Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Mucopolysaccharidosis IV a (Morquio A): An International Retrospective Study of 40 Children
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».