Hematopoietic Stem Cell Transplantation As a Successful Salvage Strategy for Relapsed Acute Promyelocytic Leukemia (APL): A Mayo Clinic Series

Abstract

Background: Relapse after ATRA-based induction therapy is relatively uncommon in patients with acute promyelocytic leukemia (APL). Long term follow up studies have estimated a 15-25% relapse rate. Autologous and allogeneic hematopoietic stem cell transplantation (HCT) has been used as an effective salvage strategy. We present a single institution study of the outcomes of patients with relapsed APL that underwent HCT.Methods: After due IRB approval, the Mayo Clinic Transplant Database was retrospectively reviewed to identify all patients across three Mayo Clinic sites with relapsed APL that underwent HCT from 1995-2013. Data was abstracted at diagnosis and at relapse. The aims of this study were to report the descriptive characteristics of patients, with a focus on HCT outcomes.Results:Baseline Patient CharacteristicsA total of 15 patients (9 (60%) males) with relapsed APL that underwent HCT were identified. Median age was 36 years (range: 19-63) and median follow up from diagnosis was 8.8 years (range: 1.7-17). 2 (13%) deaths (1 from relapse) were recorded. 14 (93%) received ATRA and anthracycline-based induction therapy and 1 received anthracycline-based induction without ATRA. All relapsed patients achieved a complete remission (CR) after induction. Median time to relapse was 1.6 years (range: 0.6-3.9). 10 (67%) patients had a medullary relapse (hematologic-7(70%), cytogenetic -2 (20%) and molecular-1(10%)), 3 (20%) had additional extramedullary (EM) disease (CNS-2, myeloid sarcoma-1), while 2 (13%) presented with EM disease only (CNS-2). Salvage regimens included ATRA in 5 (33%) patients and arsenic trioxide (ATO) in 8 (53%) patients. 12 (80%) patients were transplanted in CR2 and 1 in CR3 (7%), while 2 (13%) had persistent disease (PD) at time of HCT.Allogeneic HCT4 (27%) patients with a median age of 37 years (range: 33-49) underwent allogeneic HCT. 2 (50%) patients received myeloablative (MA) conditioning and 2 received reduced-intensity conditioning (RIC). 2 patients who underwent MA HCT had PD at time of transplant, while 1 patient in CR3 received a RIC. 2 (50%) patients developed acute GVHD while 2 (50%) had extensive stage chronic GVHD. At a median follow up of 2.6 years (range: 0.3-10.9), 3 (75%) patients remain alive and disease-free. 1 patient died of infectious complications within 100 days of transplant.Autologous Transplantation11 (73%) patients with a median age of 40 years (range: 23-68) underwent autologous HCT with MA conditioning. 7 (64%) patients were in molecular remission at time of HCT, 3 (27%) patients transplanted before 2004 were in cytogenetic remission and information about type of remission was unavailable in 1 patient. At a median follow up of 6.8 years (range: 0.5-16) since HCT, 1 (9%) patient had a documented relapse at 175 days after HCT and died of disease-related complications. 10 (91%) are alive and in remission.Conclusions:Our single-institution study reaffirms the efficacy of HCT for APL patients with medullary and EM relapse. Autologous HCT has excellent long-term results in selected patients in CR2. Allogeneic HCT was mainly reserved for patients with high risk disease (CR3) and persistent disease at time of HCT.Table 1:Baseline Patient CharacteristicsN (%)Number of patients15Follow up (years) (median, range)8.8 (1.7-17)Age at diagnosis (years) (median, range)36 (19-53)GenderMale9 (60%)Female6 (40%)Sanz risk scoreHigh4 (29%)Intermediate8 (57%)Low2 (14%)Induction RegimenATRA + anthracycline14 (93%)Anthracycline-based1 (7%)Response to induction therapyCR15 (100%)Time from diagnosis to relapse (years) (median, range)1.6 (0.6 - 3.9)Type of relapseHematologic7 (47%)Cytogenetic2 (13%)Molecular1 (7%)Hematologic and EM3 (20%)CNS only2 (13%)Salvage regimenATRA-based5 (33%)ATO-based8 (53%)Chemotherapy only2 (13%)Table 2:Outcomes at HCTN (%)Age at HCT (years) (median, range)38 (23-68)Disease status at HCTCR212 (80%)CR31 (7%)PD2 (13%)Type of HCTAllogeneic4 (27%)Autologous11 (73%)Conditioning regimenMyeloablative13 (87%)Non-myeloablative2 (13%)Follow up since HCT (years) (median, range)4.5 (0.3 - 16.3)Disease status at last follow upCR13 (86%)Relapsed disease1 (7%)Unable to assess1 (7%)Alive at last follow up13 (87%) DisclosuresNo relevant conflicts of interest to declare.