Published online 10 November 2009
Haematologica, Vol 95, Issue 3, 476-484 doi:10.3324/haematol.2009.011429
Copyright © 2010 by Ferrata Storti Foundation

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Stem Cell Transplantation

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

Emilio Paolo Alessandrino¹, Matteo Giovanni Della Porta¹, Andrea Bacigalupo², Luca Malcovati¹, Emanuele Angelucci³, Maria Teresa Van Lint², Michele Falda⁴, Francesco Onida⁵, Massimo Bernardi⁶, Stefano Guidi⁷, Barbarella Lucarelli⁸, Alessandro Rambaldi⁹, Raffaella Cerretti¹⁰, Paola Marenco¹¹, Pietro Pioltelli¹², Cristiana Pascutto¹, Rosi Oneto², Laura Pirolini¹³, Renato Fanin¹⁴, Alberto Bosi⁷

¹ Department of Hematology Oncology, University of Pavia, Fondazione Policlinico San Matteo, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Pavia;
² Division of Hematology, Ospedale San Martino, Genova;
³ Hematology and Bone Marrow Transplantation Unit, Ospedale Oncologico di Riferimento Regionale "Armando Businco", Cagliari;
⁴ Division of Hematology, Ospedale San Giovanni Battista, Torino;
⁵ Department of Hematology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano;
⁶ Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milano;
⁷ Department of Hematology, University of Florence, Florence
⁸ Division of Hematology, Department of Cellular Biotechnologies and Hematology, University La Sapienza, Roma;
⁹ Division of Hematology, Ospedali Riuniti, Bergamo;
¹⁰ Hemato-Oncology Transplant Unit, University Tor Vergata, Roma;
¹¹ Department of Hematology, Ospedale Niguarda Ca’ Granda, Milano;
¹² Division of Hematology and Transplant Unit, Ospedale San Gerardo, University of Milano-Bicocca, Monza;
¹³ Department of Clinical Chemistry, Fondazione IRCCS Policlinico San Matteo, Pavia and
¹⁴ Division of Hematology and Bone Marrow Transplantation, University of Udine, Udine, Italy

Correspondence: Emilio Paolo Alessandrino, MD, Department of Hematology Oncology, Fondazione, IRCCS Policlinico San Matteo and University of Pavia, Piazzale Camillo Golgi, 2, 27100 Pavia, Italy. E-mail: alessandrino{at}smatteo.pv.it

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.

Key words: transfusion-dependency, myelodysplastic syndromes, secondary iron overload.

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