title: Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: A report from the multi-center study of iron overload.
abstract: 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 Thal 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.
authors.affiliation: Department of Hematology, Children's Hospital & Research Center, Oakland, California, USA. efung@mail.cho.org
authors.forename: Ellen B
authors.initials: EB
authors.lastname: Fung
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.forename: Meredith
authors.initials: M
authors.lastname: Milet
authors.forename: Samir K
authors.initials: SK
authors.lastname: Ballas
authors.forename: Laura
authors.initials: L
authors.lastname: De Castro
authors.forename: Ward
authors.initials: W
authors.lastname: Hagar
authors.forename: William
authors.initials: W
authors.lastname: Owen
authors.forename: Nancy
authors.initials: N
authors.lastname: Olivieri
authors.forename: Kim
authors.initials: K
authors.lastname: Smith-Whitley
authors.forename: Deepika
authors.initials: D
authors.lastname: Darbari
authors.forename: Winfred
authors.initials: W
authors.lastname: Wang
authors.forename: Elliott
authors.initials: E
authors.lastname: Vichinsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000150:complications / Q000401:mortality / Q000628:therapy; D002170:Canada / Q000453:epidemiology; D002648:Child; D015331:Cohort Studies; D017707:Erythrocyte Transfusion / Q000009:adverse effects* / Q000401:mortality; D005260:Female; D005293:Ferritins / Q000097:blood; D006760:Hospitalization; D006801:Humans; D019190:Iron Overload / Q000209:etiology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D013789:Thalassemia / Q000150:complications / Q000401:mortality / Q000628:therapy; D014481:United States / Q000453:epidemiology
chemical_list: D005293:Ferritins