Feasibility and Prognostic Value of VO2_peak in Patients Undergoing Hematopoietic Cell Transplantation (HCT)

Peak oxygen consumption (VO2_peak, in mL/kg*min) is assessed by cardiopulmonary exercise testing (CPET) and reflects overall physical fitness. VO2_peak has prognostic value in healthy and chronically ill patients, including patients with solid tumor malignancies. To our knowledge, direct measurement of peak oxygen uptake has not previously been examined in patients undergoing HCT, an area in which prognostic models are needed to understand and limit treatment-related toxicity. Current HCT prognostic models measure disease-related risk or indirectly measure patient fitness by assessing comorbidity burden. The purpose of this study was to evaluate the feasibility of assessing functional status in HCT patients by exercise testing and physiological measurements, and to investigate the potential prognostic usefulness of these variables in this population.

We evaluated the feasibility of assessing cardiopulmonary fitness (CPET with gas exchange on cycle ergometer), body composition (Dual Energy X-ray Absorptiometry-DEXA), and physical function (6 minute walk test-6MW) in 32 patients undergoing planned HCT (10 autologous HCT patients, 11 myeloablative allogeneic HCT patients, 11 reduced intensity allogeneic HCT patients). Tests were conducted prior to receipt of conditioning chemotherapy and again at 100 days following stem cell infusion (D+100). Feasibility was determined by the ability of patients to successfully and safely complete a full set of tests. Exploratory analyses to investigate the relationships of variables with one another and with survival utilized Kruskal-Wallis and Wilcoxon Signed Rank tests, Pearson Correlation coefficients, and Cox regression analyses.

Median age of the sample was 55 years (range 18–70). Sixteen patients (50%) were female. Most autologous HCT patients had myeloma (N=8, 80%) and most allogeneic HCT patients had acute leukemia (16, 72%); other diagnoses included NHL (4), CML, MDS and AA. Twenty-six patients (84%) had intermediate or late stage disease, and 16 patients (50%) had a Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) score of > 3.

VO2_peak testing was successfully completed prior to HCT in 29 (91%) patients with no adverse events during testing. Two patients had lower limb limitations preventing participation in cycle ergometry, and one patient had baseline EKG abnormalities with exclusion per clinician discretion. No significant differences in median VO2_peak were observed at baseline among patients undergoing autologous, myeloablative allogeneic, and reduced intensity allogeneic HCT (20.1 (15.20–28.0), 20.8 (9.2–35.4), and 23.8 (10.8–28.7) mL/kg*min respectively, p=0.9). Across cohorts, eight (28%) patients had a VO2_peak <16ml/kg*min, which has been shown in other studies to be associated with lack of functional independence. Physical function assessed via 6MW at baseline was not significantly different between groups (448 (305–590), 480 (320–690), and 493 (313–600) meters respectively, p=0.44). Baseline VO2_peak was correlated with 6MW (r=0.65, p<0.001) but not with age, HCT-CI, or other baseline variables. D+100 testing was completed in 14 (44%) patients, with significant post-HCT changes observed in median total mass (−2056g, p=0.01) and median lean mass (−1601g, p=0.01) among these 14 patients. With a median follow-up of 9 months, 24 (75%) patients were alive. When including all patients, a baseline VO2_peak of > 16 mg/kg*min was associated with a lower risk for mortality after transplant (HR 0.11 (0.02–0.59), p<0.01). No associations between age (p=0.30), HCT-CI (p=0.17), or EBMT risk score (p=0.17) with post-HCT mortality were observed. The association of 6MW with post-HCT mortality approached significance (p=0.09).

Baseline comprehensive functional and exercise testing that includes CPET with gas exchange is feasible in patients undergoing HCT, including older patients with comorbid illness and advanced disease. The feasibility and potential prognostic usefulness of D+100 testing were limited by post-HCT morbidity and logistical concerns, though data from patients undergoing testing showed significant attrition in muscle mass. Baseline VO2_peak reflects underlying physiological fitness and may be a novel prognostic marker in patients undergoing HCT. Larger studies are warranted to confirm this finding.

No relevant conflicts of interest to declare.