Reduced‐intensity conditioning allogeneic transplant with dual T‐cell depletion in myelofibrosis

Abstract

Background There remains a significant mortality in recipients with MF who undergo allogeneic stem cell transplant (allo‐HSCT). The combination of antithymocyte globulin (ATG) and post‐transplant cyclophosphamide (PTCy) provides good control of graft‐versus‐host disease (GVHD) when peripheral blood stem cell grafts are used. Methods We report the outcome of 37 recipients with myelofibrosis who underwent reduced‐intensity conditioning (RIC) allo‐HSCT with ATG and PTCy. Median follow‐up was 16.4 months. Results Nine (24.3%) recipients received 10/10 MRD grafts, 17 (45.9%) 10/10 MUD grafts, 4 (10.8%) 9/10 MUD grafts, and 7 (18.9%) haploidentical donor grafts. Six (16.3%) patients had graft failure. The cumulative incidence of grade II‐IV and grade III‐IV aGVHD at day +100 and moderate/severe chronic GVHD at 1 year was as follows: 13.5%, 5.4%, and 17%. There were no deaths secondary to GVHD. One‐year overall survival (OS), relapse‐free survival (RFS), non‐relapse mortality (NRM), and GVHD‐free/RFS (GRFS) were respectively 74.4%, 71.3%, 23%, and 43.3%. Those recipients who had worse KPS ≤ 80% had worse OS and RFS. Conclusion RIC allo‐HSCT with ATG and PTCy results in high OS and RFS in patients with myelofibrosis and absence of mortality secondary to GVHD. Further investigations are required to reduce NRM and graft failure rates.

Improved donor chimerism in relapse myelofibrosis post allogenic stem cell transplant with azacitidine and oral decitabine—First case report

“…Despite advances in allogenic stem cell transplant (ASCT), relapse following ASCT for MF remains concerning [ 1 , 2 ]. The type of donor such as a haploidentical‐donor can have an impact on outcomes such as non‐relapse mortality and graft failure [ 3 , 4 ]. However, once disease relapse (DR) occurs post‐ASCT, treatment options are limited to donor lymphocyte infusion (DLI) and second ASCT; and overall survival (OS) is poor [ 1 , 2 , 3 , 4 ].…”

2021 Update on allogeneic hematopoietic stem cell transplant for myelofibrosis: A review of current data and applications on risk stratification and management

“… 28 A transient hyperbilirubinemia has been reported in MF patients receiving ATG, with no effect on non‐relapse mortality (NRM). 29 Other regimens for GvHD prophylaxis in patients with MF, have been the combination of ATG and post‐transplant cyclophosphamide (PTCY), 30 ruxolitinib and PTCY, 31 peritransplant ruxolitinib, 32 and tacrolimus‐sirolimus, with or without methotrexate (MTX). 33 In these studies, the risk of acute GvHD grade III‐IV ranges between 10% and 60%, and the risk of moderate/severe chronic GvHD, requiring treatment, between 15% and 60%.…”

Allogeneic Hemopoietic Stem Cell Transplantation for Myelofibrosis: 2021

“…However, modified regimens of GvHD prophylaxis, including the use of post-transplant cyclophosphamide (PT-CY) have reduced post-transplant complications in alternative donor grafts, especially for HLA haplo-identical donor ( 36 ). A combination of calcineurin inhibitor with ATG and PTCy after reduced intensity conditioning may further reduce the risk of GvHD, improving TRM and survival, without an increased risk of relapse ( 41 ). Very recently, an interesting pilot study was conducted by Morozova and colleagues: GvHD prophylaxis with PTCY and ruxolitinib showed promising results in terms of GvHD control in a small cohort of patients with acceptable TRM ( 42 ).…”