Hydroxyurea for Children with Sickle Cell Disease

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Hydroxyurea therapy offers promise for ameliorating the clinical course of children with sickle cell disease (SCD). Hydroxyurea is a prototypic therapeutic option; it can be administered with minimal side effects, has a relatively wide therapeutic window, and has mechanisms of action that address pathophysiologic pathways of sickling, vaso-occlusion, hemolysis, and organ damage. There are limited data regarding hydroxyurea's ability to prevent or diminish organ dysfunction, and the long-term risks of hydroxyurea therapy remain incompletely defined. Although clinical trials are underway to address long-term issues, hydroxyurea remains an effective but underutilized therapy for SCD.

Section snippets

An ideal drug for sickle cell disease?

Hydroxyurea may be an ideal therapeutic agent for use in children with SCD. It has excellent bioavailability after oral administration; requires only once-daily dosing, which improves medication adherence; has few if any immediate side effects; has predictable hematologic toxicities that are dose dependent, transient, and reversible; and has potential benefits against multiple pathophysiologic mechanisms of SCD. Although several therapeutic agents currently under development address specific

Clinical experience

Preclinical studies in anemic cynomolgus monkeys showed that hydroxyurea increased HbF levels.33 Pilot trials in patients with SCD demonstrated that hydroxyurea also increased HbF in humans and caused little short-term toxicity.29, 30, 31, 32 These proof-of-principle experiments were critical first steps toward an important multicenter phase I/II trial involving adults with HbSS, which identified the short-term efficacy and toxicities of hydroxyurea used at maximum tolerated dose (MTD).32

Practical considerations

Hydroxyurea therapy cannot be prescribed, monitored, and adjusted properly according to exact and specific written guidelines. Instead, optimal treatment with hydroxyurea (as with many other medications) requires careful attention to the details of each patient's treatment response; such individualized therapy often involves as much art as science. The following sections represent the distillation of a combined 25 years of experience with hydroxyurea (>300 treated children), but none of the

Summary

Hydroxyurea is a powerful therapeutic agent with proved laboratory and clinical efficacy for children with SCD. Although there are important questions regarding its long-term efficacy and safety, hydroxyurea has the potential to ameliorate many of the signs and symptoms of the disease. Ongoing clinical trials will help answer questions about the proper clinical indications for its use and, in particular, its ability to prevent organ damage and preserve organ function and long-term safety.

Acknowledgments

The authors thank Nicole A. Mortier, MHS PA-C, and William H. Schultz, MHS PA-C, for years of experience and dedication to treating children with SCD. We appreciate their insights and advice regarding the optimal use of hydroxyurea in this patient population.

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  • Cited by (0)

    A version of this article was previously published in the Pediatric Clinics of North America, 55:2.

    Dr. Heeney is supported by NIH K12 HL087164 and U54 HL070819. Dr. Ware is supported by U54 HL070590, U01 HL078787, N01 HB 07155, and American Syrian Lebanese Associated Charities.

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