First prospective study of allogeneic peripheral blood stem cell (PBSC) transplantation in patients with myelofibrosis in the United States: Interim analysis of MPD-RC 101 protocol.

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6535 Background: The Myeloproliferative Disorder-Research Consortium (MPD-RC) designed the first U.S. prospective phase II study of allogeneic PBSC transplantation in patients with primary myelofibrosis (PMF) or MF secondary to essential thrombocythemia (ET-MF) or polycythemia vera (PV-MF). Methods: Between April 2007 and December 2009, 42 patients were transplanted with HLA matched PBSC from related (MRD) (n = 23) or unrelated (MUD) (n = 19) donors. A regimen with fludarabine/melphalan (FluMel) ± ATG was used. Patients with PMF (n = 25), ET-MF (n = 13) or PV-MF (n = 4) were all at intermediate/high risk according to the Lille score system and the majority had grade 3 marrow fibrosis. Median age was 54 years (range: 36-64). Splenomegaly was present in 79% of the patients while 17% had prior splenectomy. Results: Neutrophil and platelet engraftment occurred on d26 (range: 9-57) and d27 (range: 9-365), respectively. Graft failure/rejection occurred in 5 MUD patients. At a median follow-up of 185 days (range: 15-742), 78% of MRD patients are alive; 9 of 19 MUD cases (47%) died and 3 were taken off study. Causes of death in 5 cases in the MRD group were: GVHD (n = 2), hemorrhage, secondary cancer and relapse; and in 9 cases in the MUD group were: GVHD (n = 2), hemorrhage (n = 2), renal failure (n = 2), pulmonary toxicity, venous occlusive disease and infection. Acute GVHD ≥ grade 2 in MRD and MUD was 45% (15% grade 3-4) and 47% (10% grade 3-4), respectively. Overall clinical response according to the International Working Group criteria in patients with > 6 months follow-up in the MRD group was 79%, with CR/PR 47% and clinical improvement 32%.Transplant-related mortality (TRM) was 13%. Analysis of response rate in MUD cases has been limited by the high TRM (47%). Overall and event-free survival were superior in MRD vs MUD transplants (p = 0.005). Conclusions: Our initial findings confirm that FluMel regimen is effective and causes low toxicity in MRD transplant in MF patients. The higher TRM observed in MUD transplants may suggest a need for a more reduced intensity chemotherapy in this setting. No significant financial relationships to disclose.