Depletion of Pre-Transplant Skeletal Muscle Is a Significant Poor Prognostic Factor in Allogeneic Hematopoietic Cell Transplantation

Introduction

Depletion of skeletal muscle is a poor prognostic factor for patients with various malignancies; however its significance for allogeneic hematopoietic cell transplantation (allo-HCT) in patients with hematological disease is unclear. Generally, muscle mass is measured by the methods established by the European Working Group on Sarcopenia in Older People, which require the use of dual energy X-ray absorptiometry or bioimpedance analysis, methods that are not performed in routine practice. Therefore, cross-sectional imaging using computed tomography (CT) has been suggested as an alternative method for analyzing muscle mass in clinical practice. Especially, lumbar total muscle cross-sectional area using CT, normalized for body height, which was named lumbar skeletal muscle mass index (SMI), is reported as an indicator of nutritional status, sarcopenia and cancer cachexia in patients with solid organ malignancy.

Aims

To clarify the usefulness of a pre-transplant lumber SMI as a prognostic indicator for allo-HCT patients.

Methods

Among 208 patients with hematological disease who underwent allo-HCT between 2006 and 2017 at our facility, 191 patients (95 males and 96 females) underwent CT scans for routine pre-transplant status assessment. Ninety patients had acute myeloid leukemia, 38 patients had acute lymphoblastic leukemia, 24 patients had myelodysplastic syndrome, 20 patients had malignant lymphoma, and 19 patients had other diseases. The median age of the patients was 42 years old (range: 16-66 years). Seventy-eight patients received myeloablative conditioning and the others received reduced intensity conditioning regimens. The number of patients in each HCT-comorbidity index (HCT-CI) risk group was as follows: low: 72, intermediate: 54 and high: 65. Axial images at the iliac crest were selected for analysis of lumber total muscle cross-sectional area (cm²). The rectus abdominus, psoas and paraspinal muscles were identified and quantified. Lumbar total muscle cross-sectional area was normalized for body height in meters squared (m²) and used to calculate lumbar SMI (cm²/m²). This study was performed in accordance with the Japanese Ethical Guidelines for Medical and Health Research Involving Humans and approved by the Ethical Committee of our facility.

Results

The median pre-transplant lumber SMI of the male patients was significantly higher than that of the female patients (42.7 (24.9-60.2) mm²/m² vs. 31.9 (20.7-44.6) mm²/m², p<0.01). We defined the cutoff value of lumber SMI as 42.7cm²/m² for male and 31.9cm²/m² for female patients. In the Kaplan-Meier estimate analysis, low lumber SMI was a significant poor prognostic factor for overall survival (p=0.016). In multivariate analysis using Cox regression model, adjusting for age, refined disease risk index, conditioning and HCT-CI, low lumber SMI was extracted as a significant poor prognostic factor for overall survival (hazard ratio 1.56, 95% confidence interval (CI) 1.03-2.36, p=0.036). By logistic regression analysis, adjusted odds ratio of 1-year non-relapse mortality for low lumber SMI was 2.47 (95% CI 1.13-5.41, p=0.024).

Conclusion

Low pre-transplant lumber SMI is a significant poor prognostic factor in allo-HCT, independent of other risk factors including HCT-CI and refined disease risk index in patients with hematological disease. It is affected by the high rate of non-relapse mortality in the early phase following allo-HCT in patients with low lumber SMI.