Baseline Body Mass Index Among Children and Adults Undergoing Allogeneic Hematopoietic Cell Transplantation: Clinical Characteristics and Outcomes

Abstract

Obesity is a serious public health problem accompanying changes in diet and physical activity. The rising prevalence of obesity may influence the outcomes of hematopoietic cell transplantation (HCT). We studied 898 children and adults receiving first-time allogeneic bone marrow or peripheral blood stem cell transplants between 2004 and 2012 at the University of Michigan. Pre-transplant body mass index (BMI) was calculated using height and weight measurements and treated as a continuous variable. Recipients were then classified as underweight, normal weight, overweight, or obese according to BMI for adults using the World Health Organization classification system, or age-adjusted BMI percentiles for children based on Center for Disease Control and Prevention charts. The study population was predominantly Caucasian, and the median age was 51 years (5 months – 73 years). The cumulative 3-year incidence of non-relapse mortality (NRM) in underweight, normal weight, overweight, and obese patients was 20%, 19%, 20%, and 33% (p=0.04) (Figure 1A). Major causes of NRM were acute and chronic graft-versus-host disease (GVHD) (Figure 1B). The corresponding incidence of relapse was 30%, 41%, 37%, and 30% (p=0.002) (Figure 1C). Three-year overall survival was 59%, 48%, 47%, and 43% (p=0.55) (Figure 1D). Multivariate analysis showed that obesity was associated with higher NRM (hazard ratio [HR] 1.43, p=0.04), and lower relapse (HR 0.65, p=0.002) (Table 1). Pre-transplant plasma levels of ST2 and TNFR1 biomarkers were significantly higher in obese than in normal weight patients (p=0.04 and p=0.05, respectively) (Table 2). The increase in NRM observed in obese patients was partially offset by lower incidence of relapse, resulting in no significant difference in overall survival. [Display omitted] Table 1Results of multivariate regression analysis by BMI category.NRMAcute GVHDChronic GVHDRelapseOverall survivalHazard ratio (95% confidence intervals), p valueNormal weight1.001.001.001.001.00Underweight1.74 (0.76−4.01), 0.191.11 (0.56−2.21), 0.760.99 (0.46−2.12), 0.980.70 (0.32−1.50), 0.361.02 (0.54−1.95), 0.95Overweight0.95 (0.65−1.37), 0.771.03 (0.78−1.35), 0.851.07 (0.83−1.38), 0.600.79 (0.61−1.03), 0.080.85 (0.68−1.07), 0.17Obese1.43 (1.02−2.01), 0.041.15 (0.89−1.50), 0.291.21 (0.94−1.55), 0.140.65 (0.49−0.86), 0.0020.93 (0.75−1.16), 0.55Other covariatesContinuous age1.01 (1.00−1.02), 0.181.00 (0.99−1.00), 0.371.00 (0.99−1.01), 0.691.00 (1.00−1.01), 0.361.01 (1.00−1.02), 0.003MalignancyNon−malignant1.001.001.001.001.00Malignant0.37 (0.10−1.33), 0.131.73 (0.82−3.68), 0.151.29 (0.72−2.31), 0.3826.50 (3.49−201.02), 0.0022.05 (0.92, 4.58), 0.08RelatednessRelated1.001.001.001.001.00Unrelated2.20 (1.65−2.94), <0.0011.88 (1.50−2.35), <0.0011.13 (0.92−1.39), 0.230.61 (0.48−0.77), <0.0011.24 (1.03−1.49), 0.02Transplant typePeripheral blood1.001.001.001.001.00Bone marrow0.23 (0.09−0.58), 0.0020.66 (0.44−0.99), 0.040.91 (0.61−1.36), 0.651.09 (0.72−1.66), 0.680.56 (0.38−0.82), 0.003HLA matchMatched1.001.001.001.001.00Mismatched1.59 (1.16−2.22), 0.0041.69 (1.30−2.17), <0.0010.95 (0.73−1.25), 0.730.83 (0.60−1.18), 0.291.41 (1.12−1.79), 0.003ConditioningMyeloablative1.001.001.001.001.00Reduced1.02 (0.76−1.35), 0.911.19 (0.94−1.49), 0.141.02 (0.82−1.27), 0.820.90 (0.69−1.16), 0.420.89 (0.74−1.09), 0.24Year of transplant2004−20081.001.001.001.001.002009−20130.79 (0.60−1.05), 0.100.76 (0.61−0.95), 0.020.96 (0.79−1.17), 0.700.76 (0.60−0.95), 0.020.78 (0.65−0.94), 0.01Table 2Baseline levels of plasma biomarkers suppression of tumorigenicity 2 (ST2) and tumor necrosis factor receptor 1 (TNFR1) by BMI category.ST2TNFR1BMI categoryNMedian concentration (IQR), pg/mlp valueNMedian concentration (IQR), pg/mlp valueNormal weight115131 (0-628)−882129 (1486-3232)−Underweight7256 (82-659)0.5171596 (1467-2971)0.57Overweight115208 (0-845)0.22812266 (1708-3725)0.32Obese110257 (0-1045)0.04992644 (1922-3395)0.05 DisclosuresNo relevant conflicts of interest to declare.