Impact of Obesity on Graft-Versus-Host Disease and Transplant Outcomes in Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Hematologic Malignancies

Introduction and Objectives Obesity has been shown to modulate immune responses and exacerbate inflammatory states, leading to worse outcomes in various disease states. Pre-clinical studies have demonstrated the deleterious effects of obesity on graft-versus-host disease. Several retrospective studies have investigated the impact of obesity on allogeneic hematopoietic cell transplant (HCT) outcomes, with varying results. We sought to further investigate the impact of obesity, as measured by body mass index (BMI), on the incidence, severity, and response to therapy of graft-versus-host disease (GVHD) in a contemporary cohort. Methods We conducted a retrospective study of patients undergoing first allogeneic HCT for acute myelogenous leukemia and myelodysplastic syndrome between January 2010 and December 2021 at the Cleveland Clinic. BMI was calculated from pre-HCT height and weight. Patients were analyzed by CDC defined BMI categories (kg/m2): underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9), class 1 obese (30-34.9), and class 2-3 obese (≥35). Incidence, grade, organ involvement, and response to therapy of acute and chronic GVHD were compared between obese (≥30) and non-obese groups. Secondary outcomes included relapse, non-relapse mortality (NRM), and overall survival (OS). Results 531 patients were identified, with a median follow-up of 19 months (range, 7-49). Mean (SD) BMI was 29.1 (6.3) kg/m2. Patient characteristics and BMI distribution are shown in Table 1. There was no statistically significant difference in demographic and HCT characteristics between obese (N=199) and non-obese (N=332) patients except for co-morbidity index. Development of any acute (42% vs. 43%) or chronic (30% vs. 30%) GVHD was similar in obese and non-obese cohorts respectively. There were no significant differences in organ affected, grade, type of treatment, or response to treatment of acute GVHD for obese and non-obese groups (Table 1). Among patients with chronic GVHD, obese patients were more likely to have skin involvement (70% vs. 52%, p=0.03), and have more moderate-severe chronic GVHD (68% vs. 47%, p=0.01). Although differences in chronic GVHD treatment and response were not significant, obese patients were more likely to receive second-line agents with lower response rates compared to non-obese (Table 1). There were no significant differences in OS, NRM, or relapse in obese and non-obese groups. Conclusion We demonstrate an association between obesity and increased incidence of moderate-severe chronic GVHD in a contemporary cohort of allogeneic HCT recipients. Increasing evidence has demonstrated a multi-factorial role of obesity and body composition as a modulator of immune processes and transplant outcomes. Additional studies are needed to further understand the role of obesity and GVHD.