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.
Transplant outcomes according to BMI categories. Cumulative incidence of NRM (A), chronic GVHD (B), relapse (C), and probability of overall survival (D) according to BMI groups. N = 20 underweight (UW), 290 normal weight (NW), 287 overweight (OW), 301 obese (OB).
Transplant outcomes according to BMI categories. Cumulative incidence of NRM (A), chronic GVHD (B), relapse (C), and probability of overall survival (D) according to BMI groups. N = 20 underweight (UW), 290 normal weight (NW), 287 overweight (OW), 301 obese (OB).
Results of multivariate regression analysis by BMI category.
| NRM | Acute GVHD | Chronic GVHD | Relapse | Overall survival | |
|---|---|---|---|---|---|
| Hazard ratio (95% confidence intervals), p value | |||||
| Normal weight | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Underweight | 1.74 (0.76−4.01), 0.19 | 1.11 (0.56−2.21), 0.76 | 0.99 (0.46−2.12), 0.98 | 0.70 (0.32−1.50), 0.36 | 1.02 (0.54−1.95), 0.95 |
| Overweight | 0.95 (0.65−1.37), 0.77 | 1.03 (0.78−1.35), 0.85 | 1.07 (0.83−1.38), 0.60 | 0.79 (0.61−1.03), 0.08 | 0.85 (0.68−1.07), 0.17 |
| Obese | 1.43 (1.02−2.01), 0.04 | 1.15 (0.89−1.50), 0.29 | 1.21 (0.94−1.55), 0.14 | 0.65 (0.49−0.86), 0.002 | 0.93 (0.75−1.16), 0.55 |
| Other covariates | |||||
| Continuous age | 1.01 (1.00−1.02), 0.18 | 1.00 (0.99−1.00), 0.37 | 1.00 (0.99−1.01), 0.69 | 1.00 (1.00−1.01), 0.36 | 1.01 (1.00−1.02), 0.003 |
| Malignancy | |||||
| Non−malignant | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Malignant | 0.37 (0.10−1.33), 0.13 | 1.73 (0.82−3.68), 0.15 | 1.29 (0.72−2.31), 0.38 | 26.50 (3.49−201.02), 0.002 | 2.05 (0.92, 4.58), 0.08 |
| Relatedness | |||||
| Related | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Unrelated | 2.20 (1.65−2.94), <0.001 | 1.88 (1.50−2.35), <0.001 | 1.13 (0.92−1.39), 0.23 | 0.61 (0.48−0.77), <0.001 | 1.24 (1.03−1.49), 0.02 |
| Transplant type | |||||
| Peripheral blood | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Bone marrow | 0.23 (0.09−0.58), 0.002 | 0.66 (0.44−0.99), 0.04 | 0.91 (0.61−1.36), 0.65 | 1.09 (0.72−1.66), 0.68 | 0.56 (0.38−0.82), 0.003 |
| HLA match | |||||
| Matched | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Mismatched | 1.59 (1.16−2.22), 0.004 | 1.69 (1.30−2.17), <0.001 | 0.95 (0.73−1.25), 0.73 | 0.83 (0.60−1.18), 0.29 | 1.41 (1.12−1.79), 0.003 |
| Conditioning | |||||
| Myeloablative | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Reduced | 1.02 (0.76−1.35), 0.91 | 1.19 (0.94−1.49), 0.14 | 1.02 (0.82−1.27), 0.82 | 0.90 (0.69−1.16), 0.42 | 0.89 (0.74−1.09), 0.24 |
| Year of transplant | |||||
| 2004−2008 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| 2009−2013 | 0.79 (0.60−1.05), 0.10 | 0.76 (0.61−0.95), 0.02 | 0.96 (0.79−1.17), 0.70 | 0.76 (0.60−0.95), 0.02 | 0.78 (0.65−0.94), 0.01 |
| NRM | Acute GVHD | Chronic GVHD | Relapse | Overall survival | |
|---|---|---|---|---|---|
| Hazard ratio (95% confidence intervals), p value | |||||
| Normal weight | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Underweight | 1.74 (0.76−4.01), 0.19 | 1.11 (0.56−2.21), 0.76 | 0.99 (0.46−2.12), 0.98 | 0.70 (0.32−1.50), 0.36 | 1.02 (0.54−1.95), 0.95 |
| Overweight | 0.95 (0.65−1.37), 0.77 | 1.03 (0.78−1.35), 0.85 | 1.07 (0.83−1.38), 0.60 | 0.79 (0.61−1.03), 0.08 | 0.85 (0.68−1.07), 0.17 |
| Obese | 1.43 (1.02−2.01), 0.04 | 1.15 (0.89−1.50), 0.29 | 1.21 (0.94−1.55), 0.14 | 0.65 (0.49−0.86), 0.002 | 0.93 (0.75−1.16), 0.55 |
| Other covariates | |||||
| Continuous age | 1.01 (1.00−1.02), 0.18 | 1.00 (0.99−1.00), 0.37 | 1.00 (0.99−1.01), 0.69 | 1.00 (1.00−1.01), 0.36 | 1.01 (1.00−1.02), 0.003 |
| Malignancy | |||||
| Non−malignant | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Malignant | 0.37 (0.10−1.33), 0.13 | 1.73 (0.82−3.68), 0.15 | 1.29 (0.72−2.31), 0.38 | 26.50 (3.49−201.02), 0.002 | 2.05 (0.92, 4.58), 0.08 |
| Relatedness | |||||
| Related | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Unrelated | 2.20 (1.65−2.94), <0.001 | 1.88 (1.50−2.35), <0.001 | 1.13 (0.92−1.39), 0.23 | 0.61 (0.48−0.77), <0.001 | 1.24 (1.03−1.49), 0.02 |
| Transplant type | |||||
| Peripheral blood | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Bone marrow | 0.23 (0.09−0.58), 0.002 | 0.66 (0.44−0.99), 0.04 | 0.91 (0.61−1.36), 0.65 | 1.09 (0.72−1.66), 0.68 | 0.56 (0.38−0.82), 0.003 |
| HLA match | |||||
| Matched | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Mismatched | 1.59 (1.16−2.22), 0.004 | 1.69 (1.30−2.17), <0.001 | 0.95 (0.73−1.25), 0.73 | 0.83 (0.60−1.18), 0.29 | 1.41 (1.12−1.79), 0.003 |
| Conditioning | |||||
| Myeloablative | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Reduced | 1.02 (0.76−1.35), 0.91 | 1.19 (0.94−1.49), 0.14 | 1.02 (0.82−1.27), 0.82 | 0.90 (0.69−1.16), 0.42 | 0.89 (0.74−1.09), 0.24 |
| Year of transplant | |||||
| 2004−2008 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| 2009−2013 | 0.79 (0.60−1.05), 0.10 | 0.76 (0.61−0.95), 0.02 | 0.96 (0.79−1.17), 0.70 | 0.76 (0.60−0.95), 0.02 | 0.78 (0.65−0.94), 0.01 |
Baseline levels of plasma biomarkers suppression of tumorigenicity 2 (ST2) and tumor necrosis factor receptor 1 (TNFR1) by BMI category.
| ST2 | TNFR1 | |||||
|---|---|---|---|---|---|---|
| BMI category | N | Median concentration (IQR), pg/ml | p value | N | Median concentration (IQR), pg/ml | p value |
| Normal weight | 115 | 131 (0-628) | − | 88 | 2129 (1486-3232) | − |
| Underweight | 7 | 256 (82-659) | 0.51 | 7 | 1596 (1467-2971) | 0.57 |
| Overweight | 115 | 208 (0-845) | 0.22 | 81 | 2266 (1708-3725) | 0.32 |
| Obese | 110 | 257 (0-1045) | 0.04 | 99 | 2644 (1922-3395) | 0.05 |
| ST2 | TNFR1 | |||||
|---|---|---|---|---|---|---|
| BMI category | N | Median concentration (IQR), pg/ml | p value | N | Median concentration (IQR), pg/ml | p value |
| Normal weight | 115 | 131 (0-628) | − | 88 | 2129 (1486-3232) | − |
| Underweight | 7 | 256 (82-659) | 0.51 | 7 | 1596 (1467-2971) | 0.57 |
| Overweight | 115 | 208 (0-845) | 0.22 | 81 | 2266 (1708-3725) | 0.32 |
| Obese | 110 | 257 (0-1045) | 0.04 | 99 | 2644 (1922-3395) | 0.05 |
No relevant conflicts of interest to declare.
