Prognostic impact of pretransplantation transfusion-dependency and serum ferritin level in patients with myelodysplastic syndrome undergoing allogeneic stem cell transplantation: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

We evaluated the impact of pretransplantation transfusion-dependency and serum ferrtin level on the outcome of patients with myelodysplastic syndrome (MDS) receiving allogeneic stem-cell transplantation (allo-SCT). We studied 360 patients reported to the GITMO between 1997 and 2007. According to the WHO criteria, 23 patients were diagnosed as refractory anemia (RA) with or without ringed sideroblasts (6%), 61 patients as refractory cytopenia with multilineage dysplasia (RCMD; 17%), 53 patients as RA with excess blasts, type 1 (RAEB-1; 15%), 107 patients as RAEB-2 (30%) and 116 patients as AML from MDS (31%). There were 229 HLA-matched sibling and 131 unrelated donor SCT. The source of hematopoietic stem cells was peripheral blood in 224 patients and bone marrow in 136. Two hundred nineteen patients received a myeloablative conditioning regimen, whereas a reduced-intensity regimen (RIC) was performed in 141 patients. Regular transfusion need was reported in 223 of 328 evaluable subjects (68%). Transfusion-dependency was independently associated with a reduced overall survival (OS, HR=1.48, P=.017) and increased probability of transplant-related mortality (TRM, HR=1.68, P=.024). The negative impact of transfusion-dependency on survival was noticed only in patients receiving myeloablative conditioning (OS HR 1.76, P=.003; TRM HR 1.70 P=.02) with an inverse relationship between severity of transfusion requirement and both OS (P=.022) and TRM (P=.021). In transfusion-dependent patients receiving myeloablative allo-SCT, pretransplantation serum ferritin level showed a significant effect on OS (P=.02) and TRM (P=.04). This effect was maintained adjusting for both transfusion burden and duration (P=.038 and P=.04 for OS and TRM respectively), suggesting that the negative impact of transfusion-dependency might be determined at least in part by iron overload. Finally, transfusion-dependency was found to be an independent risk factor for acute graft versus host disease in a multivariate regression analysis (P=.04). In conclusion, pretransplantation transfusion-dependency and serum ferritin have prognostic value in MDS patients undergoing myeloablative allo-SCT, through a significant increase in TRM. These results suggest that transfusion dependency should be taken into account in transplant decision-making: patients with a long history of blood transfusion and evidence of iron overload might benefit from a reduced-intensity conditioning.