Determinants of cardiorespiratory fitness in very long-term survivors of allogeneic hematopoietic stem cell transplantation: a national cohort study

Purpose: Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for cardiopulmonary adverse events. Data on long-term effects on cardiorespiratory fitness are limited. To address the gap in knowledge, we aimed to determine peak oxygen uptake (V̇O₂peak) and identify associations between cardiorespiratory fitness and clinical characteristics, self-reported physical activity, cardiac, and pulmonary function.

Methods: In a nationwide, single-center cross-sectional study, 90 survivors [aged median (range) 35 (17-54) years, 56% females] were examined, 17 (6-26) years after allo-HSCT. Myeloablative conditioning comprised busulfan/cyclophosphamide or cyclophosphamide only. Methods included pulmonary function tests, echocardiography, and cardiopulmonary exercise test.

Results: Chronic graft-versus-host disease (cGVHD) was found in 31% of the subjects, of whom 40% had bronchiolitis obliterans syndrome (BOS). Seventy-one percent of the survivors did not meet WHO recommendations for physical activity and 42% were overweight. Reduced gas diffusion (DL_CO) and systolic ventricular dysfunction (LVEF) were found in 44% and 31%, respectively. For the group, mean (95% CI), V̇O₂peak was 36.4 (34.7-38.0) mL/min/kg [89 (85-93)% of predicted]. V̇O₂peak was low at 43%. Cardiopulmonary factors and deconditioning were equally common limitations for exercise. In a multiple linear regression model, low V̇O₂peak was associated with low DL_CO, low LVEF, BOS, overweight, and inactivity.

Conclusion: Half of the survivors had reduced cardiorespiratory fitness median 17 years after allo-HSCT. Cardiopulmonary factors and deconditioning were equally common limitations to exercise. We encourage long-term cardiopulmonary monitoring of allo-HSCT survivors and targeted advice on modifiable lifestyle factors.

Keywords: Allogeneic hematopoietic stem cell transplantation; Cardiac function; Cardiorespiratory fitness; Long-term follow-up; Pulmonary function.