Background

  • Sickle cell disease (SCD) is the most common inherited hematologic disease in sub-Saharan Africa (SSA).

  • In SSA, the rate of administration of hydroxyurea to patients with SCD is low because of the lack of accessibility and the lack of local evidence on safety and efficacy.

  • Kamuzu Central Hospital (KCH) (Figure 1) is a national teaching hospital in Lilongwe, Malawi, where we have established a pediatric SCD clinic.

Figure 1.

Kamuzu Central Hospital.

Figure 1.

Kamuzu Central Hospital.

Figure 2.

Median laboratory results for all patients receiving hydroxyurea (N = 130; range per month, 2-32). Error bars show interquartile range.

Figure 2.

Median laboratory results for all patients receiving hydroxyurea (N = 130; range per month, 2-32). Error bars show interquartile range.

Objectives

  • To examine the feasibility of introducing hydroxyurea in an SSA pediatric SCD clinic.

  • To investigate the hematologic safety of hydroxyurea for children with SCD at KCH.

Methods

  • This study was an observational, prospective cohort study at KCH that began in 2015 after the disease diagnosis was confirmed by hemoglobin electrophoresis.

  • Patients made clinic visits every 1 to 3 months and study visits every 6 months.

  • Study data included monitoring of complete blood count (CBC), serum renal function, liver function chemistries, and urinalysis.

  • From 2015, low- to medium-dose (10-20 mg/kg/day) hydroxyurea began being administered to children with recurrent or major crises at KCH.

  • From the last quarter of 2017, this clinic began prescribing hydroxyurea to all patients with the aim of having all SCD patients receiving hydroxyurea.

Capacity building

  • This is one of the few clinics dedicated to providing care to SCD patients in Malawi.

  • In the absence of monitoring high-risk SCD patients with transcranial Doppler ultrasound and performing prophylactic exchange transfusions, upscaling hydroxyurea therapy would benefit patients and reduce morbidity in SSA.

  • Analysis of the occurrence of complications along with CBC parameters after initiating hydroxyurea therapy would provide medical evidence to support its use in SSA.

Results

Conclusions

  • The KCH pediatric SCD clinic has been successfully upscaling the administration of hydroxyurea in children since late 2017 and now has near universal coverage.

  • Myelosuppressive effects of hydroxyurea in the patients at the SCD clinic have so far been shown to be transient.

  • There are ongoing efforts to monitor clinical efficacy and myelosuppressive effects of hydroxyurea therapy in children with SCD as KCH continues to upscale administration of hydroxyurea.

Table 1.

Characteristics of participants with recorded 6-month study visits taking hydroxyurea for 6 months or longer (N = 39)

CharacteristicNo. (%)MedianRange or IQR
Age at enrollment, y — 0 to 16 (range) 
Sex    
 Female 20 (53) — — 
 Male 18 (47) — — 
Length of follow-up time at KCH (months) 39 29 16-38 (range) 
Hemoglobin since starting hydroxyurea (g/dL) 129* 7.4 6.5-8.1 (IQR) 
Lactate dehydrogenase since starting hydroxyurea (U/L) 108* 664 525.5-769.0 (IQR) 
CharacteristicNo. (%)MedianRange or IQR
Age at enrollment, y — 0 to 16 (range) 
Sex    
 Female 20 (53) — — 
 Male 18 (47) — — 
Length of follow-up time at KCH (months) 39 29 16-38 (range) 
Hemoglobin since starting hydroxyurea (g/dL) 129* 7.4 6.5-8.1 (IQR) 
Lactate dehydrogenase since starting hydroxyurea (U/L) 108* 664 525.5-769.0 (IQR) 

IQR, interquartile range.

*

All laboratory results for multiple patient visits combined.

Table 2.

Complications of participants with study visits

 
 

*Thrombocytopenia: platelets <80 × 103/µL; neutropenia: neutrophils <2.0 × 103/µL.

Acknowledgments

The authors thank J. Brett Heimlich, Graham Ellis, Robert Krysiak, Godwin Chipoka, and Yacinta Majawa (University of North Carolina Project-Malawi).

This study was supported by the Fulbright-Fogarty Training Program, National Institutes of Health Fogarty International Center, National Heart, Lung, and Blood Institute (U01HL117659).

Authorship

Conflict-of-interest disclosure: N.K. received research funding from UniQure BV. K.A. has received honoraria from Modus Therapeutics, Novartis Pharmaceuticals, Bioverativ, Global and Blood Therapeutics; has received research funding from Pfizer and Global Blood Therapeutics; and is on the board of directors or an advisory committee for Bioverativ and Global Blood Therapeutics. All other authors declare no competing financial interests.

Correspondence: Tisungane Mvalo, University of North Carolina Project-Malawi, Lilongwe, Malawi; e-mail: tmvalo@unclilongwe.org.