Global perspectives on cellular therapy for children with sickle cell disease

Abstract

Purpose of reviewLow-income and middle-income countries (LMICs), primarily in sub-Saharan Africa (SSA), predominantly experience the burden of sickle cell disease (SCD). High frequency of acute and chronic complications leads to increased utilization of healthcare, which burdens fragile health systems. Mortality for children with limited healthcare access remains alarmingly high. Cellular based therapies such as allogeneic hematopoietic stem cell transplant (HSCT) are increasingly used in resource-rich settings as curative therapy for SCD. Broad access to curative therapies for SCD in SSA would dramatically alter the global impact of the disease. Recent findingsCurrently, application of cellular based therapies in LMICs is limited by cost, personnel, and availability of HSCT-specific technologies and supportive care. Despite the challenges, HSCT for SCD is moving forward in LMICs. Highly anticipated gene modification therapies have recently proven well tolerated and feasible in clinical trials in resource-rich countries, but access remains extremely limited.

The effectiveness of hematopoietic stem cell transplantation in treating pediatric sickle cell disease: Systematic review and meta-analysis

“…These comprise, among other things, the possibility of graft failure (GF), graft-versus-host disease (GVHD), and a lack of compatible related donors who match the patient's HLA, though the latter has recently improved due to the availability of haploidentical and matched unrelated donors (MUDs) ( Bolaños-Meade et al, 2012 , Dallas et al, 2013 , Gluckman et al, 2017 ). Regrettably, individuals in low-income nations also have restricted access to HSCT, which raises the mortality rate from SCD ( John et al, 2022 , Krishnamurti, 2021 ).…”

Challenges in the treatment of melanoma with BRAF and MEK inhibitors in patients with sickle cell disease: case report and review of the literature

“…3 Novel therapies include anti-sickling agents, targeting adhesion molecules and radical approaches such as gene therapy or gene editing, while hemopoietic stem cell transplantation is the only established curative approach. 4–7…”

“…3 Novel therapies include anti-sickling agents, targeting adhesion molecules and radical approaches such as gene therapy or gene editing, while hemopoietic stem cell transplantation is the only established curative approach. [4][5][6][7] Patient counseling and education are a crucial part of the management of patients with SCD and focuses on appreciating the importance of routine health-care encounters and early intervention for Challenges in the treatment of melanoma with BRAF and MEK inhibitors in patients with sickle cell disease: case report and review of the literature acute and chronic complications of the disease, as well as on recognizing warning signs of acute illness. Factors that trigger sickling and may cause acute complications such as VOC include dehydration, physical exhaustion, exposure to cold, sudden temperature or altitude changes, fever and infections, and their avoidance and reversal is mandatory.…”

Excellent outcome of stem cell transplantation for sickle cell disease

“…Potentially curative gene-modifying treatments are in clinical testing and early efficacy results look promising, but long-term safety still needs to be demonstrated [ 4 , 5 ]. Even if approved, these treatments will not be available to the majority of SCD patients for socio-economic reasons [ 6 ]. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative option for symptomatic SCD and can improve quality of life of affected patients and families [ 7 , 8 ], but can be associated with significant therapy-related morbidity and mortality.…”

“…HSCT from MMFD was increasingly successful over the last years due to improved methods of GVHD prevention by in vitro or in vivo lymphodepletion [ 17 – 20 ]. In vivo manipulation of alloreactive T-cells with post transplantation cyclophosphamide (PTCY) is attractive because of low GVHD rates reported in malignant disorders and its minimal economic impact, making it a feasible option also at HSCT centers in low to middle-income countries [ 6 , 16 , 21 ]. The published evidence of haploidentical HSCT with PTCY in SCD is growing but still limited [ 22 ].…”