Children with infantile-onset lysosomal acid lipase deficiency (LAL-D) who receive enzyme replacement therapy (ERT) prior to hematopoietic cell transplantation (HCT) may have higher survival rates than children not treated with ERT, according to a study published in Bone Marrow Transplantation.

This retrospective registry study was conducted on behalf of the Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation (EBMT). The researchers identified a cohort of 24 children with LAL-D who underwent HCT between 1999 and 2019.

Several outcomes were evaluated, including overall survival, event-free survival (an event was defined as death or graft failure), toxicity, graft-vs-host disease, and long-term graft function and disease outcomes. The study authors used the log-rank test to examine the predictors of overall survival, including ERT, age at transplant, donor, stem cell source, and conditioning.

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According to the results, the 5-year overall survival and event-free survival rates for the entire cohort were 38% and 33%, respectively. The overall survival rate was not affected by the age at transplant, conditioning, donor type, or stem cell source.

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There were 16 deaths in the cohort. Eight patients suffered transplant-related complications (4 veno-occlusive disease, 4 multiorgan failure), 6 suffered disease-related complications, and 2 causes of death remain unknown.

Of 6 patients who died after experiencing graft failure, 2 had grade 1 or 2 acute graft-vs-host disease and 1 had the chronic form of the condition. There were no reports of grade 3 or 4 acute graft-vs-host disease.

Of the patients who received ERT and reduced toxicity conditioning, 80% survived the transplantation (4 out of 5), while only 21% survived among those who did not (4 out of 19). Of the 4 surviving infants who received ERT, 2 kept receiving a lower dose at increased intervals and 2 discontinued the treatment.

Successful transplantation led to the improvement and resolution of gut symptoms as well as normal liver function tests. Only 1 patient received antilipid treatment with pravastatin.

“The challenges of ERT are the development of antibodies that renders the therapy less effective, and the need for a life-long expensive therapy,” Lum and colleagues wrote. “As the donor’s monocyte intestinal engraftment is slow as evidenced from serial gut biopsy changes, ERT has been gradually reduced and discontinued with close monitoring of rebound of disease manifestation. Therefore, there is a potential of stopping ERT in these patients after HCT.”

Without any treatment, infants with LAL-D suffer growth failure and rapidly progressive hepatic disease, leading to death in the first 6 months of life.


Lum SH, Minkov M, Jones SA, et al. Outcome of haematopoietic cell transplantation in children with lysosomal acid lipase deficiency: a study on behalf of the EBMT Inborn Errors Working PartyBone Marrow Transplant. Published online February 14, 2023. doi:10.1038/s41409-023-01918-4