Moderate to Severe Marrow Fibrosis As a More Advanced Risk Factor for MDS and MDS-AML Patients With Excess of Blasts Receiving Allogeneic Hematopoietic Stem Cell Transplantation

ABSTRACT

Marrow fibrosis (MF) is usually accompanied with primary myelodysplastic syndromes (MDS) and no consensus has been reached on the relationship between MF and prognosis. We retrospectively analyzed 239 MDS and MDS derived acute myeloid leukemia patients with known grade of MF who received allogeneic stem cell transplantation (allo-HSCT). Of these, it included 121 (50.6%) without fibrosis (MF-0), 81 (33.9%) with mild fibrosis (MF-1), 37 (15.5%) with moderate to severe fibrosis (MF-2/3). MF-2/3 was associated with more pronounced dysmegakaryopoiesis (P =.002), more frequent karyotype abnormality (P = .039) and increased leukemic transformation. Spliceosome and ras pathway mutation occurred more frequently in patients with MF-2/3. After allo-HSCT, neutrophil and platelet engraftment was significantly delayed in patients with MF-2/3 than those with MF-1 and MF-0 (P = .031, P = .05, respectively). The estimated 3-year overall survival (OS) rates and disease-free survival (DFS) rates were significantly lower in patients with MF-2/3 than in those with MF-0 or MF-1 (P = .018, P = .018, respectively). Notably, in the subgroup of patients with more than 10% bone marrow blasts, MF-2/3 was independently associated with shorter OS and DFS (P = .012, P = .012, respectively) and has improved outcomes for these patients who achieved complete remission (CR) before allo-HSCT. Overall, MF-2/3 as an additional risk factor have the inferior prognosis for MDS and MDS-AML patients with bone marrow blasts ≥10%. Using pretransplantation cytoreductive therapy to obtain CR for these patients may benefit from allo-HSCT.