Long Term Follow-up of the Prospective Multicenter Study of reduced-Intensity Allogeneic Stem Cell Transplantation for Primary or Post ET/PV Myelofibrosis

Abstract 1019

Allogeneic stem cell transplantation is the only curative treatment for myelofibrosis. Here we present a long–term follow up of patients with myelofibrosis treated with reduced-intensity allogeneic stem cell transplantation in the prospective multicenter study conducted by the MDS subcommittee of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT) (study registration NCT 00599547).

From 2002 to 2007, a total of 103 patients with primary (63 pts) or post-polycythemia vera and –essential thrombocythemia myelofibrosis (40 pts) from seventeen transplantation centers in three nations were included in the study. There were 62 males and 41 females with a median age of 55 years (range, 32–68 years). Risk profile according to Lille score was low risk with constitutional symptoms (17%), intermediate risk (53%) and high risk (30%). All but three of the patients received peripheral stem cells as stem cell source from either related (n=33) or unrelated donor (n=70) and a conditioning with Busulfan (10mg/kg orally or 8mg/kg intravenously),Fludarabin (180 mg/m²) and antithymocyte-globulin (ATG-Fresenius®) according a previously published protocol. According to high-resolution HLA typing, 21 patients had at least one allele or antigen HLA mismatch. From 88 patients with a known JAK2V617F-status 63 harbored the mutation.

After a median follow up of 60 months (range 9–109 months), 41 patients had chronic graft vs. host disease which was extensive in the half of cases. The 5-year and 8-year estimated overall survival (OS) was 68% and 65%, respectively with a stable plateau after 5,3 years follow up (Figure-1). Estimated 5-year disease-free survival was 40%. The cumulative incidence of relapse/progression at 3 and 5 years was 22% and 28% and the non-relapse mortality at 1 and at 3 years was 18% ands 21%, respectively.

Figure-1

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Within the overall follow up period, relapse/progression occurred in 28 patients. Twenty one of them were treated with donor-lymphocyte infusions (DLI) and/or a second allogeneic transplantation (n=11). Sixteen of those were at the last follow up alive. The estimated OS of all relapsed patients after a median follow up of 46 months (range 4–62 months) beginning from the time of relapse was 55%.

In multivariate analysis advanced age >55years (HR: 4.69, p=0.001), absence of JAK2V617F mutation (HR: 2.50, p=0.02), mismatched donor (HR: 3.62, p=0.002) were significant independent predictors for reduced OS.

This update of a prospective trial using reduced intensity conditioning followed by allogeneic stem cell transplantation for myelofibrosis confirmed a very good long-term OS. Relapse still occurs in about 30% and remains the main problem after transplantation. However, with adoptive immunotherapy using DLI or even second allogeneic transplantation a second remission with long term survival can be induced in about 50% of the relapsed patients. Developing methods for remission monitoring and early prediction and treatment of relapse should be the focus of future studies.