Allogeneic Hematopoietic Cell Transplantation for Morquio A Syndrome: An International Retrospective Study

Background: Mucopolysaccharidosis IV A (MPS IVA) or Morquio A syndrome is a lysosomal storage disorder that results from a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), causing deposition of glycosaminoglycans, keratan sulfate, and chondroitin-6-sulfate in multiple organs. The main clinical manifestations include severe short stature, severe cervical spine stenosis, and progressive skeletal dysplasia, which leads to severe mobility limitation resulting in patients becoming wheelchair-bound in their second decade of life, and overall shortened life span. The current standard of care for Morquio A is weekly enzyme replacement therapy (ERT). However, ERT is expensive, not widely available worldwide, and offers limited long-term benefits. Allogeneic hematopoietic cell transplantation (HCT) is a way to provide a life-long endogenous enzyme and has the potential to improve outcomes. Objective: The main objectives of this study were to investigate the safety and assess the benefits of allogeneic HCT in the treatment of patients with Morquio A. Study Design: We performed a retrospective study of 41 patients who underwent allogeneic HCT at 9 international centers. Results: Forty-one patients with Morquio A received allogeneic HCT. Three patients experienced graft failure and underwent second transplants. Most (77%) of the transplants were performed using either matched or mismatched unrelated donors, and 71% of the transplants utilized peripheral blood stem cells as the graft source. The overall 3-year survival rate was 90.5%. Graft-versus-host disease (GVHD) was a direct or indirect contributor to mortality in 3 out of 4 patients. The median myeloid engraftment was 100% at the last follow-up, with a median follow-up of 3 years; the median times for neutrophil and platelet engraftment were 12 and 13 days, respectively. The incidence of grade II to IV acute GVHD was 35.5%. Interestingly, in patients who had received pretransplant ERT, the incidence of acute grade II to IV GVHD was 14.9%, compared to 45% in those who had not received pretransplant ERT (P = .075). The incidence of grades III to IV acute and chronic GVHD was 14.2% and 12.7%, respectively. When available, disease-specific outcomes showed complete to near normalization of metabolic biomarkers, as well as improvement in movement scores, stability of heart function, eyes, and cervical spine stenosis. Notably, in patients transplanted below the age of 3 years, growth continued in 6 out of 8 patients, while this effect was less notable in the older cohort. Conclusion: Allogeneic HCT for patients with Morquio A is safe and feasible. This treatment can potentially lead to significantly improved biochemical markers of the disease, preservation of organs, and better clinical manifestations. Additionally, when performed at a young age, ideally before the age of 3 years, allogeneic HCT may result in improved growth. The use of bone marrow as a stem cell source whenever possible, combined with effective GVHD prophylaxis, may enhance transplant success and disease-related outcomes. Long-term benefits and risks require further investigation.