Hematopoietic cell transplantation (HCT) is associated with significant improvements in health-related quality of life (HRQoL) in patients with sickle cell disease (SCD) and transfusion-dependent thalassemia (TDT), according to a systematic review published in Blood Advances. The authors, led by Sherif Badawy, MD, of the Lurie Children’s Hospital of Chicago, suggest that ongoing trials of curative options such as HCT, gene therapy, and gene-editing trials in SCD and TDT should continue to report QoL outcomes to further understand how HCT impacts subjective health domains in patients with these hemoglobinopathies.
With this systematic review, Dr. Badawy and colleagues evaluated recent available longitudinal and cross-sectional data for evidence of the effects of both HCT and gene therapy or gene-editing on HRQoL outcomes in patients with TDT or SCD. Eligible studies reported on changes in patient- and caregiver-reported HRQoL scores from baseline through follow-up.
The researchers also compared HRQoL outcomes in these populations with those of various control groups, including healthy controls and patients with TDT or SCD who were receiving other therapies.
Across the 16 studies included in this analysis, a total of 517 patients and/or their parents were included in the assessed studies, including 101 patients with SCD and 416 patients with TDT. All studies included at least one of the following validated instruments to measure HRQoL: Pediatric Quality of Life Inventory, 36-Item Short Form Survey, World Health Organization Quality of Life Brief Version, Child Health Rating Inventories, European Organization for Research Treatment of Cancer Quality of Life Questionnaire, European Quality of Life Five Dimension Five Level Scale, Functional Assessment of Cancer Therapy-Bone Marrow Transplant survey.
Overall, HCT was associated with small to large positive effects in most HRQoL domains, with a median increase in scores of 0.37 (range = 0.27-2.05).
Different studies reported several factors that correlated with better or worse HRQoL scores following HCT, the authors noted. For example, certain studies evaluating patients with TDT found a correlation between longer time after transplant and better emotional and psychosocial domain scores while, in studies evaluating patients with SCD, factors such as insurance type and brain imaging were correlated with HRQoL outcomes.
However, graft-versus-host disease (GVHD) was significantly associated with poorer HRQoL scores in both patient populations, particularly on physical domains. Conversely, HCT recipients without GVHD reported better emotional and psychosocial domain scores. Another study found that physical function worsened during the three months following HCT but improved at six to 18 months. The researchers noted that parents in this study slightly underestimated their children’s QoL.
The authors also compared QoL scores among HCT recipients and controls, finding no differences regarding mobility, self-care, and usual activities. In contrast, those who received HCT reported better improvements in pain, discomfort, anxiety, and depression. One study demonstrated better QoL scores among HCT recipients compared with controls.
Another study found that recipients of HCT had similar long-term HRQoL profiles as the general population, but had a better HRQoL versus conventionally treated patients with TDT. Patients who received HCT also scored better on physical function, bodily pain, and emotional function versus nontransplant patients. In a 2018 study of patients with TDT, HCT improved overall QoL compared with controls, scoring significantly higher in all domains, aside from social functioning.
Dr. Badawy and colleagues noted in their paper that improvements in the understanding of post-HCT HRQoL outcomes can support patients in the overall treatment decision-making process. “Therefore, assessing HRQoL outcomes using reliable and valid generic and/or disease-specific measures in all future prospective HCT, gene therapy, or gene-editing trials is essentially needed,” they wrote.
A primary limitation of this systematic review was the inclusion some studies with small sample sizes and studies that lacked control arms. In addition, the lack of a meta-analysis of the reviewed data limited the ability to determine significant pooled effects of HCT on QoL. Potential publication bias caused by the inclusion of only published studies from peer-reviewed journals represents another limitation of this systematic review.
Study authors report no relevant conflicts of interest.
Badawy SM, Beg U, Liem RI, Chaudhury S, Thompson AA. A systematic review of quality of life in sickle cell disease and thalassemia after stem cell transplant or gene therapy. Blood Adv. 2021;5(2):570-583.