Exercise Duration during a Brief Step Test Independently Predicts Outcomes after Hematopoietic Cell Transplantation

Pretransplant pulmonary function testing (PFT) is standard before hematopoietic cell transplantation (HCT), but few centers complement it with objective functional capacity assessment. At our institution, a 3-min step exercise test is performed at the time of PFTs, generating two distinct measures: exercise duration (a functional capacity surrogate) and oxygen desaturation (a gas exchange measure). Whether either component adds prognostic value beyond PFTs is unknown. The primary objective of the study was whether step-derived variables added predictive value beyond a baseline model containing age, sex, transplant type, FEV₁z-score, DLCO z-score, and hemoglobin. Outcomes of interest were overall survival, ICU admission within 120 d, and invasive mechanical ventilation within 120 d. This is a single-center retrospective cohort of 3458 adult HCT recipients (2648 autologous, 810 allogeneic) who underwent a 3-min step exercise test before HCT between 2005 and 2024. Pulse oximetry and heart rate were recorded during the step test. Pretransplant PFTs were interpreted using Global Lung Initiative reference equations and reported as z-scores. Overall survival was analyzed using Cox proportional hazards regression, and ICU admission and invasive mechanical ventilation were analyzed using logistic regression. Additive value of exercise variables was evaluated with a prespecified baseline model containing established predictors of HCT outcomes. Median follow-up was 4.5 yr. During follow-up, 1149 patients (33.2%) died, 495 (14.3%) were admitted to the ICU within 120 d, and 131 (3.8%) required invasive mechanical ventilation. Of 3431 patients with exercise time recorded, 718 (20.9%) stopped before completing the 3-min protocol. Exercise time predicted all three outcomes after full adjustment: each additional minute was associated with lower mortality (HR 0.90, 95% CI 0.82 to 0.99, P = .025), lower odds of ICU admission (OR 0.80, 95% CI 0.69 to 0.92, P = .003), and lower odds of invasive mechanical ventilation (OR 0.70, 95% CI 0.55 to 0.89, P = .004). Model fit improved with the addition of exercise time for all three outcomes. In contrast, oxygen desaturation did not predict any outcome after hemoglobin adjustment (overall survival HR 0.99, 95% CI 0.96 to 1.02, P = .53). An apparent association between desaturation and mortality without hemoglobin adjustment (HR 0.96, P = .003) was fully absorbed by measured hemoglobin, confirming confounding by oxygen-carrying capacity. Exercise duration during a brief pretransplant step test independently predicts overall survival, ICU admission, and invasive mechanical ventilation after HCT, capturing a dimension of pretransplant fitness not measured by resting PFTs or hemoglobin. Oxygen desaturation does not add prognostic value, and the apparent signal in unadjusted analyses reflects hemoglobin confounding. These findings support emphasizing exercise capacity assessment before HCT.