High Body Mass Index (BMI) Is Associated with Lower Survival and Increased Chronic GVHD after Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract

Introduction Contrary to conventional wisdom, the obesity epidemic is not restricted to industrialized societies. over 115 million people suffer from obesity-related problems in developing countries.(1) The traditional view of adipose tissue as a passive storage depot of excess energy has been challenged. Adipose tissue is a highly active endocrine organ with the capacity to synthesize and secrete a variety of adipokines creating a chronic inflammatory state. (2) We tested whether pre-transplant BMI can affect transplant outcomes in a homogeneous population of patients underwent HLA-identical sibling transplant with PBSCT graft. Objectives To investigate the impact of Pre-transplant BMI on HSCT outcome. Methods Adult patients who underwent Allo HSCT (2000-2014) at Nasser Institute for Research and Treatment, Cairo, Egypt, were included. Patients received their 1st allo HSCT from 6/6 HLA-matched sibling donors using PBSC graft for treatment of SAA, MDS, AML, ALL or CML. Patients aged >50 years and those who received syngeneic transplant were excluded. The final data set included 971 patients. Patients were classified according to pre-transplant BMI into five groups following WHO 2007 BMI classification system: underweight BMI HSCT outcome was assessed with the following parameters: time to engraft, development of acute GVHD, development of chronic extensive GVHD, relapse, non-relapse mortality and overall survival. Each outcome was adjusted for other statistically significant variables. Cox regression models were used to evaluate the impact of BMI on overall mortality, NRM, relapse, and cGVHD. Logistic regression was used to evaluate the relationship between BMI and AGVHD. Results Our results showed that obesity class II and III was associated with increased risk of developing chronic extensive GVHD (HR=1.98, 95% CI 1.12-3.53, P value 0.02), lower OS (HR=1.51, 95% CI 1.04-2.20, p=0.03) and higher non-relapse mortality rates (HR=1.55, 95% CI 1.04-2.30, p=0.03) compared to the average BMI group. Interestingly, overweight and obese class I but not Obese class II and III patients showed statistically significant earlier engraftment in the form of documented increase of absolute neutrophilic count (ANC) to 500/µL (P value 0.01 and Conclusions BMI ≥35 is a risk factor for increased mortality after allogenic HSCT after accounting for impacts of comorbidities. Pre-transplant weight reduction to a goal of BMI There is a rationale to consider T cell depletion for patients with pre-transplant BMI ≥ 35.