Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) as a Curative Therapy in Primary and Secondary Myelofibrosis (MF): A 14-Year Period Oligocentric French Experience.
Authors: Lissandre Severine , Bay Jacques-Olivier , Cahn Jean-Yves , Cacheux Victoria , Cabrespine Aurélie , Guyotat Denis , Cassinat Bruno , de Latour Regis Peffault , Socie Gerard , Robin Marie 
Published: April 2020

Abstract
Background: MF patients (pts) with intermediate or high Lille score have a median survival from one to 2 years. After transformation into acute myeloid leukemia (AML), short-term survival is less than 5%. Until now, chemotherapy or other investigative drugs have not been reported to improve survival in pts with primary or secondary MF.
Aim of the study: To describe the outcome of pts who underwent HSCT from 1994 to 2008 in 4 hematological French centers.
Method: Thirty-nine pts with MF were identified. Overall survival (OS) and relapse free survival (RFS) were estimated by Kaplan-Meier method and cumulative incidence of non-relapse mortality (NRM) with relapse as a competing event, by Fine and Gray method (R Sofware).
Patient and disease characteristics: Median age of pts at time of HSCT was 49 years (15–65). Twenty-seven pts had primary MF whereas 12 patients had MF secondary to polycythemia vera (PV) (n=7) or to essential thrombocythemia (ET) (n= 5). Among 25 pts with a cytogenetic analysis, 12 had clonal abnormalities. A JAK2 mutation was detected in 6 out of 22 tested patients (3/13 primitive MF, 1/2 MF secondary to TE and 2/3 MF secondary to PV). Treatment before transplantation mainly consisted of hydroxyurea or busulfan (26 pts). Before HSCT, 12 pts required platelet transfusions and 19 required blood transfusions. Twenty-three pts experienced a splenectomy in median 3 months before HSCT. Ten patients were transformed in AML before HSCT. Dupriez score was low in 9, intermediate in 16 and high in 14 pts at time of transplantation.
Results: 25 pts received a HSCT from an HLA-identical sibling and all pts were transplanted with an HLA matched donor (3 9/10 HLA identities). Fifteen pts received a myeloablative conditioning regimen (MAC) and 24 received a fludarabine-based reduced intensity conditioning regimen (RIC). Graft-versus-Host disease (GVHD) prophylaxis consisted of cyclosporine plus mycophenolate in 21, cyclosporine plus methotrexate in 13 and cyclosporine alone in 5 pts. All but one pts engrafted in median 15 days (range:0–129) after transplantation. Median follow-up after HSCT was 729 days (79–1004). Thirty-one pts developed grade I-IV acute GVHD. Among 35 evaluable pts, 18 developed a chronic GVHD. Median time to discharge was shorter with RIC regimen (23 days) than with MAC regimen (46 days). Median OS was estimated at 4 years and 8 months. Three-year OS was 61% (95%Confidence Interval (CI): 47–80). 3-year RFS was 55% (41–75). 3-year NRM, was similar with RIC or MAC (32% (95%CI: 12–51) versus 20% (1–39). OS was not correlated to pre-transplantation Dupriez score (Low, OS: 57% (95%CI: 29–100)/Intermediate: 73% (95%CI: 53–99)/High: 56% (95%CI: 35–90)). Splenectomy, age, sex mismatch, CMV serology, conditioning regimen (RIC vs MAC) had no impact on outcome. Transformation into acute AML before HSCT was not a significant marker for poor OS (OS at 64%(95%CI: 48–85) versus 53% (95%CI: 18–28)). Patients who received platelet transfusions before HSCT had poorer OS: 25% (95%CI: 9–67) versus 78% (95%CI: 64–97), p &lt; 0.0001).
Conclusion: In these high risk MF pts, median OS after HSCT is much better than reported with alternative treatment. The main risk factor for poor outcome is thrombocytopenia requiring platelet transfusion before transplantation whereas other usual risk factors have no more impact after HSCT.