Introduction: Assessment of health-related quality of life (HRQOL) provides crucial information for evaluating the benefits of treatments such as hematopoietic cell transplantation (HCT) for individuals with sickle cell disease (SCD). Caring for a child with SCD, especially one undergoing HCT, can significantly impact caregiver HRQOL and parental functioning, which in turn can be an important determinant of child HRQOL. Few studies have examined HRQOL in children and young adults with SCD undergoing HCT as well as their caregivers. We aimed to examine patient HRQOL, caregiver proxy report of HRQOL, and caregiver HRQOL before and after HCT for SCD.

Methods: Children and young adults with SCD ages 8-23 received either a matched sibling donor (MSD) or a haploidentical donor (HAPLO) HCT following reduced toxicity conditioning with alemtuzumab, thiotepa and low dose total body irradiation (NCT04362293). Sirolimus was used for graft-vs-host-disease prophylaxis for 6-12 months post-HCT in all patients, with additional post-transplant cyclophosphamide in patients with HAPLO donors. Patients completed Patient-Reported Outcomes Measurement Information System (PROMIS) measures, with lower scores indicating improvement for Anxiety, Depression, Pain Interference, Pain Behavior, Sleep Disturbance, and Fatigue, and higher scores indicating improvement for Physical Function, Life Satisfaction, Positive Affect, Peer Relationships, and Family Relationships. Caregivers completed PROMIS proxy measures in the same domains except Pain Behavior, Sleep Disturbance, and Family Relationships and with the addition of Psychological Stress (lower scores indicating improvement). Caregivers also completed the PROMIS Global Health scale as a measure of their own HRQOL. Patients and caregivers completed HRQOL measures at admission, 6 and 12 months after HCT. We conducted paired samples t-tests to examine changes in HRQOL at different time points. Statistical significance was established at p<0.05. A 5-point difference between scores was deemed a minimal clinically important difference according to PROMIS guidelines.

Results: Twenty individuals with SCD were treated and engrafted after HCT, of which 16 patients (mean age=14.1±4.6 years; 69% male, 63% HAPLO) and 18 caregivers completed HRQOL measures at two or more timepoints. There were 3 deaths on study; two patients did not have data for more than one timepoint and therefore were excluded from analysis. Patients reported improvement in Pain Interference from admission (M=56.1±10.7) to 6 months (M=51.3±10.2; t(15)=2.55, p=0.022). There was a nonsignificant but clinically meaningful improvement in Anxiety from admission (M=49.5±8.6) to 6 months (M=44.5±9.6; t(14)=1.99, p=0.067), which was significant by caregiver report from admission (M=54.8±8.3) to 6 months (M=45.3±8.9; t(13)=4.36, p=0.001). There were no patient or caregiver-reported significant changes in HRQOL from 6 to 12 months post-HCT. Patients did not report changes in HRQOL between admission to 12 months, however caregivers reported improvement in Physical Function (M=41.3±7.5 v. M=49.5 ±7.8; t(10)=-3.55, p=0.005), Anxiety (M =57.3±6.5 v. M=42.1±6.8; t(9)=6.74, p<0.001), Depression (M=51.6±8.9 v. M=41.3±7.9; t(10)=4.36, p=0.001), Fatigue (M=56.4±10.8 v. M=44.5±9.5; t(10)=2.98, p=0.014), Pain Interference (M=60.3±9.4 v. M=48.8±10.1; t(10)=3.29, p=0.008), and Psychological Stress (M=57.1±11.1 v. M=43.9±9.9; t(10)=2.94, p=0.015). Caregivers reported worsened Peer Relationships for their child comparing admission (M=47.8±11.3) to 6 months (M=39.2±10.2; t(14)=2.66, p=0.019). There were no significant differences in caregiver report of their own HRQOL for the timepoints.

Conclusion: Patients reported improvement in Pain Interference from admission to 6 months post-HCT but overall HRQOL measures did not change from admission to 12 months post-HCT. Conversely, caregivers reported that their child's HRQOL improved from admission to 12 months post-HCT in 6/8 domains. These differing perspectives highlight the variability in HRQOL outcomes post-HCT between patients and caregivers and underscore the importance of considering both perspectives. Future research is needed with larger sample sizes and longer follow-up to better understand the impact of HCT on HRQOL and the incongruity between patient and caregiver report.

Disclosures

Leonard:bluebird bio: Consultancy. Gottschalk:Immatics: Other: DSMB; Be Biopharma: Consultancy; CARGO: Consultancy; T cell and/or gene therapy for cancer: Other: Patent and patent applications. Sharma:Editas Medicine: Consultancy; Medexus Inc: Consultancy; CRISPR Therapeutics: Other: Clinical Trial site-PI and Research funding ; Novartis: Other: Clinical Trial site-PI; BEAM therapeutics: Other: Clinical Trial site-PI; Sangamo Therapeutics: Consultancy; Vertex Pharmaceuticals: Consultancy, Other: Clinical Trial site-PI.

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2024
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