A systematic review comparing allogeneic hematopoietic stem cell transplant to gene therapy in sickle cell disease

Hematology. 2023 Dec;28(1):2163357. doi: 10.1080/16078454.2022.2163357.


Introduction: Allogeneic hematopoietic stem cell transplant (HSCT) and gene therapy (GT) are two potentially curative approaches for sickle cell disease (SCD), but they have never been compared in clinical trials.

Objective: To compare the safety and efficacy of HSCT and GT to assist clinicians and patients in making informed treatment decisions.

Methods: Phase I-III clinical trials and case reports/series were included. Regimens included HSCT from all stem cell sources, lentiviral gene therapy, and gene editing, with any conditioning regimen. We searched Medline and EMBASE databases as of 1st June 2020 for studies reporting HSCT and GT outcomes in SCD. The Newcastle-Ottawa scale was used to assess the risk of bias. Descriptive statistics and post-hoc imputation for standard deviations of mean change in FEV1 and FVC were performed.

Results: In total, 56 studies (HSCT, n = 53; GT, n = 3) representing 1,198 patients met inclusion criteria (HSCT, n = 1,158; GT, n = 40). Length of follow-up was 3,881.5 and 58.7 patient-years for HSCT and GT, respectively. Overall quality of evidence was low, with no randomized controlled trials identified. Two-year overall survival for HSCT was 91%; mortality was 2.5% for GT. Acute chest syndrome and vaso-occlusive episodes were reduced post-HSCT and GT. Meta-analysis was not possible due to lack of comparator and heterogeneity in outcome measures reporting. Very few studies reported post-transplant end-organ function. Six secondary malignancies (5 post-HSCT, 1 post-GT) were reported.

Discussion: Reporting of SCD-related complications and patient-important outcomes is lacking for both strategies. We advocate for standardized reporting to better compare outcomes within and between treatment groups.

Keywords: Sickle cell disease; allogeneic hematopoietic stem cell transplant; gene therapy; systematic review.

Publication types

  • Systematic Review

MeSH terms

  • Acute Chest Syndrome*
  • Anemia, Sickle Cell* / complications
  • Anemia, Sickle Cell* / genetics
  • Anemia, Sickle Cell* / therapy
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans