Impact of Sarcopenia on Adverse Outcomes After Allogeneic Hematopoietic Cell Transplantation

Abstract

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.

Risks of Muscle Atrophy in Patients with Malignant Lymphoma after Autologous Stem Cell Transplantation

“…There were several reports with regards to changes in skeletal muscle mass and the effects of exercise therapy after HSCT 14 ) . The association between skeletal muscle reduction clinical outcomes and prognosis after HSCT has also been suggested in the previous reports 13,15,16) . While patients with hematological malignancies are treated with HSCT, the influence of HSCT on skeletal muscle mass have not been previously described in detail despite the known relationship between auto-HSCT and muscle atrophy.…”

Evaluation of nutritional risk factors in hematopoietic stem cell transplantation-eligible patients

“…(4) Therefore, sarcopenia seems to be a significant factor in nonrelapse mortality following HSCT and may assist in decision making in different phases of the transplantation process, including conditioning regimen intensity, nutritional optimization, enhanced support and resistance training, in an effort to mitigate HSCTrelated complications. (4) Muscle wasting is often related to insufficient nutrient intake. Therefore, treatment strategies should include proper food intake combined with protein and amino acid supplementation.…”

“…Sarcopenia has been associated with high risk of solid tumor relapse and higher risk of non-relapse mortality in oncologic patients submitted to HSCT. (4) Proper food intake may help control oxidative stress and maintain or improve nutritional status. (5) Therefore, nutritional aspects must be understood for efficient multidisciplinary treatment of hematologic patients eligible for HSCT.…”

Pre-transplant hepatic steatosis (fatty liver) is associated with chronic graft-vs-host disease but not mortality

“…The significant role of IL-6 in GVHD development is illustrated by improved GVHD with use of an IL-6 antagonist [34,35]. Skeletal muscle depletion (sarcopenia, defined in men as BMI < 25 with muscle mass less than 43 cm2/m2 or BMI � 25 with muscle mass < 53 cm2/m2; in women regardless of BMI, 41 cm2/m2) has also been associated with lower non-relapse mortality and overall poorer outcomes in allogeneic stem cell transplant [36], however we did not find an association between skeletal muscle area and HCT outcomes. Our finding that pre-HCT hepatic steatosis, but not other imaging measures of metabolic syndrome/obesity, is associated with chronic GVHD suggests it may be a uniquely useful marker.…”