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

Ole Henrik Myrdal,Phoi Phoi Diep,Johny Kongerud,May B Lund,Elisabeth Edvardsen,Ellen Ruud,Lorentz Brinch,Richard John Massey,Liv Ingunn Sikkeland

doi:10.1007/s00520-020-05644-1

Abstract

PurposeSurvivors 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.MethodsIn 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.ResultsChronic 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 (DLCO) 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 DLCO, low LVEF, BOS, overweight, and inactivity.ConclusionHalf 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.

Highlights

MethodsSurvivors of allogeneic hematopoietic stem cell transplantation are at risk for both cardiac and pulmonary adverse events, caused by the myeloablative conditioning prior to allo-HSCT and the immunological response induced by the hematopoietic stem cell graft after allo-HSCT [1, 2]
The most frequent Late-onset non-infectious pulmonary complications (LONIPCs) is bronchiolitis obliterans syndrome (BOS), which is linked to chronic graft-versus-host disease [4]
Myeloablative conditioning with busulfan/ cyclophosphamide or cyclophosphamide had been applied in 98% of the subjects

Summary

Introduction

MethodsSurvivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for both cardiac and pulmonary adverse events, caused by the myeloablative conditioning prior to allo-HSCT and the immunological response induced by the hematopoietic stem cell graft after allo-HSCT [1, 2]. Late-onset non-infectious pulmonary complications (LONIPCs) occur in up to one-fifth after allo-HSCT and comprise leading causes of morbidity and mortality [3]. The most frequent LONIPC is bronchiolitis obliterans syndrome (BOS), which is linked to chronic graft-versus-host disease (cGVHD) [4]. Cardiovascular disease is another cause of morbidity and mortality in long-term allo-HSCT survivors [5]. Risk factors for cardiovascular disease have been reported to be > 4-fold higher in allo-HSCT survivors than in the general population [6], with a clear association between multiple risk factors and subsequent development of cardiovascular disease [2]

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