Morbidity and mortality in chronically transfused subjects with Thalassemia and Sickle Cell Disease: A report from the multi-center study of iron overload


Ellen B. Fung, UCSF Benioff Children's Hospital Oakland
Paul Harmatz, UCSF Benioff Children's Hospital Oakland
Meredith Milet, UCSF Benioff Children's Hospital Oakland
Samir K. Ballas, Thomas Jefferson University
Laura De Castro, Duke University Medical Center
Ward Hagar, UCSF Benioff Children's Hospital Oakland
William Owen, Children's Hospital of The King's Daughters Health System
Nancy Olivieri, Toronto General Hospital
Kim Smith-Whitley, The Children's Hospital of Philadelphia
Deepika Darbari, The Center For Sickle Cell Disease
Winfred Wang, St. Jude Children's Research Hospital
Elliott Vichinsky, UCSF Benioff Children's Hospital Oakland
Vinod Balasa, Cincinnati Children's Hospital Medical Center
Rita Bellevue, New York Methodist Hospital
James Cassela, John Hopkins Medical Center
Thomas Coates, Children's Hospital Los Angeles
Charles Davis, Egleston Scottish Rite Children's Health Care System
Patricia Giardina, Weill Cornell Medicine
Lee Hilliard, The University of Alabama at Birmingham
Jeffrey Hord, Akron Children's Hospital
Michael Jeng, Stanford University
Melody Kirby, Hospital for Sick Children University of Toronto
Abdullah Kutlar, Medical College of Georgia
Kenneth McClain, Baylor College of Medicine
William Mentzer, University of California, San Francisco
Robert Mignaca, Children's Hospital Central California
Charles Pegelow, University of Miami
John Porter, University College London
Gloria Ramirez, St. Luke's-Roosevelt Hospital Center
Mark Ranalli, Nationwide Children’s Hospital
Sreedhar Rao, SUNY Downstate Health Sciences University
Charles Scher, Tulane Medical Center
Frank Shafer, St. Christopher's Hospital for Children Philadelphia
Mary Gail Smith, University of Mississippi Medical Center

Document Type


Publication Date



A natural history study was conducted in 142 Thalassemic (Thal), 199 transfused Sickle Cell Disease (Tx-SCD, n = 199), and 64 non-Tx-SCD subjects to describe the frequency of iron-related morbidity and mortality. Subjects recruited from 31 centers in the US, Canada or the UK were similar with respect to age (overall: 25 ± 11 years, mean ± SD) and gender (52% female). We found that Tx-SCD subjects were hospitalized more frequently compared with Thai or non-Tx-SCD (P < 0.001). Among those hospitalized, Tx-SCD adult subjects were more likely to be unemployed compared with Thal (RR = 1.6, 95% CI 1.0-2.5) or non-Tx-SCD (RR = 3.1, 95% CI 1.3-7.3). There was a positive relationship between the severity of iron overload, assessed by serum ferritin, and the frequency of hospitalizations (r = 0.20; P = 0.009). Twenty-three deaths were reported (6 Thal, 17 Tx-SCD) in 23.5 ± 10 months of follow-up. Within the Tx-SCD group, those who died began transfusion (25.3 vs. 12.4 years, P < 0.001) and chelation therapy later (26.8 vs. 14.2 years, P = 0.01) compared with those who survived. The unadjusted death rate in Thal was lower (2.2/100 person years) compared with that in Tx-SCD (7.0/100 person years; RR = 0.38: 95% CI 0.12-0.99). However, no difference was observed when age at death was considered. Despite improvements in therapy, death rate in this contemporary sample of transfused adult subjects with Thal or SCD is 3 times greater than the general US population. Long term follow-up of this unique cohort of subjects will be helpful in further defining the relationship of chronic, heavy iron overload to morbidity and mortality. © 2006 Wiley-Liss, Inc.

This document is currently not available here.