Treatment of Relapsed Acute Promyelocytic Leukemia by Arsenic-Based Strategies without Hematopoietic Stem Cell Transplantation in Hong Kong: A Seven-Year Experience.

Background: The optimal therapy for relapsed acute promyelocytic leukemia (APL) after arsenic trioxide (As₂O₃)-induced remission is unclear. Hematopoietic stem cell transplantation (HSCT) is associated with high morbidity and mortality. Moreover, lasting remission is observed in many patients who are not candidates for HSCT, owing to advanced age or lack of donors, implying that HSCT is not mandatory for durable remission. We evaluated our results of an As₂O₃-based, non-HSCT regimen for patients with relapsed APL.

Materials and methods: Forty-two consecutive patients (18 men, 24 women, median age: 35 years, 12–72) with relapsed (relapse 1, R1=39, R2=3) APL were treated with an-As₂O₃ based, non-HSCT regimen. The time from last complete remission (CR) was 22 (6–243) months (mo). Initial treatment was As₂O₃ (10 mg/day) either intravenously (n=16) or orally (n=28) until CR, followed by idarubicin consolidation (6 mg/m²/day x 9). Twenty-five patients received oral-As₂O₃ maintenance. Post-As₂O₃ relapses were treated with oral As₂O₃ + all-trans retinoic acid (ATRA, 45 mg/m²/day) until CR, followed by maintenance (two weeks of ATRA+As₂O₃ every 2 mo. for 2 years). Post-As₂O₃/ATRA relapses were treated with oral As₂O₃+ATRA+ascorbic acid (1g/day) until CR, followed by consolidation/maintenance with the same regimen (2 weeks every 2 mo. for 2 years). Part of the induction and all of the maintenance therapies were given in the outpatient clinic.

Results: Forty-one patients (98%) achieved CR after initial As₂O₃ treatment. One 72-year old man with XYY syndrome, diabetes and mental retardation died of pneumonia. Thirteen relapses occurred at a median of 15 (6–22) mo. As₂O₃-maintenance significantly decreased further relapses (3/24 with versus 10/17 without As₂O₃-maintenance, p=0.003). Two relapses died of cerebral APL before further treatment could be administered. Of eleven patients treated with As₂O₃+ATRA, 10 achieved CR, 8 of whom have remained in remission (median follow-up: 33 mo.). Two post-As₂O₃/ATRA relapses achieved CR again with As₂O₃+ATRA+ascorbic acid, and have remained in remission after maintenance treatment with As₂O₃+ATRA+ascorbic acid. All patients in continuous remission (n=38) were PML/RARa negative on polymerase chain reaction (sensitivity 10⁻³ to 10⁻⁴).

Conclusion: Our regimen resulted in a leukemia-free-survival of 89.3%. The results suggest that an oral and mainly outpatient As₂O₃-based, non-HSCT strategy is efficacious for relapsed APL. In terms of survival, costs, treatment side effects and patient tolerance, the results appear to be comparable to, if not more favorable than, other treatment options based on high dose chemotherapy, graft-versus-leukemia effect, or anti-myeloid antibody therapy.