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Persistent Splenomegaly Is Associated with Morbidity in Tanzanian Children with Sickle Cell Anemia: Secondary
Emmanuela E Ambrose1,2, George Tomlinson3,4, Patrick S Ngoya5
1Department of Paediatrics and Child Health, Catholic University of Health and Allied Sciences, Mwanza, Tanzania, emmanuelaambrose@gmail.com.
Insights
Splenomegaly is common in Tanzanian children with sickle cell anemia (SCA), often persisting and worsening outcomes. Persistent splenomegaly complicates hydroxyurea treatment and requires further investigation for better management.
Area of Science:
- Pediatric Hematology
- Sickle Cell Disease Research
- Clinical Trial Analysis
Background:
- Sickle cell anemia (SCA) in African children typically presents with splenomegaly and recurrent cytopenias, unlike the splenic atrophy seen in other populations.
- Management of SCA in children is complicated by splenomegaly and associated cytopenias.
Purpose of the Study:
- To analyze the presence, persistence, and impact of splenomegaly in Tanzanian children with SCA receiving dose-escalated hydroxyurea.
- To evaluate the relationship between splenomegaly and adverse events, including hydroxyurea dose-limiting toxicities.
Main Methods:
- Analysis of data from the SPHERE trial (NCT03948867) involving dose-escalated hydroxyurea for stroke prevention in Tanzanian children with SCA.
- Longitudinal assessment of palpable splenomegaly and annual ultrasound measurements.
- Categorization of splenomegaly as infrequent, intermittent, or persistent.
- Comparison of adverse events and hydroxyurea dose-limiting toxicities based on splenomegaly categories.
Main Results:
- At enrollment, 25% of children had palpable splenomegaly, and 40% had splenomegaly by ultrasound.
- Across 221 patient-years, splenomegaly was intermittent in 19% and persistent in 21% of children.
- Children with persistent splenomegaly experienced more vaso-occlusive adverse events (IRR=3.8), transfusions (IRR=7.1), and dose-limiting toxicities (IRR=3.2) compared to those with infrequent splenomegaly, despite similar hydroxyurea doses and hemoglobin levels.
Conclusions:
- Splenomegaly is a common and often persistent finding in Tanzanian children with SCA.
- Persistent splenomegaly is associated with worse clinical outcomes and complicates hydroxyurea therapy.
- Further research is urgently needed to understand the etiology of splenomegaly in SCA and optimize its management.
Introduction:
African children with sickle cell anemia (SCA) often have splenomegaly with recurrent cytopenias that complicate management, rather than the splenic atrophy typically observed in SCA.
Methods:
We analyzed the presence, persistence, and impact of splenomegaly in the Stroke Prevention with Hydroxyurea Enabled through Research and Education (SPHERE) trial (NCT03948867), an open-label trial of dose-escalated hydroxyurea to prevent stroke in Tanzanian children with SCA. Palpable splenomegaly was recorded at each visit. Annual ultrasound measurements were compared to age- and height-related references. Longitudinally, palpable splenomegaly was categorized as infrequent (present in <5% visits), intermittent (10-50% visits), or persistent (>50% visits). Adverse events (AEs) and hydroxyurea dose-limiting toxicities (DLTs) were compared using incidence rate ratios (IRRs) among the three categories.
Results:
At enrollment, splenomegaly was identified in 48/196 (25%) by palpation and 78 (40%) by ultrasound. Across 221 patient-years of treatment in 53 children, splenomegaly was intermittent in 19% and persistent in 21%. At 12 months, children with persistent splenomegaly were compared to those with infrequent splenomegaly and had achieved similar hydroxyurea dose (23.1 vs. 27.6 mg/kg/day, p = 0.136), hemoglobin (9.0 vs. 9.1 g/dL, p = 0.877), and HbF (23.8 vs. 24.3%, p = 0.481), but experienced more vaso-occlusive AE (IRR = 3.8, p value 0.122), transfusions (IRR = 7.1, p value 0.014), and DLTs (IRR = 3.2, p value 0.073).
Conclusion:
Splenomegaly is common in Tanzanian children with SCA, often persistent, worsens clinical outcomes, and complicates hydroxyurea. Its cause remains unclear, and further investigation is urgently needed to clarify its etiology, improve its management, and ensure optimal hydroxyurea treatment.
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