Allogeneic Hematopoietic Stem-Cell Transplantation with Reduced-Intensity Conditioning in Patients with High Risk Multiple Myeloma: Comparative Analysis of Outcomes Between Unrelated and Related Donor
Authors: El-Cheikh Jean , Furst Sabine , Stoppa Anne Marie , Crocchiolo Roberto , Faucher Catherine , Castagna Luca , Granata Angela , Oudin Claire , Ladaique Patrick , Calmels Boris , Lemarie Claude , schiano De Colella jean Marc , Chabannon Christian , Blaise Didier 
Published: October 2019

Abstract
Abstract 4513

Introduction:
The purpose of this study was to assess the results of allogeneic stem cell transplantation (Allo-SCT) after reduced-intensity conditioning (RIC) from an unrelated donor in patients with high-risk multiple myeloma (MM) in a single centre. From January 2007 to January 2011 we consecutively transplanted 40 patients with MM.

Patients and methods:
Seventeen (43%) (Group 1) and 23 patients (57%) (Group 2) had unrelated and related donor respectively. The median age was 48 years (39–63) in the first group and 56 years (40–67) in the second group (P=0.0769).
Thirty nine patients (98%) received one or more autologous transplantation. Ten patients (Group 1: N=5 (29%); Group 2: N=5 (22%)) were transplanted within whereas 30 patients were treated beyond (Group 1: N=12 (71%); Group 2: N=18 (78%) the first line treatment strategy. The disease status at transplantation was Complete Remission (CR) or VGPR in (35%) vs (43%), Partial remission (PR) in (59%) vs (52%) and Progression or Refractory Disease in (6%) vs (4%) (PD/RD) in the first and second group respectively (p=0.1770). Graft was peripheral blood stem cells (PBSC) in all patients in the related donor group and in 14 patients (82%) in the second group, the other 3 patients (18%) receiving marrow.
Thirty-three patients (Group 1: N=14 (82%); Group 2: N=19 (83%) were treated with a RIC based on Fludarabine (30mg/m2/d × 5); Busulfan (4 mg/kg/d p.o. or 3.2 mg/kg/d IV over 2 to 3 days) and rabbit ATG (2.5 mg/kg/d × 2). Seven patients received Fludarabine (25mg/kg/d for 3 days) and 2 Gys total body irradiation (TBI).
Post-graft immunosuppression consisted of cyclosporine (CSA) alone in 26 patients (65%), CSA and mycophenolate mofetil in 14 patients (35%).

Result:
The median follow-up was 22 months (1–49). None of our patient experienced a graft rejection. The cumulative incidence of grade II-III acute graft versus-host disease (GVHD) tended to be higher after unrelated donor graft (41% vs 17%) (p= 0.12). The cumulative incidence of chronic GVHD was no different between the first and second group (24% vs 30% respectively). At last follow up 24 patients (group 1: N=11 (65%); Group 2:N=14 (61%) were still alive of whom 17 are in CR (group 1: N=9 (53%); Group 2:N=8 (35%), 5 in PR (group 1: N=1 (6%); Group 2:N=4 (17%)and 2 in progressive disease (group 1: N=1; Group 2:N=1).
The estimated probability of non relapse mortality (NRM) at day 100 was 0% in the two groups and not statically different at 2 years. (12% vs. 22% (P=0.4)) Also 2 year overall and progression-free survivals were not statiscally different after unrelated and related donor transplants (59% vs. 66% (P=0.110) and 42% vs. 44% (p=0.241)). The incidence of acute GVHD, OS, PFS and NRM were not significantly different between the two groups.

Conclusion:
Our experience, although limited, supports that high risk MM patients can benefit from a RIC Allo-SCT with unrelated donor when a HLA matched sibling donor is not available conducting to acceptable and comparable outcomes. This deserves further analysis in larger populations.

Disclosures:
No relevant conflicts of interest to declare.