Outcome of treatment in children with philadelphia chromosome-positive acute lymphoblastic leukemia

Background: Children with Philadelphia chromosome-positive acute lymphoblas tic leukemia (Ph-positive ALL) have a poor prognosis, and there is no conse nsus on the optimal treatment for this variant of ALL. Methods: We reviewed the medical records of patients with Ph-positive ALL w ho were treated with intensive chemotherapy, with or without bone marrow tr ansplantation, by 10 study groups or large single institutions from 1986 to 1996. Data on 326 children and young adults, who ranged in age from 0.4 to 19.9 years (median, 8.1), were analyzed to determine the rate of complete remission and the probability of event-free, disease-free, and overall surv ival according to standard prognostic factors and type of treatment. Results: The 267 patients who had a complete remission after induction chem otherapy (82 percent) were stratified into three subgroups according to the age and leukocyte count at the time of diagnosis: those with the best prog nosis (a leukocyte count of less than 50,000 per cubic millimeter and an ag e of less than 10 years; 95 patients); those with an intermediate prognosis (intermediate-risk features; 92 patients); and those with the worst progno sis (a leukocyte count of more than 100,000 per cubic millimeter; 80 patien ts). The estimates of disease-free survival at five years (+/-SE) were 49+/ -5 percent (for patients with the best prognosis), 30+/-5 percent (for thos e with an intermediate prognosis), and 20+/-5 percent (for those with the w orst prognosis) (P<0.001 for the overall comparison). We also found that tr ansplantation of bone marrow from an HLA-matched related donor offered sign ificantly greater benefit than intensive chemotherapy alone in terms of pro tecting patients from relapse or other adverse events (relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.5; P<0.001). This finding was cons istent in all three subgroups. Conclusions: Unlike the usual type of ALL, Ph-positive ALL is associated wi th a poor prognosis. Nevertheless, in some patients with favorable prognost ic features, the disease can be controlled by intensive chemotherapy. Trans plantation of bone marrow from an HLA-matched related donor is superior to other types of transplantation and to intensive chemotherapy alone in prolo nging initial complete remissions. (N Engl J Med 2000;342:998-1006.) (C) 20 00, Massachusetts Medical Society.