thioguanine-anhydrous and Hematologic-Diseases

Topics: Alkylating Agents; Androgens; Anemia, Hemolytic, Autoimmune; Benzene; Blood Transfusion; Bone Marrow Transplantation; Chloramphenicol; Chromosome Aberrations; Chromosome Disorders; Hematologic Diseases; Humans; Immunotherapy; Infection Control; Karyotyping; Leukemia; Meninges; Nitrosourea Compounds; Patient Isolators; Radiation Effects; Retroviridae; Thioguanine

Overall chemotherapeutic treatment results in pediatric acute lymphoblastic leukemia (ALL) are good, with event-free survival (EFS) rates over 70%. However, for a subset of patients characterized by high-risk (HR) features the outcome is less favorable, with EFS rates below 50%. Intensification of chemotherapy may improve the outcome for those patients, but increased toxicity, particularly myelosuppression, limits the escalation of dose intensity. Recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF) is known to reduce myelosuppression after cancer chemotherapy in adults. The objective of this study was to examine the effect of r-metHuG-CSF on myelosuppression in HR pediatric ALL patients and on the overall response rate to chemotherapy. Patients with HR pediatric ALL were randomized to receive nine alternating cycles of chemotherapy according to the German ALL-Berlin-Frankfurt-Münster 90 protocol either alone or followed by r-metHuG-CSF administered prophylactically at a dose of 5 microg/kg/d subcutaneously. In both groups, the planned interval between chemotherapy courses was a minimum of 21 days. We report here interim results of 34 patients. The incidence of febrile neutropenia (absolute neutrophil count <0.5 x 10(9)/L and oral temperature > or = 38.5 degrees C) was 17% in children receiving r-metHuG-CSF, as compared with 40% in the control group (P = .007). In addition, the median total duration of febrile neutropenia was reduced from 20.3 to 6.2 days per patient (P = .02). Culture-confirmed infections occurred less frequently in the r-metHuG-CSF group (8% v 15%; P = .04), and the total duration of intravenous antibiotic use was significantly reduced from 32.2 days to 18.2 days per patient (P = .02). A tighter adherence to the planned treatment schedule was also facilitated by r-metHuG-CSF (P = .007). With a median follow-up of 3.3 years, the estimated EFS of 4 years is 41% +/- 12%. In conclusion, r-metHuG-CSF administered prophylactically in the interval between chemotherapy courses significantly reduced febrile neutropenia, culture-confirmed infections, and duration of intravenous antibiotic administration and allowed for tighter adherence to the treatment schedule.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Cytarabine; Daunorubicin; Dexamethasone; Disease-Free Survival; Etoposide; Female; Fever; Filgrastim; Gastrointestinal Diseases; Germany; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Humans; Ifosfamide; Infant; Infection Control; Life Tables; Male; Mercaptopurine; Methotrexate; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Prospective Studies; Recombinant Proteins; Risk; Survival Analysis; Thioguanine; Vincristine; Vindesine

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

Twenty patients treated with maintenance chemotherapy for acute nonlymphoblastic leukemia after achieving complete remission were compared with 13 patients who underwent bone marrow transplantation from an HLA-identical sibling. The median age was 27 years for both maintenance chemotherapy patients (range 17-42 years) and for patients undergoing bone marrow transplantation (range 16-42 years). The 1-year survival for maintenance chemotherapy was 80% vs. 54% with bone marrow transplantation (p = NS). Complete remission durability was 70% at 1 year for maintenance chemotherapy (34% projected for 5 years) compared with no relapses in the first year with bone marrow transplantation (p = 0.01). Patients on maintenance chemotherapy were hospitalized for an average of 22 days (range 0-171 days) during the first 12 months of treatment. Patients undergoing bone marrow transplantation were hospitalized for an average of 82 days (range 41-113 days) in the same time period. Severe hematologic toxicity was seen in 13/13 bone marrow transplantation patients and 6/20 maintenance chemotherapy patients. Chronic graft-vs.-host disease occurred in 3/7 surviving bone marrow transplantation patients. Maintenance chemotherapy had an average first year cost of +3,076.00 for patients who did not relapse and +48,827.00 for patients that relapsed. The first year costs for bone marrow transplantation averaged +84,102.00. Thus, maintenance chemotherapy was associated with a better early survival, less toxicity, and lower cost than bone marrow transplantation in the first year after initiating therapy. However, fewer relapses with bone marrow transplantation suggest that it will yield a higher long-term survival rate.

Topics: Acute Disease; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Transplantation; Cytarabine; Female; Graft vs Host Disease; Hematologic Diseases; Humans; Leukemia; Male; Recurrence; Thioguanine

Topics: Anemia, Pernicious; Blood Cell Count; Bone Marrow Cells; Cytarabine; Cytoplasm; Follow-Up Studies; Hematologic Diseases; Humans; In Vitro Techniques; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Megakaryocytes; Mercaptopurine; Plasmacytoma; Polycythemia; Thioguanine; Thrombocytopenia

Topics: Acute Disease; Adult; Cytarabine; Fluorine; Hematologic Diseases; Hematopoiesis; Humans; Isoflurophate; Leukemia, Myeloid; Leukocyte Count; Leukocytes; Myeloproliferative Disorders; Radioisotopes; Remission, Spontaneous; Thioguanine; Time Factors