Survival Analysis in Patients with Multiple Myeloma after Allogeneic Hematopoietic Stem Cell Transplantation, a Single Center Study (1994-2013)
Authors: Hofmann Susanne , Müller Lisa , Harsdorf Stephanie , Langer Christian , Liebisch Peter , Greiner Jochen , Döhner Hartmut , Bunjes Donald 
Published: October 2019

Abstract
Introduction
The role of allogeneic stem cell transplantation (allo-HSCT) in the treatment algorithms for patients with multiple myeloma remains controversial although it is the only potentially curative approach currently available. Here we present the retrospective analysis of 95 allo-HSCT performed between 1994 and 2013 at Ulm University Hospital. We focused on the impact of cytogenetics, graft-versus-host disease (GvHD) and intensity of conditioning on overall survival (OS), progression- free survival (PFS), relapse and non-relapse mortality (NRM).
Study population
Median age at initial diagnosis was 49 years (range 25-64), median age at time of allo-HSCT was 51 years (range 26-65). Median time from initial diagnosis to allo-HSCT was 13 months (range 3-106). Indications for allo-HSCT were 1) primary allo-HSCT after induction therapy (11 pts), 2) planned tandem auto-allo-HSCT (44 pts), 3) relapse after single allo-HSCT (25 pts), 4) relapse after tandem-auto-HSCT (15 pts). The conditioning regimen in 60 pts was a reduced intensity conditioning (RIC), in 35 pts myeloablative conditioning (MAC). In 68 pts cytogenetic data were available: 13 pts were stratified into standard-, 39 pts into the intermediate- and 16 pts into the high-risk group according to the mSMART recommendations.
Results:
Median follow-up was 70 months (95% CI, 64,5-75,5). The estimate 1-, 2- and 5-year OS was 87,4 %, 74,7 % and 46,4 % with a median OS of 36 months (95 % CI, 19,7 -52,2). For both, RIC and MAC median OS was 36 months (95% CI, 24,4–47,6 versus 95% CI, 0-108,4). The cumulative incidence of TRM was not different for RIC and MAC but there was a trend for lower relapse in patients receiving MAC (p=0,0612). With respect to the indication for allo–HSCT outcomes were as follows: Median OS was 89 months for primary allo-HSCT, 47 months for tandem auto-allo-HSCT, 20 months for relapse after auto-HSCT and 26 months for relapse after double auto-HSCT. OS did not differ significantly. Median OS in the standard risk group was 20 months (95% CI, 6,7-33,3), in the intermediate group 41 months (95% CI, 17,3-64,7) and in the high-risk group 7 months (95% CI, 0-14,8), showing no statistical significance. 1-year OS was 61,5% vs 66,7% vs 43,8%, 2-year OS was 35,9% vs 66,7% vs 43,8% and 5-year OS was 35,9% vs 43,2% vs 11,7% (standard vs intermediate vs high risk). The median PFS was 12 months (95% CI 8,4-15,6). 1-year PFS was 49,2%, 2-year PFS 32,9% and 5-year PFS was 21,8%. PFS according to the cytogenetic aberration showed a median PFS of 20 vs 14 vs 5 months, 1-year PFS was 53,8% vs 51,3 % vs 30 %, 2-year PFS with 35,9% vs 30,8% vs 7,5%, and 5-year PFS with 26,9% vs 11,5 % vs 7,5% (standard vs intermediate vs high risk). These differences are not statistically significant.
Considering the impact acute GvHD, OS significantly differed between the groups with no aGvHD or aGvHD grade I and aGvHD grade II-IV with inferior survival for patients suffering from aGvHD grade II-IV. Chronic GvHD had no impact on outcome.
Conclusion
Our data of a 19 year experience in treatment of patients with advanced multiple myeloma with allo-HSCT showed an effective treatment option with a curative potential even for patients after intensive pretreatment including autologous stem cell transplantation. Patients who received MAC had a trend for lower cumulative incidence of relapse compared to RIC without increasing TRM in our study.

Disclosures
No relevant conflicts of interest to declare.