A comparison of two regimens for high-risk acute lymphocytic leukemia in childhood. A pediatric oncology group study

Abstract

Four hundred thirty patients with high-risk acute lymphoid leukemia were entered on the acute leukemia in childhood protocol (AlinC 12) of the Pediatric Division of the Southwest Oncology Group (now the Pediatric Oncology Group) between 1976 and 1979. This study was a prospective randomized comparison of two regimens that had as their primary differences: (1) an intensification period with Cytoxan (cyclophosphamide) and asparaginase after induction; (2) a period of intravenous methotrexate before initiating maintenance; and (3) in the regimen that had those two additions, triple-drug chemoprophylaxis of the central nervous system (CNS) using methotrexate, hydrocortisone, and cytosine arabinoside as compared to cranial irradiation and intrathecal methotrexate. All patients received vincristine and prednisone induction, 6-mercaptopurine and methotrexate maintenance, and vincristine and prednisone pulse intensification. There was no significant difference in the rate of bone marrow relapse. However, overall disease-free survival favored the arm with intensification and chemoprophylaxis because of a lesser incidence of extramedullary relapse. Thus, for treatment 1 versus treatment 3 the two-sided P values were for overall disease-free survival 0.16; bone marrow relapses 0.13; all CNS relapses 0.04; and all extramedullary disease relapses 0.013. It is concluded that intensification as delivered in this protocol protects against testicular relapse and that chemoprophylaxis is adequate prophylaxis against isolated CNS relapse.

Clinical characteristics and treatment outcome of children with acute lymphocytic leukemia and down's syndrome. A pediatric oncology group study

“…'~ As has been the case with other investigators, we did not find striking differences in clinical and laboratory features between patients with either DS-ALL or NDS-ALL. 20 Our report extends the findings of Robison et a1.,'* which showed that the prognostically unfavorable pre-B immunophenotype does not occur more frequently in children with DS than in those with NDS-ALL. t Relative risk = ratio of the instantaneous risk of failure at any time for a patient having the worse category of a factor relative to a patient having the better category.…”

Systematic review and meta‐analysis of randomized trials of central nervous system directed therapy for childhood acute lymphoblastic leukemia

“…Studies were grouped into 11 categories by randomized comparison. Table I gives details of the CNS‐directed treatments 11–56. Steroid use is given in supplementary Table S1.…”

The Management of High‐risk Lymphoblastic Leukaemia in Children

“…It has become apparent in the last 10 years that effective CNS‐directed treatment can be achieved, at least in standard and lower risk children, with regular intrathecal methotrexate, particularly when accompanied by intensified systemic chemotherapy ( Littman et al , 1987 ; Tubergen et al , 1993b ). The Paediatric Oncology Group, after an early randomized trial comparing cranial irradiation and intrathecal chemotherapy ( van Eys et al , 1989 ), have for many years used triple intrathecal chemotherapy for all children except those with T‐ALL ( Pullen et al , 1993 ). There have as yet been no completed randomized trials comparing regular intrathecal methotrexate and triple therapy.…”