Long-Term Outcomes of Umbilical Cord Blood Transplantation in Hurler Syndrome: A 20-Year Follow-up Study

Résumé fourni par la source

Introduction Hematopoietic cell transplantation (HCT) extends the lifespan of patients with Hurler syndrome (HS) or Mucopolysaccharidosis I, a rare autosomal recessive lysosomal storage disorder. However, the impact of successful HCT on the disease manifestations and functional abilities in adolescents and young adults (AYA) is unknown. Objectives We report outcomes of a cohort of HS patients (pts) surviving >14 years post umbilical cord blood transplantation (UCBT). Methods This retrospective study includes 32/47 HS pts who underwent UCBT after myeloablative conditioning at Duke University from 1995-2008. We excluded 15/47 pts who died within 5 years of UCBT. Functional outcomes of these 32 pts are described at a median 22.4 years (range 16.8-29.8) of age. Results Of the 32 pts (53% male), 6% had received enzyme replacement therapy and 28% required a VP shunt prior to HCT. All pts had typical HS disease manifestations. The median age at UCBT was 15.3 (range 2.1-34.8) months with a median follow-up duration of 21.2 (range 14.3-27.5) years. HCT complications included grade III/IV acute GVHD (22%), and chronic GVHD (22%). Full donor chimerism and normal α-L-Iduronidase levels were achieved in 97% and 86%, respectively, at most recent assessment. At last follow-up, 56% of pts could perform activities of daily living and demonstrated successful socio-professional integration with 25% employed, 66% completed high school, and 38% attended college (13% graduated by last follow-up). Neurocognitive impairment was seen in 53%, and 50% had anxiety/depression. Orthopedic complications/surgery included: thoracolumbar kyphosis (84%/44%), hip dysplasia (63%/44%), genu valgum (72%/66%), carpal tunnel (47%/31%), cervical spine stenosis/compression (44%/31%), and finger flexion (22%/9%). Cardiac valve disease was noted in all patients. Hypertension and cardiomyopathy occurred in 28% and 9% respectively. Ocular manifestations included corneal clouding (97%), corneal transplantation (31%), glaucoma/cataracts (25%), and retinal disease (9%). Hearing loss affected 75% and 31% required hearing aids. Short stature (< 5’3”) was present in 97% and 41% had a history of growth hormone therapy. Hypothyroidism occurred in 12%. Spontaneous puberty was reported in 69%. One male patient fathered a child. No pregnancies were reported among females. Conclusion Our study describes long-term outcomes of HS post-UCBT over decades of follow-up, enhancing our understanding of the natural history of AYA HS survivors after HCT. While musculoskeletal manifestations impact mobility and supportive devices are necessary for most patients, our cohort exhibited good social integration and independent functioning. Further studies on late effects are needed to inform practices that can enhance quality of life outcomes for adults, particularly in the new era of newborn screening.

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