INTENSIFIED THERAPY FOR INFANTS WITH ACUTE LYMPHOBLASTIC-LEUKEMIA - RESULTS FROM THE DANA-FARBER-CANCER-INSTITUTE-CONSORTIUM

BACKGROUND. Infants with acute lymphoblastic leukemia (ALL) have a ver y poor prognosis. Since 1985, we have intensified therapy for infants with ALL by including a month of high dose multiagent chemotherapy aft er remission induction. METHODS, Between 1985 and 1995, we treated 23 infants (age < 12 months). We compared the presenting characteristics and outcomes of these infants with the 11 infants treated on our proto cols between 1973 and 1985, an era prior to the intensification of the rapy. Available bone marrow samples from infants treated since 1985 we re analyzed for the presence of MLL gene rearrangements by Southern bl ot analyses and for TEL-AML1 gene fusion by reverse transcriptase-poly merase chain reaction. RESULTS. With a median follow-up of 5.6 years, the 50-month event free survival (EFS) (+/- standard error) for the 23 infants was 54 +/- 11%, a significant improvement (P = 0.001) compare d with the outcome for the 11 infants treated on our protocols prior t o 1985 (EFS = 9 +/- 9%). Of the seven infants found to have a rearrang ed MLL gene, three (43%) remained in first complete remission. None of the nine infant bone marrow specimens tested had evidence of TEL-AML1 gene fusion. The intensified therapy was complicated by a high incide nce of infections, including septicemia in 52% of patients and Pneumoc ystis carinii pneumonitis in 22% of patients. Late effects identified in the 13 long term survivors (median age, 6 years) included developme ntal delay and learning disabilities of varying severity (82% of evalu able patients), asymptomatic cataracts (67%), asymptomatic echocardiog raphic abnormalities (30%), obesity (27%), and short stature (18%). CO NCLUSIONS. Intensification of therapy significantly improved the EFS o f infants with ALL compared with previous, less intensive regimens and with the experience of other investigators. Future treatment for infa nts should attempt to improve efficacy while minimizing toxicity. (C) 1997 American Cancer Society.