Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia

Abstract

Key Points• We conducted a phase 2 study of ATO followed by autologous HCT for relapsed APL.• This sequential treatment is effective and feasible.The optimal treatments for relapsed acute promyelocytic leukemia (APL) remain equivocal. We conducted a phase 2 study to evaluate the efficacy and feasibility of a sequential treatment consisting of induction and consolidation with arsenic trioxide (ATO), peripheral blood stem cell (PBSC) harvest after high-dose cytarabine chemotherapy, and autologous hematopoietic cell transplantation (HCT). Between 2005 and 2009, 35 patients (26 with hematologic and 9 with molecular relapse) were enrolled. Induction therapy resulted in complete remission in 81% of those with hematologic relapse, and most patients became negative for PML-RARa after the first ATO consolidation course, but 4 remained positive. Administration of the second ATO consolidation course further decreased the transcript levels in 3 patients. In total, 25 patients proceeded to PBSC harvest, all of whom successfully achieved the target CD341 cell doses, and 23 underwent autologous HCT with PML-RARa-negative PBSC graft. Posttransplant relapse occurred in 3 patients, and there was no transplant-related mortality. With a median follow-up of 4.9 years, the 5-year event-free and overall survival rates were 65% and 77%, respectively. These findings demonstrate the outstanding efficacy and feasibility of the sequential treatment featuring ATO and autologous HCT for relapsed APL. This study was registered at

Role of hematopoietic stem cell transplantation for relapsed acute promyelocytic leukemia: A retrospective analysis of JALSG‐APL97

“…(9) A recent prospective study of our JALSG also observed a relatively low relapse rate, in which there were only three relapses among 23 auto-grafted patients with molecular remission at the time of stem cell harvest (5-year EFS rate, 65%). (14) These studies show a prognostic importance of MRD negativity using molecular analysis before HSCT on the outcome. However, the results of the present study differ from previous report in that the MRD negativity is well associated with the low relapse rates in auto-HSCT.…”

“…(6,9) Recently, in a phase 2 prospective study, our Japan Adult Leukemia Study Group (JALSG) reported the efficacy of sequential treatment using ATO followed by auto-HSCT for 25 patients with relapsed APL. (14) However, evidence has been lacking in terms of the role of auto-HSCT alone on the cumulative relapse rate or efficacy for patients with APL in CR2 who were ineligible for the phase 2 study regimens. Moreover, in situations where no guidelines regarding the optimal choice of auto-or allo-HSCT in CR2 have been determined, the role of HSCT alone in post-remission therapies for patients with APL in CR2 is yet to be evaluated.…”

Delayed hematopoietic recovery after auto-SCT in patients receiving arsenic trioxide-based therapy for acute promyelocytic leukemia: a multi-center analysis

“…cytarabine 16 g/m 2 over 4 days followed by PBSC mobilization with G-CSF beginning at day 6, as described previously. 17 A minimum CD34+ cell collection of 2x10 6 per kg was required. The conditioning regimen consisted of BU 12 mg/kg PO divided into 12 doses and melphalan 140 mg/m 2 divided into 2 doses.…”

“…Patients in the JALSG cohort were enrolled at 20 centers between December 2005 and June 2009, with data collected prospectively upon study entry, as previously reported. 17 Autologous HSCT Patients at UCSF underwent consolidation with i.v. cytarabine 16 g/m 2 and etoposide 40 mg/kg over 4 days, followed by PBSC mobilization with G-CSF 10 μg/kg per day and PBSC collection upon neutrophil recovery.…”

“…We additionally included data from all APL patients who underwent autologous HSCT in the only published prospective trial of ATO therapy prior to autologous HSCT by the Japan Adult Leukemia Study Group (JALSG). 17 We identify an association between ATO-based APL therapy and delayed hematopoietic recovery following autologous HSCT.…”