O-01: hydroxyurea reduces the transfusion burden in children with sickle cell anemia in sub-saharan africa: the reach experience

Purpose: Many children with sickle cell anemia (SCA) require blood transfusions, which carry risks and utilize a scarce resource globally, particularly in Africa. Realizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) has documented the safety, feasibility, and benefits of hydroxyurea for children with SCA living in sub-Saharan Africa. In REACH, hydroxyurea escalated to maximum tolerated dose (MTD) significantly decreased vaso-occlusive events, malaria, and death; transfusions were decreased by ~70% over 30 months of treatment when compared to the 2-month screening period. Characterizing and investigating how hydroxyurea reduces transfusion needs in REACH could contribute to improved clinical understanding, better outcomes, a decreased transfusion burden, and preservation of the blood supply in these limited-resource settings. Materials and methods: Transfusions were recorded prospectively in the REACH REDCap database. Transfusion rates and indications were compared during screening and treatment. Risk factors for receiving a transfusion were identified using time-varying predictors and landmark analysis. Univariate relationships were assessed using the Anderson-Gill model, plus multiple regression to estimate Hazard Ratios (HR) with 95% confidence intervals (CI). Results: A total of 635 children with HbSS from Angola, Democratic Republic of Congo, Kenya, and Uganda enrolled, and 606 started hydroxyurea treatment. During screening, 48 transfusions were administered to 43 children, and during the treatment phase 405 transfusions were administered to 214 children over a mean treatment time of 5.2 ± 1.3 years. The transfusion rate was 43.3 per 100 patient-years during screening, which decreased to 22.0 per 100 patient-years during the initial fixed dose treatment period (IRR = 0.50; 95%CI = 0.35-0.74, p<0.001 compared to screening) and then decreased further to 12.1 per 100 patient-years during the dose escalation period (IRR = 0.28; 95%CI = 0.21-0.39, p<0.001 compared to screening; IRR = 0.54; 95%CI = 0.43-0.73, p<0.001 compared to fixed-dose). For every 100 children treated for one year with hydroxyurea dose escalation, there were 31.4 fewer transfusions compared to the untreated screening period (number needed to treat = 3.2). Children with palpable splenomegaly at enrollment had a higher likelihood of receiving a transfusion during the trial (HR 1.98, 95% CI 1.59 to 2.47, p<0.0001). Age, gender, alpha thalassemia trait, and G6PD deficiency were not associated with differences in transfusion rates. Conclusion: Hydroxyurea significantly reduces blood transfusion administration in children with SCA in sub-Saharan Africa, especially when escalated to MTD. Overall, this demonstrates that treating children with SCA may not only improve individual patient outcomes through reduction in anemia, transfusion burden, and transfusion-associated complications including infections, but may also to help preserve the scarce blood supply for the benefit of the larger population. For example, applying similar outcomes to the population of Uganda predicts that about 30,000 transfusions per year are administered to patients with SCA and that with universal screening and treatment that 21,600 (72%) of these could be preventable, representing ~20% of all annual transfusions administered. The fact that treating SCA patients can benefit the entire population through reducing blood transfusion utilization reframes the importance of treating this population from an individual health decision to a public health strategy. R. WARE, MD, PHD declares a conflict of interest: Consultancy, Expert: DSMB Member for Novartis and Editas clinical trials; Medical Advisor for Nova Laboratories Research support/Scientific studies: Hydroxyurea donations from Bristol Myers Squibb and Addmedica; equipment donation from Hemex Health