LATE INTENSIFICATION CHEMOTHERAPY HAS NOT IMPROVED THE RESULTS OF INTENSIVE CHEMOTHERAPY IN ADULT ACUTE LYMPHOBLASTIC-LEUKEMIA - RESULTS OFA PROSPECTIVE MULTICENTER RANDOMIZED TRIAL (PETHEMA ALL-89)

Background and Objective. Intensive induction and post-remission thera pies have improved the prognosis in adult acute lymphoblastic leukemia (ALL). However, different from children, the impact of late intensifi cation therapy in the overall results of treatment has not been consis tently evaluated. The objective of this study was to analyze the resul ts of a multicenter prospective protocol, PETHEMA ALL-89, in which, af ter intensive induction and consolidation therapy, randomization to re ceive delayed intensification treatment was performed. Design and Meth ods. One hundred and eight adults (age greater than or equal to 15 yea rs) diagnosed with ALL (ALL L3 excluded) in 22 Spanish hospitals from 1989 to 1994 were treated with a five-drug induction therapy, followed by four cycles of early post-remission treatment during four months, and maintenance therapy for two years. Patients in remission at the en d of the first year were randomized to receive one six-week cycle of l ate intensification therapy. Uni-and multivariate analyses of early re sponse to treatment, complete remission (CR), leukemia-free survival ( LFS) and overall survival (OS) were performed. Results. The median (ra nge) age of the series was 28 (15-74) years and leukocyte count 26x10( 9)/L(1-600). ALL L1/L2 was present in 38/70 patients, early pre-B in 1 3, common in 53, pre-B in 12 and T in 30 cases. The CR rate was 86%, a nd refractory disease 9%. Median LFS was 34 months, with a 5-yr probab ility of 41% (95% CI, 29-53), whereas median OS was 51 months and 5-ye ar probability 47% (34-59%). There were no differences in either LFS a nd OS between patients who did or did not receive delayed intensificat ion therapy. Prognostic factors for CR attainment were advanced age an d slow response to therapy. These two features were, in addition to hi gh leukocyte counts, the parameters with negative influence in both LF S and OS. Interpretation and Conclusions. The results of PETHEMA ALL-8 9 are similar to those referred in other chemotherapy-based protocols In adult ALL. Delayed intensification has not improved the length of r emission and survival. Efforts to improve the prognosis of adult ALL p atients must be mainly focused in early intensification treatment. (C) 1998, Ferrata Storti Foundation.