Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Mucopolysaccharidosis IV a (Morquio A): An International Retrospective Study of 40 Children
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".