mercaptopurine and Hemorrhage

Topics: Asparaginase; Bacterial Infections; Central Nervous System Diseases; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Synergism; Hemorrhage; Humans; Immunotherapy; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Mitosis; Neoplasms, Nerve Tissue; Prednisone; Remission, Spontaneous; Testicular Neoplasms; Uric Acid; Vincristine

Shortly before the all-trans retinoic acid (ATRA) era, the GIMEMA cooperative group initiated a randomized study comparing idarubicin (IDA) alone with IDA plus arabinosylcytosine (Ara-C) as induction treatment in patients with newly diagnosed hypergranular acute promyelocytic leukemia (APL). Of the 257 patients evaluable for induction treatment, 131 were randomized to receive IDA alone (arm A) and 126 to receive IDA + Ara-C (arm B). Treatment in arm A consisted of 10 mg/m(2) IDA daily for 6 consecutive days, whereas in arm B it consisted of 12 mg/m(2) IDA daily for 4 days combined with 200 mg/m(2) Ara-C daily in continuous infusion for 7 days. Once in complete remission (CR), patients received 3 consolidation courses of standard chemotherapy, and those still in CR at the end of the consolidation were randomized to receive or not receive 1 mg/kg 6-mercaptopurine daily and intramuscular injections of 0.25 mg/kg methotrexate weekly for 2 years. Overall, 100 (76.3%) patients in arm A and 84 (66.6%) patients in arm B achieved CR (P = NS). Event-free survival (EFS) rates were 35% and 23% for patients in arm A and arm B, respectively (P =.0352). Multivariate analysis revealed that EFS was favorably influenced by induction treatment with IDA alone (P =.0352) and unfavorably influenced by white blood cell (WBC) counts greater than 3000/microL (P =.0001) and increasing age (P =.0251). These results indicate that anthracycline monochemotherapy with IDA favorably influences the EFS of patients with newly diagnosed hypergranular APL.

Topics: Adolescent; Adult; Age Factors; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Child; Cytarabine; Disease-Free Survival; Female; Follow-Up Studies; Hemorrhage; Humans; Idarubicin; Infections; Leukemia, Promyelocytic, Acute; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Middle Aged; Remission Induction; Treatment Outcome; Vomiting

Early hemorrhagic death (within the first 10 d of treatment [EHD]) is reported as the main cause of death during induction therapy for acute promyelocytic leukemia (APL). In order to evaluate possible differences in the incidence of EHD during induction regimens based on all-trans retinoic acid (ATRA), we retrospectively analyzed a consecutive series of 86 APL patients, diagnosed and treated at our Institution from 1982. Forty-three patients received combination chemotherapy with anthracyclines and cytosine arabinoside (January 1982 to December 1991), while induction of the remaining 43 was based on ATRA alone or on a combination of ATRA and anthracyclines (January 1992 to October 1996). There were significantly less induction deaths in the ATRA group [9 (chemotherapy group-CT) vs. 2 (ATRA group-RA) overall and 8(CT) vs. 1(RA) of EHD; p = 0.01]. Hemostatic evaluations showed an earlier reduction of D-dimer in the ATRA group. No cases of morphological resistance were observed in the ATRA group after induction. In addition, the number of relapses occurring in the first 24 months from the achievement of complete remission (CR) was significantly lower in the ATRA group (15 vs. 7; p = 0.01), with a disease free survival at 2 yr of 67% vs. 31%. In conclusion, ATRA appears to be able to significantly reduce the incidence of EHD, increasing the number of possible long-term remissions.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Cytarabine; Daunorubicin; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Mercaptopurine; Methotrexate; Remission Induction; Retrospective Studies; Tretinoin

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

We report here a case of acute monocytic leukemia (M5b subtype according to the French-American-British [FAB] classification) with chromosomal translocation t(11;20)(p15;q11.2). Fluorescence in situ hybridization analysis with a probe for the NUP98 gene, which is located at chromosome band 11p15, showed that the probe hybridized to both derivative chromosomes 11 and 20 as well as to the remaining normal chromosome 11, indicating that the NUP98 gene was split and involved in this translocation. This is the first report of t(11;20)(p15;q11.2) involving the NUP98 gene in overt leukemia.

Topics: Aclarubicin; Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 20; Combined Modality Therapy; Cytarabine; Disease Progression; Fatal Outcome; Female; Hemorrhage; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Leukemia, Monocytic, Acute; Mercaptopurine; Middle Aged; Neoplasm Proteins; Nuclear Pore Complex Proteins; Prednisolone; Sepsis; Translocation, Genetic

Sixty patients with acute promyelocytic leukemia were treated between 1973 and 1984. The overall median survival was 16 months with a five-year survival rate of 31 percent. The complete remission rate was 53 percent and was similar whether they received amsacrine- or anthracycline-based regimens (60 percent versus 51 percent). The median remission duration was 29 months. At five years, 43 percent of patients with responses to treatment had continuous remission and 57 percent were alive. Salvage therapy produced remissions in 53 percent of patients during first relapse, with two long-term survivors after further consolidation with bone marrow transplantation. Early fatal hemorrhage associated with disseminated intravascular coagulopathy during induction therapy occurred in 16 patients (26 percent). Multivariate analysis of the pretreatment patient characteristics significantly associated with an increased risk of fatal hemorrhage identified four that have primary prognostic importance: thrombocytopenia, elevated absolute blast and promyelocyte counts, old age, and anemia. Patients having up to two unfavorable features had a low risk of fatal hemorrhage compared with those who had more than two (5 percent versus 58 percent; p less than 0.0001). Overall, patients who received heparin had a lower incidence of fatal hemorrhage than those who did not (19 percent versus 32 percent). Heparin therapy was not beneficial to those at low risk but was associated with a trend towards decreased hemorrhagic deaths among high-risk patients (45 percent versus 67 percent). Cytogenetic studies demonstrated the characteristic 15;17 translocation in 73 percent of patients with analyzable metaphases, whereas 12 percent had other karyotypic abnormalities. Remission induction was often associated with a gradual atypical morphologic evolution into remission without intermediate hypoplasia with the interim marrows showing a high proportion of blasts. It is concluded that acute promyelocytic leukemia is a unique disease with a high potential for cure. Knowledge of its prognosis using present frontline and salvage therapy, of the factors related to fatal hemorrhage, and of the unusual patient marrow profiles during remission induction may improve the therapeutic approach.

Topics: Aminoacridines; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cytarabine; Daunorubicin; Disseminated Intravascular Coagulation; Doxorubicin; Female; Hemorrhage; Hospitals, Teaching; Hospitals, University; Humans; Karyotyping; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Risk; Texas; Time Factors; Vincristine

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

A 34% response was obtained in 202 evaluable patients in the terminal phase of chronic granulocytic leukemia using combinations of hydroxyurea, 6-mercaptopurine, and corticosteroids. Twelve percent of responses were complete and 22% partial. Overall median survival was 12 wk. A 30 wk median survival for responding patients was statistically superior to the 7-wk survival for nonresponders (p less than 0.001). Response was inversely correlated with toxicity. No responses were obtained in patients sustaining both severe infectious and bleeding complications. No benefit could be demonstrated from the addition of vincristine in induction and daunorubicin for consolidation. Although the response frequency and duration of survival with this combination chemotherapy were generally superior to those previously reported by our group, the terminal phase of chronic granulocytic leukemia still remains a formidable and generally refractory disease.

Topics: Daunorubicin; Dexamethasone; Drug Therapy, Combination; Gastrointestinal Diseases; Hemorrhage; Humans; Hydroxyurea; Infections; Leukemia, Myeloid; Mercaptopurine; Prednisone; Remission, Spontaneous; Terminal Care

Topics: Adolescent; Anaphylaxis; Asparaginase; Child; Child, Preschool; Confusion; Daunorubicin; Female; Hallucinations; Hemorrhage; Humans; Injections, Spinal; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Mercaptopurine; Methotrexate; Pancreatitis; Prednisolone; Retroperitoneal Space; Vinblastine; Vincristine

Topics: Agranulocytosis; Anemia, Aplastic; Anti-Bacterial Agents; Antineoplastic Agents; Asparaginase; Blood Platelets; Blood Transfusion; Cytarabine; Daunorubicin; Drug Therapy, Combination; Hemorrhage; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Leukocytes; Mercaptopurine; Methotrexate; Prednisone; Thrombocytopenia; Vincristine

Topics: Allopurinol; Blood Cell Count; Cell Movement; Colchicine; Diet; Drug Synergism; Gastrointestinal Diseases; Gout; Hemorrhage; Humans; Indomethacin; Leukocytes; Mercaptopurine; Phenylbutazone; Probenecid; Purines; Uric Acid

Topics: Adrenal Cortex Hormones; Anemia; Autopsy; Bone Marrow Examination; Dyspnea; Female; Hemorrhage; Humans; Leukemia, Myeloid; Lung; Mercaptopurine; Middle Aged; Pulmonary Alveolar Proteinosis; Radiography; Splenomegaly

Topics: Adolescent; Agranulocytosis; Anemia; Bone Marrow; Bone Marrow Cells; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Synergism; Female; Hemorrhage; Humans; Infant; Injections, Intravenous; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Mercaptopurine; Neutrophils; Prednisolone; Thrombocytopenia; Vincristine

Topics: Adolescent; Adult; Anti-Bacterial Agents; Blood Platelets; Blood Transfusion; Female; Hemorrhage; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Prednisolone; Remission, Spontaneous

Topics: Animals; Antineoplastic Agents; Asparaginase; Blood Platelets; Bone Marrow Cells; Cyclophosphamide; Cytarabine; Daunorubicin; Disease Models, Animal; Drug Synergism; Hemorrhage; Humans; Infections; Leukemia L1210; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Mice; Prednisone; Prognosis; Thrombocytopenia; Vincristine

Topics: Adrenal Glands; Adult; Cicatrix; Diabetes Insipidus; Hemorrhage; Humans; Leukemia, Myeloid, Acute; Leukopenia; Male; Mercaptopurine; Metyrapone; Pituitary Gland, Posterior; Pituitary-Adrenal Function Tests; Sodium Chloride; Specific Gravity; Urine

Topics: Abdomen; Adrenochrome; Aminocaproates; Animals; Carcinoma, Ehrlich Tumor; Clone Cells; Diphenhydramine; Female; Hemorrhage; Hydrocortisone; Karyotyping; Male; Mercaptopurine; Mice; Neoplasm Transplantation; Omentum; Pancreas; Semicarbazides; Time Factors; Virulence

Topics: Adolescent; Adult; Aged; Anemia; Blood Platelets; Blood Transfusion; Blood Urea Nitrogen; Bone Marrow Cells; Bone Marrow Examination; Chromosome Aberrations; Cytomegalovirus; Female; Fever; Hemorrhage; Humans; Jaundice; Leukemia, Myeloid; Leukocyte Count; Leukocytes; Leukopenia; Male; Mercaptopurine; Methotrexate; Middle Aged; Nocardia Infections; Pneumonia; Prednisone; Proteus Infections; Pseudomonas Infections; Sepsis; Thrombocytopenia; Vincristine

Topics: Adult; Bilirubin; Blood Cell Count; Blood Transfusion; Bone Marrow Examination; Coombs Test; Female; Hematocrit; Hemoglobinuria, Paroxysmal; Hemorrhage; Humans; Hysterectomy; Leukemia, Myeloid, Acute; Mercaptopurine; Oral Hemorrhage; Osmotic Fragility; Prednisone; Pyoderma; Reticulocytes; Staphylococcus; Tooth Extraction

Topics: Absorption; Animals; Chromium Isotopes; Cortisone; Erythrocytes; Eye Diseases; Hemoglobins; Hemorrhage; Hypersensitivity; Infections; Inflammation; Injections; Iron; Mercaptopurine; Prednisolone; Rabbits; Uveitis; Vitreous Body

The therapy of acute leukemia has improved rapidly in the last two decades. Using available therapeutic agents, complete clinical and hematological remission can be achieved regularly in children with acute lymphocytic leukemia. The choice of chemotherapeutic agent, management of complications of hemorrhage and infection, and recognition of prognostic factors are important for the induction of a hematological remission. While patients in complete hematological remission are free of evidence of disease they still have residual leukemic cells, but in our present state of knowledge and with available techniques, we are unable to detect these. For this reason it is important to treat patients while in remission. The importance of dosage schedule for remission maintenance chemotherapy is stressed.In patients studied to date, regardless of the treatment used, the disease has recurred eventually. Available therapeutic agents are highly effective and highly selective, but they still fall short of providing ideal control of the disease. The continuing search for new chemotherapeutic agents is aided by the knowledge gained and techniques developed with current agents.

Topics: Adult; Anti-Bacterial Agents; Child; Cyclophosphamide; Hemorrhage; Humans; Infections; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Uric Acid; Vincristine

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

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

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

Topics: Anemia; Anemia, Myelophthisic; Blood Cell Count; Blood Sedimentation; Bone Marrow Examination; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Mercaptopurine; Neoplasms; Pathology; Prednisone

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

Topics: Anemia; Anemia, Hemolytic; Female; Hemorrhage; Humans; Hypersensitivity; Mercaptopurine; Postpartum Hemorrhage; Postpartum Period