Hematopoietic cell transplantation (HCT) is an established cure for sickle cell disease (SCD) supported by long-term survival, but long-term organ function data are lacking. We sought to describe organ function and assess predictors for dysfunction in a retrospective cohort (n = 247) through the Sickle cell Transplant Advocacy and Research alliance. Patients with <1-year follow-up or graft rejection/second HCT were excluded. Organ function data were collected from last follow-up. Primary measures were organ function, comparing pre- and post-HCT. Bivariable and multivariable analyses were performed for predictors of dysfunction. Median age at HCT was 9.4 years; the majority had HbSS (88.2%) and severe clinical phenotype (65.4%). Most received matched related (76.9%) bone marrow (83.3%) with myeloablative conditioning (MAC; 57.1%). Acute and chronic graft-versus-host disease (GVHD) developed in 24.0% and 24.8%. Thirteen patients (5.3%) died ≥1 year after HCT, primarily from GVHD or infection. More post-HCT patients had low ejection or shortening fractions than pre-HCT (0.6% → 6.0%, P = .007 and 0% → 4.6%, P = .003). The proportion with lung disease remained stable. Eight patients (3.2%) had overt stroke; most had normal (28.3%) or stable (50.3%) brain magnetic resonance imaging. On multivariable analysis, cardiac dysfunction was associated with MAC (odds ratio [OR] = 2.71; 95% confidence interval [CI], 1.09-6.77; P = .033) and severe acute GVHD (OR = 2.41; 95% CI, 1.04-5.62; P = .041). Neurologic events were associated with central nervous system indication (OR = 2.88; 95% CI, 2.00-4.12; P < .001). Overall organ dysfunction was associated with age ≥16 years (OR = 2.26; 95% CI, 1.35-3.78; P = .002) and clinically severe disease (OR = 1.64; 95% CI, 1.02-2.63; P = .043). In conclusion, our results support consideration of HCT at younger age and use of less intense conditioning.

An increasing number of neuropsychologists are evaluating children with congenital heart disease (CHD). When conceptualizing results, the provider must consider medical risks such as abnormal neuroimaging and comorbidities, along with social risks such as socioeconomic status. The aim of the current study was to examine the influence of parent income and education on IQ and achievement across race groups in adolescents with CHD, while also accounting for medical risk (e.g., gestational age, number of ventricles, neuroimaging). This is a single-center cross-sectional study, including 92 children ages 12–19 years (median 14.9 years; 59% male; 71% White; 29% Black) with high risk CHD (i.e., cardiac surgery <12 months) who were referred for a neuropsychological evaluation. Retrospective data were retrieved from a larger clinical registry. Patients completed an intellectual assessment (WISC-V; WAIS-IV; WASI-II), Word Reading and Math Calculation tests. Parents completed questionnaires assessing the family environment [income, parent education]. Results revealed significant differences in IQ when comparing children who were Black versus White (11.4 point IQ difference); however, around 70% of this variance was explained by parent income and education. Medical variables accounted for 12% of the variance in IQ. For academics, parent income and education accounted for 91.5% and 78.8% of the variance in race group differences for reading and math, respectively. Medical risk and sex explained 11.7% and 14.7% of the variance in reading and math, respectively. Findings suggest that sociodemographic factors should be weighed heavily during the neuropsychological evaluation, including prioritizing risk, making recommendations, and facilitating referrals.

Conditioning regimens for hematopoietic cell transplant (HCT) in patients with sickle cell disease (SCD) place patients at risk for reproductive health issues. The purpose of this study was to assess reproductive health and reports of fertility counseling in patients with SCD who received a transplant. This was a secondary analysis of gonadal hormone production, future infertility risk assessment, and parent-proxy/patient reports of fertility counseling in SCD transplant recipients who are currently pubertal and were enrolled in the Atlanta sites of the Sickle Cell Transplant Evaluation of Long-term and Late Effects Registry (STELLAR) between May 2017 and October 2023. Clinical information was abstracted from medical records and reproductive health survey data from the STELLAR database. Descriptive statistics were reported as median (interquartile range [IQR]) or percentages. There were 20 females and 12 males in the study population. Females were median (IQR) 19.6 (9.4) years old and males 20.8 (11.4) years old at the time of the study. Transplants most commonly occurred in the decade 2010 to 2019 at 10.7 (4.8) years old for females and 11.1 (4.1) years old for males. Most participants received bone marrow stem cells (95.0% females, 100.0% males) from matched sibling donors (90.0% females, 100.0% males). Participants received one of seven HCT conditioning regimens with cyclophosphamide equivalent doses ranging from 3388 to 9706 mg/m². The majority of females (90.0%) had diminished ovarian reserve with low anti-Mullerian hormone levels, and 61.1% had premature ovarian insufficiency with two follicle-stimulating hormone levels (FSH) ≥40 mIU/mL post-HCT. All males had normal testosterone levels, but 63.6% had elevated FSH levels suggestive of impaired spermatogenesis post-HCT. Parent proxies (for patients <18 years old) and patients ≥18 years old completed surveys 9.0 years (5.2) and 7.9 years (9.3) since HCT in females and males respectively. Twenty-five percent of parent proxies and 45% of patients reported that they had not been informed by a healthcare provider of the risk of infertility post-transplant. There are high rates of gonadal dysfunction post-HCT, but many parent proxies and patients do not recall being told of the risk for future infertility. More effective methods of education are warranted to ensure SCD patients and their families clearly understand the risk for reproductive health issues post-HCT.

Background: Prenatal maternal folate intake is associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL), but how this interacts with children’s genetic predisposition to folate deficiency remains unclear. Methods: We used Mendelian randomization to investigate the causal link among serum folate, total homocysteine, and B vitamins on ALL using independent genetic instruments. These were evaluated in two independent childhood ALL genome-wide association studies: the California Childhood Cancer Record Linkage Project and the California Childhood Leukemia Study, the latter with available self-reported periconceptional nutrition data. Logistic regressions assessed the interrelationship between maternal nutrition and children’s folate metabolism–related polygenic risk score (PRS) and methylenetetrahydrofolate reductase rs1801133 genotype. Results: Mendelian randomization analyses showed that higher genetically predicted serum folate was associated with reduced ALL risk [meta-analysis OR, 0.58; 95% confidence interval (CI), 0.34–0.97]. In Latinos, higher periconceptional folate intake from food mitigated and reversed the elevated risk associated with low folate PRS and the rs1801133 T allele. As the total folate intake increased, the odds of ALL shifted from 1.31 (95% CI, 1.01–1.69) to 0.53 (95% CI, 0.30–0.91) per 0.05-unit decrease in folate PRS and from 1.71 (95% CI, 1.02–2.88) to 0.24 (95% CI, 0.07–0.79) per T allele. In contrast, among non-Latino Whites, the corresponding ORs remained at 1.24 (95% CI, 1.07–1.43) and 1.40 (95% CI, 1.04–1.91). Conclusions: Maternal folate intake mitigated genetic liability against ALL in Latinos only, whereas genetic liability persisted in non-Latino Whites. Impact: This study highlights the need for personalized approaches to maximize the benefits of folic acid supplementation programs.