Pulmonary Complications of Malignancies and Blood and Marrow Transplantation

  • Geshani Jayasuriya
  • Beryl Lin
  • Steven J. Keogh
  • Hiran Selvadurai
Part of the Respiratory Medicine book series (RM)


Advances in childhood cancer therapies and blood and marrow transplantation (BMT) have dramatically improved survival in the past decade, with 5-year survival now approaching 85% (Australian Institute of Health and Welfare, Cancer in Australia: an overview 2014. Cancer series no 90 Cat no CAN 88 Canberra, AIHW2014). Pulmonary complications however remain an important cause of short- and long-term morbidity and mortality in childhood malignancies (Meyer et al., Pediatr Hematol Oncol 21(2):175–195, 2004; Jenney, Paediatr Respir Rev 1(3):279–286, 2000). The development of acute respiratory complications should prompt consideration of a wide range of differentials as appropriate management can be a major predictor of survival, especially in children undergoing BMT (Meyer et al., Pediatr Hematol Oncol 21(2):175–195, 2004; McCahon, Paediatr Respir Rev 7(3):191–196, 2006; Krowka et al., Chest 87(2):237–246, 1985). In childhood cancer survivors, permanent and late-onset respiratory dysfunction have been found in up to 45% of patients and continue to have important impacts on quality of life and premature mortality (Mertens et al., Cancer 95(11):2431–2441, 2002; Versluys and Bresters, Paediatr Respir Rev 17:63–70, 2015; Huang et al., Chest 140(4):881–901, 2011; Mulder et al., Thorax 66(12):1065–1071, 2011). This chapter provides an overview of respiratory complications of childhood cancer and BMT, with a focus on mechanisms of injury.


Children Lung tumours Leukaemia Bone marrow transplant Chemotherapy complications 



Acute interstitial pneumonitis


Acute lymphoblastic anaemia


Acute myeloid leukaemia


Acute promyelocytic leukaemia


Acute respiratory distress syndrome


Bone marrow transplantation


Bronchiolitis obliterans with organising pneumonia


Bronchiolitis obliterans syndrome


Constrictive bronchiolitis obliterans


Chronic graft-versus-host disease




Cryptogenic organising pneumonia


Diffuse alveolar haemorrhage


Diffusing capacity for carbon monoxide


Epstein-Barr virus


Graft-versus-host disease


Hodgkin lymphoma


Idiopathic pneumonia syndrome


Langerhans cell histiocytosis




Non-cardiogenic pulmonary oedema


Pulmonary arterial hypertension


Pulmonary artery wedge pressure


Peri-engraftment respiratory distress syndrome


Pulmonary hypertension


Post-transplant lymphoproliferative disease


Pulmonary veno-occlusive disease


Superior vena cava


  1. 1.
    Meyer S, Reinhard H, Gottschling S, Nunold H, Graf N. Pulmonary dysfunction in pediatric oncology patients. Pediatr Hematol Oncol. 2004;21(2):175–95. PubMed PMID: 15160517. Epub 2004/05/27. eng.PubMedCrossRefGoogle Scholar
  2. 2.
    Turcios NL, Fink RJ. Pulmonary manifestations of pediatric diseases. Philadelphia: Elsevier Health Sciences; 2009.Google Scholar
  3. 3.
    Hildebrand F, Rosenow EC III, Habermann TM, Tazelaar HD. Pulmonary complications of leukemia. Chest. 1990;98(5):1233–9.PubMedCrossRefGoogle Scholar
  4. 4.
    McCahon E. Lung tumours in children. Paediatr Respir Rev. 2006;7(3):191–6. PubMed PMID: 16938641. Epub 2006/08/30. eng.PubMedCrossRefGoogle Scholar
  5. 5.
    Dishop MK, Kuruvilla S. Primary and metastatic lung tumors in the pediatric population: a review and 25-year experience at a large children’s hospital. Arch Pathol Lab Med. 2008;132(7):1079–103. PubMed PMID: 18605764.PubMedGoogle Scholar
  6. 6.
    McCarville MB. Malignant pulmonary and mediastinal tumors in children: differential diagnoses. Cancer Imaging. 2010;10(1A):S35–41. PubMed PMID: PMC2967153.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Al-Qahtani AR, Di Lorenzo M, Yazbeck S. Endobronchial tumors in children: Institutional experience and literature review. J Pediatr Surg. 2003;38(5):733–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Lichtman MA, Rowe JM. Hyperleukocytic leukemias: rheological, clinical, and therapeutic considerations. Blood. 1982;60(2):279–83. PubMed PMID: 7046844. Epub 1982/08/01. eng.PubMedGoogle Scholar
  9. 9.
    Bunin NJ, Pui C-H. Differing complications of hyperleukocytosis in children with acute lymphoblastic or acute nonlymphoblastic leukemia. J Clin Oncol. 1985;3(12):1590–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Vernant JP, Brun B, Mannoni P, Dreyfus B. Respiratory distress of hyperleukocytic granulocytic leukemias. Cancer. 1979;44(1):264–8. PubMed PMID: 287551. Epub 1979/07/01. eng.PubMedCrossRefGoogle Scholar
  11. 11.
    Carroll WL, Finlay JL. Cancer in children and adolescents. London: Jones & Bartlett Learning; 2010.Google Scholar
  12. 12.
    Porcu P, Cripe LD, Ng EW, Bhatia S, Danielson CM, Orazi A, et al. Hyperleukocytic leukemias and leukostasis: a review of pathophysiology, clinical presentation and management. Leuk Lymphoma. 2000;39(1–2):1–18.PubMedCrossRefGoogle Scholar
  13. 13.
    Cuttner J, Conjalka MS, Reilly M, Goldberg J, Reisman A, Meyer RJ, et al. Association of monocytic leukemia in patients with extreme leukocytosis. Am J Med. 1980;69(4):555–8. PubMed PMID: 6932815. Epub 1980/10/01. eng.PubMedCrossRefGoogle Scholar
  14. 14.
    Lichtman MA, Weed RI. Peripheral cytoplasmic characteristics of leukocytes in monocytic leukemia: relationship to clinical manifestations. Blood. 1972;40(1):52–61. PubMed PMID: 4504250. Epub 1972/07/01. eng.PubMedGoogle Scholar
  15. 15.
    Lowe EJ, Pui C-H, Hancock ML, Geiger TL, Khan RB, Sandlund JT. Early complications in children with acute lymphoblastic leukemia presenting with hyperleukocytosis. Pediatr Blood Cancer. 2005;45(1):10–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Lester TJ, Johnson JW, Cuttner J. Pulmonary leukostasis as the single worst prognostic factor in patients with acute myelocytic leukemia and hyperleukocytosis. Am J Med. 1985;79(1):43–8. PubMed PMID: 3860006. Epub 1985/07/01. eng.PubMedCrossRefGoogle Scholar
  17. 17.
    Tanaka N, Matsumoto T, Miura G, Emoto T, Matsunaga N, Satoh Y, et al. CT findings of leukemic pulmonary infiltration with pathologic correlation. Eur Radiol. 2002;12(1):166–74.PubMedCrossRefGoogle Scholar
  18. 18.
    Van Buchem M, Wondergem J, Kool L, Te Velde J, Kluin P, Bode P, et al. Pulmonary leukostasis: radiologic-pathologic study. Radiology. 1987;165(3):739–41.PubMedCrossRefGoogle Scholar
  19. 19.
    Aswanetmanee P, Edriss H, Limsuwat C. Pulmonary leukostasis as a complication of leukemia. Southwest Respir Crit Care Chronicles. 2015;3(10):17–22.Google Scholar
  20. 20.
    Hijiya N, Metzger ML, Pounds S, Schmidt JE, Razzouk BI, Rubnitz JE, et al. Severe cardiopulmonary complications consistent with systemic inflammatory response syndrome caused by leukemia cell lysis in childhood acute myelomonocytic or monocytic leukemia. Pediatr Blood Cancer. 2005;44(1):63–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Azoulay É, Fieux F, Moreau D, Thiery G, Rousselot P, Parrot A, et al. Acute monocytic leukemia presenting as acute respiratory failure. Am J Respir Crit Care Med. 2003;167(10):1329–33.PubMedCrossRefGoogle Scholar
  22. 22.
    Azoulay E, Canet E, Raffoux E, Lengline E, Lemiale V, Vincent F, et al. Dexamethasone in patients with acute lung injury from acute monocytic leukaemia. Eur Respir J. 2012;39(3):648–53. PubMed PMID: 21828031. Epub 2011/08/11. eng.PubMedCrossRefGoogle Scholar
  23. 23.
    Tryka AF, Godleski JJ, Fanta CH. Leukemic cell lysis pneumonopathy. A complication of treated myeloblastic leukemia. Cancer. 1982;50(12):2763–70. PubMed PMID: 6958352. Epub 1982/12/15. eng.PubMedCrossRefGoogle Scholar
  24. 24.
    Stover DE, Kaner RJ. Pulmonary complications in cancer patients. CA Cancer J Clin. 1996;46(5):303–20.PubMedCrossRefGoogle Scholar
  25. 25.
    Soares FA, Landell GAM, Cardoso MCM. Pulmonary leukostasis without hyperleukocytosis: a clinicopathologic study of 16 cases. Am J Hematol. 1992;40(1):28–32.PubMedCrossRefGoogle Scholar
  26. 26.
    Kovalski R, Hansen-Flaschen J, Lodato RF, Pietra GG. Localized leukemic pulmonary infiltrates. Diagnosis by bronchoscopy and resolution with therapy. Chest. 1990;97(3):674–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Braier J, Latella A, Balancini B, Castaños C, Rosso D, Chantada G, et al. Outcome in children with pulmonary Langerhans cell histiocytosis. Pediatr Blood Cancer. 2004;43(7):765–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Ha SY, Helms P, Fletcher M, Broadbent V, Pritchard J. Lung involvement in Langerhans’ cell histiocytosis: prevalence, clinical features, and outcome. Pediatrics. 1992;89(3):466–9.PubMedGoogle Scholar
  29. 29.
    Kilborn TN, Teh J, Goodman TR. Paediatric manifestations of Langerhans cell histiocytosis: a review of the clinical and radiological findings. Clin Radiol. 2003;58(4):269–78.PubMedCrossRefGoogle Scholar
  30. 30.
    Smets A, Mortelé K, Praeter DG, François O, Benoit Y, Kunnen M. Pulmonary and mediastinal lesions in children with Langerhans cell histiocytosis. Pediatr Radiol. 1997;27(11):873–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Picarsic J, Jaffe R. Nosology and pathology of Langerhans cell histiocytosis. Hematol Oncol Clin North Am. 2015;29(5):799–823.PubMedCrossRefGoogle Scholar
  32. 32.
    Lehrnbecher T, Foster C, Vazquez N, Mackall CL, Chanock SJ. Therapy-induced alterations in host defense in children receiving therapy for cancer. J Pediatr Hematol Oncol. 1997;19(5):399–417. PubMed PMID: 9329461. Epub 1997/11/05. eng.PubMedCrossRefGoogle Scholar
  33. 33.
    Wiegering V, Schlegel PG, Winkler B. Immune function in newly diagnosed children with malignancy. J Pediatr Hematol Oncol. 2012;34(7):559–64. PubMed PMID: 22735887. Epub 2012/06/28. eng.PubMedCrossRefGoogle Scholar
  34. 34.
    Martin Ibanez I, Arce Casas A, Cruz Martinez O, Estella Aguado J, Martin Mateos MA. Humoral immunity in pediatric patients with acute lymphoblastic leukaemia. Allergol Immunopathol. 2003;31(6):303–10. PubMed PMID: 14670284. Epub 2003/12/13. eng.CrossRefGoogle Scholar
  35. 35.
    Jenney M. Malignant disease and the lung. Paediatr Respir Rev. 2000;1(3):279–86.PubMedGoogle Scholar
  36. 36.
    Lehrnbecher T, Phillips R, Alexander S, Alvaro F, Carlesse F, Fisher B, et al. Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation. J Clin Oncol. 2012;30(35):4427–38.PubMedCrossRefGoogle Scholar
  37. 37.
    El Saleeby CM, Somes GW, DeVincenzo JP, Gaur AH. Risk factors for severe respiratory syncytial virus disease in children with cancer: the importance of lymphopenia and young age. Pediatrics. 2008;121(2):235–43. PubMed PMID: 18245413. Epub 2008/02/05. eng.PubMedCrossRefGoogle Scholar
  38. 38.
    Hakim H, Dallas R, Zhou Y, Pei D, Cheng C, Flynn PM, et al. Acute respiratory infections in children and adolescents with acute lymphoblastic leukemia. Cancer. 2016;122(5):798–805. PubMed PMID: 26700662. Pubmed Central PMCID: PMC4764417. Epub 2015/12/25. eng.PubMedCrossRefGoogle Scholar
  39. 39.
    Furuya MEY, González-Martínez F, Vargas MH, Miranda-Novales MG, Bernáldez-Ríos R, Zúñiga-Vázquez G. Guidelines for diagnosing and treating pulmonary infiltrates in children with acute leukaemia: impact of timely decisions. Acta Paediatr. 2008;97(7):928–34.PubMedCrossRefGoogle Scholar
  40. 40.
    Specchia G, Pastore D, Carluccio P, Mele G, Montagna MT, Liso A, et al. Pneumonia in acute leukemia patients during induction therapy: experience in a single institution. Leuk Lymphoma. 2003;44(1):97–101. PubMed PMID: 12691147. Epub 2003/04/15. eng.PubMedCrossRefGoogle Scholar
  41. 41.
    Erdur B, Ylmaz S, Ören H, Demircioglu F, Çakmakç H, Irken G. Evaluating pulmonary complications in childhood acute leukemias. J Pediatr Hematol Oncol. 2008;30(7):522–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Keengwe I, Stansfield F, Eden O, Nelhans N, Dearlove O, Sharples A. Paediatric oncology and intensive care treatments: changing trends. Arch Dis Child. 1999;80(6):553–5. PubMed PMID: PMC1717963.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Phillips B, Wade R, Westwood M, Riley R, Sutton AJ. Systematic review and meta-analysis of the value of clinical features to exclude radiographic pneumonia in febrile neutropenic episodes in children and young people. J Paediatr Child Health. 2012;48(8):641–8. PubMed PMID: 22050289. Epub 2011/11/05. eng.PubMedCrossRefGoogle Scholar
  44. 44.
    Mustafa MM, Buchanan GR, Winick NJ, McCracken GH, Tkaczewski I, Lipscomb M, et al. Immune recovery in children with malignancy after cessation of chemotherapy. J Pediatr Hematol Oncol. 1998;20(5):451–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Roberts SD, Wells GM, Gandhi NM, York NR, Maron G, Razzouk B, et al. Diagnostic value of routine chest radiography in febrile, neutropenic children for early detection of pneumonia and mould infections. Support Care Cancer. 2012;20(10):2589–94. PubMed PMID: 22278307. Epub 2012/01/27. eng.PubMedCrossRefGoogle Scholar
  46. 46.
    Stokes DC, Shenep JL, Parham D, Bozeman PM, Marienchek W, Mackert PW. Role of flexible bronchoscopy in the diagnosis of pulmonary infiltrates in pediatric patients with cancer. J Pediatr. 1989;115(4):561–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Girmenia C, Martino P. Pulmonary infections complicating hematological disorders. Semin Respir Crit Care Med. 2005;26(5):445–57. PubMed PMID: 16267697. Epub 2005/11/04. eng.PubMedCrossRefGoogle Scholar
  48. 48.
    Nucci M, Nouér SA, Anaissie E. Distinguishing the causes of pulmonary infiltrates in patients with acute leukemia. Clin Lymphoma Myeloma Leuk. 2015;15:S98–S103.PubMedCrossRefGoogle Scholar
  49. 49.
    Jenney ME, Faragher EB, Jones PHM, Woodcock A. Lung function and exercise capacity in survivors of childhood leukaemia. Med Pediatr Oncol. 1995;24(4):222–30.PubMedCrossRefGoogle Scholar
  50. 50.
    Ek T, Mellander L, Andersson B, Abrahamsson J. Immune reconstitution after childhood acute lymphoblastic leukemia is most severely affected in the high risk group. Pediatr Blood Cancer. 2005;44(5):461–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Charpidou AG, Gkiozos I, Tsimpoukis S, Apostolaki D, Dilana KD, Karapanagiotou EM, et al. Therapy-induced toxicity of the lungs: an overview. Anticancer Res. 2009;29(2):631–9. PubMed PMID: 19331213. Epub 2009/04/01. eng.PubMedGoogle Scholar
  52. 52.
    Vahid B, Marik PE. Pulmonary complications of novel antineoplastic agents for solid tumors. Chest. 2008;133(2):528–38.PubMedCrossRefGoogle Scholar
  53. 53.
    Andre N, Meille C. Taxanes in paediatric oncology: and now? Cancer Treat Rev. 2006;32(2):65–73. PubMed PMID: 16497442. Epub 2006/02/25. eng.PubMedCrossRefGoogle Scholar
  54. 54.
    Latiff ZA, Kamal NA, Jahendran J, Alias H, Goh BS, Zakaria SZS, et al. Vincristine-induced vocal cord palsy: case report and review of the literature. J Pediatr Hematol Oncol. 2010;32(5):407–10.PubMedCrossRefGoogle Scholar
  55. 55.
    Dhakal S, Weiner D, Schwartz C, Constine LS. Pulmonary effects of antineoplastic therapy. In: Schwartz C, Hobbie W, Constine L, Ruccione K, editors. Survivors of childhood and adolescent cancer. Cham: Springer; 2015. p. 201–27.CrossRefGoogle Scholar
  56. 56.
    Matsuno O. Drug-induced interstitial lung disease: mechanisms and best diagnostic approaches. Respir Res. 2012;13(1):39. PubMed PMID: PMC3426467.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Borzone G, Moreno R, Urrea R, Meneses M, OyarzÚN M, Lisboa C. Bleomycin-induced chronic lung damage does not resemble human idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2001;163(7):1648–53.PubMedCrossRefGoogle Scholar
  58. 58.
    Huang T-T, Hudson MM, Stokes DC, Krasin MJ, Spunt SL, Ness KK. Pulmonary Outcomes in Survivors of Childhood Cancer: A Systematic Review. Chest. 2011;140(4):881–901. PubMed PMID: PMC3904488.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Mertens AC, Yasui Y, Liu Y, Stovall M, Hutchinson R, Ginsberg J, et al. Pulmonary complications in survivors of childhood and adolescent cancer. Cancer. 2002;95(11):2431–41.PubMedCrossRefGoogle Scholar
  60. 60.
    McDonald S, Rubin P, Phillips TL, Marks LB. Injury to the lung from cancer therapy: clinical syndromes, measurable endpoints, and potential scoring systems. Int J Radiat Oncol Biol Phys. 1995;31(5):1187–203. PubMed PMID: 7713782. Epub 1995/03/30. eng.PubMedCrossRefGoogle Scholar
  61. 61.
    Sleijfer S. Bleomycin-induced pneumonitis. Chest. 2001;120(2):617–24.PubMedCrossRefGoogle Scholar
  62. 62.
    Mucci GA, Torno LR. Handbook of long term care of the childhood cancer survivor. Boston: Springer; 2015.CrossRefGoogle Scholar
  63. 63.
    Azambuja E, Fleck JF, Batista RG, Menna Barreto SS. Bleomycin lung toxicity: who are the patients with increased risk? Pulm Pharmacol Ther. 2005;18(5):363–6. PubMed PMID: 15939315. Epub 2005/06/09. eng.PubMedCrossRefGoogle Scholar
  64. 64.
    Tantawy AAG, Elbarbary N, Ahmed A, Mohamed NA, Ezz-Elarab S. Pulmonary complications in survivors of childhood hematological malignancies: single-center experience. Pediatr Hematol Oncol. 2011;28(5):403–17.PubMedCrossRefGoogle Scholar
  65. 65.
    De A, Guryev I, LaRiviere A, Kato R, Wee CP, Mascarenhas L, et al. Pulmonary function abnormalities in childhood cancer survivors treated with bleomycin. Pediatr Blood Cancer. 2014;61(9):1679–84.PubMedCrossRefGoogle Scholar
  66. 66.
    Kaplan E, Sklar C, Wilmott R, Michaels S, Ghavimi F. Pulmonary function in children treated for rhabdomyosarcoma. Med Pediatr Oncol. 1996;27(2):79–84. PubMed PMID: 8649324. Epub 1996/08/01. eng.PubMedCrossRefGoogle Scholar
  67. 67.
    White DA, Stover DE. Severe bleomycin-induced pneumonitis. Clinical features and response to corticosteroids. Chest. 1984;86(5):723–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Chen J, Stubbe J. Bleomycins: towards better therapeutics. Nat Rev Cancer. 2005;5(2):102–12. PubMed PMID: 15685195. Epub 2005/02/03. eng.PubMedCrossRefGoogle Scholar
  69. 69.
    Hagimoto N, Kuwano K, Nomoto Y, Kunitake R, Hara N. Apoptosis and expression of Fas/Fas ligand mRNA in bleomycin-induced pulmonary fibrosis in mice. Am J Respir Cell Mol Biol. 1997;16(1):91–101.PubMedCrossRefGoogle Scholar
  70. 70.
    Eigen H, Wyszomierski D. Bleomycin lung injury in children: Pathophysiology and guidelines for management. J Pediatr Hematol Oncol. 1985;7(1):71–8.Google Scholar
  71. 71.
    Cooper JA Jr, White DA, Matthay RA. Drug-induced pulmonary disease. Part 1: cytotoxic drugs. Am Rev Respir Dis. 1986;133(2):321–40. PubMed PMID: 3511808. Epub 1986/02/01. eng.PubMedGoogle Scholar
  72. 72.
    Ohnuma T, Holland JF, Masuda H, Waligunda JA, Goldberg GA. Microbiological assay of bleomycin: inactivation, tissue distribution, and clearance. Cancer. 1974;33(5):1230–8.CrossRefGoogle Scholar
  73. 73.
    Lazo JS, Merrill WW, Pham, Lynch TJ, McCallister J, Ingbar D. Bleomycin hydrolase activity in pulmonary cells. J Pharmacol Exp Ther. 1984;231(3):583–8.Google Scholar
  74. 74.
    Sausville EA, Peisach J, Horwitz SB. Effect of chelating agents and metal ions on the degradation of DNA by bleomycin. Biochemistry. 1978;17(14):2740–6.PubMedCrossRefGoogle Scholar
  75. 75.
    Ortiz LA, Lasky J, Hamilton RF Jr, Holian A, Hoyle GW, Banks W, et al. Expression of TNF and the necessity of TNF receptors in bleomycin-induced lung injury in mice. Exp Lung Res. 1998;24(6):721–43. PubMed PMID: 9839161. Epub 1998/12/05. eng.PubMedCrossRefGoogle Scholar
  76. 76.
    Weiss RB, Muggia FM. Cytotoxic drug-induced pulmonary disease: update 1980. Am J Med. 1980;68(2):259–66. PubMed PMID: 6153504. Epub 1980/02/01. eng.PubMedCrossRefGoogle Scholar
  77. 77.
    Limper AH. Chemotherapy-induced lung disease. Clin Chest Med. 2004;25(1):53–64. PubMed Epub 2004/04/06. eng.PubMedCrossRefGoogle Scholar
  78. 78.
    Oakhill A, Green I, Knowlson G, Cameron A, Shah K, Hill F, et al. Busulphan lung in childhood. J Clin Pathol. 1981;34(5):495–500.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Pearl M. Busulfan lung. Am J Dis Child. 1977;131(6):650–2.PubMedGoogle Scholar
  80. 80.
    Abid SH, Malhotra V, Perry MC. Radiation-induced and chemotherapy-induced pulmonary injury. Curr Opin Oncol. 2001;13(4):242–8. PubMed PMID: 11429481. Epub 2001/06/29. eng.PubMedCrossRefGoogle Scholar
  81. 81.
    Kayton ML. Pulmonary metastasectomy in pediatric patients. Thorac Surg Clin. 2006;16(2):167–83.PubMedCrossRefGoogle Scholar
  82. 82.
    Fuchs J, Seitz G, Handgretinger R, Schäfer J, Warmann SW. Surgical treatment of lung metastases in patients with embryonal pediatric solid tumors: an update. Semin Pediatr Surg. 2012;21(1):79–87.PubMedCrossRefGoogle Scholar
  83. 83.
    Meyers RL, Katzenstein HM, Krailo M, McGahren ED, Malogolowkin MH. Surgical resection of pulmonary metastatic lesions in children with hepatoblastoma. J Pediatr Surg. 2007;42(12):2050–6.PubMedCrossRefGoogle Scholar
  84. 84.
    McBride JT, Wohl MEB, Strieder DJ, Jackson AC, Morton JR, Zwerdling RG, et al. Lung growth and airway function after lobectomy in infancy for congenital lobar emphysema. J Clin Investig. 1980;66(5):962.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Spurbeck WW, Davidoff AM, Lobe TE, Rao BN, Schropp KP, Shochat SJ. Minimally invasive surgery in pediatric cancer patients. Ann Surg Oncol. 2004;11(3):340–3. PubMed PMID: 14993031. Epub 2004/03/03. eng.PubMedCrossRefGoogle Scholar
  86. 86.
    Harting MT, Blakely ML, Jaffe N, Cox CS Jr, Hayes-Jordan A, Benjamin RS, et al. Long-term survival after aggressive resection of pulmonary metastases among children and adolescents with osteosarcoma. J Pediatr Surg. 2006;41(1):194–9.PubMedCrossRefGoogle Scholar
  87. 87.
    Laros C, Westermann C. Dilatation, compensatory growth, or both after pneumonectomy during childhood and adolescence. A thirty-year follow-up study. J Thorac Cardiovasc Surg. 1987;93(4):570–6.PubMedGoogle Scholar
  88. 88.
    Kreisel D, Krupnick AS, Huddleston CB. Outcomes and late complications after pulmonary resections in the pediatric population. Semin Thorac Cardiovasc Surg. 2004;16(3):215–9.PubMedCrossRefGoogle Scholar
  89. 89.
    Abel RM, Brown J, Moreland B, Parikh D. Pulmonary metastasectomy for pediatric solid tumors. Pediatr Surg Int. 2004;20(8):630–2. PubMed PMID: 15258816. Epub 2004/07/20. eng.PubMedCrossRefGoogle Scholar
  90. 90.
    Werner H, Pirie G, Nadel H, Fleisher A, LeBlanc J. Lung volumes, mechanics, and perfusion after pulmonary resection in infancy. J Thorac Cardiovasc Surg. 1993;105(4):737–42.PubMedGoogle Scholar
  91. 91.
    Parisi MT, Fahmy JL, Kaminsky CK, Malogolowkin MH. Complications of cancer therapy in children: a radiologist's guide. Radiographics. 1999;19(2):283–97.PubMedCrossRefGoogle Scholar
  92. 92.
    Cournard A, Himmelstein A, et al. A follow-up study of the cardiopulmonary function in four young individuals after pneumonectomy. J Thorac Surg. 1947;16(1):30–49. PubMed PMID: 20286102. Epub 1947/02/01. eng.PubMedGoogle Scholar
  93. 93.
    Powell RW, Luck SR, Raffensperger JG. Pneumonectomy in infants and children: the use of a prosthesis to prevent mediastinal shift and its complications. J Pediatr Surg. 1979;14(3):231–7.PubMedCrossRefGoogle Scholar
  94. 94.
    Westfelt JN, Nordwall A. Thoracotomy and scoliosis. Spine. 1991;16(9):1124–5.PubMedCrossRefGoogle Scholar
  95. 95.
    Uderzo C, Marraro G, Riva A, Bonanomi E, Vaj P, Marchi P, et al. Pulmonary thromboembolism in leukaemic children undergoing bone marrow transplantation. Bone Marrow Transplant. 1993;11(3):201–3.PubMedGoogle Scholar
  96. 96.
    Lee EY, Kritsaneepaiboon S, Arellano CMR, Grace RF, Zurakowski D, Boiselle PM. Unsuspected pulmonary emboli in pediatric oncology patients: detection with MDCT. Am J Roentgenol. 2010;194(5):1216–22.CrossRefGoogle Scholar
  97. 97.
    Marraro G, Uderzo C, Masera G, Marchi P, Castagnini G, Vaj PL. Acute respiratory failure and pulmonary thrombosis in leukemic children. Cancer. 1991;67(3):696–702.PubMedCrossRefGoogle Scholar
  98. 98.
    Andrew M, David M, Adams M, Ali K, Anderson R, Barnard D, et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood. 1994;83(5):1251–7.PubMedGoogle Scholar
  99. 99.
    Brandao LR, Kletzel M, Boulad F, Kurtzberg J, Maloney K, Fligman I, et al. A prospective longitudinal multicenter study of coagulation in pediatric patients undergoing allogeneic stem cell transplantation. Pediatr Blood Cancer. 2008;50(6):1240–6.PubMedCrossRefGoogle Scholar
  100. 100.
    Nowak-Göttl U, Kenet G, Mitchell LG. Thrombosis in childhood acute lymphoblastic leukaemia: epidemiology, aetiology, diagnosis, prevention and treatment. Best Pract Res Clin Haematol. 2009;22(1):103–14.PubMedCrossRefGoogle Scholar
  101. 101.
    Versluys AB, Bresters D. Pulmonary complications of childhood cancer treatment. Paediatr Respir Rev. 2015;17:63–70.PubMedGoogle Scholar
  102. 102.
    Thurlbeck WM. Postnatal growth and development of the lung 1. Am Rev Respir Dis. 1975;111(6):803–44.PubMedGoogle Scholar
  103. 103.
    Narayanan M, Owers-Bradley J, Beardsmore CS, Mada M, Ball I, Garipov R, et al. Alveolarization continues during childhood and adolescence: new evidence from helium-3 magnetic resonance. Am J Respir Crit Care Med. 2012;185(2):186–91.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Thomas ED, Lochte HL Jr, Cannon JH, Sahler OD, Ferrebee JW. Supralethal whole body irradiation and isologous marrow transplantation in man. J Clin Invest. 1959;38:1709–16.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Australasian Bone Marrow Transplant Recipient Registry. Australasian Bone Marrow Transplant Recipient Registry: Annual Data Summary 2014. Darlinghurst: ABMTRR; 2015.Google Scholar
  106. 106.
    Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143–238.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Quigg TC, Kim Y-J, Goebel WS, Haut PR. Lung function before and after pediatric allogeneic hematopoietic stem cell transplantion: a predictive role for DLCO/VA. J Pediatr Hematol Oncol. 2012;34(304–309):304.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Bruno B, Souillet G, Bertrand Y, Werck-Gallois MC, So Satta A, Bellon G. Effects of allogeneic bone marrow transplantation on pulmonary function in 80 children in a single paediatric centre. Bone Marrow Transplant. 2004;34(2):143–7. PubMed PMID: 15170172.PubMedCrossRefGoogle Scholar
  109. 109.
    Gower WA, Collaco JM, Mogayzel PJ Jr. Lung function and late pulmonary complications among survivors of hematopoietic stem cell transplantation during childhood. Paediatr Respir Rev. 2011;11:115–22.CrossRefGoogle Scholar
  110. 110.
    Inaba H, Yang J, Pan J, Stokes DC, Krasin MJ, Srinivasan A, et al. Pulmonary dysfunction in survivors of childhood hematologic malignancies after allogeneic hematopoietic stem cell transplantation. Cancer. 2010;116(8):2020–30.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Cooke KR, Yanik GA. Lung injury following hematopoietic cell transplantation. In: Forman SJ, Negrin RS, Antin JH, Appelbaum FR, editors. Thomas’ hematopoietic cell transplantation. Chichester: Wiley-Blackwell; 2009. p. 1456–72.CrossRefGoogle Scholar
  112. 112.
    Michelson PH, Goyal R, Kurland G. Pulmonary complications of haematopoietic cell transplantation in children. Paediatr Respir Rev. 2007;8:46–61.PubMedCrossRefGoogle Scholar
  113. 113.
    Khurshid I, Anderson LC. Non-infectious pulmonary complications after bone marrow transplantation. Postgrad Med J. 2002;78:257–62.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Panoskaltsis-Mortari A, Griese M, Madtes DK, Belperio JA, Haddad IY, Folz RJ, et al. An official American Thoracic Society research statement: noninfectious lung injury after hematopoietic stem cell transplantation: idiopathic pneumonia syndrome. Am J Respir Crit Care Med. 2011;183(9):1262–79. PubMed PMID: 21531955.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Coomes SM, Hubbard LLN, Moore BB. Impaired pulmonary immunity post-bone marrow transplant. Immunol Res. 2011;50(1):78–86. PubMed PMID: PMC3310400.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Soubani AO, Pandya CM. The spectrum of noninfectious pulmonary complications following hematopoietic stem cell transplantation. Hematol Oncol Stem Cell Ther. 2010;3(3):143–57.PubMedCrossRefGoogle Scholar
  117. 117.
    Collin BA, Leather HI, Wingard JR, Ramphal R. Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients. Clin Infect Dis. 2001;33(7):947–53.PubMedCrossRefGoogle Scholar
  118. 118.
    Stiff P. Mucositis associated with stem cell transplantation: current status and innovative approaches to management. Bone Marrow Transplant. 2001;27(Suppl 2):S3–11.PubMedCrossRefGoogle Scholar
  119. 119.
    Sano H, Kobayashi R, Iguchi A, Suzuki D, Kishimoto K, Yasuda K, et al. Risk factor analysis of idiopathic pneumonia syndrome after allogeneic hematopoietic SCT in children. Bone Marrow Transplant. 2014;49(1):38–41.PubMedCrossRefGoogle Scholar
  120. 120.
    Sakaguchi H, Takahashi Y, Watanabe N, Doisaki S, Muramatsu H, Hama A, et al. Incidence, clinical features, and risk factors of idiopathic pneumonia syndrome following hematopoietic stem cell transplantation in children. Pediatr Blood Cancer. 2012;58(5):780–4.PubMedCrossRefGoogle Scholar
  121. 121.
    Gorak E, Geller N, Srinivasan R, Espinoza-Delgado I, Donohue T, Barrett AJ, et al. Engraftment syndrome after nonmyeloablative allogeneic hematopoietic stem cell transplantation: incidence and effects on survival. Biol Blood Marrow Transplant. 2005;11:542–50.PubMedCrossRefGoogle Scholar
  122. 122.
    Kambham N, Higgins JP, Sundram U, Troxell ML. Hematopoietic stem cell transplantation: graft versus host disease and pathology of gastrointestinal tract, liver, and lung. Adv Anat Pathol. 2014;21(5):301–20.PubMedCrossRefGoogle Scholar
  123. 123.
    Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. 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. 2015;21:389–401.PubMedCrossRefGoogle Scholar
  124. 124.
    Shulman HM, Cardona DM, Greenson JK, Hingorani S, Horn T, Huber E, et al. NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. The 2014 Pathology Working Group Report. Biol Blood Marrow Transplant. 2015;21:589–603.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Haddad IY. Stem cell transplantation and lung dysfunction. Curr Opin Pediatr. 2013;25(3):350–6.PubMedCrossRefGoogle Scholar
  126. 126.
    Epler GR. Diagnosis and treatment of constrictive bronchiolitis. Med Rep. 2010;2:32. PubMed PMID: PMC2948389.Google Scholar
  127. 127.
    Flowers ME, Martin PJ. How we treat chronic graft-versus-host disease. Blood. 2015;125(4):606–15.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Holbro A, Lehmann T, Girsberger S, Stern M, Gambazzi F, Lardinois D, et al. Lung histology predicts outcome of bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation. Am Soc Blood Marrow Transplant. 2013;19:973–80.CrossRefGoogle Scholar
  129. 129.
    Barker AF, Bergeron A, Rom WN, Hertz MI. Obliterative bronchiolitis. N Engl J Med. 2014;370:1829–8.CrossRefGoogle Scholar
  130. 130.
    Bhatia S, Ramsay NK, Steinbuch M, Dusenbery KE, Shapiro RS, Weisdorf DJ, et al. Malignant neoplasms following bone marrow transplantation. Blood. 1996;87:3633–9.PubMedGoogle Scholar
  131. 131.
    Curtis RE, Travis LB, Rowlings PA, Socie G, Kingma DW, Banks PM, et al. Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. Blood. 1999;94(7):2208–16.PubMedGoogle Scholar
  132. 132.
    Jagadeesh D, Woda BA, Draper J, Evens AM. Post transplant lymphoproliferative disorders: risk, classification, and therapeutic recommendations. Curr Treat Options Oncol. 2012;13(1):122–36. PubMed PMID: 22241590.PubMedCrossRefGoogle Scholar
  133. 133.
    Catani L, Gugliotta L, Vianelli N, Nocentini F, Baravelli S, Bandini G, et al. Endothelium and bone marrow transplantation. Bone Marrow Transplant. 1996;17(2):277–80.PubMedGoogle Scholar
  134. 134.
    Bunte MC, Patnaik MM, Pritzker MR, Burns LJ. Pulmonary veno-occlusive disease following hematopoietic stem cell transplantation: a rare model of endothelial dysfunction. Bone Marrow Transplant. 2008;41(8):677–86.PubMedCrossRefGoogle Scholar
  135. 135.
    Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood. 1998;91(10):3527–61.PubMedGoogle Scholar
  136. 136.
    Dandoy CE, Hirsch R, Chima R, Davies SM, Jodele S. Pulmonary hypertension after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2013;19(11):1546–56.CrossRefGoogle Scholar
  137. 137.
    Rabinovitch M. Molecular pathogenesis of pulmonary aterial hypertension. J Clin Invest. 2012;122:4306–13.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Jodele S, Hirsch R, Laskin B, Davies S, Witte D, Chima R. Pulmonary arterial hypertension in pediatric patients with hematopoietic stem cell transplant-associated thrombotic microangiopathy. Am Soc Blood Marrow Transplant. 2013;19:202–7.CrossRefGoogle Scholar
  139. 139.
    Steward CG, Pellier I, Mahajan A, Ashworth MT, Stuart AG, Fasth A, et al. Severe pulmonary hypertension: a frequent complication of stem cell transplantation for malignant infantile osteopetrosis. Br J Haematol. 2004;124(1):63–71.PubMedCrossRefGoogle Scholar
  140. 140.
    Rosenzweig E, Barst R. Pulmonary arterial hypertension in children: A medical update. Curr Opin Pediatr. 2008;20:288–93.PubMedCrossRefGoogle Scholar
  141. 141.
    Frazier AA, Franks TJ, Mohammed TL, Ozbudak IH, Galvin JR. From the Archives of the AFIP: pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis. Radiographics. 2007;27(3):867–82.PubMedCrossRefGoogle Scholar
  142. 142.
    Mandel J, Mark EJ, Hales CA. Pulmonary veno-occlusive disease. Am J Respir Crit Care Med. 2000;162(5):1964–73.PubMedCrossRefGoogle Scholar
  143. 143.
    Holcomb BW Jr, Loyd JE, Ely EW, Johnson J, Robbins IM. Pulmonary veno-occlusive disease: a case series and new observations. Chest. 2000;118(6):1671–9.PubMedGoogle Scholar
  144. 144.
    Almagro P, Alvarez M, Garau J. Lung biopsy in pulmonary veno-occlusive disease. Chest. 2001;120(4):1421–2.PubMedCrossRefGoogle Scholar
  145. 145.
    Izbicki G, Shitrit D, Schechtman I, Bendayan D, Fink G, Sahar G, et al. Recurrence of pulmonary veno-occlusive disease after heart-lung transplantation. Lung biopsy in pulmonary veno-occlusive disease. J Heart Lung Transplant. 2005;24(5):635–7.PubMedCrossRefGoogle Scholar
  146. 146.
    Serota FT, August CS, Koch PA, Fox W, D'Angio GJ. Pulmonary function in patients undergoing bone marrow transplantation. Med Pediatr Oncol. 1984;12(2):137–43. PubMed PMID: 6366504.PubMedCrossRefGoogle Scholar
  147. 147.
    Uderzo C, Rovelli A, Meloni G, Balduzzi A, Pezzini C, Colombini A, et al. Evaluation of late side-effects after bone marrow transplantation in children with leukemia. Bone Marrow Transplant. 1991;8(Suppl 1):44–6. PubMed PMID: 1760638.PubMedGoogle Scholar
  148. 148.
    Kaplan EB, Wodell RA, Wilmott RW, Leifer B, Lesser ML, August CS. Late effects of bone marrow transplantation on pulmonary function in children. Bone Marrow Transplant. 1994;14(4):613–21. PubMed PMID: 7858537.PubMedGoogle Scholar
  149. 149.
    Cerveri I, Fulgoni P, Giorgiani G, Zoia MC, Beccaria M, Tinelli C, et al. Lung function abnormalities after bone marrow transplantation in children: has the trend recently changed? Chest. 2001;120(6):1900–6. PubMed PMID: 11742920.PubMedCrossRefGoogle Scholar
  150. 150.
    Nenadov Beck M, Meresse V, Hartmann O, Gaultier C. Long-term pulmonary sequelae after autologous bone marrow transplantation in children without total body irradiation. Bone Marrow Transplant. 1995;16(6):771–5. PubMed PMID: 8750268.PubMedGoogle Scholar
  151. 151.
    Kaya Z, Weiner DJ, Yilmaz D, Rowan J, Goyal RK. Lung function, pulmonary complications, and mortality after allogeneic blood and marrow transplantation in children. [Erratum appears in Biol Blood Marrow Transplant. 2009 Sep;15(9):1141]. Biol Blood Marrow Transplant. 2009;15(7):817–26. PubMed PMID: 19539213.PubMedCrossRefGoogle Scholar
  152. 152.
    Fulgoni P, Zoia MC, Corsico A, Beccaria M, Georgiani G, Bossi G, et al. Lung function in survivors of childhood acute lymphoblastic leukemia. Chest. 1999;116(5):1163–7. PubMed PMID: 10559071.PubMedCrossRefGoogle Scholar
  153. 153.
    Yen KT, Lee AS, Krowka MJ, Burger CD. Pulmonary complications in bone marrow transplantation: a practical approach to diagnosis and treatment. Clin Chest Med. 2004;25(1):189–201.PubMedCrossRefGoogle Scholar
  154. 154.
    Pulsipher MA, Skinner R, McDonald GB, Hingorani S, Armenian SH, Cooke KR, et al. 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. Am Soc Blood Marrow Transplant. 2012;18:334–47.CrossRefGoogle Scholar
  155. 155.
    Uhlving HH, Mathiesen S, Buchvald F, Green K, Heilmann CJ, Gustafsson PM, et al. Small airways dysfunction in long term survivors of pediatric stem cell transplantation. Pediatr Pulmonol. 2014;50(7):704–12.PubMedCrossRefGoogle Scholar
  156. 156.
    Lahzami S, Schoefel RE, Pechey V, Greenwood M, Salome CM, Berend N, et al. Small airways function declines after allogeneic haematopoietic stem cell transplantation. Eur Respir J. 2011;38(5):1180–8.PubMedCrossRefGoogle Scholar
  157. 157.
    Australian Institute of Health and Welfare. Cancer in Australia: an overview 2014. Cancer series no 90 Cat no CAN 88 Canberra, AIHW2014.Google Scholar
  158. 158.
    Krowka MJ, Rosenow rEC, Hoagland HC. Pulmonary complications of bone marrow transplantation. Chest. 1985;87(2):237–46.PubMedCrossRefGoogle Scholar
  159. 159.
    Mulder RL, Thönissen NM, van der Pal HJ, Bresser P, Hanselaar W, Koning CC, et al. Pulmonary function impairment measured by pulmonary function tests in long-term survivors of childhood cancer. Thorax. 2011;66(12):1065–71.PubMedCrossRefGoogle Scholar
  160. 160.
    Doll DC, Ringenberg QS, Yarbro J. Vascular toxicity associated with antineoplastic agents. J Clin Oncol. 1986;4(9):1405–17.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Geshani Jayasuriya
    • 1
    • 2
  • Beryl Lin
    • 3
  • Steven J. Keogh
    • 2
    • 4
  • Hiran Selvadurai
    • 1
    • 2
  1. 1.Department of Respiratory MedicineThe Children’s HospitalSydneyAustralia
  2. 2.Discipline of Child and Adolescent HealthThe University of SydneyCamperdownAustralia
  3. 3.The University of New South WalesSydneyAustralia
  4. 4.Department of OncologyThe Children’s HospitalSydneyAustralia

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