Sarcopenia, Gonadal, Metabolic and Bone Mass Changes in Young and Middle-Age Patients with Lymphoma Post an Autologous Stem Cell Transplantation
Authors: Leal Christianne Tolêdo de Souza , Ezequiel Danielle Guedes Andrade , Xavier Ana C. , Hallack Neto Abrahão Elias 
Published: December 2024

Background: Survival rates among adult patients with chemotherapy-sensitive lymphoma submitted to an autologous stem cell transplant (ASCT) have significantly improved in recent years. However, high-burden morbidity associated with this procedure has been well-described and known to compromise quality-of-life (QOL) and/or long-term survival. Outcomes of patients with lymphoma post-ASTC are also affected by their nutrition status and skeletal muscle mass. Sarcopenia has been described as a powerful predictor of inferior progression-free survival in lymphoma patients post-ASCT (Sumransub et al, Transplantation and Cell Therapy, 2023). The occurrence of sarcopenia is variable, reaching up to 70% in cancer patients (Xin-Tian Xu et al, Frontiers in Nutrition, 2022), and is still few described in patients post an ASCT. The loss of bone mass in association with other co-morbidities, such as gonadal dysfunction, insulin resistance, and obesity, contribute to decrease in muscle strength, functional limitations, and frailty. In this study, we sought to evaluate the occurrence of sarcopenia, gonadal dysfunction, insulin-resistance, and obesity in a cohort of Brazilian young to middle-age adults with (Hodgkin or non-Hodgkin) lymphoma submitted to an ASCT.

Methods This is a cross-sectional study that prospective analyzed 39 patients with lymphoma treated with an ASCT at our institution between 2005 and 2023. Eligible patients were invited to participate via phone to come for evaluation. Body composition was measured using anthropometric and Dual X-ray Absorptiometry (DXA body composition analysis), in addition to complete physical examination. We evaluated muscle strength by handgrip, and gait speed, with sarcopenia being defined if grip strength rating (in Kgf) &lt;16 in women and &lt;27 in men, associated with an Appendicular Lean Mass Index (IMMA) &lt;5.5 Kg/m2 and &lt;7.0 Kg/m2 in female and male patients, respectively. We used the International Diabetes Federation (IDF) criteria to diagnose metabolic syndrome (MS) and determined total body fat using 2 criteria: the Fat Mass Index (FMI) by DXA assessment [total fat mass (Kg)/(height)2(m)] and Body Mass Index (BMI). The FMI cut-off point for obesity was &gt;9 in men and &gt;13 in women. In all patients, we evaluated gonadal function measuring LH, FSH, TSH and prolactin, 17-estradiol (female) and total testosterone (male). This study was approved by the Institutional Ethics Committee and Brazilian Clinical Trial Identification number is RBR-4xtk65g.

Results Median age at the time of ASCT was 34 (range: 19-63), with average time from transplant of 53 months (range:2-180), 16 males and 23 females, and most patients having Hodgkin lymphoma (64.1%). Sarcopenia was diagnosed in 15.4% with all patients being &lt;4 years from ASCT. Low bone mass was observed in 23%. Obesity was found in 30.7% and 33,3% using IMC and FMI criteria, respectively. We found type 2 diabetes mellitus (T2DM) in 10.2% with a mean age at diagnosis of 41.7 years (range: 33-52), and MS in 33.3% of this cohort. High blood pressure and T2DM were found to be the main risk factors associated with an increased abdominal circumference. Of the 23 women evaluated, 13% (n=3) were in menopause prior to the ASCT and 14 (70%) had gonadal failure (FSH &gt;40 mIU/mL), with mean age at ASCT of 33,5 years (range: 21-49). As for men, the average total testosterone was 687.3 ng/dl (reference value: 249- 836 ng/dl) (range:334- 1674) and 81.2% had FSH levels above the upper limit of normal, demonstrating a high risk of infertility.

Conclusion Sarcopenia is common and occurs early after ASCT in young and middle-age adult patients with lymphoma. We also found high obesity rates, and elevated proportions of T2DM or MS, female gonadal failure, and decreased male infertility among those survivors. These data highlight the need to emphasize and promote health habits, and to establish approaches to prevent early gonadal dysfunction/infertility in young/middle age adult lymphoma survivors post-ASCT in a low-income setting.