Salvage Chemotherapy Followed By Autologous Peripheral Stem Cell Transplantation for Relapsed Acute Promyelocytic Leukemia; A Single Center Experience

Background: After the addition of differentiating agents such as all-transretinoic acid (ATRA) to conventional chemotherapy, treatment outcomes of acute promyelocytic leukemia (APL) had been markedly improved. However, about 10% of patients with APL still have experienced relapse and have to receive salvage chemotherapy. Although arsenic trioxide (ATO) plays an important role in salvage chemotherapy as well as induction chemotherapy, the optimal treatment strategy remains unclear, especially for patients in whom autologous peripheral stem cell transplantation (AutoHCT) is planned. We tried to find the role of salvage chemotherapy including ATO-based regimen in relapsed APL patients, and want to share our experience in these patients.

Patients and Methods: Among 77 patients diagnosed with APL from 2005 to 2014 at Yonsei University Severance Hospital, 11 (14.3 %) relapsed patients were enrolled. Clinical data of these patients was retrospectively reviewed. Except one patient refused further treatment at the time of relapse, 10 patients were included in the final analysis for treatment outcome.

Results: All patients received remission induction chemotherapy with modified PETHEMA regimen, and achieved complete remission (CR) confirmed at the molecular level. The median duration of the first CR was 38.8 months (range 28.0–88.0 months). As pre-transplant salvage chemotherapy, earlier 3 patients received conventional chemotherapy regimen without ATO, but later 7 patients received ATO-based regimen after ATO was available in our country. There was no statistical difference in median duration to the second CR from salvage chemotherapy according to the regimen (68 days in conventional chemotherapy patients vs. 60 days in ATO-based chemotherapy, P>0.05). However, 3 patients receiving conventional regimen without ATO did not received AutoHCT because they died due to treatment-related complications during additional salvage chemotherapies. In contrast, 7 patients receiving ATO-based regimen received AutoHCT successfully, and all patients remains alive without further relapse. The median duration from the time of second CR to AutoHCT was 3.8 months (range 1.3–7.6 months), and median follow up duration after AutoHCT was 8.3 months (range 0.6–45.9 months). In these 7 patients receiving ATO-based regimens, duration of ATO treatment was variable (median 72 days, range 42-113 days), and a range of total dose of ATO given before AutoHCT was also variable (median 701.23 mg, range 420-1242.8 mg). Total dose and treatment duration of ATO was mainly determined by the time of molecular CR achieved again. The peripheral hematopoietic stem cells were harvested when molecular complete remission was confirmed, and median number of stem cells harvested was 5.14 x 10^6 cells/kg of recipient (range 2.90–7.76 x 10^6 cells/kg). The yield of harvest peripheral stem cells and the outcomes of followed AutoHCT were not significantly related to the total dose or treatment duration of pre-transplant ATO-based salvage therapy.

Conclusion: In this study, ATO-based chemotherapy followed by AutoHCT was safe and excellent salvage treatment strategy for relapsed APL patients. The achievement of second molecular CR might be more important in this treatment strategy than total dose or treatment duration of ATO-based salvage therapy before AutoHCT.