Oral Arsenic Trioxide - Based Maintenance Without Hematopoietic Stem Cell Transplantation At Second Remission In Acute Promyelocytic Leukemia - A Prospective Follow-Up Study Of 65 Patients

Approximately 20 percent of patients with acute promyelocytic leukemia (APL) relapse after initial remission. More than 80 percent of these patients achieve a second complete remission (CR2). Autologous hematopoietic stem cell transplantation (HSCT) at CR2 is a widely accepted post-remission strategy. However, only a few prospective trials have examined the optimal post-remission therapy for relapsed APL.

In this study, we prospectively evaluated the outcome of 65 patients with APL in their first relapse (R1) treated with oral arsenic trioxide (As₂O₃) and chemotherapy-based re-induction followed by oral arsenic trioxide-based maintenance. Sixty-five patients (men=37; women=28) at a median age of 39 (3-76) years were treated with oral As₂O₃, all-trans retinoic acid (ATRA), and ascorbic acid combined with idarubicin (6mg/m²/day for 5 days) for re-induction. On achieving CR2, 2 cycles of idarubicin consolidation (6mg/m²/day for 2 days each cycle) were given. That was followed by oral As₂O₃-based maintenance (2 weeks every 2 months) for 2 years.

The median duration of follow-up was 90 (21–378) months. All evaluable patients achieved CR2. Twenty-one patients (32.8%) subsequently had a second relapse (R2). On multivariate analysis, male gender was associated with an increased risk of second relapse (P=0.01). The age, white blood cell (WBC) count, platelet count, peak WBC during reinduction and the occurrence of differentiation syndrome did not impact on the risk of second relapse. The median overall survival (OS) was not reached. The 5-year and 10-year OS were 82.2% and 74.4% respectively. Significantly inferior OS was associated with male gender (P=0.02), prior oral As₂O₃-based maintenance at CR1 (P=0.01) and central nervous system (CNS) involvement at relapse (P<0.001). The median leukemia-free survival (LFS) after CR2 was not reached. The 2-year and 5-year LFS were 72.4% and 64.1% respectively. Male gender and relapse from prior oral As₂O₃-based maintenance at CR1 were associated with worse LFS (P=0.01 and P=0.04 respectively).

In conclusion, our study showed that durable remissions and long-term survival were achieved with oral As₂O₃-based maintenance without the need of autologous HSCT at CR2.