Hydroxyurea Dose Escalation to Maximum Tolerated Dose in Pediatric Sickle Cell Disease: Hematologic and Clinical Outcomes in a Resource-Limited Setting in Cameroon. A Quasi-Experimental Study.
DOI:
https://doi.org/10.51168/6zd3jy11Keywords:
hydroxyurea, maximum tolerated dose, dose escalation, sickle cell disease, fetal hemoglobin, pediatric, resource-limited settings, Cameroon, Sub-Saharan Africa, vaso-occlusive crisisAbstract
Background:
Hydroxyurea (HU) dose escalation to maximum tolerated dose (MTD) has demonstrated superior fetal hemoglobin (HbF) induction in high-income settings, yet evidence from resource-limited sub-Saharan African contexts remains scarce. This study aimed to evaluate the hematologic, clinical safety, and feasibility of structured HU dose escalation to MTD in the paediatric SCD population in Cameroon.
Methods:
A quasi-experimental prospective single-arm study was conducted over 12 months (June 2024–June 2025) at Bonaberi Baptist Hospital Douala (BBHD), Cameroon. Thirty children aged 1–18 years with HbSS SCD receiving fixed-dose HU (15 mg/kg/day) were enrolled and escalated by 5 mg/kg/day every eight weeks toward MTD. Primary outcomes were %HbF and Hgb (g/dL). Secondary outcomes were frequencies of VOC, ACS, ED visits, and hospitalizations. Paired t-tests were used (significance: p<0.05).
Results:
Twenty-five of 30 participants (83.3%) completed the post-maximum tolerated dose phase (mean age: 9.4 ± 3.2 years; 60% female). Mean MTD achieved was 25.6 ± 3.4 mg/kg/day. HbF increased significantly from 20.3% ± 3.8 to 28.7% ± 4.1 (p=0.03), and Hgb improved from 9.6 ± 1.0
to 10.4 ± 0.8 g/dL (p=0.04). VOC frequency declined by 50% (1.2 ± 0.7 to 0.6 ± 0.4; p=0.04), ACS
by 66.7% (0.3 ± 0.2 to 0.1 ± 0.1; p=0.05), ED visits by 62.5% (p=0.03), and hospitalizations by 66.7% (p=0.04). No severe myelosuppression occurred.
Conclusions:
HU dose escalation to MTD is safe, feasible, and significantly improves hematologic and clinical outcomes in paediatric SCD in a resource-limited setting.
Recommendation:
Structured HU dose escalation to MTD under monthly CBC surveillance and clinician training on dose escalation protocol and safety should be incorporated into standard SCD care protocols at dedicated paediatric clinics in resource-limited African settings.
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Copyright (c) 2026 Collins Pivadga, RN, BSN, MSN, Ph.D, Ehimen Phyllis Odum, MBBS, MSC, FMCPath, MedEd, Balafama Abinye Alex-Hart, MBBS, MSC, FWACP
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