Impact of Obesity and Weight-Based Chemotherapy Dosing Adjustments on Outcomes of Allogeneic Hematopoietic Cell Transplant for Acute Myeloid Leukemia.

[BACKGROUND] Data on transplant outcomes of obese patients undergoing allogeneic hematopoietic cell transplant (alloHCT) have demonstrated conflicting results both in regard to the prognostic significance of obesity and appropriate dosing of chemotherapy to balance toxicity and efficacy.

[OBJECTIVES] We retrospectively evaluated 751 acute myeloid leukemia (AML) patients who underwent alloHCT at the Moffitt Cancer Center from 2010-2021 to compare transplant outcomes of obese (BMI ≥30 kg/m) and non-obese patients (BMI <30 kg/m). Transplant related outcomes included time to engraftment, acute graft-versus-host disease (aGVHD), moderate-severe chronic graft-versus-host disease (cGVHD), relapse, non-relapse mortality (NRM), relapse free survival (RFS), and overall survival (OS).

[STUDY DESIGN] Data was collected via internal database supplemented by direct records review. Univariate Cox regression models were developed using baseline variables, and multivariate Cox regression models were built using significant variables from univariate analysis and backwards selection. Similarly, Fine & Gray subdistribution hazard models were built when competing risks were present. Kaplan Meier curves were utilized to show RFS and OS. The time-to-event outcomes with competing risks were summarized by cumulative incidence curves. In the subgroup of patients with BMI ≥30 kg/m receiving melphalan based conditioning (n = 78), we compared outcomes in patients who received melphalan dosed on total body weight versus adjusted body weight.

[RESULTS] The cohort of 751 patients included 246 (32.8%) with BMI ≥30 kg/m, and 505 (67.2%) with BMI <30 kg/m. Median follow up time was 50 months. Engraftment did not differ between groups. The cumulative incidence of grade 2-4 aGVHD was 49% for patients with BMI ≥30 kg/m and 44% for patients with BMI <30 kg/m, (P = .28), while the cumulative incidence of moderate to severe cGVHD was 24% versus 25% (P = .56). The cumulative incidence of relapse at 2 years was 23% versus 27% for patients with BMI ≥30 kg/m and BMI <30 kg/m respectively (P = .41), and cumulative incidence of NRM at 1 year was 14% versus 15% (P = .94). OS at 2 years was 64% versus 59% for patients with BMI ≥30 kg/m and BMI <30 kg/m, respectively (P = .35). In multivariable analysis, BMI was not shown to affect aGVHD, moderate to severe cGVHD, NRM, RFS, relapse, or OS. In the analysis of obese patients who received melphalan, no significant differences in outcomes were found between those receiving melphalan dosed by total body weight versus adjusted body weight.

[CONCLUSIONS] In this study of North American AML patients receiving alloHCT with varying conditioning and GVHD prophylaxis, including post-transplant cyclophosphamide, there were no significant differences in clinical outcomes between patients with BMI ≥30 kg/m compared to patients with BMI <30 kg/m.