The efficacy of intrathecal (i.t.) chemoprophylaxis was compared with cranial radiotherapy plus i.t. methotrexate (MTX) in a Southwest Oncology Group (SWOG) study accessing 408 patients from September 10, 1974, to October 29, 1976. Randomization was stratified by prognostic groups (PGs) based on age and white blood cell count at diagnosis. All received induction therapy with vincristine and prednisone (Pred); maintenance therapy consisted of daily 6-mercaptopurine and weekly MTX. Consolidation for arm 1 employed cyclophosphamide and L-asparaginase followed by biweekly 5-day courses of parenteral MTX. The first dose of each course of MTX was given i.t. in triple chemoprophylaxis (MTX, hydrocortisone, and cytosine arabinoside). During maintenance, i.t. chemoprophylaxis was bimonthly and 28-day Pred “pulses” were given every 3 mo. Arm 2 i.t. chemoprophylaxis was initiated on achievement of remission, and arm 3 i.t. on treatment day 1; both continued 1 yr. Arm 4 induction included two doses of L-asparaginase. On achievement of remission, CNS prophylaxis (radiotherapy, 2400 rad plus i.t. MTX) was given. For all, therapy was discontinued after 3 yr of continuous complete remission. Survival and the incidence of extramedullary relapse were similar for the treatments employing either i.t. chemoprophylaxis or radiotherapy plus i.t. MTX upon achievement of remission. Among poor prognosis patients, the duration of complete remission was significantly better with the regimen using i.t. chemoprophylaxis as a component of consolidation therapy than with the regimen employing i.t. chemoprophylaxis early in induction or with the treatment using radiotherapy plus i.t. MTX for CNS prophylaxis. In poor prognosis patients, the initiation of i.t. chemoprophylaxis during consolidation was also associated with hematologic remissions that were significantly better than those achieved with the treatment employing early CNS chemoprophylaxis or with the regimen using radiotherapy plus i.t. MTX. Among average prognosis patients, therapy with CNS chemoprophylaxis during consolidation, as well as the regimen employing radiotherapy and i.t. MTX for CNS prophylaxis, produced hematologic remissions that were significantly longer than those obtained with the regimen using early CNS chemoprophylaxis. Hematologic remissions of good prognosis patients who received treatment with the regimen employing i.t. chemoprophylaxis during consolidation were statistically superior when compared to the regimen employing CNS radiotherapy plus i.t. MTX. This study indicates that i.t. chemoprophylaxis may be substituted for cranial radiotherapy when utilizing effective systemic regimens. Additionally, chemoprophylaxis may be reduced from 3 to 1 yr in patients with good prognostic factors.

No abstract

In an attempt to improve the poor outlook for children with T-cell leukemia (T-ALL), the Southwest Oncology Group, Pediatric Division, used a modified LSA2-L2 multidrug regimen to treat 53 patients with E- rosette-positive T-ALL. This regimen was chosen because of its demonstrated efficacy in T-cell (mediastinal) non-Hodgkin's lymphoma. Complete remission (CR) rate was 88%. Range of follow-up for those patients remaining in CR is 24–49 mo (median 39 mo). Life table analysis estimates that 40% (SE 8.3%) of all patients who started induction therapy will remain failure-free at 3 yr. For patients achieving CR, 46% (SE 9%) are projected to remain in both marrow and extramedullary CR at 3 yr. Median failure-free duration was 13 mo, but only 1 patient has relapsed beyond 16 mo. Twenty-nine percent of initial relapses were isolated CNS relapses. The following presenting factors did not relate significantly to outcome: hemoglobin, platelet count, uric acid, race, and mediastinal mass. Age greater than 10 yr was a poor prognosis indicator only in the less than 50,000/microliter WBC group. Sex was not a significant factor after adjusting for WBC. WBC was the most important prognostic factor: 19% (SE 8%) of patients with WBC greater than 50,000/microliter are projected to remain failure- free at 3 yr as compared to 67% (SE 11%) of patients with WBC less than 50,000/microliter. Although the overall results are better than those previously reported for pediatric patients with T-ALL, the long-term failure-free rate remains low for patients presenting with greater than 50,000/microliter WBC.

An 11-yr-old child with mild chronic hemolytic anemia was found to have decreased red cell hexokinase activity in spite of the reduced mean age of her red cell population. Similar decreases in red cell hexokinase activity were documented in the patient's parents and in one sib. The red cells were morphologically normal. Red cell 2,3-DPG levels were normal and ATP and glucose-6-phosphate levels were diminished. The kinetic properties, electrophoretic mobility, and thermal stability of the residual red cell hexokinase were normal or nearly so. Glucose consumption of the hexokinase-deficient cells was not appreciably decreased, probably because less of the potent inhibitor glucose-6- phosphate was present in the erythrocytes. It is likely, although not certain, that in this patient nonspherocytic hemolytic anemia resulted from hexokinase deficiency.

An 11-yr-old child with mild chronic hemolytic anemia was found to have decreased red cell hexokinase activity in spite of the reduced mean age of her red cell population. Similar decreases in red cell hexokinase activity were documented in the patient's parents and in one sib. The red cells were morphologically normal. Red cell 2,3-DPG levels were normal and ATP and glucose-6-phosphate levels were diminished. The kinetic properties, electrophoretic mobility, and thermal stability of the residual red cell hexokinase were normal or nearly so. Glucose consumption of the hexokinase-deficient cells was not appreciably decreased, probably because less of the potent inhibitor glucose-6- phosphate was present in the erythrocytes. It is likely, although not certain, that in this patient nonspherocytic hemolytic anemia resulted from hexokinase deficiency.