Acute promyelocytic leukemia: All-trans retinoic acid (ATRA) along with chemotherapy is superior to ATRA alone

This study was conducted to compare the results of treatment of acute promy elocytic leukemia (APL) with all-trans retinoic acid alone (ATRA) or a comb ination therapy of ATRA followed by chemotherapy. Forty-three patients trea ted between February 1992 and February 1996 were included in this study. Ei ghteen patients were treated with ATRA alone and 25 patients were treated w ith ATRA followed by chemotherapy. The cytogenetic analysis was done in 41 patients at presentation, following treatment, and at follow-up. A complete response (CR) was achieved in 13(72%) patients on ATRA and 19 (76%) on ATR A followed by chemotherapy. Eleven of 13 patients with response to ATRA alo ne relapsed with median survival of eight months (range, 1 to 28). One pati ent died of hepatitis in CR and one patient is alive 2 years after diagnosi s. In the combination therapy arm, 10 patients are in CR with a median foll ow-up of 22 months (range, 6 to 56 months). After achieving a CR, four pati ents died due to infections during chemotherapy therapy, and only 5 of 19 p atients have relapsed. Major cytogenetic response was seen in 8 of the 10 p atients in whom cytogenetic date was available after treatment with ATRA at the time of remission. Similarly, 13 of 15 for whom data was available sho wed a major cytogenetic response after treatment with ATRA plus chemotherap y. Prior to relapse, 80% of the patients had an increase in the percentage of t(15;17) cells in the marrow. Patients with a complete hematological res ponse but no cytogenetic response relapsed within six months. Ten patients died prior to response evaluation. Two patients who received ATRA died of r etinoic acid syndrome, one of pneumonia, and one of intracranial hemorrhage . Of the six patients on ATRA and chemotherapy, four died of retinoic acid syndrome (RAS), one of intracranial hemorrhage, and one of left ventricular failure. Only one patient is alive at 24 months following treatment with A TRA alone. The relapse-free survival is 42% at four years for patients trea ted with ATRA followed by chemotherapy. This trial is a historical comparis on of ATRA alone and ATRA with subsequent combination chemotherapy. Nonethe less, the trial shows a significant improvement in the event free survival of patients receiving chemotherapy as consolidation following ATRA. (C) 199 9 Wiley-Liss, Inc.