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

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

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.

Conflict of interest statement

The authors declare no competing interests.

© 2021. The Author(s).

Figures

Fig. 1. Longitudinal pulmonary function trajectories in…
Fig. 1. Longitudinal pulmonary function trajectories in childhood cancer survivors following HSCT.
Longitudinal trajectories of (a) FEV1 z-score, (b) FVC z-score, and (c) DLCO z-score over time, upper part showing the trajectory of each patient, lower part showing the median of all observations.
Fig. 2. Median FEV1 and FVC z-scores…
Fig. 2. Median FEV1 and FVC z-scores in 24 childhood cancer survivors with pulmonary function testing before HSCT.
a Course of FEV1, b Course of FVC. T-test comparing before HSCT with follow-up categories.

References

    1. Hoffmeister PA, Madtes DK, Storer BE, Sanders JE. Pulmonary function in long-term survivors of pediatric hematopoietic cell transplantation. Pediatric Blood Cancer. 2006;47:594–606. doi: 10.1002/pbc.20531.
    1. Inaba H, et al. Pulmonary dysfunction in survivors of childhood hematologic malignancies after allogeneic hematopoietic stem cell transplantation. Cancer. 2010;116:2020–30. doi: 10.1002/cncr.24897.
    1. Madanat-Harjuoja LM, et al. Pulmonary function following allogeneic stem cell transplantation in childhood: a retrospective cohort study of 51 patients. Pediatric Transpl. 2014;18:617–24. doi: 10.1111/petr.12313.
    1. Uhlving HH, et al. Lung function after allogeneic hematopoietic stem cell transplantation in children: a longitudinal study in a population-based cohort. Biol Blood Marrow Transpl J Am Soc Blood Marrow Transpl. 2013;19:1348–54. doi: 10.1016/j.bbmt.2013.06.005.
    1. Hildebrandt GC, et al. Diagnosis and treatment of pulmonary chronic GVHD: report from the consensus conference on clinical practice in chronic GVHD. Bone Marrow Transpl. 2011;46:1283. doi: 10.1038/bmt.2011.35.
    1. Saglio F, et al. Occurrence of long-term effects after hematopoietic stem cell transplantation in children affected by acute leukemia receiving either busulfan or total body irradiation: results of an AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) retrospective study. Bone Marrow Transpl. 2020;55:1918–27. doi: 10.1038/s41409-020-0806-8.
    1. Skinner R, Kaplan R, Nathan PC. Renal and pulmonary late effects of cancer therapy. Seminars Oncol. 2013;40:757–73. doi: 10.1053/j.seminoncol.2013.09.009.
    1. Liles A, et al. Monitoring pulmonary complications in long-term childhood cancer survivors: guidelines for the primary care physician. Cleveland Clin J Med. 2008;75:531–9. doi: 10.3949/ccjm.75.7.531.
    1. Armenian SH, et al. Long-term pulmonary function in survivors of childhood cancer. J Clin Oncol. 2015;33:1592–600. doi: 10.1200/JCO.2014.59.8318.
    1. Mulder RL, et al. Pulmonary function impairment measured by pulmonary function tests in long-term survivors of childhood cancer. Thorax. 2011;66:1065–71. doi: 10.1136/thoraxjnl-2011-200618.
    1. Cerveri I, et al. Lung function abnormalities after bone marrow transplantation in children: has the trend recently changed? Chest. 2001;120:1900–6. doi: 10.1378/chest.120.6.1900.
    1. Griese M, et al. Pulmonary complications after bone marrow transplantation in children: twenty-four years of experience in a single pediatric center. Pediatric Pulmonol. 2000;30:393–401. doi: 10.1002/1099-0496(200011)30:5<393::AID-PPUL5>;2-W.
    1. Kuehni CE, et al. Cohort profile: the Swiss childhood cancer survivor study. Int J Epidemiol. 2012;41:1553–64. doi: 10.1093/ije/dyr142.
    1. Michel G, et al. The Swiss Childhood Cancer Registry: rationale, organisation and results for the years 2001-2005. Swiss Med Weekly. 2007;137:502–9.
    1. Stanojevic S, et al. Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians. Eur Respir J. 2017;50.
    1. Zapletal A. Lung function in children and adolescents. Methods, reference values. Basel: Karger AG; 1987.
    1. Quanjer PHD,A, Van Zomeren BH. Summary equations of reference values. Bull Europ Physiopathol Respir. 1983;19:45–51.
    1. Quanjer PH, et al. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012;40:1324–43. doi: 10.1183/09031936.00080312.
    1. Baur X. Recommendation of new reference values for spirometry and body plethysmography. Pneumologie. 2013;67:401–5. doi: 10.1055/s-0033-1344331.
    1. Criée CP, et al. Standardization of spirometry: 2015 update. Published by German Atemwegsliga, German Respiratory Society and German Society of Occupational and Environmental Medicine. Pneumologie. 2015;69:147–64.. doi: 10.1055/s-0034-1391345.
    1. Graham BL, et al. Standardization of spirometry 2019 update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med. 2019;200:e70–e88. doi: 10.1164/rccm.201908-1590ST.
    1. Children’s Oncology Group [COG]. Long Term Follow-Up guidelines Version 5.0. 2018. .
    1. United Kingdom Children’s Cancer Study Group. Therapy based long term follow-up - Practice Statement. 2005. .
    1. DCOG LATER Study. . Access Date June 22, 2020.
    1. Ciurea SO, Andersson BS. Busulfan in hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2009;15:523–36. doi: 10.1016/j.bbmt.2008.12.489.
    1. Cerveri I, et al. Late pulmonary sequelae after childhood bone marrow transplantation. Thorax. 1999;54:131–5. doi: 10.1136/thx.54.2.131.
    1. Nysom K, et al. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma. Arch Dis Childhood. 1996;74:432–6. doi: 10.1136/adc.74.5.432.
    1. Stone A, et al. Assessment of pulmonary outcomes, exercise capacity, and longitudinal changes in lung function in pediatric survivors of high-risk neuroblastoma. Pediatric Blood Cancer. 2019;66:e27960. doi: 10.1002/pbc.27960.
    1. Langhammer A, et al. Global Lung Function Initiative 2012 reference equations for spirometry in the Norwegian population. Eur Respir J. 2016;48:1602–11. doi: 10.1183/13993003.00443-2016.
    1. Fasola S, La Grutta S, Cibella F, Cilluffo G, Viegi G. Global Lung Function Initiative 2012 reference values for spirometry in South Italian children. Respir Med. 2017;131:11–7. doi: 10.1016/j.rmed.2017.07.061.
    1. Quanjer PH, Weiner DJ, Pretto JJ, Brazzale DJ, Boros PW. Measurement of FEF25-75% and FEF75% does not contribute to clinical decision making. Eur Respir J. 2014;43:1051–8. doi: 10.1183/09031936.00128113.
    1. Fanfulla F, et al. Pulmonary complications and respiratory function changes after bone marrow transplantation in children. Eur Respir J. 1997;10:2301–6. doi: 10.1183/09031936.97.10102301.
    1. Miller MR, et al. General considerations for lung function testing. Eur Respir J. 2005;26:153–61. doi: 10.1183/09031936.05.00034505.
    1. Hsia CC, Hyde DM, Ochs M, Weibel ER. An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med. 2010;181:394–418. doi: 10.1164/rccm.200809-1522ST.
    1. Beydon N, et al. An official American Thoracic Society/European Respiratory Society statement: pulmonary function testing in preschool children. Am J Respir Crit Med. 2007;175:1304–45. doi: 10.1164/rccm.200605-642ST.
    1. Rueegg CS, et al. No evidence of response bias in a population-based childhood cancer survivor questionnaire survey - results from the Swiss Childhood Cancer Survivor Study. PloS One. 2017;12:e0176442. doi: 10.1371/journal.pone.0176442.

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