Therapy of molecular relapse in acute promyelocytic leukemia

Fourteen patients with PML/RAR alpha-positive acute promyelocytic leukemia (APL) were given salvage therapy at the time of first molecular relapse. All patients had achieved first molecular remission after the AIDA protocol (all-trans retinoic acid [ATRA] + idarubicin) and were being prospectively monitored by reverse transcriptase-polymerase chain reaction (RT-PCR), Molecular relapse was defined as reappearance of RT-PCR-positivity for the PML/RAR alpha fusion (sensitivity 10(-4)) in 2 successive marrow samples collected during postconsolidation monitoring. The median duration of first molecular remission was 7.5 months (range, 2 to 25). Salvage therapy consisted of oral ATRA for 30 days followed by 4 daily courses of chemotherapy (CHT) with cytarabine 1 g/m(2)/d and mitoxantrone 6 mg/m(2)/d. Second molecular remission was obtained in 12 of 14 patients (86%), Seven of these 12 attained molecular remission after ATRA alone. Of the 2 patients who persisted PCR+ after CHT, 1 died in remission and 1 progressed to hematologic relapse. Of 12 patients PCR-, 8 received consolidation with autologous bone marrow transplantation (ABMT), and 4 received ATRA-containing maintenance. Ten patients in this group are in sustained second molecular remission at a median time of 9.5+ months (range, 4 to 22+) and 2 underwent hematologic relapse 6 and 13 months, respectively, after transient second molecular remission. The 2-year Kaplan and Meier survival estimate from time of relapse was 92% (95% confidence interval [CI]: 61% to 98%) in this series, and 44% (95% CI: 35% to 52%) in a previous series of 37 patients who received the same treatment at the time of hematologic recurrence (P < .05, by log-rank test). This study suggests that early administration of salvage therapy is advantageous in APL and represents the first experience on therapy of molecular relapse in acute leukemia. (C) 1999 by The American Society of Hematology.