In this report, assessment of body composition by CCT in older patients undergone allogeneic transplantation showed that high muscle radiodensity was associated with higher risk of death persisting even after adjusting for age, KPS, and sex e greater risk of acute GVHD controlling for kinship degree and sex. While the age had a positive association with risk of death only in patients undergone autologous transplantation.
Hematologic malignancies are a group of diseases that are associated with aging. With the growth of the older population in Brazil, more candidates will be eligible for HSCT.(14) This therapeutic modality has high morbidity and mortality, associated with a high incidence of acute and chronic complications. 2,15,16 Our Onco-hematology service is accredited by the Foundation for the Accreditation of Cellular Therapy (FACT)(17), performing a significant number of HSCT in older patients. All patients undergone oncogeriatric clinical evaluation before the procedure. 18,19
Age should not be used as an exclusion criterion in isolation as a limiting factor for transplantation once based on currently data, age alone is not the best predictor of toxicity and outcomes; rather, the comorbidities and functional status of the older patient are likely better predictors of toxicity than chronologic age in both the autologous and allogeneic setting. A comprehensive geriatric assessment (CGA) in older adults being considered for either an autologous and allogeneic transplant may identify additional problems or geriatric syndromes, which may not be detected during the standard pre-transplant evaluation.20,21 The measurement of skeletal muscle mass can be a tool of choice for evaluation of frailty.22
In regard to outcomes by transplantation type, studies suggest that elderly patients undergone HSCT are at high risk for treatment-related mortality. Our death results related to TRM after one year were similar to those found in the literature. We observed a rate of 20% at 1 year for autologous transplantation, whereas in recent studies with the adoption of better supportive care and the advent of reduced-intensity conditioning, TRM rates for older patients of 4–12%. TRM rate of 35% for allogeneic in our study that in literature varying between 33% and 35%.2
Regarding BMI, our data showed few malnourished patients in pre-transplantation, as in other studies. 23 Although some studies have shown a positive association between BMI and overall survival, we did not find such an association. BMI alone does not properly evaluate lean mass and fat mass changes and does not reflect patients’ body composition, which helps to explain conflicting literature results for HSCT outcomes in the elderly when only BMI or is considered. 24,25
Currently, the measurement of body composition by analysis of muscle area at the fourth thoracic vertebra level is not validated, although it has already been used in other studies. Future studies are still needed to determine the relationship between various cutoff points of the various vertebral levels and clinical outcomes. 10
The use of abdominal CT scans is not routinely done for staging in HSCT, only CCT. CCT, besides being routinely performed in this group of patients, was used for assessment of muscle mass, since it has good correlation with total skeletal muscle mass.4
In allogeneic HSCT patients, our results demonstrated a significant association between T4 muscle area (p = 0.015) and radiodensity (p = 0.028) with chance of GVHD. Our body composition findings are conflicting with the literature. Kyle et al. demonstrated that changes in lean mass were significantly associated with GVHD. Chughtai et al. did not demonstrate a significant association between muscle area and acute GVHD. In allogeneic transplant pediatric patients with long-term survival, there was no such relationship, either.26,27 However, none of these studies evaluate the older adults or reported radiodensity. There is no evidence of association between radiodensity and risk of death in patients undergoing autologous HSCT. We also identified, in the allogeneic transplant group, an association between radiodensity and risk of death after controlling for age, sex, and KPS (p = 0.032), with a reduction in risk of death by 20.1%. In patients with melanoma, kidney cancer, colorectal cancer, and follicular lymphoma, lower muscle radiodensity is found when there are fewer muscle fibers and more fatty infiltration and is associated with worse survival. However, our study did not demonstrate this result.28 We found no studies in the literature showing an association between radiodensity and GVHD. Our results showed a positive relationship between GVHD and radiodensity.
In evaluating BMI by categories, eutrophic patients who received allogeneic transplantation had a positive association with neutrophil recovery. Although there are studies showing earlier recovery in patients with high BMI in underweight patients, this finding occurred 3 days and 4 days later than in normal and overweight patients, respectively.29
The influence of age on transplant outcomes remains a controversy. Until two decades ago, 60 years old was considered maximum age for autologous transplantation and 55 for allogeneic. After the introduction of reduced intensity conditioning regimens, age has been shown to have minimal influence on outcomes. Unlike other studies, among our patients, in which age ranged between 60 and 76 years with a median of 67 years, we found a significant association with mortality only in cases of autologous transplantation. 30
Our study findings suggest that there is no significant association between age, KPS, and risk of death in allogeneic HSCT, although these associations were significant in patients undergone autologous HSCT in either the simple or multiple models. One of the hypotheses to explain this result would be that patients submitted to allogeneic HSCT, in principle, have more severe underlying diseases and, as a result, have already undergone several treatment lines prior to transplantation. This finding suggests that the severity of the underlying disease has a greater impact than age and KPS on morbidity and mortality, as described in other studies. 25
Although older adults have been identified as being vulnerable to the side effects of cancer treatment, few studies have specifically incorporated health condition measurement metrics in addition to ECOG or Karnofsky functional status to identify those at higher risk.1,19
Albeit our sample has been the largest case series published, our small number of patients was a limiting factor for quantitative analysis with higher power, however the qualitative findings and study trends encouraged us to evaluate the results.
In future prospective studies, assessment of body composition by CCT should be performed early in the initial staging and during treatment to increase the sensitivity of our assessment of body composition and variation during treatment.
The risks and benefits of HSCT in older adults remain poorly defined in the transplant community. Our evidence that the use of chest CT as a body assessment tool in the pre- transplantation clinical routine is extremely relevant, as this exam is part of patient diagnosis and follow-up as a tool that could be explored to estimate morbidity and mortality of these patients.