Effect of trimethoprim/sulfamethoxazole prophylaxis on outcome of childhood lymphocytic leukemia. A Pediatric Oncology Group Study.

The Pediatric Oncology Group (POG) undertook a prospective randomized trial using a single chemotherapy regimen with or without trimethoprim/sulfamethoxazole (TS). In a previous acute lymphocytic leukemia (ALL) study of initial therapy, investigators were free to use TS prophylaxis or not. Analysis of those data seemed to favor TS for duration of continuous complete remission. In the study reported here, of 126 randomized patients with ALL, 63 received TS. There was no effect of TS on disease-free survival after 3 years follow-up. Overall severe toxicity did not differ. However, granulocytopenia was somewhat more severe in the TS group. Hepatic toxicity, measured by enzyme elevation approached significance in the TS group versus controls. Some institutions declined randomization and treated with or without TS as a routine. Outcome and toxicities did not differ from randomized patients. There was no statistically significant effect on severe, life-threatening or fatal infection between the randomized TS versus control groups. Children not receiving TS developed varicella more often, a disease for which one would not expect TS to show a preventative effect. Pneumocystis pneumonias were not reported. The authors conclude that TS prophylaxis did not increase the continuous complete remission rate in children with ALL or decrease the incidence of infection. Toxicity is somewhat higher on TS.

Pediatric Oncology Group experience with modified LSA2-L2 therapy in 107 children with non-Hodgkin's lymphoma (Burkitt's lymphoma excluded).

From September 1976 to August 1979 the Pediatric Oncology Group accessed 145 children to study the effectiveness of modified LSA2-L2 therapy for the treatment of non-Hodgkin's lymphoma (NHL). Burkitt's lymphoma patients were ineligible; E-rosette-positive patients with greater than or equal to 25% blasts in the marrow entered after February 1977 were reported separately. Radiotherapy could be used to treat patients with compressive mediastinal disease at diagnosis and was prescribed for those with residual abdominal disease as demonstrated by second-look surgery on completion of induction chemotherapy. Confirmation of diagnosis by the Pathology Panel and Repository Center for Lymphoma Clinical Trials was mandatory. Diagnostic tissues of 131 patients were reviewed. Among 107 evaluable patients, 91 (85%) achieved complete remission. Differences in response rates among the three major histologic groups (lymphoblastic, undifferentiated, and large cell) were of statistical significance, with response being poorest for diffuse undifferentiated lymphoma (P = 0.03). Failure-free survival did not differ significantly for the three major histologic diagnoses. While response rate was lowest for Murphy Stage III patients (79%), the differences among the stages were not significant. Stage was not a significant prognostic factor for failure-free survival (P = 0.08). The number of patients still at risk and the Kaplan-Meier estimate of percentage of patients remaining at risk after 3 years is: Stage I, 8 (100%); Stage II, 10 (67%); Stage III, 28 (57%); Stage IV, 6 (39%); and greater than 25% blasts, 1 (13%). Stage III failure curves for lymphoblastic disease show continuing stepwise failure through 3 years. Among patients with diffuse large cell and undifferentiated disease, most failures occurred by 8 months. M1 and M2 levels of marrow involvement were not prognostic among children with lymphoblastic disease. The presence of a mediastinal mass was a significant factor contributing to failure in children with lymphoblastic disease without marrow involvement. Leucocytosis greater than 10,000/1, was a significant (P = less than 0.001) factor predicting failure-free survival for patients with large cell lymphoma. The delivery of radiotherapy was not a significant factor in achieving remission. No consistent benefit resulted from using radiotherapy to treat postinduction residual disease demonstrated on second-look exploration. The LSA2-L2 regimen was associated with considerable toxicity, severe or worse in 77% and life-threatening to 40% of these patients. Four died of toxicity. However, therapy was given more easily and safely as investigator experience increased.(ABSTRACT TRUNCATED AT 400 WORDS)

High-dose methotrexate as part of remission maintenance therapy for childhood acute lymphocytic leukemia: a Pediatric Oncology Group pilot study.

Seventeen children with acute lymphocytic leukemia (ALL) in remission were treated with parenteral high-dose methotrexate (HDM) pulses every eight weeks during standard 6-mercaptopurine and methotrexate (MTX) oral maintenance therapy. MTX (1,000 mg/m2) was infused over one hour followed by one hour of intravenous hydration for the purpose of achieving plasma and cerebrospinal fluid (CSF) levels greater than 10(-6) M for a period of 24 hours. Leucovorin (15 mg/m2) was administered orally six, 12, and 18 hours after completion of the HDM. Plasma and CSF concentrations of MTX were evaluated serially in the first 48 hours. During the first 24 hours, the plasma MTX level was maintained at greater than 10(-6) M. The patients receiving intrathecal MTX at a dose of 15 mg/m2 had an adequate, sustained MTX level in the CSF, but when no intrathecal MTX was administered, the CSF levels were less than 10(-6) M. For that reason, intrathecal MTX in a low dose (6 mg/m2) was injected intrathecally one hour after the HDM infusion, allowing the MTX level in CSF to approximate 10(-6) M over the 24 hours. The toxicity of this therapy was minimal. Due to the facts that the plasma and CSF MTX levels could be sustained above the desired concentrations and this regimen could be given in the outpatient clinic, this program has been incorporated into an ongoing study in an effort to prolong complete remissions.

Phase II study demonstrating failure of both a five-drug continuous-therapy regimen and a two-drug pulse-therapy regimen in the treatment of metastatic neuroblastoma: Southwest Oncology Group Study 822.

Twenty-six children greater than 1 year of age with previously untreated stage IV neuroblastoma were randomized to receive either a five-drug regimen (prednisone, cyclophosphamide, actinomycin D, vincristine, and daunorubicin) or a two-drug regimen (cyclophosphamide and vincristine). Complete response rates were 6% and 9% for the five-drug and the two-drug regimens respectively. Partial response rates were 13% and 27% for the five-drug and the two-drug regimens respectively. The mean duration of the seven responses was 9 months, and all 26 patients had died within 2 years. Neither regimen was effective for long-term disease control in these children with neuroblastoma.

Safety and efficacy of jet anesthesia for bone marrow aspirations.

Aspirations or Jamshidi needle biopsies (n = 287) of bone marrow were performed on children and adolescents with acute leukemia or other malignant disease following the use of a spring-loaded instrument that delivered local anesthetic in a jet spray; 89% of the patients were receiving chemotherapy, 12% were thrombocytopenic, and 23% of the 269 patients who were afebrile at the time of the procedure were severely neutropenic. None of these patients had an infection or a hemorrhage as a complication of the procedure. We conclude that not only is this procedure safe, but it is also much less painful than the traditional method of local anesthetic infiltration using a syringe and needle.