Journal Article

Long term disease burden post-transplantation: three decades of observations in 25 Hurler patients successfully treated with hematopoietic stem cell transplantation (HSCT)

Guffon, N., Froissart, R., Pettazzoni, M., Lina-Granade, G., Plault, C., Fouilhoux, A., Garin, C., Mottolese, C., Pangaud, N.

2021

Overview

Background Mucopolysaccharidosis type I-Hurler syndrome (MPSI-H) is a lysosomal storage disease characterized by severe physical symptoms and cognitive decline. Early treatment with hematopoietic cell transplant (HSCT) is critical to the survival of these patients. While survival rates and short-term outcomes are known to be improved by HSCT, the long-term cognitive, adaptive and psychosocial functional outcomes of children with (MPSI-H) post-HSCT are not well documented. This manuscript focuses on retrospective long-term follow-up (7–33 years) of 25 MPSI-H patients, transplanted between 1986 and 2011. Results The median age at transplantation was 21 months (range 12–57 months). Except for one death, all successfully transplanted MPSI-H patients surviving at least 1 year after HSCT are alive to-date, with a median age of 21 years (range 8–36 years) at the last follow-up evaluation. A majority of HSCT grafts were bone marrow transplants (BMT), resulting in durable full chimerism in 18 (72%). Pre-HSCT, the onset of first symptoms occurred very early, at a median age of 3 months (range birth-16 months). The most prevalent symptoms before MPSI-H diagnosis involved progressive dysostosis multiplex; almost all patients suffered from hip dysplasia and thoracolumbar spine Kyphosis. Despite HSCT, considerable residual disease burden and ensuing corrective surgical interventions were observed in all, and at every decade of follow-up post HSCT. Late-onset psychiatric manifestations were significant (n = 17 patients; 68%), including depression in 13 patients at a median onset age of 18 years (range 13–31 years), hyperactivity and attention deficit disorder (n = 4), and multiple acute psychotic episodes (APE), independent of depression observed (n = 3) at a median onset age of 18 years (range 17–31 years). The adult Welscher Intelligence Scale results (n = 16) were heterogenous across the four scale dimensions; overall lower scores were observed on both working memory index (median WMI = 69.5) and processing speed index (median PSI = 65), whereas verbal comprehension index (median VCI = 79) and perceptual reasoning index (median PRI = 74) were higher. Conclusion With advanced treatment options, MPSI-H are living into 3rd and 4th decades of life, however not disease free and with poor adaptation. Residual disease (loss of mobility, limited gross and fine motor skills; low cognitive ability; suboptimal cardiopulmonary function, vision and hearing) negatively impacts the quality of life and psychosocial functioning of affected individuals.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adaptation / Age / Attention deficit hyperactivity disorder / Bone dysplasia / Bone marrow / Bone marrow transplantation / Bone surgery / Care and treatment / Chimerism / Cognitive ability / Depression / Dysostosis / Enzymes / Hematopoietic cell transplantation / Hematopoietic stem cells / Human Genetics / Hurler's syndrome / Inherited metabolic diseases / Intelligence / Kyphosis / Life expectancy / Long-term outcomes / Lysosomal storage diseases / Medical research / Medicine / Medicine & Public Health / Mental depression / Motor skill / Mucopolysaccharidosis / Mucopolysaccharidosis type I-Hurler syndrome / Mutation / Patient outcomes / Patients / Pharmacology/Toxicology / Psychosocial function / Quality of life / Rare diseases / Residual disease burden / Short term memory / Social interactions / Spine / Stem cell transplantation / Stem cells / Transplantation / Transplants & implants