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Lung function after allogeneic hematopoietic stem cell transplantation in children: a longitudinal study in a
Hilde Hylland Uhlving1, Caecilie Larsen Bang, Ib Jarle Christensen
1Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Denmark. hilde.hylland.uhlving@rh.regionh.dk
Insights
Pulmonary function decline is common in pediatric hematopoietic stem cell transplantation (HSCT) patients. Acute graft-versus-host disease (GvHD) is a key factor linked to this lung function decrease.
Area of Science:
- Pediatric Pulmonology
- Hematology
- Transplantation Immunology
Background:
- Pulmonary function (PF) reduction affects up to 85% of pediatric patients post-hematopoietic stem cell transplantation (HSCT).
- The causes of decreased lung function after HSCT remain poorly understood.
Purpose of the Study:
- To describe PF changes in a pediatric HSCT cohort.
- To identify transplantation-related factors associated with PF decline.
Main Methods:
- Retrospective, population-based, single-center study.
- Longitudinal analysis of PF over time using a mixed linear model.
- Inclusion of 130 pediatric HSCT patients with 1084 PF tests over a median follow-up of 3.3 years.
Main Results:
- 62% of patients showed >10% PF decline within 3-9 months post-HSCT.
- Decline in FEV1, FEV1/FVC, and DLCO was strongly associated with acute graft-versus-host disease (GvHD).
- Other associated factors included malignant diagnosis, busulfan conditioning, patient/donor age, and donor-recipient sex mismatch.
Conclusions:
- Mild to moderate PF decline is frequent after pediatric HSCT.
- Acute GvHD and factors predisposing to chronic GvHD are associated with PF decline.
- Alloreactivity appears central to the pathogenesis of reduced pulmonary function post-HSCT in children.
Abstract:
Reduction in pulmonary function (PF) has been reported in up to 85% of pediatric patients during the first year after hematopoietic stem cell transplantation (HSCT). Our understanding of the etiology for this decrease in lung function is, however, sparse. The aim of this study was to describe PF during follow-up in a population-based pediatric HSCT cohort and to investigate factors in the transplantation process associated with PF decline. A retrospective, population-based, single-center study of HSCT patients spanning 2 decades was performed. Longitudinal changes in PF over time and associations to transplantation-related factors were investigated using a mixed linear model. One hundred thirty patients were included in the longitudinal analysis and observed for a median (range) of 3.3 (.2 to 16.8) years, during which 1084 PF tests were performed. Sixty-two percent of the patients experienced a decline in lung function of more than 10% during the first 3 to 9 months after HSCT. The decline in forced expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital capacity and diffusion capacity of the lung for carbon monoxide were strongly associated with acute graft-versus-host disease (GvHD). Other factors associated with PF decline were malignant diagnosis, busulfan-based conditioning, patient and donor age, female donor to male recipient, as well as chronic GvHD. Mild to moderate decline in PF is frequent and appears associated with acute GvHD and other parameters that are risk factors for chronic GvHD in children. This indicates that alloreactivity is central in pathogenesis of the decrease in PF that follows HSCT in children.
