CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Therapy of Molecular Relapse in Acute Promyelocytic Leukemia

Fourteen patients with PML/RARa-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] 1 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/RARa fusion (sensitivity 1024) 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/m2/d and mitoxantrone 6 mg/m2/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 PCR1 after CHT, 1 died in remission and 1 progressed to hematologic relapse. Of 12 patients PCR2, 8 received consolidation with autologous bone marrow transplantation (ABMT), and 4 received ATRAcontaining maintenance. Ten patients in this group are in sustained second molecular remission at a median time of 9.51 months (range, 4 to 221) 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 F .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. r 1999 by The American Society of Hematology.