Allogeneic Stem Cell Transplantation in Idiopathic Myelofibrosis: The Italian Experience.

Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative treatment for idiopathic myelofibrosis (IM), but it is associated with a high transplantation-related (TRM) mortality rate, especially in advanced and elderly patients. Recently, reduced-intensity conditioning (RIC) regimens were reported to be feasible in these subgroups of patients. Herein, we reported a preliminary analysis of the data of the Gruppo Italiano Trapianto Midollo Osseo (G.I.T.M.O.) Registry regarding a total of 92 patients with IM, who underwent allogeneic HSCT in 25 different Italian Transplant Centres between 1986 and 2005. One Centre performed 26 transplants, 4 Institutions performed between 6 and 10 transplants and the other 20 Centres realized five or less procedures. Ten transplants (11 %) were performed before 1995, 26 (28%) between 1996 and 2000 and 56 (61%) between 2001 and 2005. Sixty patients (65%) were male and median age was 49 years ( range 21–68). Thirty-nine patients (42%) were older than 50 and 8 older than 60 years. Forty-four (48%) received myeloablative conditioning and 48 (52%) a RIC regimen. Myeloablative conditioning was based on cyclophosphamide plus thiotepa ( 42% of the patients) or busulfan (37%) or total body irradiation at the dose of 10–12 Gy (21%). RIC transplants consisted of a combination of fludarabine and 2 Gy TBI (44%) or cyclophosphamide (4%) or busulphan (4%) or an association of thiotepa and cyclophospamide (48%). GVHD prophylaxis included cyclosporin-A and short-course methotrexate, with the association of ATG in 11 patients. Stem cells came from matched sibling donors for 70 patients (76%), missmatched sibling donors for 10 patients (11%) and from matched unrelated donors for the remaining 12 patients (13%). Forty-nine patients (53%) received BM cells and the other 53 cases (47%) PBSC. Seventy-eight out 92 (85%) achieved full engrafment. One-year TRM was 35%. Causes of TRM were as following: GVHD (33% of the patients), infections (36%), bleeding (12%), veno-occlusive disease (3%), thrombotic thrombocytopenic purpura (6%). We observed a trend of higher TRM rate in patients transplanted before 2000 in comparison with those transplanted later (48% vs 33%). However, other potential risk factors for TRM, such as patient age > 50 years, conventional conditioning and unrelated or mismatched donors did not significantly increase TRM rate. There are 43 patients (47%) alive 12 to 156 months after transplantation ( median, 35 months).

We conclude that, albeit TRM rate has been lowered in transplants performed in the last 5 years, it still involves one-third of the patients and remains a matter of concern. The ongoing analysis will focus on the impact of the clinical and biological factors at transplant on the outcome of the patient population.