mercaptopurine and Agranulocytosis

Topics: Adult; Agranulocytosis; Animals; Azathioprine; Child; Cyclophosphamide; Fertility; Glomerulonephritis; Humans; Leukopenia; Mercaptopurine; Mice; Nephrotic Syndrome; Prednisolone; Rats; Remission, Spontaneous

Children from the UKALL V trial were studied to assess the clinical importance of myelosuppression during uninterrupted 'maintenance' treatment of 'standard risk' lymphoblastic leukaemia. Those receiving daily 6-mercaptopurine and weekly methotrexate who were in first remission 20 months from diagnosis were divided into two groups on the basis of whether or not they had ever had an absolute neutrophil count of less than 0.5 x 10(9)/l recorded during maintenance treatment up to that time. Of 105 evaluable children, 45 (43%) became neutropenic at least once, and 60 (57%) did not. Seven (16%) of the neutropenic group subsequently relapsed compared with 27 (45%) of the remainder. This difference was still significant if the analysis was stratified by total treatment time (two or three years), age, sex, or diagnostic white cell count. Seven (16%) neutropenic children died in remission, compared with one (2%) of the non-neutropenic children. Therapeutic myelosuppression during standard maintenance treatment of 'standard risk' lymphoblastic leukaemia is associated with increased toxicity but a reduced risk of relapse. The unexplained improvement in long term survival in the United Kingdom in recent years may in large part be due to this.

Topics: Adolescent; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Child; Child, Preschool; Female; Humans; Infant; Leukemia, Lymphoid; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Neutropenia; Prognosis; Randomized Controlled Trials as Topic; Survival Rate; United Kingdom

The degree of drug-induced neutropenia resulting from a controlled trial (UKALL I) of treatment in acute lymphoblastic leukaemia was analysed. The main agent associated with severe neutropenia was methotrexate, and methotrexate-induced neutropenia was significantly greater in patients who had received craniospinal irradiation. The synergistic toxic effect of irradiation followed by methotrexate treatment seems to have contributed to three of the five deaths which occurred in complete remission in this trial; all deaths in remission occurred in patients who had received central nervous system prophylaxis. Analysis of patients who subsequently relapsed compared with those still in remission after 18 months of treatment indicated that the former, on average, had slightly lower neutrophil counts. This suggests that the children who relapsed did not receive any less aggressive treatment than those who remained in remission.

Topics: Agranulocytosis; Central Nervous System; Child; Child, Preschool; Clinical Trials as Topic; Cytarabine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Injections, Spinal; Leukemia, Lymphoid; Lymphocytes; Mercaptopurine; Methotrexate; Neutropenia; Prednisolone; Radiation Effects; Radiotherapy Dosage; Remission, Spontaneous; Time Factors; Vincristine

A 54-year-old female was admitted to our hospital for gingival bleeding and was diagnosed as acute promyelocytic leukemia (APL). She received induction therapy according to the AML92 protocol of the Japan Adult Leukemia Study Group (JALSG) with all-trans retinoic acid (ATRA) plus chemotherapeutic agents. She achieved complete remission, but one year later had a relapse in her external auditory canal without leukemic cell in the bone marrow. Extramedullary disease is rare in APL. This case suggests the importance of careful observation for extramedullary relapse in patients who are treated with ATRA.

Topics: Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Combined Modality Therapy; Cytarabine; Daunorubicin; Ear Canal; Female; Granulocyte Colony-Stimulating Factor; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Mercaptopurine; Middle Aged; Mitoxantrone; Neoplasm Proteins; Oncogene Proteins, Fusion; Radiotherapy; Recurrence; Remission Induction; Salvage Therapy; Tretinoin; Vindesine

The fungus Fusarium moniliforme causes fusariosis, which can be invasive and fatal in immunocompromised patients. We report a case of oral Fusarium infection in a granulocytopenic patient with acute myelogenous leukemia who developed necrotic ulceration of the gingiva, extending to the alveolar bone, but was otherwise free of any active systemic lesions. Fusarium moniliforme was identified, by histopathology and culture, to be present in the lesion and was deduced to be the causative organism for this invasive oral infection.

Topics: Acute Kidney Injury; Aged; Agranulocytosis; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Epirubicin; Etoposide; Fatal Outcome; Fusarium; Gingival Diseases; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Male; Maxillary Diseases; Mercaptopurine; Mycoses; Necrosis; Prednisolone; Ulcer; Vindesine

A phase II pediatric trial of a continuous intravenous infusion of 6-mercaptopurine (6-MP) in patients with refractory solid tumors or lymphoma was performed. The dosing schedule of 50 mg/m2 per hour for 48 h was chosen to produce optimal cytotoxic concentrations of 6-MP. There were no complete or partial responses in the 40 patients entered in the trial. Accrual was sufficient for the conclusion to be drawn that there was greater than 95% probability that the true response rate was no greater than 22% and 26% in osteosarcoma and Ewing's sarcoma, respectively. Dose-limiting toxicity was observed in one-third of the patients and included reversible hepatotoxicity, myelosuppression, and mucositis. The excellent penetration of drug into the cerebrospinal fluid (CSF) suggests that future trials of this intravenous dosing schedule should be conducted on tumors of the CNS.

Topics: Adolescent; Adult; Agranulocytosis; Child; Child, Preschool; Drug Evaluation; Humans; Infant; Infusions, Intravenous; Liver; Mercaptopurine; Neoplasms; Thrombocytopenia

Neutropenic enterocolitis, also known as typhlitis or ileocecal syndrome, in leukemic patients undergoing chemotherapy has a high reported mortality. A recent increase in the incidence of neutropenic enterocolitis is associated with aggressive chemotherapy for acute leukemia. In this report, we report the incidence, diagnosis, and treatment of neutropenic enterocolitis during low-dose DCMP and high-dose DCMP regimen for 95 adults with acute nonlymphocytic leukemia, and review the literature pertaining appropriate medical and surgical management, and method of prevention. Finally we propose the favorable results of gut sterilization for the treatment and prevention of the disease.

Topics: Adult; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Cytarabine; Daunorubicin; Enterocolitis, Pseudomembranous; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Middle Aged; Neutropenia; Prednisolone

6-Mercaptopurine is extensively used in the treatment of childhood lymphoblastic leukaemia to prolong the duration of remission achieved with other drugs. The response to remission maintenance therapy varies widely. We investigated the relationship between red blood cell 6-thioguanine nucleotide, a metabolite of 6-mercaptopurine, and myelosuppression in 22 children with acute lymphoblastic leukaemia in remission. The peripheral neutrophil count was used as an index of myelosuppression. 6-Mercaptopurine dose was related to 6-thioguanine nucleotide concentration (r = 0.4; P less than 0.001; n = 90; y = 18.51 + 0.36 x). Large individual variations around the regression line are observed. Neither 6-mercaptopurine dose nor 6-thioguanine nucleotide concentration was related to the neutrophil count at the time of sampling (day 0) or 7 days later. Both 6-mercaptopurine dose and 6-thioguanine nucleotide concentration correlated with the neutrophil count at day 14 (r = -0.33; P less than 0.01; n = 90 and r = -0.3; P less than 0.01; n = 90 respectively). This delay is compatible with a cytotoxic action on bone marrow stem cells. Excluding children with other, uncontrolled, potentially myelosuppressive influences the correlation between 6-thioguanine nucleotide concentration and neutropenia improved (r = -0.6; P less than 0.001; n = 37). A significant degree of neutropenia was observed by day 14 if the 6-thioguanine nucleotide concentration (day 0) was greater than 210 pmol/8 X 10(8) RBCs. The assay of 6-thioguanine nucleotide may highlight those individuals with pharmacokinetic resistance. Two children on continuous high dose 6-mercaptopurine, had low red blood cell 6-thioguanine nucleotide concentrations and neutropenia was not observed.

Topics: Adolescent; Agranulocytosis; Bone Marrow Diseases; Child; Child, Preschool; Erythrocytes; Female; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Neutropenia; Thioguanine

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: Agar; Agranulocytosis; Animals; Bone Marrow; Bone Marrow Cells; Cell Division; Cells, Cultured; Chloramphenicol; Clone Cells; Dose-Response Relationship, Drug; Gold; HeLa Cells; Humans; L Cells; Malates; Mercaptopurine; Methimazole; Mice; Neutrophils; Phenylbutazone; Sulfides; Thiouracil

Topics: Agranulocytosis; Asparaginase; Blood Cell Count; Bone Marrow Examination; Child; Cyclophosphamide; Cytarabine; Daunorubicin; Hemoglobins; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Pneumonia; Prednisone; Recurrence; Vincristine

Topics: Agranulocytosis; Allopurinol; Animals; Blood Cell Count; Body Weight; Bone Marrow; Bone Marrow Cells; Drug Synergism; Hematopoiesis; Male; Mercaptopurine; Neutrophils; Rabbits

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

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

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Agranulocytosis; Anemia, Hemolytic, Autoimmune; Azathioprine; Child; Child, Preschool; Female; Hematologic Diseases; Humans; Immunosuppressive Agents; Infant; Infant, Newborn; Male; Mercaptopurine; Middle Aged; Prednisone; Purpura, Thrombocytopenic; Splenectomy; Thrombocytopenia

Topics: Adolescent; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Agranulocytosis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Azathioprine; Child; Child, Preschool; Female; Humans; Immunosuppressive Agents; Infant; Male; Mercaptopurine; Middle Aged; Prednisone; Purpura, Thrombocytopenic; Splenectomy; Thrombocytopenia

Topics: Adolescent; Adult; Age Factors; Agranulocytosis; Aminopterin; Azathioprine; Chemical and Drug Induced Liver Injury; Cholinesterase Inhibitors; Dactinomycin; Drug Synergism; Female; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Methotrexate; Middle Aged; Myasthenia Gravis; Time Factors

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Agranulocytosis; Anti-Bacterial Agents; Blood Platelets; Bone Marrow; Chronic Disease; Cortisone; Female; Humans; Immunosuppressive Agents; Leukocyte Count; Male; Mercaptopurine; Middle Aged; Prednisone

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: Agranulocytosis; Female; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Middle Aged; Proctitis

Topics: Agranulocytosis; Aminopterin; Animals; Azaguanine; Biopsy; Chloramphenicol; Connective Tissue; Cyclophosphamide; Dactinomycin; Fluorouracil; Glycosaminoglycans; Histocytochemistry; Inflammation; Leukopenia; Lymphocytes; Mercaptopurine; Mice; Neutrophils; Photomicrography; Puromycin; Rabbits; Research