Caregiver-reported disease burden in Krabbe disease: evaluating outcomes of hematopoietic stem cell transplantation

Krabbe disease (KD) is a rapidly progressive neurodegenerative disorder caused by β-galactocerebrosidase deficiency. While KD has been added to the Recommended Uniform Screening Panel (RUSP), only 15 states have an active KD newborn screening (NBS) program. It is uncertain at what rate states will adopt RUSP recommendations, with a frequently cited barrier being the absence of investigations addressing the impact of hematopoietic stem cell transplantation (HSCT) on quality-of-life. We developed a 90-minute caregiver interview to gather qualitative and quantitative data (including the validated Leukodystrophy Quality-of-Life Assessment – LQLA) evaluating patient/family-centered outcomes of HSCT. The interview was designed to explore the following: 1) disease burden on the patient; 2) physical burden on the caregiver; and 3) emotional/social burden on the caregiver. Comparisons were made between children not transplanted/transplanted late and children transplanted early. Infantile KD (IKD) and late infantile KD (LIKD) were analyzed independently. Forty caregivers participated (non-transplanted/transplanted late: IKD = 19, LIKD = 7; transplanted early: IKD = 10, LIKD = 4). Analysis of the LQLA revealed a relative reduction in disease burden in both IKD and LIKD groups who were transplanted early. Specifically, the early transplanted cohorts achieved statistically significant higher overall scores on the LQLA, as well as better scores in various subcategories in comparison to their non-transplanted/transplanted late counterparts. For IKD, analysis of Likert scale and weighted analysis demonstrated a tendency towards decreased physical burden on caregivers of children transplanted early. Although all groups experienced significant social/emotional burdens, caregivers of IKD transplanted early benefitted from improved sleep, mental health, and familial/spousal relationships compared to IKD non-transplanted/transplanted late. This study provides convincing evidence that HSCT improves quality-of-life and reduces caregiver burden in IKD. The evidence is somewhat less clear for LIKD due to the small LIKD sample size. This data will be critical in the decision-making process for states not currently screening for KD but debating the addition of KD to their NBS panels. Lastly, it will allow families to weigh the risks and benefits of HSCT more confidently when contemplating the life-altering decision of whether to proceed with transplantation.