Feasibility of Cardiopulmonary Exercise Testing and Longitudinal Patient-Reported Outcome (PRO) Assessment in Patients Undergoing Hematopoietic Cell Transplantation

Background: Hematopoietic Cell Transplantation (HCT) is a potentially curative therapy for high risk malignancies but remains limited by treatment-related toxicity. Pre-HCT cardiopulmonary exercise testing and longitudinal post-HCT patient-reported outcome (PRO) surveillance are new techniques that may help to predict risk and tailor interventions to improve long term outcomes. Patients and Methods: We performed a feasibility study enrolling 32 patients into three cohorts (10 autologous HCT recipients, 11 full intensity allogeneic HCT recipients, and 11 reduced intensity allogeneic HCT recipients). Pre-transplant physiological measurements included VO_2peak assessment by cycle ergometer and 6-minute walk testing (6MWT). PRO measurements included daily and weekly symptom inventories derived from the NCI’s PRO-CTCAE, and weekly HRQOL assessments using the NIH’s PROMIS Global Health measure. Spearman correlation coefficients, Wilcoxon Signed Rank tests, and univariable Cox regression models were used to determine the associations of variables with each other and with outcomes. Results: Median age at the time of transplantation was 57.6 years. Eighty-one percent of patients had intermediate or advanced disease and 41% had a high school education or lower. Pre-defined feasibility criteria for enrollment (>60%) and data collection were achieved. Ninety-one percent of patients completed VO_2peak and 6MWT prior to HCT. Ninety-four percent of patients opted to use the electronic mode of survey assessments. Weekly symptom surveys were completed in a median of 4.3 minutes, and weekly HRQOL surveys were completed in a median of 3 minutes. The median weekly completion rate was 100% in all cohorts from the start of conditioning through hospital discharge. VO_2peak was positively correlated with 6MWT (r=0.65, p<0.001) and negatively correlated with months of prior chemotherapy (r=-0.43, p=0.03), and was not correlated with age or HCT-CI. A VO_2peak >16mL/kg*min (N=21/29) was associated with a decreased risk of mortality after HCT (HR 0.11 (0.02-0.59), p=0.001). Patients with VO_2peak ≤16mL/kg*min had higher overall symptom scores and worse physical and mental HRQOL at baseline and throughout the period of observation than patients with VO_2peak > 16mL/kg*min.  In general, symptoms were correlated with physical and mental HRQOL. Individual symptoms differed in frequency and severity by cohort and by time point, in clinically expected ways. Statistically significant differences were seen when comparing all three cohorts by overall symptom scores and by physical and mental HRQOL. Conclusions:  Pre-HCT cardiopulmonary exercise testing and post-HCT longitudinal PRO surveillance are feasible, meaningful, and potentially prognostic. These techniques should be explored further in larger studies.