Myelofibrosis: 15 Years of Allogeneic Transplantation - Single Center Experience

Background: Myelofibrosis (MF) is a clonal hematopoietic stem cell disorder associated with a significative risk of evolution to acute leukemia. It can either present as primary disease or secondary to other myeloproliferative neoplasms. It's predominantly a disease of the elderly, with a median age at diagnosis of 65 years. Pharmacological therapy directed at symptom control has not shown to improve survival and, despite therapeutic advances with the Janus-Kinase (JAK) inhibitors, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potentially curative treatment. Due to most patients advanced age and comorbidities, increased risk of graft failure, HSCT is challenging and requires specialized teams.

Aim: To assess the results of allo-HSCT in myelofibrosis patients in our center and identify prognostic factors.

Methods: Observational retrospective study including patients with previous diagnosis of MF (primary or secondary), referred to our center who underwent allo-HSCT between May 2001 and May 2016. Pre-transplant DIPSS, HCT-CI and Lille scores were applied. Neutrophil and platelet engraftment were defined as the first of three and seven consecutive days above 500/μL and 20,000/μL respectively. Correlations between factors were calculated using Spearman's rho (ρ). Survival was estimated using Kaplan-Meyer method. Statistical significance was defined as p<0.05.

Results: In time period, 21 patients were transplanted in our center, with a median age of 51 years (21-67y); male:female ratio 1:1.1. Six patients had a previous story of Essential Thrombocytemia (ET). At diagnosis splenomegaly was present in 18 patients, 6 of them having been submitted to splenectomy and 5 of them having achieved spleen reduction with pharmacological therapy (hydroxicarbamide or ruxolitinib). Previous lines of treatment also included best supportive care, erythropoietin, danazol, interferon, and anagrelide. Prognostic score DIPSS was Intermediate-1 in 10 patients and intermediate-2 in the remaining 11. Thirteen had HCT-CI score of zero, 4 of 1 and 3 of 2. Eight patients had a Lille score of zero, 8 of 1, and 3 scored 2 points. Conditioning regimen was applied as follows: 11 patients had fludarabin-busulphan based reduced intensity (RIC) regimen, and the remainder had busulfan-cyclophosphamide based myeloablative (MAC) regimen. All patients underwent allo-HSCT, 18 from matched related donor and 3 from matched unrelated donor. Median time to neutrophil and platelet engraftment was 14.0 days (8;28) and 14.0 days (5;41) respectively. A significant correlation between time to neutrophil engraftment and overall survival (OS) (ρ=-0.589; p=0.006). Ten patients developed chronic GVHD. At present time 12 patients are alive, 11 in hematological remission. Median Karnofsky score is 90% (60-90). Median overall survival is 50 months; survival at 5 year is 90%. Nine patients died (8 due to transplant related complications). No statistical significant difference for OS was found comparing primary vs secondary MF, splenomegaly, JAK2 status, MAC or RIC and DIPSS risk categories. No graft failure occurred. Neither donor lymphocyte infusions nor second transplants were performed.

Conclusion: MF remains a very challenging condition to treat with a very poor prognosis. Shorter neutrophil engraftment was correlated with better OS. Often, older patients are not eligible for more aggressive therapies. In our group of patients there were no significant statistical differences in OS between the use of MAC or RIC. No other prognostic factors were found in this analysis, having to be taken into account its small size.