Conflict of interest: Nothing to report.
Article first published online: 2 MAR 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Hematology
Volume 85, Issue 6, pages 403–408, June 2010
How to Cite
Steinberg, M. H., McCarthy, W. F., Castro, O., Ballas, S. K., Armstrong, F. D., Smith, W., Ataga, K., Swerdlow, P., Kutlar, A., DeCastro, L. and Waclawiw, M. A. (2010), The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up. Am. J. Hematol., 85: 403–408. doi: 10.1002/ajh.21699
Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia and MSH Patients' Follow-up are:
University of North Carolina, Chapel Hill, NC: E Orringer, K Ataga, S Jones, D Strayhorn; Duke University, Durham, NC: L DeCastro, W Rosse, G. Phillips, D Peace, A Johnson-Telfair; Medical College of Georgia, Augusta, GA: A Kutlar, L Daitch, P Milner, A Tracy; Thomas Jefferson University, Philadelphia, PA: SK Ballas, S Valdez, GE Allen, J Moshang, B. Scott; University of Mississippi, Jackson, MS: C Bigelow, M Steinberg, A Anderson, V Sabahi; University of Miami, Miami, FL: D Armstrong, T Harrington, W Labrousse, C Pegelow, D Temple, E Case, R Harrell, S Childerie; San Francisco General Hospital, San Francisco, CA: S Embury, B Schmidt, D Davies; University of Illinois, Chicago, IL: Y Saunthararajah, M Koshy, N Talischy-Zahed, L Dorn, G Pendarvis, M McGee; Michael Reese Hospital, Chicago, IL: M Telfer, A Davis; Howard University, Washington, DC: O Castro, OC Onyekwere, C Nwokolo, H Finke, E Perlin, J Siteman; University of Medicine and Dentistry of New Jersey, Newark, NJ: M Bryan, T Saunders, Y Barber, P Gascon, P di Paolo, S Gargiulo; Emory University, Atlanta, GA: J Eckman, E Carter-Randall, JH Bailey, A Platt, L Waller; St. Luke's—Roosevelt Medical Center, New York, NY: G Ramirez, V Knors, S Hernandez, EM Rodriguez, E Wilkes; Children's Hospital of Oakland, Oakland, CA: E Vichinsky, W Hagar, C Hoehner, E Hackney-Stevens, S Claster, A Earles, K Kleman, K McLaughlin; Medical College of Virginia, Richmond, VA: W Smith, L White, P Swerdlow, B Maddox, L Usry, A Brenner, K Williams, R O'Brien, K Genther; Case Western Reserve University, Cleveland, OH: S Shurin, B Berman, K Chiarucci, L Keverline; Hospital for Sick Children (Toronto General Hospital), Toronto, Ontario: N Olivieri, J Chow, M Hui, D Shaw, N Lewis; Brigham and Women's Hospital, Boston, MA: M Okam, E Mandell, A Palmer, K Bridges, B Tynan, C Winograd; Interfaith Medical Center (New York Methodist Hospital), Brooklyn, NY: R Bellevue, H Dosik, M Sheikhai, P Ryans, H Souffrant; University of Alabama, Birmingham, AL: B Adler, A Johnson-Telfair, L Eskridge, J Prchal, J Braddock, T McArdle; University of Pittsburgh, Pittsburgh, PA: T Carlos, A Roundtree-Schmotzer, D Gardner
Clinical Trial Central Office Staff (Johns Hopkins University, Baltimore, MD): S Charache, R Moore, G Dover, M Bergner, C Ewart, S Eckert, C Lent, J Ullrich, L Fishpaw, G Tirado, J Gibson, T Moeller, T Nagel
Data Coordinating Center (Maryland Medical Research Institute, Baltimore, MD): W McCarthy, R Bauserman, N Guo, A Brandon, B Barton, M Terrin, FB Barton, RP McMahon, C Handy, D Harris, M Canner, J Depkin, N Meinert, M Carroll, R Giro, S Karabelas, C Kelly
Clinical Trial Crisis Review Committee: M Heyman, P Beilinson, M Druskin, P Ellis, WA Flood, S Kravitz, S Lanzkron, V Lorica, A Moliterno, A Nahum, JA Nesbitt III, L Rosenthal, W Sharfman, M Streiff, M Wachsman, P Bray, C Van Dang, J Casella, M McGuire, L Patrick, H Schaad, C Steiner; Follow-Up Event Classification Medical Officer: M Steinberg, M Terrin
Clinical Trial Data and Safety Monitoring Board: C Johnson, A Bank, G Cutter, CE Davis, O Huntley, L Lessin, O Platt, M Gray-Secundy
Follow-Up Data Safety and Monitoring Board: L Benjamin, P Adams-Graves, C Joiner, DC Moore, J Verter, E Wagner, B Moore, M Waclawiw
Project Office (National Heart, Lung, and Blood Institute, Bethesda, MD): H Luksenburg, B Moore, D Bonds, W Ware, C Reid, N Geller, M Waclawiw
- Issue published online: 25 MAY 2010
- Article first published online: 2 MAR 2010
- Accepted manuscript online: 2 MAR 2010 12:00AM EST
- Manuscript Received: 25 FEB 2010
- Manuscript Accepted: 25 FEB 2010
- NHLBI. Grant Number: NO1-HB-6712
A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at α = 0.05 level (P-value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc.