Patrick T. McGann

Burnout is associated with physician attrition, medical errors, and decreased productivity. Around 45% of hematology-oncology physicians in the United States report burnout. However, burnout rates among hematologist-oncologists specializing in sickle cell disease (SCD) are unknown. The complex, high-acuity nature of SCD along with systemic barriers may put SCD providers at high risk. We compared burnout prevalence between SCD and non–SCD physicians. We conducted a nationwide survey of US hematology-oncology physicians assessing burnout, grit, resilience, and career characteristics. Respondents self-identified as SCD focused (n = 55) or non–SCD focused (n = 104). Between-group comparisons used χ2/Fisher exact tests and t tests/Mann-Whitney U tests. Logistic regression evaluated confounders. Burnout was more prevalent among SCD physicians than non–SCD-focused physicians (60% vs 44%, P = .046), despite similar grit and resilience. Work hours were similar between groups, but SCD physicians participated less in recreational activities (45% vs 59% ≥2 times per week, P = .006), expressed less job pride (47% vs 65% strongly agreed, P = .031), and were more likely to earn <$350 000 annually (64% vs 40%, P = .005). They also had more years in practice and more often worked in academia or leadership roles (all P< .05). Recreation and job pride mediated burnout in SCD physicians. SCD physicians experience higher burnout than non–SCD physicians in the overall field of hematology-oncology, despite comparable grit and resilience. Less recreation and job pride may affect burnout in SCD physicians. This suggests that higher burnout in SCD physicians may be driven by systemic factors that disproportionately affect those who care for persons with SCD.

Hydroxyurea provides effective disease-modifying treatment for people with sickle cell anemia (SCA), especially when escalated to maximum tolerated dose (MTD), which has wide interpatient dosing variability due to pharmacokinetic (PK) differences. Whether hydroxyurea PK parameters differ among children with SCA in different global regions is unknown. We compared hydroxyurea PK parameters among children with SCA from 5 clinical trials: HUSTLE (United States), TREAT (United States), NOHARM (Uganda), REACH (Uganda and Kenya), and EXTEND (Jamaica). Key hydroxyurea PK parameters were determined using HdxSim, a validated hydroxyurea PK software program. The results were compared across regions by analysis of variance. PK profiles from 451 children with SCA (146 from the United States, 265 from Africa, and 40 from the Caribbean) were included. Children from Africa had slightly lower volumes of distribution, but absorption rate and clearance were similar across regions. The PK-recommended doses to achieve MTD were statistically different but clinically similar across the United States (26.6 ± 5.9 mg/kg per day), Africa (27.6 ± 6.5 mg/kg per day), and the Caribbean (25.2 ± 4.7 mg/kg per day) (P = .04). In multivariable regression, younger age and increased reticulocyte counts were associated with higher PK-recommended doses. Hydroxyurea PK parameters in children with SCA differ minimally across global populations, predicting clinically similar doses to achieve MTD. Individualized hydroxyurea dosing based on a PK-population model derived from US children with SCA can be used broadly to maximize the benefits of this critical medication in other global populations. These trials were registered at www.ClinicalTrials.gov as #NCT00305175 (HUSTLE), #NCT02286154 (TREAT), #NCT01976416 (NOHARM), #NCT01966731 (REACH), and #NCT02556099 (EXTEND).

Crizanlizumab and voxelotor were several of the first drugs to receive the US Food and Drug Administration (FDA) approval for sickle cell disease (SCD) since the approval of hydroxyurea in 1998. Although initially exciting, additional data regarding efficacy and safety have since emerged for both drugs, first with the removal of crizanlizumab from the European market in August 2023. This was followed by Pfizer’s abrupt decision in September 2024 to pull voxelotor from global markets owing to higher mortality in those on the drug vs placebo. These drugs highlight the importance and limitations of the FDA’s accelerated approval process. In addition, the impact of these events, without transparent messaging, potentially threatened the fragile trust that providers have more recently been able to build with the SCD population regarding the medical system and research. Although there is a need for new therapies in SCD, we must prioritize both safety and efficacy and maintain trust in this population.

Globally, an estimated 300 million individuals have sickle cell trait (SCT), the carrier state for sickle cell disease (SCD). Although SCD is associated with increased morbidity and shortened life span, SCT has a life span comparable with that of the general population. However, “sickle cell crisis” has been used as a cause of death for decedents with SCT in reports of exertion-related death in athletes, military personnel, and individuals in police custody. To appraise this practice, the American Society of Hematology convened an expert panel of hematologists and forensic pathologists to conduct a systematic review of the literature relating to the occurrence of sickle cell pain crises and exertion-related mortality in people with SCT. Multiple bibliographic databases were searched with controlled vocabulary and keywords related to “sickle cell trait,” “vaso-occlusive pain,” and “death,” yielding 18 of 1474 citations. Independent pairs of reviewers selected studies and extracted data. We found no studies comparing uncomplicated acute pain crises in individuals with SCT and SCD. Additionally, no study was identified to support the occurrence of acute vaso-occlusive pain crises in individuals with SCT. Furthermore, this systematic review did not identify any evidence to support an association between SCT and sudden unexplained death in the absence of exertion-related rhabdomyolysis. We conclude that there are no data to support the diagnosis of acute vaso-occlusive sickle cell crisis as a cause of death in SCT, nor does the available evidence support the use of SCT as a cause of exertion-related death without rhabdomyolysis.

Sickle cell disease (SCD) is a common and life‐threatening global health problem, with more than 500 000 affected infants born annually. The burden of SCD in sub‐Saharan Africa is well established, but the comparably high prevalence in India is not well recognized and many consider SCD in India to be less severe. In their paper, a national study in India demonstrated the significant impact of SCD for patients, families and the healthcare system, supporting a call to action to recognize and address SCD as a serious and common health condition in India.Commentary on: Seth et al. Burden of vaso‐occlusive crisis, its management, and impact on quality of life of Indian sickle cell disease patients. Br J Haematol 2025; 206:296‐309.