mercaptopurine and Pneumonia--Pneumocystis

Topics: Alkanesulfonates; Amidines; Bone Marrow Examination; Chickenpox; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; gamma-Globulins; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Nervous System Diseases; Phenyl Ethers; Physician-Patient Relations; Pneumonia, Pneumocystis; Prednisone; Pseudomonas Infections; Recurrence; Testicular Neoplasms; Vincristine

Trimethoprim-sulfamethoxazole (TMP/SMX) is used in children with acute lymphoblastic leukemia (ALL) to prevent Pneumocystis pneumonia (PCP). We explored to which extent TMP/SMX influenced methotrexate (MTX)/6-mercaptopurine (6MP) dosage, myelosuppression, and event-free survival (EFS) during maintenance therapy. Of 447 study patients treated by the NOPHO ALL92 protocol, 120 patients received TMP/SMX continuously for 2-7 d/wk (TMP/SMX(2-7) ) and 287 patients never received TMP/SMX (TMP/SMX(never) ). Ten patients (all TMP/SMX(never) ) developed PCP, eight of which occurred within 7 months from the start of maintenance therapy. The TMP/SMX(2-7) group received lower oral 6MP doses than TMP/SMX(never) patients (50.6 vs. 63.9 mg/m(2) /d; P<0.001) but had lower absolute neutrophil counts (ANC) (median 1.7 vs. 2.0 × 10(9) /L; P<0.001). In Cox multivariate analysis, higher ANC levels (P=0.04) and male gender (P=0.06) were related to reduced EFS. ANC had no effect on EFS among TMP/SMX(2-7) patients (P=0.40) but did for TMP/SMX(never) patients (P=0.02). The difference in the effect on EFS between TMP/SMX(2-7) and TMP/SMX(never) patients was not significant (P=0.46). EFS did not differ between TMP/SMX(2-7) and TMP/SMX(never) patients (0.83 vs. 0.83; P=0.82). These results suggest that TMP/SMX is effective in preventing PCP and may have an antileukemic effect. TMP/SMX should be given the entire duration of maintenance therapy.

Topics: Administration, Oral; Anti-Infective Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Disease-Free Survival; Female; Humans; Male; Mercaptopurine; Methotrexate; Pneumocystis carinii; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

One hundred and forty-nine children with acute lymphocytic leukemia treated according to a prospective protocol were randomized after induction of remission and central nervous system (CNS) irradiation to receive maintenance chemotherapy with 1, 2, 3, or 4 chemotherapy agents. The incidence of P. carinii pneumonitis (PCP) was 5.0, 2.3, 2.2, and 22.4%, respectively, during the period of maintenance therapy. An additional 31 patients enrolled in the same study were placed in special categories to receive three drugs for maintenance plus supplemental chemotherapy or irradiation because of CNS leukemia on admission, remission failure, ediastinal mass, or generalized lymphosarcoma without bone marrow involvement. The incidences of PCP in these groups were 16.7, 30.0, 35.7, and 0%, respectively, during the period of maintenance therapy.

Topics: Antineoplastic Agents; Asparaginase; Child, Preschool; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Female; Humans; Immunosuppression Therapy; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Pneumonia, Pneumocystis; Prednisone; Vincristine

A 68-yr-old man with steroid refractory distal ulcerative colitis was treated with low-dose 6-mercaptopurine, and corticosteroids were successfully discontinued. He later presented with dyspnea and fever, was diagnosed with Pneumocystis carinii pneumonia by bronchoalveolar lavage, and died despite aggressive therapy. Serological tests for HIV were negative, and his white blood cell count was normal. This is the first report of P. carinii pneumonia complicating therapy of inflammatory bowel disease with 6-mercaptopurine. Although the mechanism is not entirely clear, 6-mercaptopurine appears to decrease cell-mediated immunity. Opportunistic infections such as P. carinii pneumonia should be added to the list of potential bronchopulmonary complications of antimetabolite immunosuppressive therapy of inflammatory bowel disease.

Topics: Aged; Aminosalicylic Acids; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antimetabolites; Betamethasone; Bronchoalveolar Lavage Fluid; Colitis, Ulcerative; Fatal Outcome; Glucocorticoids; HIV Seronegativity; Humans; Immunity, Cellular; Immunosuppressive Agents; Male; Mercaptopurine; Mesalamine; Opportunistic Infections; Pneumonia, Pneumocystis; Prednisolone; Sulfasalazine

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

Ten of 70 children (14%) with acute lymphoblastic leukemia developed severe interstitial pneumonitis within three weeks after induction of central nervous system prophylactic therapy. The clinical picture was characterized by fever, cough, progressive dyspnea, and hypoxemia with complete resolution in one to three weeks, except in one patient who died during the acute illness from respiratory failure. P. carinii organisms were found in the lung tissue of only one patient. The etiology of the pneumonitis in the other nine children was probably viral, acquired or activated during a period of lymphopenia and immunosuppression. The morbidity and potential mortality from the pneumonitis warrants early recognition by open lung biopsy and intensive supportive therapy.

Topics: Central Nervous System Diseases; Humans; Immunosuppression Therapy; Leukemia, Lymphoid; Leukocyte Count; Mercaptopurine; Methotrexate; Pneumonia, Pneumocystis; Pulmonary Fibrosis

An overview is presented of the improvements in the prognosis of acute lymphocytic leukemia due to combined modality therapy. With the best available regimens, approximately 50% of these children have remained leukemia-free for 5 years or more. Because of these results, there is growing concern for the quality of survival and for the side effects of therapy. A case in point is a completely unexpected side effect in a current study. Nonleukemic leukoencephalopathy has developed in 8 of 20 children given intravenous methotrexate, 50-80 mg/m2 per week, as the sole agent following remission induction and CNS therapy. Thus, with longer remissions and survivals now commonly observed, a concerted effort is needed to minimize side effects while trying to improve further the efficacy of therapy.

Topics: Child; Cyclophosphamide; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Mercaptopurine; Methotrexate; Pneumonia, Pneumocystis; Remission, Spontaneous

Topics: Bone Marrow Examination; Child; Chromosome Aberrations; Drug Therapy, Combination; Endomyocardial Fibrosis; Eosinophilia; Heart Murmurs; Humans; Hydrocortisone; Leukemia, Lymphoid; Liver; Lymph Nodes; Male; Mercaptopurine; Methotrexate; Myocardium; Organ Size; Pneumonia, Pneumocystis; Prednisone; Recurrence; Tachycardia; Vincristine

Topics: Adolescent; Anemia, Aplastic; Antineoplastic Agents; Central Nervous System; Child; Child, Preschool; Cyclophosphamide; Daunorubicin; Diarrhea; Drug Combinations; Female; Follow-Up Studies; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Nausea; Pneumonia, Pneumocystis; Prednisone; Radiotherapy; Recurrence; Remission, Spontaneous; Stomatitis, Aphthous; Vincristine; Vomiting

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