Clinical outcomes following hematopoietic stem cell transplantation for the treatment of mucopolysaccharidosis VI

Abstract

Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) is one of approximately 50 known lysosomal storage disorders. MPS VI is characterized by an absence or deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B) resulting in accumulation of dermatan sulfate. Prior to the availability of enzyme replacement therapy (ERT) the clinical management of MPS VI was limited to supportive care and allogeneic hematopoietic stem cell transplantation (HSCT); however, due to the rarity of this disease, little is known about the long-term outcomes of HSCT for MPS VI. The following retrospective study was performed using aggregate data gathered by the Center for International Blood and Marrow Transplant Research (CIBMTR) between 1982 and 2007 to determine survival probability for patients with MPS VI following allogeneic HSCT. This analysis identified 45 MPS VI patients with a median age of 5 years (range, 1-22 years) at the time they received an allogeneic HSCT. Cumulative incidence (95% CI) of acute graft vs. host disease at 100 days was 36% (21-53%). Probability of survival was 78% (65-89%) at 100 days and 66% (52-79%) at 1 and 3 years. While these data are based upon small numbers of recipients, they represent the largest series to date and may help clinicians assess the relative risks and benefits of currently available therapies.

Therapies for the bone in mucopolysaccharidoses

“…Center for International Blood and Marrow Transplant Research (CIBMTR), long-term improvements in facial dysmorphism, hepatosplenomegaly, joint mobility, and cardiac manifestations has been demonstrated [95][96][97][98]; however, skeletal disease known as dysostosis multiplex tends to persist or progress despite HSCT [26,[82][83][84]. [4,30,99,100].…”

A multinational, multidisciplinary consensus for the diagnosis and management of spinal cord compression among patients with mucopolysaccharidosis VI

“…For 45 patients receiving HSCT, the probability of survival at 1 year and at 3 years after HSCT was approximately 66%; risks such as infection, organ failure, and graft-vs-host disease must be weighed carefully against the potential benefit of HSCT in improving MPS VI symptoms [30].…”

Combined Enzyme Replacement Therapy and Hematopoietic Stem Cell Transplantation in Mucopolysacharidosis Type VI

“…HSCT restores endogenous production of inherently deficient enzyme. The morbidity and mortality associated with HSCT in patients with MPS has improved since HSCT was introduced but the general results have been poor compared to the reduction in morbidity and mortality seen in patients receiving HSCT for hemopoietic malignancies (Turbeville et al 2011). ERT with Galsulfase ® , which became available with the first trials commencing in 2002, resulted in significant improvement in endurance, respiratory, cardiovascular, and musculoskeletal function in patients with MPS VI (Hamartz et al 2008;Giugliani et al 2007).…”