Hydroxyurea-increased fetal hemoglobin is associated with less organ damage and longer survival in adults with sickle cell anemia

Courtney D. Fitzhugh, Matthew M. Hsieh, Darlene Allen, Wynona A. Coles, Cassie Seamon, Michael Ring, Xiongce Zhao, Caterina P. Minniti, Griffin P. Rodgers, Alan N. Schechter, John F. Tisdale, James G. Taylor

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Adults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea. Objectives: We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010. Methods: An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials. gov, number NCT00011648. Results: Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003-1.006, p<0.0.0001), kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00-1.27, p = 0.043), and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23-4.02, p = 0.0082). Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34-0.97, p = 0.040). This effect was most pronounced in those taking the recommended dose of 15-35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17-0.73, p = 0.0050). Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004). While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively), other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels. Conclusions: Our data suggest that adults should be treated with the maximum tolerated hydroxyurea dose, ideally before organ damage occurs. Prospective studies are indicated to validate these findings.

Original languageEnglish (US)
Article numbere0141706
JournalPLoS One
Volume10
Issue number11
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

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sickle cell anemia
hydroxyurea
Fetal Hemoglobin
Hydroxyurea
Sickle Cell Anemia
hemoglobin
Survival
Hazards
dosage
Alkaline Phosphatase
alkaline phosphatase
Electronic medical equipment
Tissue Survival
Maximum Tolerated Dose
Electronic Health Records
prospective studies
Regression analysis
creatinine
electronics
Creatinine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Fitzhugh, C. D., Hsieh, M. M., Allen, D., Coles, W. A., Seamon, C., Ring, M., ... Taylor, J. G. (2015). Hydroxyurea-increased fetal hemoglobin is associated with less organ damage and longer survival in adults with sickle cell anemia. PLoS One, 10(11), [e0141706]. https://doi.org/10.1371/journal.pone.0141706

Hydroxyurea-increased fetal hemoglobin is associated with less organ damage and longer survival in adults with sickle cell anemia. / Fitzhugh, Courtney D.; Hsieh, Matthew M.; Allen, Darlene; Coles, Wynona A.; Seamon, Cassie; Ring, Michael; Zhao, Xiongce; Minniti, Caterina P.; Rodgers, Griffin P.; Schechter, Alan N.; Tisdale, John F.; Taylor, James G.

In: PLoS One, Vol. 10, No. 11, e0141706, 01.11.2015.

Research output: Contribution to journalArticle

Fitzhugh, CD, Hsieh, MM, Allen, D, Coles, WA, Seamon, C, Ring, M, Zhao, X, Minniti, CP, Rodgers, GP, Schechter, AN, Tisdale, JF & Taylor, JG 2015, 'Hydroxyurea-increased fetal hemoglobin is associated with less organ damage and longer survival in adults with sickle cell anemia', PLoS One, vol. 10, no. 11, e0141706. https://doi.org/10.1371/journal.pone.0141706
Fitzhugh, Courtney D. ; Hsieh, Matthew M. ; Allen, Darlene ; Coles, Wynona A. ; Seamon, Cassie ; Ring, Michael ; Zhao, Xiongce ; Minniti, Caterina P. ; Rodgers, Griffin P. ; Schechter, Alan N. ; Tisdale, John F. ; Taylor, James G. / Hydroxyurea-increased fetal hemoglobin is associated with less organ damage and longer survival in adults with sickle cell anemia. In: PLoS One. 2015 ; Vol. 10, No. 11.
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