mercaptopurine and Heart-Diseases

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Antineoplastic Agents; Busulfan; Carcinogens; Central Nervous System Diseases; Chemical and Drug Induced Liver Injury; Child; Female; Heart Diseases; Humans; Lung Diseases; Male; Menstruation Disturbances; Mercaptopurine; Methotrexate; Neoplasms; Neoplasms, Radiation-Induced; Pregnancy; Radiotherapy; Urinary Bladder Diseases

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

Isoproterenol produces myocardial necrosis in rats. To investigate the possible role of oxygen free radicals generated by xanthine oxidase and neutrophils, we examined the effects of the xanthine oxidase inhibitors, 6-mercaptopurine (6MP) and 6-thioguanine (6TG) combined and allopurinol, or of irradiation (to induce leukopenia) on isoproterenol-induced myocardial necrosis (ISOMN). The incidence and severity of ISOMN was significantly reduced by 6MP + 6TG but not by the specific inhibitor of xanthine oxidase, allopurinol, indicating that the protective effects of 6MP + 6TG may be due to its free radical scavenging activity rather than its xanthine oxidase inhibitory activity. Irradiation provided complete protection against ISOMN in all rats. Marked leukopenia or other radiation-induced protective factors could play a role in the mechanism of the protection.

Topics: Allopurinol; Animals; Heart Diseases; Isoproterenol; Leukocytes; Leukopenia; Male; Mercaptopurine; Myocardium; Necrosis; Radiation Injuries, Experimental; Rats; Rats, Inbred Strains; Thioguanine

The idiopathic hypereosinophilic syndrome, a disorder characterized by peripheral blood and bone marrow eosinophilia associated with single or multiple organ system dysfunction attributable to tissue invasion by eosinophils has, in the past, been associated with an extremely poor prognosis. Recently, we reported the favorable impact of a therapeutic protocol consisting of prednisone and/or hydroxyurea on the morbidity and mortality of this syndrome. We have reviewed the clinical and hematologic features upon admission and the subsequent clinical courses of 32 patients with this disease referred to the NIH between 1965 and 1979 in an effort to determine which features suggest a more rapidly progressive course. A grading system based on 22 clinical features involving the 8 organ systems commonly affected by the illness was devised. The disease followed a more aggressive course in patients with evidence of cardiac or neurologic dysfunction at the time of initial NIH evaluation. Although splenomegaly, in and of itself, caused little morbidity, splenic enlargement at presentation appeared to be a predictor of a more aggressive course. The clinical grading system accurately predicted which patients would require no specific antihypereosinophilic therapy, which patients would respond adequately to corticosteroids, and which patients would require therapy with cytotoxic agents. It is proposed that this clinical grading system, and the hematologic grading system outlined in the accompanying report be used as aids in the selection of initial therapy in this group of patients.

Topics: Adolescent; Adult; Aged; Child; Cyclophosphamide; Eosinophilia; Heart Diseases; Humans; Hydroxyurea; Mercaptopurine; Middle Aged; Mortality; Prednisone; Splenomegaly; Syndrome

Topics: Adolescent; Adult; Age Factors; Aged; Central Nervous System Diseases; Child; Child, Preschool; Daunorubicin; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Heart; Heart Diseases; Humans; Infant; Leukemia, Lymphoid; Male; Meninges; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Remission, Spontaneous; Sex Factors; Time Factors; Vincristine

Topics: Abscess; Anti-Bacterial Agents; Aspergillosis; Candidiasis; Clostridium; Electrocardiography; Escherichia coli Infections; Geriatrics; Heart Diseases; Humans; Klebsiella; Mechlorethamine; Mercaptopurine; Pathology; Proteus; Staphylococcal Infections; Statistics as Topic; Steroids; Streptococcal Infections; Surgical Procedures, Operative