The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up

Martin H. Steinberg, William F. McCarthy, Oswaldo Castro, Samir K. Ballas, F. Danny Armstrong, Wally Smith, Kenneth Ataga, Paul Swerdlow, Abdullah Kutlar, Laura DeCastro, Myron A. Waclawiw, E. Orringer, S. Jones, D. Strayhorn, W. Rosse, G. Phillips, D. Peace, A. Johnson-Telfair, Lisa H Daitch, P. MilnerA. Tracy, S. Valdez, G. E. Allen, J. Moshang, B. Scott, C. Bigelow, A. Anderson, V. Sabahi, T. Harrington, W. Labrousse, C. Pegelow, D. Temple, E. Case, R. Harrell, S. Childerie, S. Embury, B. Schmidt, D. Davies, Y. Saunthararajah, M. Koshy, N. Talischy-Zahed, L. Dorn, G. Pendarvis, M. McGee, M. Telfer, A. Davis, O. C. Onyekwere, C. Nwokolo, H. Finke, E. Perlin, J. Siteman, M. Bryan, T. Saunders, Y. Barber, P. Gascon, P. Di Paolo, S. Gargiulo, J. Eckman, E. Carter-Randall, J. H. Bailey, A. Platt, L. Waller, G. Ramirez, V. Knors, S. Hernandez, E. M. Rodriguez, E. Wilkes, E. Vichinsky, W. Hagar, C. Hoehner, E. Hackney-Stevens, S. Claster, A. Earles, K. Kleman, K. McLaughlin, L. White, B. Maddox, L. Usry, A. Brenner, K. Williams, R. O'Brien, K. Genther, S. Shurin, B. Berman, K. Chiarucci, L. Keverline, N. Olivieri, J. Chow, M. Hui, D. Shaw, N. Lewis, M. Okam, E. Mandell, A. Palmer, K. Bridges, B. Tynan, C. Winograd, R. Bellevue, H. Dosik, M. Sheikhai, P. Ryans, H. Souffrant, B. Adler, A. Johnson-Telfair, L. Eskridge, J. Prchal, J. Braddock, T. McArdle, T. Carlos, A. Roundtree-Schmotzer, D. Gardner

Research output: Contribution to journalArticle

249 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)403-408
Number of pages6
JournalAmerican Journal of Hematology
Volume85
Issue number6
DOIs
StatePublished - Jun 1 2010

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Hydroxyurea
Sickle Cell Anemia
Mortality
Withholding Treatment
Cohort Studies
Randomized Controlled Trials
Stroke
Confidence Intervals
Safety
Lung
Survival
Infection
Neoplasms

ASJC Scopus subject areas

  • Hematology

Cite this

Steinberg, M. H., McCarthy, W. F., Castro, O., Ballas, S. K., Armstrong, F. D., Smith, W., ... Gardner, D. (2010). The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up. American Journal of Hematology, 85(6), 403-408. https://doi.org/10.1002/ajh.21699

The risks and benefits of long-term use of hydroxyurea in sickle cell anemia : A 17.5 year follow-up. / Steinberg, Martin H.; McCarthy, William F.; Castro, Oswaldo; Ballas, Samir K.; Armstrong, F. Danny; Smith, Wally; Ataga, Kenneth; Swerdlow, Paul; Kutlar, Abdullah; DeCastro, Laura; Waclawiw, Myron A.; Orringer, E.; Jones, S.; Strayhorn, D.; Rosse, W.; Phillips, G.; Peace, D.; Johnson-Telfair, A.; Daitch, Lisa H; Milner, P.; Tracy, A.; Valdez, S.; Allen, G. E.; Moshang, J.; Scott, B.; Bigelow, C.; Anderson, A.; Sabahi, V.; Harrington, T.; Labrousse, W.; Pegelow, C.; Temple, D.; Case, E.; Harrell, R.; Childerie, S.; Embury, S.; Schmidt, B.; Davies, D.; Saunthararajah, Y.; Koshy, M.; Talischy-Zahed, N.; Dorn, L.; Pendarvis, G.; McGee, M.; Telfer, M.; Davis, A.; Onyekwere, O. C.; Nwokolo, C.; Finke, H.; Perlin, E.; Siteman, J.; Bryan, M.; Saunders, T.; Barber, Y.; Gascon, P.; Di Paolo, P.; Gargiulo, S.; Eckman, J.; Carter-Randall, E.; Bailey, J. H.; Platt, A.; Waller, L.; Ramirez, G.; Knors, V.; Hernandez, S.; Rodriguez, E. M.; Wilkes, E.; Vichinsky, E.; Hagar, W.; Hoehner, C.; Hackney-Stevens, E.; Claster, S.; Earles, A.; Kleman, K.; McLaughlin, K.; White, L.; Maddox, B.; Usry, L.; Brenner, A.; Williams, K.; O'Brien, R.; Genther, K.; Shurin, S.; Berman, B.; Chiarucci, K.; Keverline, L.; Olivieri, N.; Chow, J.; Hui, M.; Shaw, D.; Lewis, N.; Okam, M.; Mandell, E.; Palmer, A.; Bridges, K.; Tynan, B.; Winograd, C.; Bellevue, R.; Dosik, H.; Sheikhai, M.; Ryans, P.; Souffrant, H.; Adler, B.; Johnson-Telfair, A.; Eskridge, L.; Prchal, J.; Braddock, J.; McArdle, T.; Carlos, T.; Roundtree-Schmotzer, A.; Gardner, D.

In: American Journal of Hematology, Vol. 85, No. 6, 01.06.2010, p. 403-408.

Research output: Contribution to journalArticle

Steinberg, MH, McCarthy, WF, Castro, O, Ballas, SK, Armstrong, FD, Smith, W, Ataga, K, Swerdlow, P, Kutlar, A, DeCastro, L, Waclawiw, MA, Orringer, E, Jones, S, Strayhorn, D, Rosse, W, Phillips, G, Peace, D, Johnson-Telfair, A, Daitch, LH, Milner, P, Tracy, A, Valdez, S, Allen, GE, Moshang, J, Scott, B, Bigelow, C, Anderson, A, Sabahi, V, Harrington, T, Labrousse, W, Pegelow, C, Temple, D, Case, E, Harrell, R, Childerie, S, Embury, S, Schmidt, B, Davies, D, Saunthararajah, Y, Koshy, M, Talischy-Zahed, N, Dorn, L, Pendarvis, G, McGee, M, Telfer, M, Davis, A, Onyekwere, OC, Nwokolo, C, Finke, H, Perlin, E, Siteman, J, Bryan, M, Saunders, T, Barber, Y, Gascon, P, Di Paolo, P, Gargiulo, S, Eckman, J, Carter-Randall, E, Bailey, JH, Platt, A, Waller, L, Ramirez, G, Knors, V, Hernandez, S, Rodriguez, EM, Wilkes, E, Vichinsky, E, Hagar, W, Hoehner, C, Hackney-Stevens, E, Claster, S, Earles, A, Kleman, K, McLaughlin, K, White, L, Maddox, B, Usry, L, Brenner, A, Williams, K, O'Brien, R, Genther, K, Shurin, S, Berman, B, Chiarucci, K, Keverline, L, Olivieri, N, Chow, J, Hui, M, Shaw, D, Lewis, N, Okam, M, Mandell, E, Palmer, A, Bridges, K, Tynan, B, Winograd, C, Bellevue, R, Dosik, H, Sheikhai, M, Ryans, P, Souffrant, H, Adler, B, Johnson-Telfair, A, Eskridge, L, Prchal, J, Braddock, J, McArdle, T, Carlos, T, Roundtree-Schmotzer, A & Gardner, D 2010, 'The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up', American Journal of Hematology, vol. 85, no. 6, pp. 403-408. https://doi.org/10.1002/ajh.21699
Steinberg, Martin H. ; McCarthy, William F. ; Castro, Oswaldo ; Ballas, Samir K. ; Armstrong, F. Danny ; Smith, Wally ; Ataga, Kenneth ; Swerdlow, Paul ; Kutlar, Abdullah ; DeCastro, Laura ; Waclawiw, Myron A. ; Orringer, E. ; Jones, S. ; Strayhorn, D. ; Rosse, W. ; Phillips, G. ; Peace, D. ; Johnson-Telfair, A. ; Daitch, Lisa H ; Milner, P. ; Tracy, A. ; Valdez, S. ; Allen, G. E. ; Moshang, J. ; Scott, B. ; Bigelow, C. ; Anderson, A. ; Sabahi, V. ; Harrington, T. ; Labrousse, W. ; Pegelow, C. ; Temple, D. ; Case, E. ; Harrell, R. ; Childerie, S. ; Embury, S. ; Schmidt, B. ; Davies, D. ; Saunthararajah, Y. ; Koshy, M. ; Talischy-Zahed, N. ; Dorn, L. ; Pendarvis, G. ; McGee, M. ; Telfer, M. ; Davis, A. ; Onyekwere, O. C. ; Nwokolo, C. ; Finke, H. ; Perlin, E. ; Siteman, J. ; Bryan, M. ; Saunders, T. ; Barber, Y. ; Gascon, P. ; Di Paolo, P. ; Gargiulo, S. ; Eckman, J. ; Carter-Randall, E. ; Bailey, J. H. ; Platt, A. ; Waller, L. ; Ramirez, G. ; Knors, V. ; Hernandez, S. ; Rodriguez, E. M. ; Wilkes, E. ; Vichinsky, E. ; Hagar, W. ; Hoehner, C. ; Hackney-Stevens, E. ; Claster, S. ; Earles, A. ; Kleman, K. ; McLaughlin, K. ; White, L. ; Maddox, B. ; Usry, L. ; Brenner, A. ; Williams, K. ; O'Brien, R. ; Genther, K. ; Shurin, S. ; Berman, B. ; Chiarucci, K. ; Keverline, L. ; Olivieri, N. ; Chow, J. ; Hui, M. ; Shaw, D. ; Lewis, N. ; Okam, M. ; Mandell, E. ; Palmer, A. ; Bridges, K. ; Tynan, B. ; Winograd, C. ; Bellevue, R. ; Dosik, H. ; Sheikhai, M. ; Ryans, P. ; Souffrant, H. ; Adler, B. ; Johnson-Telfair, A. ; Eskridge, L. ; Prchal, J. ; Braddock, J. ; McArdle, T. ; Carlos, T. ; Roundtree-Schmotzer, A. ; Gardner, D. / The risks and benefits of long-term use of hydroxyurea in sickle cell anemia : A 17.5 year follow-up. In: American Journal of Hematology. 2010 ; Vol. 85, No. 6. pp. 403-408.
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abstract = "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.",
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T1 - The risks and benefits of long-term use of hydroxyurea in sickle cell anemia

T2 - A 17.5 year follow-up

AU - Steinberg, Martin H.

AU - McCarthy, William F.

AU - Castro, Oswaldo

AU - Ballas, Samir K.

AU - Armstrong, F. Danny

AU - Smith, Wally

AU - Ataga, Kenneth

AU - Swerdlow, Paul

AU - Kutlar, Abdullah

AU - DeCastro, Laura

AU - Waclawiw, Myron A.

AU - Orringer, E.

AU - Jones, S.

AU - Strayhorn, D.

AU - Rosse, W.

AU - Phillips, G.

AU - Peace, D.

AU - Johnson-Telfair, A.

AU - Daitch, Lisa H

AU - Milner, P.

AU - Tracy, A.

AU - Valdez, S.

AU - Allen, G. E.

AU - Moshang, J.

AU - Scott, B.

AU - Bigelow, C.

AU - Anderson, A.

AU - Sabahi, V.

AU - Harrington, T.

AU - Labrousse, W.

AU - Pegelow, C.

AU - Temple, D.

AU - Case, E.

AU - Harrell, R.

AU - Childerie, S.

AU - Embury, S.

AU - Schmidt, B.

AU - Davies, D.

AU - Saunthararajah, Y.

AU - Koshy, M.

AU - Talischy-Zahed, N.

AU - Dorn, L.

AU - Pendarvis, G.

AU - McGee, M.

AU - Telfer, M.

AU - Davis, A.

AU - Onyekwere, O. C.

AU - Nwokolo, C.

AU - Finke, H.

AU - Perlin, E.

AU - Siteman, J.

AU - Bryan, M.

AU - Saunders, T.

AU - Barber, Y.

AU - Gascon, P.

AU - Di Paolo, P.

AU - Gargiulo, S.

AU - Eckman, J.

AU - Carter-Randall, E.

AU - Bailey, J. H.

AU - Platt, A.

AU - Waller, L.

AU - Ramirez, G.

AU - Knors, V.

AU - Hernandez, S.

AU - Rodriguez, E. M.

AU - Wilkes, E.

AU - Vichinsky, E.

AU - Hagar, W.

AU - Hoehner, C.

AU - Hackney-Stevens, E.

AU - Claster, S.

AU - Earles, A.

AU - Kleman, K.

AU - McLaughlin, K.

AU - White, L.

AU - Maddox, B.

AU - Usry, L.

AU - Brenner, A.

AU - Williams, K.

AU - O'Brien, R.

AU - Genther, K.

AU - Shurin, S.

AU - Berman, B.

AU - Chiarucci, K.

AU - Keverline, L.

AU - Olivieri, N.

AU - Chow, J.

AU - Hui, M.

AU - Shaw, D.

AU - Lewis, N.

AU - Okam, M.

AU - Mandell, E.

AU - Palmer, A.

AU - Bridges, K.

AU - Tynan, B.

AU - Winograd, C.

AU - Bellevue, R.

AU - Dosik, H.

AU - Sheikhai, M.

AU - Ryans, P.

AU - Souffrant, H.

AU - Adler, B.

AU - Johnson-Telfair, A.

AU - Eskridge, L.

AU - Prchal, J.

AU - Braddock, J.

AU - McArdle, T.

AU - Carlos, T.

AU - Roundtree-Schmotzer, A.

AU - Gardner, D.

PY - 2010/6/1

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N2 - 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.

AB - 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.

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