Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma in Relapse after Autologous Transplantation: A Single Institution Experience with Matched Related Donors
Authors: Brás Gil , Vaz Carlos , Leite Luís , Branca Rosa , Campilho Fernando , Roncón Susana , Campos Antonio M. 
Published: October 2019

Abstract
INTRODUCTION:
Relapse in Multiple Myeloma (MM) comprises a dismal prognosis. The proteasome inhibitors and immunomodulators increased the median overall survival (OS) in relapse from 12 to 24 months. For relapsing patients, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) and also allogeneic HSCT have been considered valid options in recent consensus statement. The major concern about allogeneic HSCT is the high transplant-related mortality (TRM) even with Reduced Intensity Conditioning (RIC).
AIMS:
Single institution retrospective evaluation of RIC allogeneic HSCT from matched related donors, in a cohort of MM patients relapsing after autologous HSCT.
RESULTS:
Between 1998 and 2016, 43 MM patients received allogeneic HSCT. From this group, a cohort of 29 MM patients relapsing after autologous HSCT was selected, based on supracited inclusion criteria. The median age at allogeneic HSCT was 51 (33-62) years. Before allogeneic HSCT, 55,7% (N=16) were treated wih salvage chemotherapy alone, whereas 20,7% (N=6) received chemotherapy plus autologous HSCT. For allogeneic HSCT, the conditioning was fludarabine plus bussulphan. Acute graft-versus-host disease (GVHD) prophylaxis was cyclosporine plus mycophenolate mophetil in 25 (86,2%) and in vivo antithymocyte globulin plus cyclosporine in 4 (13,8%). All patients recieved matched related peripheral blood grafts. Responses to salvage treatment previous to allogeneic HSCT were: progressive/stable disease (PD/SD) 24,1%, partial response (PR) 41,4%, very good partial response/complete remission (VGPR/CR) 13,7%, unknown 20,7%. Best responses after allogeneic HSCT were: PD/SD 15,7%, PR 24,1%, VGPR/CR 58,6%, unknown 10,3%. Engraftment was achived in 86,2% (N=25) and full donor chimerism was observed, at least once, in 72,4% (N=21). The overall reported incidence of grade II-IV acute GVHD was 48,3% (N=14) and moderate/severe chronic GVHD was 34,5% (N=10). Cytomegalovirus (CMV) reactivation ocurred in 44,8% (N=13) and hemorrhagic cystitis in 10,3% (N=3). The median progression free survival (PFS) and overall survival (OS) was 24 (0-61) and 176 (0-376) months, respectively. The incidence of relapse/progression was 48% (N=14). In this setting, 42,9% (N=6) were treated with chemotherapy alone and 35,7% (N=5) with donor lymphocyte infusion (DLI). After DLI, 80% (N=4) achieved CR. The overall mortality and TRM were 48,3% (N=14) and 17,2% (N=5), respectively. Best response after allogeneic HSCT was the only factor that improved PFS and OS (p<0,05).
CONCLUSION:
In our cohort, the allogeneic HSCT as salvage treatment for MM relapsing after autologous HSCT showed ability to deepen responses after salvage chemotherapy/autologous HSCT and also to prolong OS. The diferences between PFS and OS probably reflect the increasing therapeutical options to rescue patients after progression/relapse (chemotherapy, immunossupression tapper and DLI). The scarce data concerning the cytogenetic risk and the short dimension of this cohort are major limitations to define the MM relapsing patients who benefit most of allogeneic HSCT.

Disclosures
No relevant conflicts of interest to declare.