Bill Wambaka, Amiirah Mpungu, Vincent Mboizi, Dennis Kalibbala, Grace Nambatya, Susan Murungi, Maxencia Kabatabaazi, Maria Nakafeero, Phillip Kasirye, Deogratias Munube, Ruth Namazzi, Richard Idro, Nancy S Green
{"title":"在乌干达的一项羟脲试验中，尽管经颅多普勒速度总体改善，儿童镰状细胞性贫血的卒中事件：先前和正在进行的风险。","authors":"Bill Wambaka, Amiirah Mpungu, Vincent Mboizi, Dennis Kalibbala, Grace Nambatya, Susan Murungi, Maxencia Kabatabaazi, Maria Nakafeero, Phillip Kasirye, Deogratias Munube, Ruth Namazzi, Richard Idro, Nancy S Green","doi":"10.1002/pbc.31722","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Transcranial Doppler ultrasound (TCD) screening for primary stroke prevention in children with sickle cell anemia (SCA) was established in higher-resource regions, targeting interventions for highest velocity (\"abnormal\"). We sought to identify additional stroke risk factors in Uganda.</p><p><strong>Methods: </strong>We conducted a 30-month open-label single-arm Ugandan hydroxyurea trial, dose-escalated to maximum-tolerated dose, aimed to test brain protection for children aged 3-9 years with SCA. Study procedures included history, clinical stroke examination, and prospective TCD and laboratory assessments.</p><p><strong>Results: </strong>Overall, 264 children received study HU, mean age 5.6 ± 1.7, hemoglobin 7.8 ± 1.2 g/dL, fetal hemoglobin (HbF) 11.9% ± 8.1%, enrolment TCD mean TAMV 148.4 ± 29.3 cm/sec; 15 (5.7%) had abnormal TCD. The mean TAMV at trial completion was 131.9 ± SD 25.7 cm/sec. Four participants without abnormal enrolment TCD developed acute stroke within the initial 16 months (incidence 0.62 per 100 person-years): two had enrolment HbF ≤3.1%, two had low oxygen saturation (90%), and one had recurring severe anemia necessitating multiple transfusions. Apparent stroke precipitants were severe malaria, acute chest syndrome, recent pain crisis, or uncertain cause. At trial completion, eight additional participants had a higher risk TCD category than at enrolment.</p><p><strong>Conclusion: </strong>The effectiveness of TCD screening for stroke prevention may vary by region, as no participant with an incident stroke was at the highest risk. Antecedent and/or ongoing SCA-related risks of anemia, low HbF, hypoxemia, infections, and/or disease complications likely contributed to stroke despite trial HU. Results suggest that TCD alone may not fully identify the highest stroke risk in the region, and there is a need for primary stroke prevention from early childhood and continuous hydroxyurea therapy.</p>","PeriodicalId":19822,"journal":{"name":"Pediatric Blood & Cancer","volume":" ","pages":"e31722"},"PeriodicalIF":2.4000,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Incident Stroke in Pediatric Sickle Cell Anemia Despite Overall Improved Transcranial Doppler Velocity in a Ugandan Hydroxyurea Trial: Antecedent and Ongoing Risks.\",\"authors\":\"Bill Wambaka, Amiirah Mpungu, Vincent Mboizi, Dennis Kalibbala, Grace Nambatya, Susan Murungi, Maxencia Kabatabaazi, Maria Nakafeero, Phillip Kasirye, Deogratias Munube, Ruth Namazzi, Richard Idro, Nancy S Green\",\"doi\":\"10.1002/pbc.31722\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Transcranial Doppler ultrasound (TCD) screening for primary stroke prevention in children with sickle cell anemia (SCA) was established in higher-resource regions, targeting interventions for highest velocity (\\\"abnormal\\\"). We sought to identify additional stroke risk factors in Uganda.</p><p><strong>Methods: </strong>We conducted a 30-month open-label single-arm Ugandan hydroxyurea trial, dose-escalated to maximum-tolerated dose, aimed to test brain protection for children aged 3-9 years with SCA. Study procedures included history, clinical stroke examination, and prospective TCD and laboratory assessments.</p><p><strong>Results: </strong>Overall, 264 children received study HU, mean age 5.6 ± 1.7, hemoglobin 7.8 ± 1.2 g/dL, fetal hemoglobin (HbF) 11.9% ± 8.1%, enrolment TCD mean TAMV 148.4 ± 29.3 cm/sec; 15 (5.7%) had abnormal TCD. The mean TAMV at trial completion was 131.9 ± SD 25.7 cm/sec. Four participants without abnormal enrolment TCD developed acute stroke within the initial 16 months (incidence 0.62 per 100 person-years): two had enrolment HbF ≤3.1%, two had low oxygen saturation (90%), and one had recurring severe anemia necessitating multiple transfusions. Apparent stroke precipitants were severe malaria, acute chest syndrome, recent pain crisis, or uncertain cause. At trial completion, eight additional participants had a higher risk TCD category than at enrolment.</p><p><strong>Conclusion: </strong>The effectiveness of TCD screening for stroke prevention may vary by region, as no participant with an incident stroke was at the highest risk. Antecedent and/or ongoing SCA-related risks of anemia, low HbF, hypoxemia, infections, and/or disease complications likely contributed to stroke despite trial HU. Results suggest that TCD alone may not fully identify the highest stroke risk in the region, and there is a need for primary stroke prevention from early childhood and continuous hydroxyurea therapy.</p>\",\"PeriodicalId\":19822,\"journal\":{\"name\":\"Pediatric Blood & Cancer\",\"volume\":\" \",\"pages\":\"e31722\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-04-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pediatric Blood & Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/pbc.31722\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Blood & Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/pbc.31722","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Incident Stroke in Pediatric Sickle Cell Anemia Despite Overall Improved Transcranial Doppler Velocity in a Ugandan Hydroxyurea Trial: Antecedent and Ongoing Risks.
Introduction: Transcranial Doppler ultrasound (TCD) screening for primary stroke prevention in children with sickle cell anemia (SCA) was established in higher-resource regions, targeting interventions for highest velocity ("abnormal"). We sought to identify additional stroke risk factors in Uganda.
Methods: We conducted a 30-month open-label single-arm Ugandan hydroxyurea trial, dose-escalated to maximum-tolerated dose, aimed to test brain protection for children aged 3-9 years with SCA. Study procedures included history, clinical stroke examination, and prospective TCD and laboratory assessments.
Results: Overall, 264 children received study HU, mean age 5.6 ± 1.7, hemoglobin 7.8 ± 1.2 g/dL, fetal hemoglobin (HbF) 11.9% ± 8.1%, enrolment TCD mean TAMV 148.4 ± 29.3 cm/sec; 15 (5.7%) had abnormal TCD. The mean TAMV at trial completion was 131.9 ± SD 25.7 cm/sec. Four participants without abnormal enrolment TCD developed acute stroke within the initial 16 months (incidence 0.62 per 100 person-years): two had enrolment HbF ≤3.1%, two had low oxygen saturation (90%), and one had recurring severe anemia necessitating multiple transfusions. Apparent stroke precipitants were severe malaria, acute chest syndrome, recent pain crisis, or uncertain cause. At trial completion, eight additional participants had a higher risk TCD category than at enrolment.
Conclusion: The effectiveness of TCD screening for stroke prevention may vary by region, as no participant with an incident stroke was at the highest risk. Antecedent and/or ongoing SCA-related risks of anemia, low HbF, hypoxemia, infections, and/or disease complications likely contributed to stroke despite trial HU. Results suggest that TCD alone may not fully identify the highest stroke risk in the region, and there is a need for primary stroke prevention from early childhood and continuous hydroxyurea therapy.
期刊介绍：
Pediatric Blood & Cancer publishes the highest quality manuscripts describing basic and clinical investigations of blood disorders and malignant diseases of childhood including diagnosis, treatment, epidemiology, etiology, biology, and molecular and clinical genetics of these diseases as they affect children, adolescents, and young adults. Pediatric Blood & Cancer will also include studies on such treatment options as hematopoietic stem cell transplantation, immunology, and gene therapy.
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