Allogeneic Hematopoietic Stem Cell Transplantation for Myelofibrosis.

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.

To prospectively study the safety and efficacy of reduced intensity HCT in patients with myelofibrosis.

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. Fifteen 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 x 3 (day -3,-2 and 1) was additionally given to patients receiving unrelated donor graft. Because of high incidence of relapse, Busulfan dose was increased to a target AUC of 4000 μmol/L or a fixed dose of 100mg/m2 × 4 (days -5, -4, -3 -2) in 11 patients. Tacrolimus and mini Methotrexate were used as graft versus host disease prophylaxis. All patients received standard supportive care.

Between 6/2005 and 07/2009, 26 consecutive patients with myelofibrosis were treated. There were 13 males and 13 females with a median age of 58 (range 27-74). Seventeen patients had primary MF, 3 post PV MF and 6 Post ET MF. Based on Lille criteria, 14 patients had intermediate risk disease and 12 had high risk disease. Ten patients had splenectomy prior to transplant; remaining 16 patients had enlarged spleen at the time of transplant. Fourteen patients had mutated Jak 2. Median peripheral blood CD 34 count was 57/μl(range 1-3770/μl). Karyotype was abnormal in 11 patients and diploid in 15. Donors were matched siblings for 10 patients, matched unrelated for 12, and one antigen or allele mismatched unrelated for 4 patients. Stem cell source was marrow in 3 and peripheral blood in 23.

All patients engrafted with a median time to neutrophil engraftment of 13 days (0-27) days) and a median time to platelet engraftment of 24 (0-105) days. Jak 2 positive patients achieved molecular remission post transplant with negative JaK 2. With a median follow up of 21 (1-43) months, 2 year overall and event free survival are 71% (SE 10%) and 46% (SE 11%), respectively. Cumulative incidence of non relapse mortality was 14% (SE 7%). Cumulative incidence of relapse was 39% (SE10%). Eight patients relapsed; 3 in blast phase and 5 in chronic phase. Four of these 8 are currently disease free after a second transplant. Including these 4 patients, 18 out of 26 patients are currently disease free. These include 10 of 11 patients treated with higher dose of busulfan compared with 8 of 15 patients treated with lower busulfan dose.

RISCT induces molecular remission with very low non relapse mortality in older patients with myelofibrosis, but the relapse rate is high. Increasing the intensity of conditioning regimen may reduce the relapse risk and needs to be studied further.

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No relevant conflicts of interest to declare.