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 & 15 others 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

Research output: Contribution to journalArticle

92 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)255-265
Number of pages11
JournalAmerican Journal of Hematology
Volume82
Issue number4
DOIs
StatePublished - Apr 1 2007

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Iron Overload
Thalassemia
Sickle Cell Anemia
Morbidity
Mortality
Chelation Therapy
Ferritins
Natural History
Canada
Hospitalization
Iron
Serum
Population
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Morbidity and mortality in chronically transfused subjects with Thalassemia and Sickle Cell Disease : A report from the multi-center study of iron overload. / Fung, Ellen B.; Harmatz, Paul; Milet, Meredith; Ballas, Samir K.; De Castro, Laura; Hagar, Ward; Owen, William; Olivieri, Nancy; Smith-Whitley, Kim; Darbari, Deepika; Wang, Winfred; Vichinsky, Elliott; Balasa, Vinod; Bellevue, Rita; Cassela, James; Coates, Thomas; Davis, Charles; Giardina, Patricia; Hilliard, Lee; Hord, Jeffrey; Jeng, Michael; Kirby, Melody; Kutlar, Abdullah; McClain, Kenneth; Mentzer, William; Mignaca, Robert; Pegelow, Charles; Porter, John; Ramirez, Gloria; Ranalli, Mark; Rao, Sreedhar; Scher, Charles; Shafer, Frank; Smith, Mary Gail; Thompson, Alexis.

In: American Journal of Hematology, Vol. 82, No. 4, 01.04.2007, p. 255-265.

Research output: Contribution to journalArticle

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
Fung, Ellen B. ; Harmatz, Paul ; Milet, Meredith ; Ballas, Samir K. ; De Castro, Laura ; Hagar, Ward ; Owen, William ; Olivieri, Nancy ; Smith-Whitley, Kim ; Darbari, Deepika ; Wang, Winfred ; Vichinsky, Elliott ; Balasa, Vinod ; Bellevue, Rita ; Cassela, James ; Coates, Thomas ; Davis, Charles ; Giardina, Patricia ; Hilliard, Lee ; Hord, Jeffrey ; Jeng, Michael ; Kirby, Melody ; Kutlar, Abdullah ; McClain, Kenneth ; Mentzer, William ; Mignaca, Robert ; Pegelow, Charles ; Porter, John ; Ramirez, Gloria ; Ranalli, Mark ; Rao, Sreedhar ; Scher, Charles ; Shafer, Frank ; Smith, Mary Gail ; Thompson, Alexis. / Morbidity and mortality in chronically transfused subjects with Thalassemia and Sickle Cell Disease : A report from the multi-center study of iron overload. In: American Journal of Hematology. 2007 ; Vol. 82, No. 4. pp. 255-265.
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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.",
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AU - Milet, Meredith

AU - Ballas, Samir K.

AU - De Castro, Laura

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AU - Owen, William

AU - Olivieri, Nancy

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AU - Vichinsky, Elliott

AU - Balasa, Vinod

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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

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KW - Morbidity

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KW - Sickle cell disease (SCD)

KW - Thalassemia (Thal)

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