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Lung evaluation in 10 year survivors of pediatric allogeneic hematopoietic stem cell transplantation

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Abstract

There is little data on the long-term respiratory development of children after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We describe the respiratory assessment 10 years after allo-HSCT of 35 children transplanted between 2000 and 2004. During this period, 90 children were transplanted at our center. Twenty-five children died, thirty were lost to follow-up, and thirty-five came to have a pulmonary investigation. The thirty-five participants answered a questionnaire asking if they had pulmonary symptoms, and pulmonary function tests (PFTs) were performed. The median age of these children 10 years after the transplant was 16 years old. Just over a third of them had pulmonary symptoms. Among them, 5/13 (38%) had bronchiolitis obliterans syndrome (BOS). The majority of children (62.8%) did not have respiratory symptoms. PFTs were abnormal in one-third of asymptomatic children, revealing restrictive lung disease that was always mild to moderate (p = 0.02).

Conclusion: In the long term, research at the time of the medical examination for the presence of chronic cough, shortness of breath on exertion, or wheezing helps to guide the clinician as to the need for further lung exploration. Similarly, informing patients and their families about these symptoms, which can be underestimated, should allow for more specific management.

What is Known:

• Pulmonary complications are a major cause of hematopoietic stem cell transplantation (HSCT) morbidity and mortality.

• A long time after allogeneic HSCT, pulmonary function tests abnormalities may occur in children, but it is not always related to symptoms.

What is New:

• The occurrence of respiratory symptoms: cough, dyspnea on exertion, chronic bronchitis, and wheezing should be systematically investigated in the follow-up of allografted patients, even at a distance.

• The presence of respiratory symptoms should lead to a respiratory functional investigation to detect the presence of an obstructive syndrome.

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Abbreviations

ATS:

American thoracic society

BOS:

Bronchiolitis obliterans syndrome

aGvHD:

Acute graft-versus-host disease

cGvHD:

Chronic graft-versus-host disease

ERS:

European respiratory society

FEV1:

Forced expiratory volume in 1 s

FVC:

Full vital capacity

GLI:

Global lung function initiative

GvHD:

Graft-versus-host disease

HSCT:

Hematopoietic stem cell transplantation

PFTs:

Pulmonary function tests

PPFE:

Pleuroparenchymal fibroelastosis

TBI:

Total body irradiation

TLC:

Total lung capacity

References

  1. (1995) Standardization of Spirometry, 1994 Update American Thoracic Society. Am J Respir Crit Care Med 152(3):1107–1136

  2. Armenian SH, Sun C-L, Kawashima T, Arora M, Leisenring W, Sklar CA, Baker KS, Francisco L, Teh JB, Mills G, Wong FL, Rosenthal J, Diller LR, Hudson MM, Oeffinger KC, Forman SJ, Robison LL, Bhatia S (2011) Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: a report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS). Blood 118(5):1413–1420

    Article  CAS  Google Scholar 

  3. Au BKC, Au MA, Chien JW (2011) Bronchiolitis obliterans syndrome epidemiology after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 17(7):1072–1078

    Article  Google Scholar 

  4. Bergeron A, Chevret S, Chagnon K, Godet C, Bergot E, Peffault de Latour R, Dominique S, de Revel T, Juvin K, Maillard N, Reman O, Contentin N, Robin M, Buzyn A, Socié G, Tazi A (2015) Budesonide/formoterol for bronchiolitis obliterans after hematopoietic stem cell transplantation. Am J Respir Crit Care Med 191(11):1242–1249

    Article  CAS  Google Scholar 

  5. Bhatia S, Francisco L, Carter A, Sun CL, Baker KS, Gurney JG, McGlave PB, Nademanee A, O’Donnell M, Ramsay NKC, Robison LL, Snyder D, Stein A, Forman SJ, Weisdorf DJ (2007) Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study. Blood 110(10):3784–3792

    Article  CAS  Google Scholar 

  6. Chien JW (2011) Preventing and managing bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplantation. Expert Rev Respir Med 5(1):127–135

    Article  Google Scholar 

  7. Chow EJ, Anderson L, Baker KS, Bhatia S, Guilcher GMT, Huang JT, Pelletier W, Perkins JL, Rivard LS, Schechter T, Shah AJ, Wilson KD, Wong K, Grewal SS, Armenian SH, Meacham LR, Mulrooney DA, Castellino SM (2016) Late effects surveillance recommendations among survivors of childhood hematopoietic cell transplantation: a Children’s Oncology Group report. Biol Blood Marrow Transplant 22(5):782–795

    Article  Google Scholar 

  8. Dudek AZ, Mahaseth H, DeFor TE, Weisdorf DJ (2003) Bronchiolitis obliterans in chronic graft-versus-host disease: analysis of risk factors and treatment outcomes. Biol Blood Marrow Transplant 9(10):657–666

    Article  Google Scholar 

  9. Eikenberry M, Bartakova H, Defor T, Haddad IY, Ramsay NKC, Blazar BR, Milla CE, Cornfield DN (2005) Natural history of pulmonary complications in children after bone marrow transplantation. Biol Blood Marrow Transplant 11(1):56–64

    Article  Google Scholar 

  10. Even-Or E, Ghandourah H, Ali M, Krueger J, Sweezey NB, Schechter T (2018) Efficacy of high-dose steroids for bronchiolitis obliterans syndrome post pediatric hematopoietic stem cell transplantation. Pediatr Transplant 22(2):e13155. https://doi.org/10.1111/petr.13155

    Article  CAS  Google Scholar 

  11. Geenen MM, Cardous-Ubbink MC, Kremer LCM, van den Bos C, van der Pal HJH, Heinen RC, Jaspers MWM, Koning CCE, Oldenburger F, Langeveld NE, Hart AAM, Bakker PJM, Caron HN, van Leeuwen FE (2007) Medical assessment of adverse health outcomes in long-term survivors of childhood cancer. JAMA 297(24):2705–2715

    Article  CAS  Google Scholar 

  12. Higo H, Miyahara N, Taniguchi A, Maeda Y, Kiura K (2019) Cause of pleuroparenchymal fibroelastosis following allogeneic hematopoietic stem cell transplantation. Respir Investig 57(4):321–324

    Article  Google Scholar 

  13. Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers MED (2015) National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant 21(3):389–401.e1

    Article  Google Scholar 

  14. Miller MR, Crapo R, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, van der Grinten C, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J, ATS/ERS Task Force (2005) General considerations for lung function testing. Eur Respir J 26(1):153–161

    Article  CAS  Google Scholar 

  15. Nishio N, Yagasaki H, Takahashi Y, Muramatsu H, Hama A, Tanaka M, Yoshida N, Watanabe N, Kudo K, Yoshimi A, Kojima S (2009) Late-onset non-infectious pulmonary complications following allogeneic hematopoietic stem cell transplantation in children. Bone Marrow Transplant 44(5):303–308

    Article  CAS  Google Scholar 

  16. Park M, Koh KN, Kim BE, Im HJ, Seo JJ (2011) Clinical features of late onset non-infectious pulmonary complications following pediatric allogeneic hematopoietic stem cell transplantation. Clin Transpl 25(2):E168–E176

    Article  Google Scholar 

  17. Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, Coates A, van der Grinten C, Gustafsson P, Hankinson J, Jensen R, Johnson DC, MacIntyre N, McKay R, Miller MR, Navajas D, Pedersen OF, Wanger J (2005) Interpretative strategies for lung function tests. Eur Respir J 26(5):948–968

    Article  CAS  Google Scholar 

  18. Prais D, Sinik MM, Stein J, Mei-Zahav M, Mussaffi H, Steuer G, Hananya S, Krauss A, Yaniv I, Blau H (2014) Effectiveness of long-term routine pulmonary function surveillance following pediatric hematopoietic stem cell transplantation. Pediatr Pulmonol 49(11):1124–1132

    Article  Google Scholar 

  19. Pulsipher MA, Skinner R, McDonald GB et al (2012) National Cancer Institute, National Heart, Lung and Blood Institute/Pediatric Blood and Marrow Transplantation Consortium First International Consensus Conference on late effects after pediatric hematopoietic cell transplantation: the need for pediatric-specific long-term follow-up guidelines. Biol Blood Marrow Transplant 18(3):334–347

    Article  Google Scholar 

  20. Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MSM, Zheng J, Stocks J, the ERS Global Lung Function Initiative (2012) Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J 40(6):1324–1343

    Article  Google Scholar 

  21. Senn-Malashonak A, Wallek S, Schmidt K, Rosenhagen A, Vogt L, Bader P, Banzer W (2019) Psychophysical effects of an exercise therapy during pediatric stem cell transplantation: a randomized controlled trial. Bone Marrow Transplant. https://doi.org/10.1038/s41409-019-0535-z

  22. Uhlving HH, Buchvald F, Heilmann CJ, Nielsen KG, Gormsen M, Müller KG (2012) Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options. Bone Marrow Transplant 47(8):1020–1029

    Article  CAS  Google Scholar 

  23. Uhlving HH, Mathiesen S, Buchvald F, Green K, Heilmann C, Gustafsson P, Muller K, Nielsen KG (2015) Small airways dysfunction in long-term survivors of pediatric stem cell transplantation. Pediatr Pulmonol 50(7):704–712

    Article  Google Scholar 

  24. Uhlving HH, Andersen CB, Christensen IJ, Gormsen M, Pedersen KD, Buchvald F, Heilmann C, Nielsen KG, Mortensen J, Moser C, Sengeløv H, Müller KG (2015) Biopsy-verified bronchiolitis obliterans and other noninfectious lung pathologies after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 21(3):531–538

    Article  Google Scholar 

  25. Wilhelmsson M, Glosli H, Ifversen M, Abrahamsson J, Winiarski J, Jahnukainen K, Hasle H (2019) Long-term health outcomes in survivors of childhood AML treated with allogeneic HSCT: a NOPHO-AML Study. Bone Marrow Transplant 54(5):726–736

    Article  Google Scholar 

  26. Williams KM (2017) How I treat bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation. Blood 129(4):448–455

    Article  CAS  Google Scholar 

  27. Williams KM, Cheng G-S, Pusic I, Jagasia M, Burns L, Ho VT, Pidala J, Palmer J, Johnston L, Mayer S, Chien JW, Jacobsohn DA, Pavletic SZ, Martin PJ, Storer BE, Inamoto Y, Chai X, Flowers MED, Lee SJ (2016) Fluticasone, azithromycin, and montelukast treatment for new-onset bronchiolitis obliterans syndrome after hematopoietic cell transplantation. Biol Blood Marrow Transplant 22(4):710–716

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Hospices Civils de Lyon (HCL), Hôpital Universitaire Femme-Mère-Enfant, service de pneumologie pédiatrique, Lyon, France

    Sophie L’excellent

  2. Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Robert Debré, Service d’Immuno-Hématologie pédiatrique, Paris, France

    Karima Yakouben & Jean-Hugues Dalle

  3. Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Robert Debré, Service de Physiologie - Explorations Fonctionnelles Pédiatriques- Paris, Paris, France

    Christophe Delclaux

  4. Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Robert Debré, Service des Maladies Digestives et Respiratoires de l’Enfant, 48 Bd Serrurier, 75019, Paris, France

    Véronique Houdouin

  5. Université Paris Diderot, Sorbonne Paris Cité, INSERM UMR 1149, Paris, France

    Véronique Houdouin

Authors
  1. Sophie L’excellent
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  2. Karima Yakouben
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  4. Jean-Hugues Dalle
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Contributions

SL: collected the data and contribute to write the manuscript. KY: She is in charge of patient follow-up. CD: contribute to write the manuscript. J-HD: He is in charge of follow-up and helps the discussion. VH: in charge of lung evaluation and wrote the manuscript.

Corresponding author

Correspondence to Véronique Houdouin.

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in this study.

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Communicated by Peter de Winter

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L’excellent, S., Yakouben, K., Delclaux, C. et al. Lung evaluation in 10 year survivors of pediatric allogeneic hematopoietic stem cell transplantation. Eur J Pediatr 178, 1833–1839 (2019). https://doi.org/10.1007/s00431-019-03447-z

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  • DOI: https://doi.org/10.1007/s00431-019-03447-z

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