ALL-TRANS-RETINOIC ACID SIGNIFICANTLY INCREASES 5-YEAR SURVIVAL IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA - LONG-TERM FOLLOW-UP OF THE NEW-YORK STUDY

All-trans retinoic acid (ATRA.) induces a high incidence of complete r emission (CR) in patients with acute promyelocytic leukemia (APL); how ever, the magnitude of this agent's contribution to increased rates of cure of this disease has not yet been established. From 1990 to 1995 we used RA as remission induction therapy in 103 APL patients (73 newl y diagnosed and 30 previously treated) who were retinoid-naive and wer e treated on the basis of initial morphology. Patients whose diagnosis was changed on the basis of the results of molecular testing (n = 13) were withdrawn from RA treatment and given chemotherapy alone. After achieving a CR, previously untreated patients received several cycles of consolidation chemotherapy, usually with idarubicin and cytosine ar abinoside. Among individuals whose diagnosis was molecularly confirmed , 54 of 65 new patients (83%) and 25 of 30 previously treated patients (83%) achieved a CR. All induction failures in molecularly diagnosed cases were due either to early death or to premature withdrawal. Media n disease-free and overall survival rates recorded for all newly diagn osed patients are currently >40+ and >43+ months, respectively. We sub sequently examined a subset of 27 newly diagnosed patients treated dur ing the first 2 years of this program whose actual median follow-up pe riod is now >5 years. Median disease-free and overall survival rates r ecorded for this group are >57+ and >58+ months, respectively; 56% of these patients are alive in first remission. These results significant ly exceed those achieved using chemotherapy alone in a historical cont rol group of 80 patients consecutively treated at this center from 197 5 to 1990, whose median disease-free and overall survival rates were 1 1 and 19 months, respectively; only 22% of these patients were alive i n first remission at 5 years. Although a high proportion of previously treated patients also achieved a CR after RA treatment, median diseas e-free and overall survival rates noted for that group were markedly l ower (i.e., 7.5 and 10.9 months, respectively). Thus, data from patien ts whose median follow-up period is now >5 years have confirmed earlie r projections and indicate that the use of RA for remission induction yields an approximately 2.5-fold increase in the proportion of patient s who have presumably been cured of this disease.