Is Severity Score Associated With Indication for Hematopoietic Stem Cell Transplantation in Individuals With Sickle Cell Anemia?

Manifestations of sickle cell disease (SCD) begin early in childhood and cause morbidity and decreased life expectancy. Hematopoietic stem cell transplantation (HSCT) is curative but associated with risk of mortality attributable to the transplant. This risk should be counterbalanced with SCD morbidity and mortality. A severity score using a Bayesian network model was previously validated to predict the risk of death in adult individuals with SCD. The objective of this study is to calculate the severity scores of participants in a multicenter cohort of Brazilians with SCD, using a previously published Bayesian network-derived score, associated with risk of death and then compare the severity scores between participants with and without an indication for HSCT as defined by the Brazilian Ministry of Health (MoH) criteria. This is an observational, retrospective study. We analyzed 2063 individuals with sickle cell anemia from the Recipient Epidemiology and Donor Evaluation Study-III Brazil SCD cohort and applied a Bayesian network-derived score to compare candidates and non-candidates for HSCT according to the Brazilian MoH transplant criteria. Classical statistical methods were used to analyze data and make comparisons. We compared severity scores between cohort members with (n = 431) and without (n = 1632) HSCT indications according to Brazilian MoH. Scores were not different in adult participants with ≥1 HSCT indication when compared to those with no indication (mean 0.342 versus 0.292; median 0.194 versus 0.183, P = .354) and receiver operating characteristic curves did not demonstrate an obvious threshold to differentiate participants with or without HSCT indications. Severity score may predict risk of death but does not differentiate HSCT candidates. Current indications should be evaluated to ensure that patients with more severe disease who might benefit from HSCT are appropriately identified.

Identification and Characterization of Hematopoietic Stem Cell Transplant Candidates in a Sickle Cell Disease Cohort.

Sickle cell disease (SCD) is associated with significant morbidity, and allogeneic hematopoietic stem cell transplantation (HSCT) remains the primary curative treatment. Recently, the Brazilian Ministry of Health released a regulation that required the publically funded healthcare system to pay for HSCT for SCD patients with defined indications. We used an existing 2794-member SCD cohort established during 2013 to 2015 to characterize candidates for HSCT and estimate the number of possible donors. Of 2064 patients with SC anemia (SCA), 152 of 974 children (16%) and 279 of 1090 adults (26%) had at least 1 HSCT indication. The most common indication for transplant was stroke (n = 239) followed by avascular necrosis (n = 96), priapism (n = 82), cerebrovascular disease (n = 55), >2 vaso-occlusive episodes (n = 38), alloantibodies and chronic transfusion therapy (n = 18), and >2 acute chest syndrome episodes (n = 11). Increasing age, number of transfusions, abnormal transcranial Doppler, retinopathy, dactylitis, and use of hydroxyurea were more frequent in the 152 children with an indication for HSCT compared with 822 without (P < .001). Of 152 children and 279 adults meeting the eligibility definition, 77 (50%) and 204 (73%), respectively, had at least 1 non-SCD full sibling who could potentially serve as a donor. In conclusion, in a large cohort of SCA patients, 16% of children and 26% of adults had at least 1 indication for HSCT; these indications were associated with the severity of the disease. This study provides clinical data necessary for estimating the costs and infrastructure that would be required to implement HSCT in a public healthcare system.

Clinical and genetic ancestry profile of a large multi-centre sickle cell disease cohort in Brazil.

Approximately 3500 children with sickle cell disease (SCD) are born in Brazil each year, but the burden of SCD morbidity is not fully characterised. A large, multi-centre cohort was established to characterise clinical outcomes in the Brazilian SCD population and create the infrastructure to perform genotype-phenotype association studies. Eligible patients were randomly selected from participating sites and recruited at routine visits. A biorepository of blood samples was created and comprehensive demographic and clinical outcome data were entered in a centralized electronic database. Peripheral blood genome-wide single nucleotide polymorphism (SNP) genotyping was performed using a customized Transfusion Medicine (TM) Array. A total of 2795 participants at six Brazilian sites were enrolled between 2013 and 2015. The cohort included slight predominance of children <18 years (55·9%) and females (53·0%). Haemoglobin (Hb) SS was the most common SCD genotype (70·7%), followed by HbSC (23%), Sß0 (3·0%) and Sß+ (2·9%). SNP data from the TM Array were analysed to evaluate the genetic ancestry of the cohort and revealed significant admixture among the population. Demographics and clinical complications, stratified by age and SCD genotype, are summarized and future studies in this cohort are discussed.