Richard B. Patterson

Favorable prognosis associated with hyperdiploidy in children with acute lymphocytic leukemia correlates with extra chromosome 6 : a pediatric oncology group study

Pretreatment bone marrow cytogenetic studies were included for 1664 patients with acute lymphoblastic leukemia (ALL) accrued to Pediatric Oncology Group (POG) 8035 laboratory classification study from May 1981 through January 1986. There was a significant difference (P = 0.0001) in distribution of stem‐line karyotype (normal, hypodiploid, pseudodiploid, or hyperdiploid) among children with early pre‐B, pre‐B, or T‐cell ALL, with early pre‐B patients demonstrating a higher proportion of hyperdiploid karyotypes with modal chromosome numbers>51. Cytogenetic classification of 1216 patients with early pre‐B or pre‐B ALL evaluable for duration of event‐free survival (EFS), with median follow‐up of 42 months, showed a significant prolongation of five‐year EFS associated with hyperdiploidy>51 (75%; standard error [SE] = 5%) compared with hyperdiploidy 47 to 51 (46%; SE = 7%), hypodiploidy (55%; SE = 11%), and pseudodiploidy (45%; SE = 7%) (P = 0.0001). Five‐year EFS was intermediate for patients with normal (58%), constitutionally abnormal (66%), or unsuccessful analyses (66%). The breakpoint defining hyperdiploidy associated with better prognosis was best defined as>51 (P = 0.0002). Of 239 children with hyperdiploid karyotypes, analysis of the contribution of each chromosome to EFS duration showed a significant association between improved EFS and additional chromosome(s) six (P = 0.02). Chromosome translocation was associated with shorter EFS (P = 0.0001).

The role of vincristine in the treatment of childhood acute leukemia

In a study of 117 patients under the age of 20 with acute leukemia, vincristine (VCR), at 2 mg. per square meter body surface per week, produced complete remissions in 55 per cent and partial remissions in 15 per cent. The drug also induced second remissions. Patients entering complete remission with VCR were randomly allocated to maintenance therapy with VCR or placebo. The median duration of remission was short: 9 weeks for VCR compared with 6 weeks for placebo. The probability of serious neurological toxicity computed according to the time of exposure to VCR, based on the supposition that VCR was not used for maintenance therapy, indicated that the minimal theoretical risk of toxicity for the highest complete remission rate occurred at 4 weeks (38 per cent remissions with 5 per cent toxicity). At 6 weeks, the corresponding probabilities were 54 and 16 per cent.

Chemotherapy of reticuloendotheliosis: Comparison of methotrexate plus prednisone vs. vincristine plus prednisone

Twenty‐eight children, ages 2 months to 13 years, with a diagnosis of reticuloendotheliosis were treated on a random basis with either vincristine (VCR) 2 mg/m2/week or methotrexate (MTX) 30 mg/m2 twice a week. Both groups received prednisone 40 mg/m2/day. The responders received randomly either MTX 30 mg/m2 twice weekly or no maintenance therapy. Of the 11 patients receiving VCR, 2 achieved complete and 5 partial remissions. Among 17 treated with MTX there were 8 complete and 1 partial remissions. The complete plus partial remission rate is 64% for VCR and 53% for MTX. The duration of response was superior in the MTX‐treated group, with a median remission duration of 315 days; the 4 patients above the median are still in remission. With VCR therapy, the median was 96 days, and all patients have relapsed. Maintenance therapy also improved the duration of remission, with a median of 20 months, compared to 79 days with no maintenance. Thus, in this clinical trial the best results were obtained when methotrexate plus prednisone were used for induction, followed by methotrexate maintenance therapy.

Vincristine, prednisone and L-asparaginase in the induction of remission in children with acute lymphoblastic leukemia following relapse.

Two hundred and twenty‐seven children with recurrent acute lymphoblastic leukemia were treated with various combinations of vincristine, prednisone, cyclophosphamide and L‐asparaginase in an approach to the induction of remission. The combination of L‐asparaginase 1,000 μ/kg iv q.d. X 10, vincristine 2.0 mg/m2iv q.w. X 4 and prednisone 40 mg/m2 p.o.q.d. X 28 days was found to be highly effective. The incidence of remission was 73%. No significant improvement was achieved when cyclophosphamide was added to this regimen. Various combinations of cytosine arabinoside, cyclophosphamide, vincristine, prednisone, BCNU or CCNU failed to maintain remission duration for more than two to three months. Neither BCNU nor CCNU prevented the development of CNS leukemia.

Comparative hemolytic activity of mephenesin, guaiacol glycerol ether and methocarbamol in vitro and in vivo.

Summary Mephenesin, guaiacol glyceryl ether (GG) and methocarbamol (AHR-85) have been compared as to their relative hemolytic activity in vitro and in vivo. Evidence is presented that GG and AHR-85 may be administered slowly as saturated aqueous solutions in large doses with little danger of an appreciable degree of hemolysis as indicated by the serum bilirubin and hemochromogen tests.