Prognostic impact of pre-transplantation transfusion history and secondary iron overload in patients with myelodysplastic syndrome undergoing allogeneic stem cell transplantation: a GITMO study

Abstract

Background: Transfusion-dependency affects the natural history of myelodysplastic syndromes. Secondary iron overload may concur to this effect. The relative impact of these factors on the outcome of patients with myelodysplastic syndrome receiving allogeneic stem-cell transplantation remains to be clarified.

Design and methods: We retrospectively evaluated the prognostic effect of transfusion history and iron overload on the post-transplantation outcome of 357 patients with myelodysplastic syndrome reported to the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) registry between 1997 and 2007.

Results: Transfusion-dependency was independently associated with reduced overall survival (hazard ratio=1.48, P=0.017) and increased non-relapse mortality (hazard ratio=1.68, P=0.024). The impact of transfusion-dependency was noted only in patients receiving myeloablative conditioning (overall survival: hazard ratio=1.76, P=0.003; non-relapse mortality: hazard ratio=1.70, P=0.02). There was an inverse relationship between transfusion burden and overall survival after transplantation (P=0.022); the outcome was significantly worse in subjects receiving more than 20 red cell units. In multivariate analysis, transfusion-dependency was found to be a risk factor for acute graft-versus-host disease (P=0.04). Among transfusion-dependent patients undergoing myeloablative allogeneic stem cell transplantation, pre-transplantation serum ferritin level had a significant effect on overall survival (P=0.01) and non-relapse mortality (P=0.03). This effect was maintained after adjusting for transfusion burden and duration, suggesting that the negative effect of transfusion history on outcome might be determined at least in part by iron overload.

Conclusions: Pre-transplantation transfusion history and serum ferritin have significant prognostic value in patients with myelodysplastic syndrome undergoing myeloablative allogeneic stem cell transplantation, inducing a significant increase of non-relapse mortality. These results indicate that transfusion history should be considered in transplantation decision-making in patients with myelodysplastic syndrome.

Figure 1.

Post-transplantation outcome according to the presence of transfusion-dependency. Probability of OS and NRM after allogeneic hematopoietic SCT in the whole MDS population (A, B, respectively) and in patients receiving myeloablative conditioning (C, D, respectively). The curves were estimated from multivariable Cox regression analysis adjusted for the patients’ age and sex, WHO category, cytogenetics, disease status at transplant, presence of comorbidities, source of stem cells, type of donor and type of conditioning.

Figure 2.

Post-transplantation outcome of MDS patients receiving standard conditioning according to transfusion burden: probability of overall survival, (A) and non-relapse mortality, (B). Patients were categorized as receiving 20 or fewer, 20–40, or more than 40 PRBC units. The curves were estimated from multivariable Cox regression analysis adjusted for patients’ age and sex, WHO category, cytogenetics, disease status at transplant, presence of comorbidities, duration of transfusion dependency, source of stem cells and type of donor.

Figure 3.

Post-transplantation outcome of transfusion-dependent patients receiving standard conditioning according to serum ferritin level: probability of overall survival, (A) and non-relapse mortality, (B) Patients were categorized as follows: serum ferrtin <1000 ng/mL, 1000–1999 ng/mL, 2000–3000 ng/mL and >3000 mg/mL. The curves were estimated from multivariable Cox regression analysis adjusted for patients’ age and sex, WHO category, cytogenetics, disease status at transplant, presence of comorbidities, source of stem cells and type of donor.