Australasian Trends in Allogeneic Stem Cell Transplantation for Myelofibrosis in the Molecular Era: A retrospective analysis from The Australasian Bone Marrow Transplant Recipient Registry.

Abstract

To review the updated trends of national practice and outcomes in transplanting myelofibrosis, we retrospectively evaluated 142 patients who underwent allogeneic hematopoietic stem cell transplantation for primary (n=94) or secondary (n=48) myelofibrosis (MF) at Australian/New Zealand transplant centers between 2006 and 2017. Median follow-up was 51.8 months (range: 3.1-148). Median age at allo-SCT was 56 years (range: 26-69). Fifty-two percent had HLA-identical sibling donors and 45% had matched unrelated donors (UD). Conditioning was predominantly reduced intensity (83%). Before transplant, 16% had splenectomy or splenic irradiation and 54 patients (38%) received JAK inhibitors. JAK2 mutation testing was performed in 66.9% of patients whilst other mutations CALR, MPL, ASXL1, SRSF2, U2AF1Q57, EZH2 and IDH1/2 were rarely tested (1.4-8.4%). Only 4.2% of patients had next generation sequencing mutation analysis. Median time to neutrophil engraftment was 19 days (range: 10-43) and median time to platelet engraftment was 27 days (range: 13-230). The cumulative incidences of grade II-IV acute graft-versus-host disease (GvHD) were 21.4% at 100 days and that of extensive chronic GvHD at 5 years was 18.1%. Overall survival (OS) was 67% at 1 year and 57% at 5 years. GvHD-free, relapse-free survival was 54% at 1 year and 42% at 5 years. The cumulative incidence of non-relapse mortality (NRM) was 16% at 100 days and 25% at 1 year. In multivariate analysis, age ≥ 65 years and use of an UD were significant unfavourable risk factors for OS and NRM. Use of an UD increased the incidence of acute GvHD whereas antithymocyte globulin/ alemtuzumab lowered the risk of both acute GvHD and chronic GvHD. Pretransplant splenectomy/splenic irradiation had a positive influence on time to engraftment. There have been no improvements in MF allo-SCT outcomes in Australasia in the last decades with low uptake of molecular genomic technology due to limited funded access.