Myelofibrosis and Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation (RISCT).

Background: Reduced intensity allogeneic transplantation was developed to harness graft versus leukemia immune effect to treat older patients and patients with comorbidities who are not eligible for conventional myeloablative transplant. Limited but encouraging data are available on outcome of patients with myelofibrosis undergoing this therapy. We therefore sought to prospectively study the safety and efficacy of reduced intensity HCT in patients with myelofibrosis.

Methods: Patients with intermediate or high risk MF were eligible if they had adequate organ function and at least 9/10 matched related or unrelated donor. Patients were conditioned with Fludarabine 40mg/m² × 4 (days −5, −4, −3 −2) and Busulfan 130mg/m2 × 2 (day −3,−2). Thymoglobulin 2.5 mg/kg × 3 (day −3,−2 and −1) was additionally given to patients receiving unrelated donor graft. Tacrolimus and mini Methotrexate were used as graft versus host disease prophylaxis. All patients received standard supportive care.

Results: Twelve consecutive patients with myelofibrosis were enrolled between 1/2006 and 7/2007. There were 6 males and 6 female with a median age of 59 (range 40–65). Four patients had primary MF, 3 post PV MF and 5 Post ET MF. Based on Lile criteria, 8 patients had intermediate risk disease and 4 had high risk disease. Eight patients had circulating blasts (1%-8%). Six patients had splenectomy prior to transplant; median spleen size was 15 cms (range 5–28cms) below the costal margin in the remaining 6 patients. Seven patients had mutated Jak 2. Median peripheral blood CD 34 count was 77/μl (range 2–3770/μl). Karyotype was abnormal in 6 patients and diploid in 6. Donors were siblings for 3 patients, matched unrelated for 6, and one antigen or allele mismatched unrelated for 3 patient. All but 1 patient received peripheral blood stem cells. All patients engrafted with a median time to neutrophil engraftment of 13 days (0–27) days) and a median time to platelet engraftment of 14 (0–74) days. Day 100 non relapse mortality was 0%. One patient developed grade 3 acute graft versus host disease (GVHD) and died. One patient developed limited chronic GVHD. All Jak 2 positive patients achieved molecular remission post transplant with negative JaK 2. Three patients relapsed: 2 in blast phase and 1 in chronic phase. With a median follow up of 177 (29–563) days, six month overall survival is 87%.

Conclusion: RISCT induces molecular remission with very low non relapse mortality in older patients with myelofibrosis.