AUGMENTED POSTINDUCTION THERAPY FOR CHILDREN WITH HIGH-RISK ACUTE LYMPHOBLASTIC-LEUKEMIA AND A SLOW RESPONSE TO INITIAL THERAPY

Background Children with high-risk acute lymphoblastic leukemia (ALL) who have a slow response to initial chemotherapy (more than 25 percent blasts in the bone marrow on day 7) have a poor outcome despite inten sive therapy. We conducted a randomized trial in which such patients w ere treated with either an augmented intensive regimen of post-inducti on chemotherapy or a standard regimen of intensive post-induction chem otherapy. Methods Between January 1991 and June 1995, 311 children wit h newly diagnosed ALL who were either 1 to 9 years of age with white-c ell counts of at least 50,000 per cubic millimeter or 10 years of age or older, had a slow response to initial therapy, and entered remissio n at the end of induction chemotherapy were randomly assigned to recei ve standard therapy (156 children) or augmented therapy (155). Those w ith lymphomatous features were excluded. Event-free survival and overa ll survival were assessed from the end of induction treatment. Results The outcome at five years was significantly better in the augmented-t herapy group than in the standard-therapy group (Kaplan-Meier estimate of event-free survival [+/-SD]: 75.0+/-3.8 vs. 55.0+/-4.5 percent, P< 0.001; overall survival: 78.4+/-3.7 vs. 66.7+/-4.2 percent, P=0.02). T he difference between treatments was most pronounced among patients on e to nine years of age, all of whom had white-cell counts of at least 50,000 per cubic millimeter (P<0.001). Risk factors for an adverse eve nt in the entire cohort included a white-cell count of 200,000 per cub ic millimeter or higher (P=0.004), race other than black or white (P<0 .001), and the presence of a t(9;22) translocation (P=0.007). The toxi c effects of augmented therapy were considerable but manageable. Concl usions Augmented post-induction chemotherapy results in an excellent o utcome for most patients with high-risk ALL and a slow response to ini tial therapy. (C) 1998, Massachusetts Medical Society.