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; Paul Harmatz; Meredith Milet; Samir K. Ballas; Laura De Castro; Ward Hagar; William Owen; Nancy Olivieri; Kim Smith-Whitley; Deepika Darbari; Winfred Wang; Elliott Vichinsky; Vinod Balasa; Rita Bellevue; James Cassela; Thomas Coates; Charles Davis; Patricia Giardina; Lee Hilliard; Jeffrey Hord; Michael Jeng; Melody Kirby; Abdullah Kutlar; Kenneth McClain; William Mentzer; Robert Mignaca; Charles Pegelow; John Porter; Gloria Ramirez; Mark Ranalli; Sreedhar Rao; Charles Scher; Frank Shafer; Mary Gail Smith; Alexis Thompson

doi:10.1002/ajh.20809

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^*, Paul Harmatz, Meredith Milet, Samir K. Ballas, Laura De Castro, Ward Hagar, William Owen, Nancy Olivieri, Kim Smith-Whitley, Deepika Darbari, Winfred Wang, Elliott Vichinsky, Vinod Balasa, Rita Bellevue, James Cassela, Thomas Coates, Charles Davis, Patricia Giardina, Lee Hilliard, Jeffrey HordMichael Jeng, Melody Kirby, Abdullah Kutlar, Kenneth McClain, William Mentzer, Robert Mignaca, Charles Pegelow, John Porter, Gloria Ramirez, Mark Ranalli, Sreedhar Rao, Charles Scher, Frank Shafer, Mary Gail Smith, Alexis Thompson

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

126 Scopus citations

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 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.

Original language	English (US)
Pages (from-to)	255-265
Number of pages	11
Journal	American Journal of Hematology
Volume	82
Issue number	4
DOIs	https://doi.org/10.1002/ajh.20809
State	Published - Apr 2007

Keywords

Hospitalization
Iron overload
Morbidity
Mortality
Sickle cell disease (SCD)
Thalassemia (Thal)

ASJC Scopus subject areas

Hematology

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10.1002/ajh.20809

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Fung, E. B., Harmatz, P., Milet, M., Ballas, S. K., De Castro, L., Hagar, W., Owen, W., Olivieri, N., Smith-Whitley, K., Darbari, D., Wang, W., Vichinsky, E., Balasa, V., Bellevue, R., Cassela, J., Coates, T., Davis, C., Giardina, P., Hilliard, L., ... Thompson, A. (2007). Morbidity and mortality in chronically transfused subjects with Thalassemia and Sickle Cell Disease: A report from the multi-center study of iron overload. American Journal of Hematology, 82(4), 255-265. https://doi.org/10.1002/ajh.20809

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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 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.",

keywords = "Hospitalization, Iron overload, Morbidity, Mortality, Sickle cell disease (SCD), Thalassemia (Thal)",

author = "Fung, {Ellen B.} and Paul Harmatz and Meredith Milet and Ballas, {Samir K.} and {De Castro}, Laura and Ward Hagar and William Owen and Nancy Olivieri and Kim Smith-Whitley and Deepika Darbari and Winfred Wang and Elliott Vichinsky and Vinod Balasa and Rita Bellevue and James Cassela and Thomas Coates and Charles Davis and Patricia Giardina and Lee Hilliard and Jeffrey Hord and Michael Jeng and Melody Kirby and Abdullah Kutlar and Kenneth McClain and William Mentzer and Robert Mignaca and Charles Pegelow and John Porter and Gloria Ramirez and Mark Ranalli and Sreedhar Rao and Charles Scher and Frank Shafer and Smith, {Mary Gail} and Alexis Thompson",

year = "2007",

month = apr,

doi = "10.1002/ajh.20809",

language = "English (US)",

volume = "82",

pages = "255--265",

journal = "American Journal of Hematology",

issn = "0361-8609",

publisher = "Wiley-Liss Inc.",

number = "4",

}

Fung, EB, Harmatz, P, Milet, M, Ballas, SK, De Castro, L, Hagar, W, Owen, W, Olivieri, N, Smith-Whitley, K, Darbari, D, Wang, W, Vichinsky, E, Balasa, V, Bellevue, R, Cassela, J, Coates, T, Davis, C, Giardina, P, Hilliard, L, Hord, J, Jeng, M, Kirby, M, Kutlar, A, McClain, K, Mentzer, W, Mignaca, R, Pegelow, C, Porter, J, Ramirez, G, Ranalli, M, Rao, S, Scher, C, Shafer, F, Smith, MG & Thompson, A 2007, 'Morbidity and mortality in chronically transfused subjects with Thalassemia and Sickle Cell Disease: A report from the multi-center study of iron overload', American Journal of Hematology, vol. 82, no. 4, pp. 255-265. https://doi.org/10.1002/ajh.20809

TY - JOUR

T1 - Morbidity and mortality in chronically transfused subjects with Thalassemia and Sickle Cell Disease

T2 - A report from the multi-center study of iron overload

AU - Fung, Ellen B.

AU - Harmatz, Paul

AU - Milet, Meredith

AU - Ballas, Samir K.

AU - De Castro, Laura

AU - Hagar, Ward

AU - Owen, William

AU - Olivieri, Nancy

AU - Smith-Whitley, Kim

AU - Darbari, Deepika

AU - Wang, Winfred

AU - Vichinsky, Elliott

AU - Balasa, Vinod

AU - Bellevue, Rita

AU - Cassela, James

AU - Coates, Thomas

AU - Davis, Charles

AU - Giardina, Patricia

AU - Hilliard, Lee

AU - Hord, Jeffrey

AU - Jeng, Michael

AU - Kirby, Melody

AU - Kutlar, Abdullah

AU - McClain, Kenneth

AU - Mentzer, William

AU - Mignaca, Robert

AU - Pegelow, Charles

AU - Porter, John

AU - Ramirez, Gloria

AU - Ranalli, Mark

AU - Rao, Sreedhar

AU - Scher, Charles

AU - Shafer, Frank

AU - Smith, Mary Gail

AU - Thompson, Alexis

PY - 2007/4

Y1 - 2007/4

N2 - 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.

AB - 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.

KW - Hospitalization

KW - Iron overload

KW - Morbidity

KW - Mortality

KW - Sickle cell disease (SCD)

KW - Thalassemia (Thal)

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SN - 0361-8609

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JO - American Journal of Hematology

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ER -

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

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