Long-term Adaptive Functioning Outcomes of Children With Inherited Metabolic and Genetic Diseases Treated With Hematopoietic Stem Cell Transplantation in a Single Large Pediatric Center

Abstract

Over the past 2 decades, hematopoietic stem cell transplantation (HSCT) has been used as therapy for selected inherited metabolic and genetic diseases (IMGDs). The primary objective of HSCT for these disorders has been to promote long-term survival, optimize quality of life, and improve neurocognitive performance. We performed 45 HSCTs for 44 children with IMGDs (13 related and 32 unrelated); 24 HSCTs for 23 children with Hurler syndrome, 8 for malignant infantile osteopetrosis, 6 for X-linked adrenoleukodystrophy, 2 for metachromatic leukodystrophy, 2 for Gaucher disease, 1 for Ganglioside Monosialic Acid (GM) gangliosidosis, 1 for sialiosis (type 2), and 1 HSCT for Niemann-Pick type A. At a median follow-up of 7.2 years (range: 2.2 to 17.6 y) 18 of 23 patients with Hurler syndrome are alive, 15 attended regular school. Thirteen of 18 were ambulatory, 2 had mobility difficulties, and 1 uses wheelchair. For non-Hurler patients, 5 children suffered secondary graft failure and 4 of them died from progressive disease. The remaining children with osteopetrosis are alive and most children attended regular school. One out of the 4 survivors with adrenoleukodystrophy has been transferred to the adult follow-up clinic and he is in full-time employment. Parents' perspectives and expectations of HSCT in these IMGDs were positive and supportive to continue to offer HSCT for these disorders.

Post‐transplant adaptive function in childhood cerebral adrenoleukodystrophy

“…Although these metrics represent essential benchmarks for evaluating the success of intervention for cALD, recent publications have commented on the failure of these endpoints to fully characterize the experience of transplant survivors in terms of their quality of life or ability to actively and fully participate in their world (i.e., to independently handle life demands) 11, 12. A more comprehensive understanding of the range of possible adaptive functional outcomes is needed to inform counseling for patients and families undergoing evaluation at transplant centers.…”

Emerging uses for pediatric hematopoietic stem cells

“…Another area in which HCT can be curative is certain inherited metabolic and genetic disorders, such as Hurler syndrome, osteopetrosis, Gaucher disease, and others (15)(16)(17)(18)(19). Many of these are lysosomal or peroxisomal storage disorders.…”

“…Overall, improvement can be quite significant, and in a single center report with follow-up of 3-20 y, more than 85% of parents reported quality of life of their children after HCT as good to excellent. Although developmentally delayed, almost 80% of these children attend regular school (19).…”

Translating rare-disease therapies into improved care for patients and families: what are the right outcomes, designs, and engagement approaches in health-systems research?

“…However, for many rare diseases, although transformative treatments have led to important reductions in the risk of catastrophic outcomes, previously unrecognized morbidities have also been uncovered, and longer-term outcomes, while substantially improved, have not been optimized. 28,29 Reflecting the gap between efficacy and effectiveness in practice, such long-term outcomes are likely to depend on patient characteristics, cointerventions, and models of service delivery that may affect uptake and adherence.…”