Background High intensity treatments such as hematopoietic cell transplantation (HCT) can be curative for patients with hematologic malignancies, but this needs to be balanced by the high risk of nonrelapse mortality (NRM) during the first 2 years after HCT. Sarcopenia (low muscle mass) is associated with physical disability and premature mortality in individuals with nonmalignant diseases and may be a predictor of NRM and poor overall survival in patients undergoing HCT. Methods This was a retrospective cohort study of 859 patients with acute leukemia or myelodysplastic syndrome who underwent a first HCT as adults (≥18 years) between 2007 and 2014. Sarcopenia was assessed from pre-HCT abdominal computed tomography scans. Two-year cumulative incidence of NRM was calculated, with relapse/progression considered as a competing risk event. Fine-Gray subdistribution hazard ratio estimates and 95% confidence intervals (CI) were obtained and adjusted for relevant covariates. Kaplan-Meier method was used to examine overall survival. All statistical tests were two-sided. Results Median age at HCT was 51 years (range = 18–74 years); 52.5% had a high [≥3] HCT-comorbidity index; 33.7% had sarcopenia pre-HCT. Sarcopenia was an independent predictor of higher NRM risk (hazard ratio = 1.58, 95% CI = 1.16 to 2.16) compared with patients who were not. The 2-year incidence of NRM approached 30% in patients with sarcopenia and high (≥3) HCT-comorbidity index. Patients with sarcopenia had on average a longer hospitalization (37.2 days vs 31.5 days, P < .001) and inferior overall survival at 2 years (55.2%, 95% CI = 49.5% to 61.0% vs 66.9%, 95% CI = 63.0% to 70.8%, P < .001). Conclusions Sarcopenia is an important and independent predictor of survival after HCT, with potential additional downstream impacts on health-economic outcomes. This information can be used to facilitate treatment decisions prior to HCT and guide interventions to decrease the risk of treatment-related complications after HCT.

Background: alloHCT is offered with curative intent to patients with malignant as well as some nonmalignant hematologic diseases, and conventionally-computed survival estimates are offered for prognosticating outcomes. However, conventionally-computed survival and mortality risk estimates do not account for patients' elapsed survival time which, among other factors, could affect subsequent mortality. Conditional survival overcomes these limitations by calculating the probability of survival after having already survived a certain period of time - such data are unavailable for alloHCT recipients. We describe conditional survival and cause-specific mortality (disease-related [DRM], non-disease-related [NDRM], and GvHD-related) after alloHCT to provide clinically relevant information for patients who have survived 6 mos, 1, 2, 5, and 10y after alloHCT. Methods: From 1976 to 2013, 4,315 consecutive patients underwent alloHCT for hematologic diseases at a single institution. Vital status and cause of death were determined using the National Death Index Plus and medical records. Results: Diagnoses included acute leukemia (54%), chronic leukemia (17%), lymphoma (11%), myelodysplastic syndrome (10%), severe aplastic anemia (5%), and other hematologic diseases (3%); median age at HCT was 38.5y (0.3-75.4). As of December 31, 2014, 1841 patients were still alive in whom the median follow-up was 8.5y (0.2-36.6). Of 2,474 deaths (57% of cohort) for whom causes of deaths are available, 42% was due to primary disease, 30% to graft versus host disease (GvHD), 12% to infection, 5% to cardiopulmonary diseases, 3% to subsequent malignant neoplasm (SMN), and 8% to other causes. Conventionally-computed probabilities of survival at 5, 10, 15, and 20y after alloHCT were 48%, 43%, 40%, and 34%, respectively. On the other hand, for patients who had survived 6 mo, 1, 2, 5, 10y after alloHCT, 5-y conditional survival rates were 62%, 72%, 80%, 88% and 93%, respectively (Figure A). Overall, the cohort was at a 24-fold (Standardized Mortality Ratio [SMR]=24.1, 95%CI=23.1-25.0) risk of any death, compared to the general population; the risk of death from pulmonary complications was 31-fold, that from SMN was 31-fold, and that from cardiovascular complications was 3.5-fold. SMR and cause-specific conditional mortality rates by primary diagnosis are shown in the Table. Significantly elevated risk of all-cause mortality persisted in patients who survived 5 and 10y post alloHCT (SMR=3.7, 2.6, respectively, p<0.05), although DRM and GvHD-related mortality in the subsequent 5y was low (<6%). In comparison, NDRM increased over time; among 5y survivors, NDRM exceeded DRM (Figure B): SMN was the most common cause (34%), followed by GvHD (26%), other causes (15%), infection (14%), and cardiopulmonary disease (11%). In 10y-survivors of acute leukemia and chronic leukemia, all-cause mortality remained significantly higher compared to the general population (SMR>1.8, p<0.05). For the overall cohort, after adjusting for primary diagnosis, relapse risk at alloHct, treatment era, and ethnicity, DRM was significantly lower for patients who developed acute GvHD (HR=0.78, 95%CI=0.66-0.93). Adjusted for the same factors, NDRM risk increased with older age at HCT (HR=1.02 per year, 95% CI=1.01-1.03), and for patients with acute GvHD (HR=1.9, 95%CI=1.6-2.2) and those exposed to Total Body Irradiation (TBI) (HR=1.4, 95%CI=1.2-1.8). Conclusions: The projected 5-y survival rates improve conditional on time survived from alloHCT; 5-y survival is nearly 90% for those who have already survived 5y. However, alloHCT recipients who have survived 10+y continue to remain at increased risk of death compared to the general population, with SMN as the most common cause. Acute GvHD is associated with decreased risk of DRM as expected, whereas acute GvHD and TBI are associated with increased risk of NDRM. DRM and GvHD-related mortality rates decline with survival time, while among ≥5y survivors, NDRM exceeds DRM. Conditional survival and mortality estimates provide clinically relevant prognostic information, helping to inform preventive and interventional strategies. Disclosures Forman: Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding.

Introduction: High intensity treatments such as autologous hematopoietic cell transplantation (HCT) can be curative for patients with relapsed/refractory lymphoma (Hodgkin [HL], non-Hodgkin [NHL]), but this needs to be balanced by the risk of non-relapse mortality (NRM) associated with HCT and potentially sub-optimal disease response with less intensive treatments. Measures of pre-treatment body composition such as quantity and quality of muscle are prognostic in patients with solid tumors, but their association with post-HCT outcomes is unknown. We examined the prognostic significance of muscle depletion prior to HCT, defined by having both low muscle quantity (lumbar skeletal muscle index [SMI]) and quality (muscle attenuation [MA]) on computed tomography (CT) imaging, in a population-based cohort of patients undergoing autologous HCT for lymphoma. Next, we examined the prognostic significance of muscle depletion after HCT in a subset of patients with normal muscle composition prior to HCT, allowing us to examine the impact of change in body composition over time. Methods: 440 consecutive patients with lymphoma, age ≥18y, who underwent a first HCT between 2009 and 2014 at a single institution were included in the study. Measures of muscle quantity (SMI) and quality (MA) were ascertained from pre- and post-HCT abdominal CT scans using image analysis software (SliceOmatic; Tomovision, Quebec, Canada). SMI was calculated as the ratio of skeletal muscle area (cm2) divided by height (m)2. Sex and body mass index (BMI)-specific cutoff values of low SMI and MA were used to identify patients with muscle depletion (J Clin Oncol 2013 31:1539). Measurements were made by trained researchers blinded to patient demographics and HCT outcome (Figure 1); 3rd lumbar vertebra was used as a landmark because of its high correlation with whole-body muscle mass (J Clin Oncol 2016 34:1339). This report is limited to 321 (73%) patients with CT scans performed ≤90 days from HCT. Cumulative incidence of NRM was calculated taking into consideration competing risk of disease-related mortality. Kaplan-Meier method was used to examine overall survival (OS). Multivariable Cox regression analysis was used to calculate the hazard ratio (HR) estimates and 95% confidence intervals (CI), adjusted for relevant covariates (demographics, diagnosis, pre-HCT Karnofsky performance score [KPS] and comorbidity index [HCT-CI]). Results: Sixty-two (19.3%) patients had muscle depletion pre-HCT. Median age at HCT was 53y (range: 18-78); 62.0% were male; 54.0% were non-Hispanic white; Diagnoses: HL (N=84 [26.2%]), NHL (N=237 [73.8%]); KPS ≤80 (N=87 [27.1%]); HCT-CI ≥3 (N=52 [16.2%]). Impact of pre-HCT muscle depletion: Patients with pre-HCT muscle depletion had significantly worse 5-y OS (56.4% vs. 77.8%, p<0.001; Figure 2) and higher NRM (11.4% vs. 5.1%, p=0.05) when compared to those with normal body composition. OS was especially poor for patients who were obese (BMI ≥30 kg/m2) and had muscle depletion (20.0% vs. 77.1%, p<0.001) pre-HCT. Median length of hospitalization was also significantly longer (27d vs. 23d; p=0.03) among patients with muscle depletion. Muscle depletion was associated with a 2.2-fold (HR=2.2 [CI: 1.0-4.5]) risk of NRM and 1.8-fold (HR=1.8 [CI: 1.1-3.1]) risk of all-cause mortality when compared to those with normal body composition. Impact of post-HCT muscle depletion: Among 223 patients with normal body composition prior to HCT, 24 (9.3%) developed muscle depletion after HCT, detected at a median 63d (range 27-165) from HCT. In these patients, there was a 3-fold (HR=3.1 [CI: 1.5-6.4]) risk of all-cause mortality compared to those who maintained normal muscle composition throughout HCT. Conclusion: Muscle depletion is an important and independent predictor of outcomes after HCT, with potential additional downstream impacts on health-economic outcomes such as length of hospitalization and the burden of chronic morbidity in long-term survivors. Taken together, these data form the basis for real-time decision making prior to HCT (e.g. pre-habilitation, less intensive treatment approaches), or during HCT (e.g. dietary optimization, increased supportive care services, resistance training), setting the stage for innovative strategies to improve outcomes after HCT. Disclosures Chen: Affimed: Research Funding; Merck & Co., Inc.: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech Inc.: Consultancy; Millennium Pharmaceuticals: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding.