Hematopoietic Stem Cell Transplantation Improves Pediatric SCD Outcomes

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A recent systematic review and meta-analysis evaluated the safety and efficacy of hematopoietic stem cell transplantation (HSCT) in children with sickle cell disease (SCD) based on a comprehensive search of six databases.

Performed from inception until January 2024, the search identified nineteen papers matching inclusion criteria and deemed as of fair quality—results from the analysis demonstrate the efficacy and safety of HSCT, with pooled survival rates exceeding 90%.

“SCD is increasingly being used as an indication of HSCT in several countries. The results of this study are in line with other studies and offer a basis for trying to improve these patients’ outcomes,” wrote the investigative team, led by Najim Z. Alshahrani, MD, PhD, MPH, department of family and community medicine, University of Jeddah.

Although the introduction of novel agents, including voxelotor and crizanlizumab, has transformed the management of SCD, leading to changes in causes of SCD-related mortality, the disease is still linked to significant morbidity and short life expectancy. The US Food and Drug Administration (FDA) recently approved two landmark cell-based gene therapies, but the only scientifically proven treatment to resolve the clinical phenotype is HSCT.

However, HSCT coexists with notable toxicities and potentially fatal complications, despite its curative effect for the majority of patients with SCD. Multi-study evidence has pointed to favorable long-term outcomes of HSCT in children with SCD, with more than 90% of transplants successful if there is an HLA-matched related donor.

Alshahrani and colleagues pointed to several remaining barriers preventing the widespread use of HSCT for the treatment of SCD, including the possibility of graft failure, graft-versus-host disease, and a lack of compatible HLA-matched donors. They noted it is “critical” to recognize patients with SCD as a potential candidate for HSCT as soon as possible.

The current systematic review and meta-analysis aimed to investigate the effect of HSCT on children with SCD, related to overall survival, event-free survival, graft failure, and mortality. From database creation to January 2024, a search was performed of Web of Science, CINAHL, Embase, Google Scholar, Cochrane Library, and PubMed/Medline.

Two reviewers separately performed the data extraction —inclusion criteria for articles included an observational study design on outcomes of HSCT in a pediatric SCD population, a sample size ≥10, publications reporting related study outcomes, a median follow-up of ≥1 year, and studies published as original articles. The Newcastle-Ottawa Quality Assessment tool was utilized to assess the quality of the identified publications.

Among 1064 studies undergoing screening, 347 abstracts were considered eligible and collected for a full-text examination. Overall, the systematic review and meta-analysis contained nineteen papers matching the inclusion criteria. Papers were either retrospective (n = 14), prospective (n = 3), or a clinical trial (n = 2), and the sample size included 1945 individuals.

Upon analysis, the pooled overall survival rate was high, at 92% (95% CI, 90.3–93.5). Alshahrani and colleagues identified a similarly high event-free survival rate, at 85.8% (95% CI, 83.7–-87.7). However, the analysis showed low pooled rates of both graft failure (6.9%; 95% CI, 5.3–8.9) and mortality (7.4%; 95% CI, 5–10.7).

In subgroup analysis, investigators detected little difference in the occurrence of overall survival, graft failure, and mortality in comparison studies published before and after 2015 (P > 0.5). However, they noted the occurrence rate of event-free survival was notably higher in studies published after 2015 (87.75 vs. 83.4%; P = .035).

Moreover, the event rates of overall survival, event-free survival, and graft failure were significantly different between retrospective, prospective, and clinical trial study designs (P < .05). No identifiable variation was observed in the mortality rate (P >.05).

Indicating referral to HSCT clinics should be recommended in early life, Alshahrani and colleagues noted further investigators are required to raise the number of patients who can receive HSCT.

“When compared to existing treatments, HSCT appears to be a promising alternative for children with severe SCD; nonetheless, its application is presently restricted to clinical protocols and reference facilities,” investigators wrote.

References

1. _{Alshahrani NZ, Algethami MR. The effectiveness of hematopoietic stem cell transplantation in treating pediatric sickle cell disease: Systematic review and meta-analysis. Saudi Pharm J. 2024;32(5):102049. doi:10.1016/j.jsps.2024.102049}