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

BackgroundTransfusion-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 MethodsWe 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. ResultsTransfusion-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. ConclusionsPre-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.

Clinical significance of pretransplant serum ferritin on the outcome of allogeneic hematopoietic SCT: a prospective cohort study by the Kanto Study Group for Cell Therapy

“…We and other groups have previously demonstrated that high serum ferritin levels before HSCT may reduce OS and EFS after HSCT. [1][2][3][4][5][6][7][8][21][22][23][24] To the best of our knowledge, the present study is the first to confirm these findings using a large prospective cohort.…”

“…Recent studies have demonstrated that pretransplant iron overload, defined as elevated serum ferritin levels, is associated with worse OS, disease-free survival and non-relapse mortality (NRM) and with an increased risk of infection in patients undergoing allogeneic HSCT. [1][2][3][4][5][6][7][8][9] Liver dysfunction caused by iron overload 10 and neutrophil dysfunction with an increase in non-transferrin-bound iron levels 11,12 may have a negative impact on HSCT outcomes. However, most previous studies involved retrospective analyses of patients with heterogeneous diseases.…”

Correction of Severe Anemia in a Patient with End Stage Renal Disease and Myelodysplastic Syndrome

“…Most of the patients with MDS become transfusion dependent. Secondary iron overload from frequent red blood cell transfusions and poor iron incorporation into red blood cells (RBCs) is associated with poor survival in these patients [2]- [4]. Transfusion requirement has been recently recognized as an independent prognostic factor for survival in MDS patients [5].…”

The Impact of Iron Overload on Transplant-Related Complications and Prognosis of Acute Leukemias.

“…27 Pretransplantation serum ferritin may have significant prognostic value in patients with MDS undergoing myeloablative allogeneic HSCT, inducing a significant increase of non-relapse mortality. 5 Thus, iron status could be considered in transplantation decision-making in MDS. Iron burden might influence toxic-infectious complications during the first 3 months after transplant in auto-transplanted patients.…”

“…4 Iron overload or hyperferritinemia irrespective of body iron status may have detrimental effects on the transplantation procedures. [5][6][7][8] Iron overload is associated with free radical generation leading to tissue damage. 9 There is also a possibility that the adverse prognostic impact of pre-transplant hyperferritinemia might be ascribed to other precipitating factors in addition to the iron overload.…”