 0.01). The median survival for patients with ALL who achieved a CR was 18.2 months, compared to 7.3 months for those who achieved a PR and 7.0 months for those who failed chemotherapy. Of patients with AGL who reveived an adequate trial of chemotherapy, 43% achieved a CR and 16% a PR; 75% of patients with ALL achieved a CR and 13% a PR. Improved survival depends on the induction of a complete or partial remission with the use of aggressive chemotherapy.

Topics: Acute Disease; Adolescent; Adult; Aged; Child; Cyclophosphamide; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Thioguanine; Thioinosine; Vincristine

Intensive chemotherapy in patients with leukemia produced immunosuppression. The level of immunocompetence correlates with prognosis. The immunological function of 29 children with acute lymphoblastic leukemia (ALL) in complete remission and on 2 different maintenance therapies was evaluated and compared with 16 normal children (Group A). Sixteen children (Group B) with ALL received 6 mercaptopurine (6MP) daily and methotrexate (MTX) twice a week, and 13 children (Group C) received 6MP and MTX weekly for maintenance. There was depression of both cellular immunity, measured by the number of T cells and skin tests, and humoral immunity, measured by number of B cells, primary antibody production to typhoid vaccine, and levels of immunoglobulins. However, continuous maintenance therapy (Group B) produced significantly more severe immunosuppression of cellular immunity than the intermittent therapy (Group C). Humoral immunity was equally depressed in both groups of leukemia patients, but was less altered than cellular immunity. Concomitantly, patients with intermittent maintenance chemotherapy had less hematologic depression, fewer episodes of infection, and fewer died in complete remission. Patients of both groups with higher levels of immunocompetence had better prognosis with longer duration of complete remission than patients with severe immunosuppression. Out of 6 patients with "favorable immunocompetence" only 1 relapsed at 7 months and the other 5 remain in complete remission from 8 to 31 months. Among 23 leukemic patients with "unfavorable immunocompetence," 15 relapsed and 8 remain in complete remission from 9 to 26 months.

Topics: Acute Disease; Adolescent; Antibody Formation; Child; Child, Preschool; Female; Humans; Immunosuppression Therapy; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prognosis

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

Azathioprine (150 mg daily) was given to 14 patients with polymyositis. Most of the patients also received prednisolone (initial dose 80-40 mg daily, maintenance dose 15-5 mg daily). Some patients additionally received 6-mercaptopurine, methotrexate and (or) cactinomycin. Symptoms practically disappeared in three patients, while in four there was marked improvement, in four others moderate improvement occurred. Four patients who were improved had previously received long-term treatment with high doses of corticoids but without response. There were three deaths; treatment had definitely failed in one, in the other two the duration of treatment had been too short. Results were best in patients under 40 years of age in whom the disease had followed an acute or subacute course: in two of seven in this group corticoid treatment had previously failed. This fact, as well as the observation of exacerbations when immuno-suppressives were reduced, indicate the value of this form of treatment.

Topics: Acute Disease; Adolescent; Adult; Age Factors; Aged; Azathioprine; Child; Dactinomycin; Female; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Methotrexate; Middle Aged; Myositis; Prednisolone; Time Factors

The quality of life in leukaemia is as important as its quantity. In fifty-one patients the quality and quantity of life were improved by less aggressive treatment than is usual. By not trying to induce complete remission at all costs, the mobidity and early mortality were reduced and at least an equivalence in survival was obtained.

Topics: Acute Disease; Adolescent; Adult; Aged; Allopurinol; Bacterial Infections; Cytarabine; Daunorubicin; Drug Therapy, Combination; Focal Infection, Dental; Follow-Up Studies; Humans; Length of Stay; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Philosophy; Quality of Life; Remission, Spontaneous

Topics: Acute Disease; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Dactinomycin; Female; Humans; Kidney Neoplasms; Leukemia, Lymphoid; Lung Neoplasms; Mercaptopurine; Methotrexate; Neoplasm Metastasis; Prednisone; Vincristine; Wilms Tumor

Topics: Acute Disease; Adolescent; Daunorubicin; Drug Therapy, Combination; Hodgkin Disease; Humans; Leukemia, Lymphoid; Male; Mechlorethamine; Mercaptopurine; Prednisone; Procarbazine; Remission, Spontaneous; Sulfates; Vincristine

Topics: Acute Disease; Age Factors; Animals; Antineoplastic Agents; Asparaginase; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Mitosis; Neutropenia; Prednisone; Remission, Spontaneous; 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; Adult; Animals; Female; Humans; Immunosuppression Therapy; Immunotherapy; Isoniazid; Jejunum; Leukemia, Lymphoid; Mercaptopurine; Prednisone; Radiography, Abdominal; Radiography, Thoracic; Strongyloides; Strongyloidiasis; Vincristine

Remission induction was assessed by clinical and cell-culture criteria for 65 patients with acute myelogenous leukemia (AML), 11 patients with chronic myelogenous leukemia (CML) in blast crisis and 19 patients with acute lymphoblastic leukemia (ALL). Cyclophosphamide, cytosine arabinoside and vincristine (CAV) therapy resulted in complete remission in 23 of 50 previously untreated patients with AML and in 3 of the 11 patients with CML. Fourteen patients with ALL responded to vincristine-prednisone induction therapy and two to induction therapy with CAV. The median duration of survival of the responding patients was 2.2 years, compared with 4 months for the patients who did not respond to treatment. Granulopoietic colony formation, assessed by assay of colony-forming units dependent on colony-stimulating activity in culture (CFU-C), was abnormal in 37 of 42 bone marrow aspirates from patients with AML before treatement. CFU-C concentration increased when leukocyte-conditioned medium (LCM) was added to the cultures; 13 cultures had normal or elevated CFU-C concentration with LCM. Marrow cells of patients with ALL or CML in blast crisis demonstrated a similar pattern. Serial studies of marrow CFU-C concentration of 31 patients with AML demonstrated a change to a normal pattern with successful remission induction. Results of this study suggest that administration of purified LCM to leukemic patients might increase granulocyte production from potential but unstimulated granulopoietic precursors. This therapy would lessen the probability of death from infection during remission induction.

Topics: Acute Disease; Adolescent; Adult; Aged; Bone Marrow; Bone Marrow Cells; Cell Division; Cells, Cultured; Clone Cells; Culture Media; Cyclophosphamide; Cytarabine; Drug Administration Schedule; Drug Therapy, Combination; Female; Granulocytes; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Remission, Spontaneous; Vincristine

Topics: Acute Disease; BCG Vaccine; Central Nervous System Diseases; Humans; Immunosuppression Therapy; Immunotherapy; Leukemia, Lymphoid; Leukocyte Count; Lymphocytes; Lymphopenia; Mercaptopurine; Methotrexate; Neutropenia

The present communication concerns the effect of azathioprine on the mitotic activity of promonocytes and the production of monocytes. In vitro and in vivo labeling with [3H]thymidine showed that during azathioprine treatment the promonocytes synthesize DNA and that, contrary to expectation, the labeling index increases. Cytospectrophotometric determination of the Feulgen-DNA content of the promonocytes during azathioprine treatment showed an increase in the percentage of tetraploid promonocytes, and determination of the various phases of the cell cycle showed significantly increased DNA synthesis and cell cycle times as compared with the normal steady state. On the basis of these results it can be concluded that azathioprine arrests the cell cycle of the promonocytes late in the DNA synthesis phase or in the postsynthesis (G2) phase and mitosis does not occur. This timing of the effect of azathioprine had not been previously observed. The diminished mitotic activity of the promonocytes during azathioprine treatment depressed monocyte production. During treatment with 3 mg/kg azathioprine the cell cycle time of the promonocytes was on the average 5.5 h longer than in the normal steady state and the rate of monocyte production was reduced by 70%. During an acute inflammatory reaction too, monocyte production is affected by azathioprine. In animals not treated with azathioprine but with an acute inflammation the cell cycle time becomes shorter and the monocyte production increases, but animals treated with (3 mg/kg) azathioprine do not show this effect. The kinetics of the monocyte also changes under the low dosage of azathioprine. As consequence of the diminished production of monocytes, far fewer (about 50%) monocytes enter and leave the circulation than during the normal steady state. During an acute inflammatory reaction the numbers in transit through the circulation are slightly augmented but remain considerably lower than in nonazathioprine-trehat of animals not treated with azathioprine.

Topics: Acute Disease; Animals; Azathioprine; Bone Marrow; Bone Marrow Cells; Cell Count; Cell Division; Cell Nucleus; DNA; Inflammation; Kinetics; Male; Mercaptopurine; Mice; Mitosis; Monocytes; Spectrophotometry; Thymidine; Time Factors; Tritium

This study presents results of single-drug and combination chemotherapy of the transplantable acute leukemia L5222 in BD IX rats. In leukemia L5222 there is a direct relationship between the number of transplanted cells and mean life expectancy. After single-drug therapy with L-asparaginase, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cyclophosphamide, cytosine arabinoside, daunomycin, 6-mercaptopurine, methylglyoxal bis(guanylhydrazone) dihydrochloride, prednisolone, or vincristine, the best therapeutic effect was observed with BCNU and cyclophosphamide. A massive-dose therapy with BCNU repeated twice or a conbination of vincristine with cyclophosphamide or BCNU with cyclophosphamide yielded a high percentage of cures. Morever, leukemia L5222 seems to be suitable for studying the influence of drugs on the proliferation kinetics of leukemia cells.

Topics: Acute Disease; Animals; Antineoplastic Agents; Asparaginase; Carmustine; Cell Division; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Hydrazones; Leukemia, Experimental; Male; Mercaptopurine; Neoplasm Transplantation; Prednisolone; Rats; Transplantation, Homologous; 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: Acute Disease; Adult; Female; Humans; Leukemia; Leukocytes; Male; Mercaptopurine; Middle Aged; Pentosephosphates; Phosphoribosyl Pyrophosphate

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

Topics: Acute Disease; Adolescent; Adult; Age Factors; Aged; Asparaginase; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Methylprednisolone; Middle Aged; Paresis; Prognosis; Radiotherapy Dosage; Remission, Spontaneous; Vincristine

Topics: Acute Disease; Child; Child, Preschool; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Time Factors; Vincristine

Topics: Acute Disease; Adult; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisolone; Skin Neoplasms

Topics: Acute Disease; Adolescent; Adult; Aged; Drug Therapy, Combination; Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Prednisone

Topics: Acute Disease; Cytarabine; Female; Humans; Infant; Leukemia, Erythroblastic, Acute; Mercaptopurine; Methotrexate; Prednisolone

Topics: Acute Disease; Asparaginase; Child, Preschool; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Pancreas; Pancreatitis; Prednisolone; 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: Acute Disease; Bone Marrow Examination; Cell Transformation, Neoplastic; Dexamethasone; Drug Therapy, Combination; Glucocorticoids; Humans; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Prednisolone; Prednisone; Remission, Spontaneous; Vincristine

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: Acute Disease; Asparaginase; Bone Marrow Examination; Bone Neoplasms; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Radiography; Remission, Spontaneous; Urticaria Pigmentosa; Vincristine

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; Bone Marrow Cells; Child; Cyclophosphamide; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisolone; Remission, Spontaneous; Vincristine

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

Topics: Acute Disease; Child; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Remission, Spontaneous; Vincristine

Topics: Acute Disease; Adolescent; Age Factors; Child; Child, Preschool; Female; Humans; Infant; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Remission, Spontaneous; Time Factors; Vincristine

Topics: Acute Disease; Age Factors; Central Nervous System; Central Nervous System Diseases; Child; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Humans; Injections, Spinal; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Radiation Effects; Remission, Spontaneous; Time Factors; Vincristine

Topics: Acute Disease; Adolescent; Female; Gangrene; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisolone; Pyoderma; Rifampin

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

Topics: Acute Disease; Antineoplastic Agents; Cyclophosphamide; Drug Synergism; Humans; Immunotherapy; Leukemia, Lymphoid; Mercaptopurine; Methods; Methotrexate; Prednisone; Prognosis; Remission, Spontaneous; Vincristine

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

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

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

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Age Factors; Aged; Amino Sugars; Antibiotics, Antineoplastic; Antineoplastic Agents; Cytarabine; Drug Synergism; Female; Follow-Up Studies; Glycosides; Humans; Injections, Intravenous; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Pregnancy; Remission, Spontaneous; Time Factors

Topics: Acute Disease; Africa, Southern; Asparaginase; Daunorubicin; Europe; Female; Government; History, 18th Century; Hydatidiform Mole; Immunization, Passive; International Cooperation; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Pregnancy; Remission, Spontaneous; Trophoblastic Neoplasms; United States; Vincristine

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

Topics: Acute Disease; Animals; Azathioprine; Chagas Disease; Cyclophosphamide; Immunity; Immunosuppression Therapy; Immunosuppressive Agents; Mercaptopurine; Mice; Radiation Effects; Time Factors

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: 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: Acute Disease; Adolescent; Adult; Aged; Azathioprine; Female; Humans; Infections; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisone; Remission, Spontaneous

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: Acute Disease; Adolescent; Adult; Aged; Azathioprine; Female; Humans; Infections; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisone; Remission, Spontaneous

Topics: Acute Disease; Allopurinol; Bone Marrow Examination; Child; Digitalis Glycosides; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Pericardium; Prednisone; Radiography; Remission, Spontaneous; Vincristine

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

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

Topics: Acute Disease; Child, Preschool; Humans; Hypertrophy; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone

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: 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: 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: Acute Disease; Adult; Azathioprine; Cyclophosphamide; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Scleroderma, Systemic

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

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

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

Topics: Acute Disease; Aged; Aneuploidy; Bone Marrow Diseases; Busulfan; Cell Transformation, Neoplastic; Chromosome Aberrations; Chromosome Disorders; Chronic Disease; Female; Humans; Leukemia, Myeloid; Mercaptopurine; Methotrexate; 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: Acute Disease; Adolescent; Child; Child, Preschool; Female; Humans; Infant; Leukemia; Male; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Vincristine

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

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

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

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

Topics: Acute Disease; Adult; Alanine Transaminase; Chronic Disease; Hepatitis; Hepatitis B; Humans; Liver Function Tests; Male; Mercaptopurine; Middle Aged

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

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: Acute Disease; Antineoplastic Agents; Asparaginase; Chronic Disease; Cyclophosphamide; Daunorubicin; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Mercaptopurine; Methotrexate; Prednisone; Vincristine

Topics: Acute Disease; Adult; Child, Preschool; Cyclophosphamide; Daunorubicin; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; 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: Acute Disease; Adolescent; Child; Child, Preschool; Drug Therapy; Humans; Leukemia; Mercaptopurine; Prednisone

Topics: Acute Disease; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Azathioprine; Biliary Tract Diseases; Biopsy; Child; Child, Preschool; Cholestasis; Chronic Disease; Diagnosis, Differential; Female; Hepatitis; Hepatitis A; Humans; Infant; Infant, Newborn; Liver Cirrhosis; Liver Cirrhosis, Biliary; Male; Mercaptopurine; Middle Aged; Necrosis

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

Topics: Acute Disease; Adolescent; Adult; Azathioprine; Child; Chronic Disease; Female; Follow-Up Studies; Hepatitis; Humans; Liver; Liver Function Tests; Male; Mercaptopurine; Middle Aged; Prednisone; Prognosis

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: Acute Disease; Adolescent; Adult; Aged; Child; Child, Preschool; Dexamethasone; Female; Humans; Infant; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone

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: Acute Disease; Antineoplastic Agents; Child, Preschool; Cyclophosphamide; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Vinblastine

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

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

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

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

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

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Acute Disease; Humans; Leukemia; Mercaptopurine

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

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

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

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

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

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

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

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

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

Topics: Acute Disease; Humans; Leukemia; Mercaptopurine

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

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

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

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

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

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

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

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

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines

Topics: Acute Disease; Leukemia; Mercaptopurine; Purines