Obesity Associations with Chronic Graft-Versus-Host Disease

Abstract

Obesity is increasing in prevalence and has been linked to inflammation, leading to worse outcomes in various disease states. Preclinical studies have demonstrated deleterious effects of obesity on graft-versus-host disease (GVHD). Several retrospective clinical studies have investigated the impact of obesity on allogeneic hematopoietic cell transplantation (HCT); however, with varying results and more limited data on the impact on chronic GVHD. We aimed to investigate the association of obesity on organ involvement, severity, and response to chronic GVHD therapy in a multicenter cohort of patients with chronic GVHD, as well as its impact on overall survival (OS), nonrelapse mortality (NRM), failure-free survival (FFS), and quality of life (QOL). We conducted a retrospective study of patients enrolled from 2007 to 2019 in two prospective longitudinal observational studies from the Chronic GVHD Consortium. Obesity was defined as a body mass index (BMI) ≥ 30, as calculated based on height and weight at the time of enrollment. Grade, organ involvement, and response to chronic GVHD therapy were compared between obese (BMI ≥ 30) and nonobese (BMI < 30) patients. Secondary outcomes included OS, NRM, FFS, and QOL measurement with the Lee symptom scale, Functional Assessment of Cancer Therapy, and Medical Outcomes Study Short Form 36. Among 487 patients identified with newly diagnosed chronic GVHD within 3 mo of study enrollment, 114 (23.4%) had BMI ≥ 30. The only significant difference between obese and nonobese patients was the presence of diabetes as a comorbidity. There were no significant differences in affected organs, grade, overall response to treatment, or organ-specific response to treatment between obese and nonobese patients. Chronic lung GVHD was more common in obese compared to nonobese patients (24.6% versus 13.9% for mild, 5.3% versus 4.8% for moderate, and 0.9% versus 0.8% for severe lung GVHD, P = .047), however, small case numbers and the lack of between group differences in OS, NRM, or FFS limit this interpretation. QOL analyses revealed greater patient-reported symptom burden and worse QOL in obese patients at enrollment and after 6 mo. We found obesity is associated with worse QOL but not with chronic GVHD phenotypes, responsiveness to treatment, or survival outcomes in a multicenter cohort of allogeneic HCT recipients. Given the increasing evidence of a multi-factorial role for obesity as a modulator of immune processes, additional studies investigating more accurate measures of obesity and body composition are needed to further understand their role in chronic GVHD.

Keywords: Allogeneic hematopoietic cell transplant; Body mass index; Graft-versus-host disease; Obesity; Quality of life.