BCG in the treatment of acute lymphocytic leukemia

Abstract

Children with acute lymphocytic leukemia, who were in remission after induction with prednisone and vincristine and consolidation with intravenous methotrexate, were randomized into three groups receiving (1) no further therapy, (2) BCG, and (3) chemotherapy with biweekly methotrexate and monthly prednisone and vincristine. Children continuing in remission after 8 mo on chemotherapy in group 3 were rerandomized into three similar groups, i.e., no therapy, BCG, and chemotherapy. In the primary randomization, the median duration of remission was identical in the groups receiving no therapy or BCG, (4 and 4.3 mo respectively), and both were significantly less than the median duration of remission on chemotherapy which had not been reached prior to secondary randomization at 8 mo. Results of secondary randomization were similar to those of primary randomization. As used in this study, BCG was ineffective in prolonging drug-induced remissions either early in remission or when the leukemic cell population might have been further reduced after 8 mo of maintenance chemotherapy.

A randomized study of intermittent chemotherapy with or without BCG inoculation in maintenance therapy of childhood ALL

“…The early encouraging reports of Mathe et a1 [ l ] on the role of immunotherapy in the maintenance of remission in chldhood acute lymphocytic leukemia (ALL) were not confirmed by randomized group studies reported from the USA [2], UK [ 3 ] , and Europe [4]. In these studies, bacillus Calmette-Guerin (BCG) was used as the sole maintenance agent, after a variable period of chemotherapy, to investigate the suggestion that immune stimulation can eradicate residual leukemic cells after reduction of the leukemia cell load by prior chemotherapy.…”

“…From our study and the other randomized studies discussed above, in which the chemotherapy during induction was either "mild" [2,3, PF group in this report] or "vigorous" [4,5, PA and PU in this report], consolidation was prolonged [4] or short [2,3,5], and maintenance chemotherapy was given [5, our study] or omitted [2,3,4]; no beneficial effect of immunotherapy has been demonstrated.…”

“…It should be noted, however, that the study design could only have detected as significant an effect that was large enough to reduce the relapse rate by more than 50%. Nevertheless, our results are in agreement with the two early randomized studies of immunotherapy in childhood ALL [2,3], which required confirmation since they were initiated before it was generally agreed that CNS prophylaxis and more than two-drug induction improved the results of treatment. Two other randomized studies, using more than two-drug remission induction and some form of CNS prophylaxis, have investigated the role of immunotherapy during remission maintenance using different experimental designs from that of our study.…”

Acute nonlymphocytic leukemia in 171 children

“…Several groups now report that the addition of immunotherapy gives longer remissions than chemotherapy alone (28,41,44). Ironically, immunotherapy was tried in ALL earlier, but after an initial report of success (459, others have not been able to confirm its efficacy (9a, 41,46).…”

L‐asparaginase reinduction and maintenance therapy in previously treated acute lymphocytic leukemia

“…J. K., a 13-year-old girl with ALL was diagnosed in September of 1971. She was entered on CCSG protocol 903 (15), and initial remission was induced in four weeks with intravenous weekly vincristine, 1.5 mg/M2, and oral daily prednisone, 40 mg/M2. She received consolidation therapy with intravenous methotrexate, 15 mg/M2 daily for 5 days each 2 weeks for 8 weeks, prior to receiving maintenance therapy with biweekly methotrexate, 30 mg/M2 orally, monthly vincristine, 1.5 mg/M2 intravenously, and prednisone, 40 mg/M2 orally daily for 5 days each month, according to CCSG protocol 903.…”