Impact of Obesity on GVHD & Transplant Outcomes in Hematologic Malignancies

New data from a Cleveland Clinic-led retrospective analysis suggest there is a connection between obesity and an increased incidence of moderate-severe chronic graft-versus-host disease (GVHD) among patients undergoing allogeneic hematopoietic cell transplant (HCT) for hematologic malignancies. These findings, which were recently presented during the Transplantation & Cellular Therapy Meetings of ATCT and CIBMTR, underscore the need for further exploration of the role of obesity in GVHD.

“Obesity has been shown to modulate immune responses and exacerbate inflammatory states, leading to worse outcomes in various disease states,” according to study author Betty K. Hamilton, MD, Department of Hematology and Medical Oncology, Cleveland Clinic Cancer Institute, and colleagues. “Pre-clinical studies have demonstrated the deleterious effects of obesity on graft-versus-host disease.”

While a number of retrospective studies have examined the impact of obesity on allogeneic HCT outcomes, the Cleveland Clinic team aimed to delve deeper. “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 GVHD in a contemporary cohort of patients,” explains Dr. Hamilton.

Study details

A retrospective study of 531 patients undergoing first allogeneic HCT for acute myelogenous leukemia and myelodysplastic syndrome between January 2010 and December 2021 was conducted. Median follow-up was 19 months.

Pre-HCT height and weight was used to calculate BMI, and patients were analyzed per 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).

The study authors compared incidence, grade, organ involvement and response to therapy of acute and chronic GVHD between obese (≥30) and non-obese patient cohorts. Relapse, non-relapse mortality (NRM) and overall survival (OS) were secondary outcomes.

Between obese (N=199) and non-obese (N=332) patients, there were no statistically significant differences in demographic and HCT characteristics, except for co-morbidity index, according to Dr. Hamilton. Mean BMI was 29.1 (6.3) kg/m2.

Findings revealed that the development of acute or chronic GVHD was similar in obese and non-obese patients. Among patients with acute GVHD, 141 patients were classified as non-obese and 82 were obese. One-hundred non-obese patients and 59 obese patients had chronic GVHD.

When comparing obese and non-obese patients with acute GVHD, Dr. Hamilton and colleagues observed no significant differences in organ affected, grade, type of treatment or response to treatment. Some differences were noted between obese and non-obese patients with chronic disease.

Obese patients with chronic GVHD were more likely to have skin involvement (70% vs. 52%) as well as more moderate-severe disease (68% vs. 47%). Differences in treatment and response were not significant; however, results showed that obese patients were more likely to undergo treatment with second-line agents (39% vs. 28%) and had lower response rates (64% vs. 73%) when compared to their non-obese counterparts with chronic GVHD.

In terms of secondary outcome measures, Dr. Hamilton reported no significant differences on overall survival, non-relapse mortality or relapse among obese and non-obese patient cohorts.

Key takeaways

Discussing the key findings from their analysis, Dr. Hamilton reviewed the potential association between obesity and more severe chronic GVHD. “Although it wasn’t statistically significant, it appears that obese patients with chronic GVHD require more second-line therapies and don’t respond as well to treatment.”

While Dr. Hamilton acknowledged that there are limitations to this study, including its single-institution nature, she noted that the analysis provides important insights into the impact of obesity on this patient population. “There has been a lot of research examining obesity and survival outcomes for transplant; however, there hasn’t actually been focused efforts in graft-versus-host-disease,” she says. “This study adds to the current literature and our understanding of how obesity impacts patients with graft-versus-host-disease.”

As a part of the multi-site Chronic Graft-vs-Host Disease Consortium, the Cleveland Clinic team plans to continue their research efforts in a larger population of patients. “Our work continues to help us better understand not only a potentially high-risk patient population that we could educate or provide intervention to, but it also helps us understand how certain aspects of graft-versus-host-disease may develop and how obesity may impact transplant outcomes in general,” Dr. Hamilton concludes. “Overall, studies like this lead to better understanding and hopefully improved care for our patients.”