Longitudinal lung function in childhood cancer survivors after hematopoietic stem cell transplantation

Maria Otth,Sophie Yammine,Jakob Usemann,Ben Spycher,Tayfun Güngör,N Von Der Weid,J Rössler,J Greiner,M Ansari,P Brazzola,J P Bourquin,Philipp Latzin,M Beck Popovic,Katrin Scheinemann,F Schilling,For The Swiss Pediatric Oncology Group (Spog) ,Claudia E Kuehni,K Scheinemann,Luzius Mader

doi:10.1038/s41409-021-01509-1

Abstract

Longitudinal data on pulmonary function after pediatric allogeneic or autologous hematopoietic stem cell transplantation (HSCT) are rare. We examined pulmonary function and associated risk factors in 5-year childhood cancer survivors (CCSs) longitudinally. We included 74 CCSs diagnosed between 1976 and 2010, treated with HSCT, and with at least two pulmonary function tests performed during follow-up. Median follow-up was 9 years (range 6–13). We described pulmonary function as z-scores for lung volumes (forced vital capacity [FVC], residual volume [RV], total lung capacity [TLC]), flows (forced expiratory volume in 1 s [FEV1], maximal mid-expiratory flow [MMEF]), and diffusion capacity for carbon monoxide (DLCO) and assessed associations with potential risk factors using multivariable regression analysis. The median z-scores for FEV1, FVC, and TLC were below the expected throughout the follow-up period. This was not the case for RV, MMEF and DLCO. Female gender, radiotherapy to the chest, and relapse were associated with lower z-scores of FEV1, FVC, MMEF, RV or DLCO. Childhood cancer survivors after HSCT are at risk of pulmonary dysfunction. The complex and multifactorial etiology of pulmonary dysfunction emphasizes the need for longitudinal prospective studies to better characterize the course and causes of pulmonary function impairment in CCSs.

Highlights

Childhood cancer survivors (CCSs) treated with hematopoietic stem cell transplantation (HSCT) are at increased risk of pulmonary dysfunction, which reflects different structural and functional damage to the lung [1,2,3,4]
Study population and design The study population consisted of participants of the Swiss Childhood Cancer Survivor Study (SCCSS), a questionnaire-based, national cohort study of all children and adolescents registered in the Swiss Childhood Cancer Registry (SCCR), who had survived ≥5 years [13, 14]
We used the RESULTS Patient characteristics Among 142 SCCSS responders treated with HSCT, we found at least two Pulmonary function testing (PFT) of good quality in the medical records of 74 CCS (Supplementary Fig. 1)

Summary

Introduction

Childhood cancer survivors (CCSs) treated with hematopoietic stem cell transplantation (HSCT) are at increased risk of pulmonary dysfunction, which reflects different structural and functional damage to the lung [1,2,3,4]. This can result from oxidative stress induced by lung-toxic chemotherapeutics (busulfan, bleomycin, carmustine and lomustine), free radical formation during radiotherapy, or transplant-specific pulmonary complications, such as idiopathic pulmonary syndrome or bronchiolitis obliterans [5,6,7,8]. Spirometry and body plethysmography measuring lung volumes and flow, are widely available but supposedly less sensitive than the diffusion capacity for carbon monoxide (DLCO) [9, 10]

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