Impact of Obesity on Outcomes Following Allogeneic Hematopoietic Stem Cell Transplantation

Background: Obesity has become a well-known global health issue and a contributor to significant health problems. It is recognized to adversely impact the immune system and cause a chronic inflammatory state. It has been identified as a potential factor contributing to complications after an allogeneic hematopoietic stem cell transplant (allo-HCT). We investigated the impact of obesity on outcomes following allo-HCT.

Methods: In this study, we conducted a retrospective multicenter analysis, including allo-HCT patients in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2013 to 2018 using P5646 data by Ramathan et al. Chi-square and t-tests were used to compare categorical and continuous baseline demographics. We examined the impact of obesity on post-transplant outcomes such as overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), acute graft-versus-host disease (aGVHD), and chronic graft-versus-host disease (cGVHD), and engraftment. The hazard ratios (HR) with 95% confidence intervals (CI) were calculated using multivariate Cox regression analyses for OS, DFS, relapse, NRM, aGVHD, cGVHD, and platelet and neutrophil engraftment. The multivariate analyses were adjusted for significant variables identified in the univariate analysis. Statistical analysis was conducted using R version 4.16, with statistical significance defined as p < 0.05.

Results: We included 7545 allo-HCT recipients. Of these, 5506 patients (72.9%) were non obese (BMI<30), and 2039 (27%) patients were obese (BMI >30). The median age at the time of transplant was 56 years. 58% of the sample were men. Ethnicities were Caucasian (76%), Hispanic (8%), African American (6%), Asian (5%), and others/not available (5%). The primary disorders included acute myeloid leukemia (47%), myelodysplastic syndrome (34%), and acute lymphoblastic leukemia (18%). Myeloablative conditioning was used in 53% of patients. Donor types were matched unrelated (49.5%), matched related (34%), and cord blood (16%). Graft sources were peripheral blood stem cells (68%), umbilical cord blood (16%), and bone marrow (15%). GVHD prophylaxis regimens included post-transplant tacrolimus or cyclosporine-based (87%), cyclophosphamide-based (9%), CD34 selection (2%), and others (1.7%). Univariate logistic and Cox regression analyses revealed that obesity (BMI ≥ 30) was significantly associated with a worse DFS (OR 1.510, 95% CI 1.381-1.650, p < 0.01), an increased incidence of chronic GVHD (OR = 1.133, 95% CI: 1.046-1.227, p < 0.01), and delayed neutrophil (HR 1.125, 95% CI 1.068-1.184, p < 0.01) and platelet engraftment (HR 1.101, 95%CI=1.044-1.160, P < 0.01). A lower NRM was seen in obese patients (OR: 0.251, 95% CI 0.225-0.280, p<0.001). OS (HR 0.99, 95% CI 0.928-1.067, p = 0.8) and acute GVHD (OR 1.015, 95% CI 0.937-1.100, p = 0.7) did not show a significant association. The multivariate analysis adjusted for significant factors identified in the univariate analyses showed a significant association of obesity with inferior DFS (HR 1.157, 95% CI 1.030-1.300, p = 0.01) and delayed neutrophil engraftment (HR 1.078, 95% CI 1.019-1.142, p = 0.01); however, results were not significant for other outcomes including NRM.

Conclusion: Our study noted a significant association of obesity with inferior disease-free survival and delayed engraftment. However, other transplant outcomes, including overall survival, were not significantly affected. This suggests that by addressing this modifiable risk factor, we have the potential to significantly improve outcomes in the allo-HCT population.

Ahmed:Bristol Myers Squibb: Consultancy; Kite, a Gilead Company: Research Funding. Hamadani:Genentech: Speakers Bureau; Forte Biosciences: Consultancy; AbbVie: Consultancy; Sanofi Genzyme: Speakers Bureau; AstraZeneca: Speakers Bureau; Byondis: Consultancy; CRISPR: Speakers Bureau; DMC, Inc: Speakers Bureau; CRISPR: Consultancy; Spectrum Pharmaceuticals: Research Funding; Genmab: Consultancy; BMS: Consultancy; Kite Pharma: Consultancy, Speakers Bureau; Astellas Pharma: Research Funding; Takeda: Research Funding; Allovir: Consultancy; Omeros: Consultancy; Caribou: Consultancy; BeiGene: Speakers Bureau; ADC Therapeutics: Consultancy, Research Funding, Speakers Bureau; Autolus: Consultancy; Myeloid Therapeutics: Speakers Bureau. McGuirk:Sana technologies: Consultancy; Autolus: Consultancy; BMS: Consultancy; NEKTAR therapeutics: Consultancy; Allo Vir: Consultancy; Kite: Consultancy; Envision: Consultancy; Caribou bio: Consultancy; CRISPR therapeutics: Consultancy; Novartis: Consultancy; Legend biotech: Consultancy. Mushtaq:Iovance Biotherapeutics: Research Funding.