Allogenic HSCT May Improve Sickle Cell Disease-Related Organ Dysfunction

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A new analysis summarized evidence on the effects of allogeneic HSCT on SCD-related organ dysfunction in pediatric and adult patients with SCD.

A systematic review and meta-analysis evaluated available evidence on organ function before and after allogeneic hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD).1

Organ complications related to SCD, secondary to frequent vaso-occlusive crises (VOCs), are the primary indication for allogeneic HSCT in patients with SCD. This review of two medical research databases revealed the effect of allogenic HSCT on pulmonary, cardiac, renal, splenic, cerebral, ophthalmological, and bone complications, among a population of children and adults with SCD.

“For more informed decision making for curative therapy, individuals with SCD and their families should better understand the impact of HSCT on their organ function,” wrote the investigative team, led by Elisabeth Dovern, MD, department of hematology, Amsterdam University Medical Centers.

Allogenic HSCT is the only currently recognized curative treatment option for SCD—previously, it had been primarily performed in children with an available matched sibling donor and myeloablative conditioning.2 Although long-term survival rates were impressive, the risk of graft-versus-host disease, infections, and other complications limited its widespread use, particularly for adults with SCD.

Updated HSCT approaches based on non-myeloablative conditioning regimens in adults with SCD have demonstrated strong safety, tolerability, and rates of successful engraftment. Dovern and colleagues noted the importance of understanding the larger impact of HSCT on SCD-related organ complications. They suggested the future usefulness of a systematic review of the effect of HSCT on complications when assessing patients with SCD for HSCT eligibility.

A systematic search was performed in the MEDLINE/PubMed and EMBASE databases up to September 2023 to identify studies reporting the effects of HSCT on organ function in patients with SCD. These identified articles were required to be a randomized controlled or retrospective study investigating the effect of allogeneic HSCT on SCD, report function on ≥1 organ of interest before and after HSCT and involve ≥1 year of follow-up.

After excluding duplicates, 823 articles were evaluated by two independent reviewers and 39 were ultimately included in the full review. Those 34 articles were assessed in the qualitative synthesis and 17 studies were used in the meta-analyses comparing organ function before and after HSCT. Characteristics of these studies showed 774 patients in the population, including 23.6% adults, 86.3% HLA-identical sibling donors, and 56.7% with a myeloablative conditioning regimen.

Evaluation of seven studies on pulmonary function before and after HSCT revealed no significant differences between the two periods, remaining stable across outcome parameters. Among three studies analyzed for tricuspid regurgitant jet velocity (TRJV), investigators observed a decline in the mean TRJV that did not reach statistical significance (P = .14).

A total of three studies evaluated renal function in children, finding the estimated glomerular filtration rate (eGFR) decreased significantly after HSCT (SMD, –0.80; P = .01). Two studies reported the presence of proteinuria before and after HSCT and showed a significant increase in the number of patients with proteinuria after HSCT (RR, 2.0; P <.01).

Among four studies evaluating splenic uptake, significantly more patients experienced splenic uptake after HSCT compared with the before period (RR, 0.31; P <.01), while an additional two studies revealed a significant decline in the presence of Howell-Jolly bodies and pitted red blood cells after HSCT (RR, 0.23; P = <.01).

In three studies assessing cerebral vasculopathy based on MRI, whole-brain cerebral blood flow significantly improved after HSCT (SMD, –1.39; P <.01). Multiple studies evaluated the occurrence of neurological events and identified no new ischemic infarcts after HSCT in successfully engrafted patients with SCD. A single study screened children with SCD for retinopathy, showing no significant changes before and after HSCT, and another found no significant changes before and after HSCT in osteonecrosis.

Overall, Dovern and colleagues indicated, that despite the improvements in SCD-related organ dysfunction after HSCT, transplantation-related toxicity may adversely impact patients with SCD and exacerbate organ decline.

“Further research, evaluating children and adults with SCD separately and accounting for the intensity (toxicity) of the conditioning regime and chimerism levels, is needed to better define which patients with SCD-related complications might benefit most from HSCT and which organ complications are likely to be irreversible,” Dovern and colleagues wrote.


  1. Dovern E, Aydin M, DeBaun MR, Alizade K, Biemond BJ, Nur E. Effect of allogeneic hematopoietic stem cell transplantation on sickle cell disease-related organ complications: A systematic review and meta-analysis. Am J Hematol. Published online March 22, 2024. doi:10.1002/ajh.27297
  2. Kassim AA, Sharma D. Hematopoietic stem cell transplantation for sickle cell disease: The changing landscape. Hematol Oncol Stem Cell Ther. 2017;10(4):259-266. doi:10.1016/j.hemonc.2017.05.008