Busulfan or thiotepa based conditioning in myelofibrosis: a phase II multicenter randomized study from the GITMO group

We are reporting a randomized study comparing fludarabine in combination with busulfan (FB) or thiotepa (FT), as conditioning regimen for hematopoietic stem cell transplantation (HSCT) in patients with myelofibrosis. The primary study endpoint was progression-free survival (PFS). Sixty patients were enrolled with a median age of 56 years and an intermediate-2 or high-risk score in 65%, according to the Dynamic International Prognostic Staging System (DIPSS). Donors were HLA-identical sibling (n=25), matched unrelated (n=25) or single allele mismatched unrelated (n=10). With a median follow-up of 22 months (range 1-68), the following outcomes at 2 years after HSCT in the FB vs. the FT arm were as follows: PFS 43% vs 55%, (P=.28), overall survival (OS) 54% vs. 70% (P=.17), relapse/progression 36% vs 24% (P=.24), non-relapse mortality (NRM) 21% in both arms (P=.99) and graft failure 14% vs. 10% (P=.96). A better PFS was observed in patients with intermediate-1 DIPSS score (P=.03). Neutrophil and platelet engraftment was significantly influenced by prior splenectomy [HR 2.28 (95% CI, 1.16-4.51) P=.02] and splenomegaly at transplant [HR 0.51 (95% CI, 0.27-0.94) P=.03]. In conclusion, the clinical outcome after HSCT was comparable when using either a busulfan or thiotepa based conditioning regimen.