Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Mucopolysaccharidosis IV a (Morquio A): An International Retrospective Study of 40 Children
Rattachement africain : us, cn, tr, jp, nl, ir, sg, ca. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Mucopolysaccharidosis IV A (MPS IVA) or Morquio A Syndrome is a lysosomal storage disorder, which results from a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) causing deposition of glycosaminoglycans, keratan sulfate and chondroitin-6-sulfate. Clinical manifestations include progressive skeletal dysplasia, and most patients become wheelchair-bound in their second decade of life. The current standard of care for Morquio A is weekly enzyme replacement therapy (ERT). However, ERT provides limited long-term benefits for this disease and is unavailable in many countries. Allogeneic hematopoietic stem cell transplant (HSCT) is a way to provide a life-long endogenous enzyme. We performed a retrospective study of 40 patients who underwent allogeneic HSCT at 9 international centers. 13 patients received ERT pre-HSCT. 43 transplants were performed due to graft failure in three patients. 77% received matched or mismatched unrelated donor transplants while 70% received peripheral blood stem cell grafts. Overall survival was 90%. There was no mortality in the bone marrow graft group. Graft-versus-host disease (GVHD) was a direct or indirect contributor to mortality in 3 out of 4 patients. Median myeloid engraftment was 100% at the last follow-up with a median follow-up of 3.7 years; and median time for neutrophil and platelet engraftment was 12 and 13 days, respectively. Incidence of grades II-IV acute and chronic GVHD were 40% and 15%, respectively. Disease-specific outcomes, including Activities of Daily Living (ADL) scores and serial growth, were available in 21 and 16 surviving patients, respectively. Baseline and post-transplant ADL data in 11 patients showed improvement, while only post-transplant ADL data in 10 patients showed high scores in all but two patients. Notably, in patients transplanted below the age of 24 months, growth continued at 3rd to <5th percentiles, and in one patient, at 5th to 10th percentile at 2-5 years after transplant. In 4 patients transplanted at greater than 2 but less than 3 years of age, growth continued at less than the 3rd percentile at 4-8 years of follow-up. One patient transplanted at less than one year of age had severe GVHD requiring long-term steroid use and flattening of the growth curve. In additional ten patients, growth according to Morquio growth charts (Montano et al. 2008) showed stabilization or improvement following HSCT, albeit at limited time points. Allogeneic HSCT for Morquio A may be considered for young patients, ideally below the age of 3 years, to optimize growth and ADL. The role of ERT before HSCT to decrease disease burden and improve outcomes needs further investigation. Use of bone marrow as stem cell source whenever possible, and robust GVHD prophylaxis may improve outcomes. Additionally, long-term benefits and risks need to be studied. Future options of gene therapy may further optimize outcomes for this rare disease.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Mucopolysaccharidosis IV a (Morquio A): An International Retrospective Study of 40 Children
- Date Crossref
- 01/02/2025
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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UCSF Benioff Children's Hospital and Blood and Marrow Transplantation pays non établi dans la noticeÉtablissement de santé
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University of California pays non établi dans la noticeUniversité ou école supérieure
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Shanghai Children's Medical Center pays non établi dans la noticeÉtablissement de santé
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Shanghai Jiao Tong University Department of Hematology/Oncology pays non établi dans la noticeUniversité ou école supérieure
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Bahçeşehir University pays non établi dans la noticeUniversité ou école supérieure
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Tokai University Hospital pays non établi dans la noticeÉtablissement de santé
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Princess Máxima Center pays non établi dans la noticeÉtablissement de santé
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Ahvaz Jundishapur University of Medical Sciences pays non établi dans la noticeUniversité ou école supérieure
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KK Women's and Children's Hospital Genetics pays non établi dans la noticeÉtablissement de santé
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The University of Texas MD Anderson Cancer Center Department of Pediatrics pays non établi dans la noticeÉtablissement de santé
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Alberta Children's Hospital Section of Oncology/Cellular Therapy pays non établi dans la noticeÉtablissement de santé
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Alfred I. duPont Hospital for Children pays non établi dans la noticeÉtablissement de santé
and Blood and Marrow Transplantation — UCSF Benioff Children's Hospital, University of California et Shanghai Children's Medical Center, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.