Pneumonia in patients after hematopoietic stem cell transplantation Review article
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Published:
Aug 9, 2017
Keywords:
pneumonia, invasive fungal disease, invasive fungal ifection, pulmonaryaspergillosis, chemotherapy, hematopoetic stem cell transplantation, amhotericin B lipid complex
Main Article Content
Abstract
Pneumonia is one of the most frequent cause of death after hematopoietic stem cell transplantation (HSCT). The objective of this review is to present various aspects of pneumonia in this group of patients, with focus on invasive pulmonary aspergillosis and cytomegalovirus disease, being the most frequent etiological causes of pneumonia after HSCT. The review is aimed at practical approach to diagnostic and therapeutic management of pneumonia after HSCT with special attention to: definitions of infections and level of diagnosis of upper and lower respiratory tract infections, including issues specific for invasive fungal disease, pneumocystosis, cytomegalovirus disease, community acquired respiratory viral infections and bacterial pneumonia. Another topics analyzed in the review are: epidemiology and risk factors for development of infection and risk of death due to pneumonia; invasive and non-invasive diagnostics, including imaging and laboratory biomarkers; methods of pharmacological and environmental prophylaxis and specific targeted therapy of pneumonia after HSCT.
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1.
Styczyński J. Pneumonia in patients after hematopoietic stem cell transplantation. OncoReview [Internet]. 2017Aug.9 [cited 2024May5];7(3(27):126-38. Available from: https://journalsmededu.pl/index.php/OncoReview/article/view/465
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HEMATO-ONCOLOGY
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright: © Medical Education sp. z o.o. This is an Open Access article distributed under the terms of the Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). License (https://creativecommons.org/licenses/by-nc/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Address reprint requests to: Medical Education, Marcin Kuźma (marcin.kuzma@mededu.pl)
References
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2. Passweg JR, Baldomero H, Bader P et al. Use of haploidenticalstem cell transplantation continuesto increase: the 2015 European Society for Blood and Marrow Transplant activity survey report. Bone Marrow Transplant 2017; 52: 811-817.
3. Styczynski J. Postępowanie diagnostyczne, profilaktyczne i terapeutyczne w powikłaniach infekcyjnych u dzieci z chorobami nowotworowymi. Standardy Medyczne Pediatria 2017; 14: 309-320.
4. Tomblyn M, Chiller T, Einsele H et al. guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 2009; 15: 1143-1238.
5. Bjorklund A, Aschan J, Labopin M et al. Risk factors for fatal infectious complications developing late after allogeneic stem cell transplantation. Bone Marrow Transplant 2007; 40: 1055-1062.
6. Martino R, Kerguelen A, Valcarcel D et al. Reduction of infection-related mortality after allogeneic PBSCT from HLA-identical siblings: longitudinal analysis from 1994 to 2008 at a single institution. Bone Marrow Transplant 2011; 46: 690-701.
7. Yang TM, Wang PN, Kao KC et al. Outcome of hematopoietic stem cell recipients who were mechanically ventilated and admitted to intensive care units. J Formos Med Assoc 2007; 106: 295-301.
8. Agarwal S, O’Donoghue S, Gowardman J et al. Intensive care unit experience of haemopoietic stem cell transplant patients. Intern Med J 2012; 42: 748-754.
9. Martin-Pena A, Aguilar-Guisado M, Espigado I et al. Prospective study of infectious complications in allogeneic hematopoietic stem cell transplant recipients. Clin Transplant 2011; 25: 468-474.
10. De Pauw B, Walsh TJ, Donnelly JP et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46: 1813-1821.
11. Chi AK, Soubani AO, White AC, Miller KB. An update on pulmonary complications of hematopoietic stem cell transplantation. Chest 2013; 144: 1913- 1922.
12. Kuzmina Z, Eder S, Bohm A et al. Significantly worse survival of patients with NIH-defined chronic graft-versus-host disease and thrombocytopenia or progressive onset type: results of a prospective study. Leukemia 2012; 26: 746-756.
13. Aguilar-Guisado M, Jimenez-Jambrina M, Espigado I et al. Pneumonia in allogeneic stem cell transplantation recipients: a multicenter prospective study. Clin Transplant 2011; 25: E629-638.
14. Chen CS, Boeckh M, Seidel K et al. Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation. Bone Marrow Transplant 2003; 32: 515-522.
15. Forslow U, Remberger M, Nordlander A, Mattsson J. The clinical importance of bronchoalveolar lavage in allogeneic SCT patients with pneumonia. Bone Marrow Transplant 2010; 45: 945-950.
16. Forslow U, Mattsson J, Ringden O et al. Decreasing mortality rate in early pneumonia following hematopoietic stem cell transplantation. Scand J Infect Dis 2006; 38: 970-976
17. Escuissato DL, Gasparetto EL, Marchiori E et al. Pulmonary infections after bone marrow transplantation: high-resolution CT findings in 111 patients. AJR Am J Roentgenol 2005; 185: 608-615.
18. Lass-Florl C, Resch G, Nachbaur D et al. The value of computed tomography-guided percutaneous lung biopsy for diagnosis of invasive fungal infection in immunocompromised patients. Clin Infect Dis 2007; 45: e101-104.
19. Georgiadou SP, Sipsas NV, Marom EM, Kontoyiannis DP. The diagnostic value of halo and reversed halo signs for invasive mold infections in compromised hosts. Clin Infect Dis 2011; 52: 1144-1155.
20. Pandey T, Maximin S, Bhargava P. Imaging of complications from hematopoietic stem cell transplant. Indian J Radiol Imaging 2014; 24: 327-338.
21. Heussel CP, Kauczor HU, Ullmann AJ. Pneumonia in neutropenic patients. Eur Radiol 2004; 14: 256-271.
22. Coussement J, Steensels D, Nollevaux MC et al. When polymerase chain reaction does not help: cytomegalovirus pneumonitis associated with very low or undetectable viral load in both blood and bronchoalveolar lavage samples after lung transplantation. Transpl Infect Dis 2016; 18: 284-287.
23. Franquet T, Rodriguez S, Martino R et al. Thin-section CT findings in hematopoietic stem cell transplantation recipients with respiratory virus pneumonia. AJR Am J Roentgenol 2006; 187: 1085-1090.
24. Gasparetto EL, Escuissato DL, Marchiori E et al. High-resolution CT findings of respiratory syncytial virus pneumonia after bone marrow transplantation. AJR Am J Roentgenol 2004; 182: 1133-1137.
25. Kowalczyk J, Stefaniak M, Kałwak K et al. Standardy postępowania diagnostyczno-terapeutycznego w inwazyjnej chorobie grzybiczej u dzieci: rekomendacje Polskiego Towarzystwa Onkologii i Hematologii Dziecięcej. Post Nauk Med 2016; 8: 528-533.
26. Maschmeyer G, Carratala J, Buchheidt D et al. Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Oncol 2015; 26: 21-33.
27. Maertens J, Marchetti O, Herbrecht R et al. European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3 – 2009 update. Bone Marrow Transplant 2011; 46: 709-718.
28. Styczyński J. Amfoterycyna B w kompleksie lipidowym na bazie polskich doświadczeń. Otomin, Asteria 2015.
29. Tissot F, Agrawal S, Pagano L et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 2017; 102: 433-444.
30. Klingspor L, Saaedi B, Ljungman P, Szakos A. Epidemiology and outcomes of patients with invasive mould infections: a retrospective observational study from a single centre (2005-2009). Mycoses 2015; 58: 470-477.
31. Groll AH, Piscitelli SC, Walsh TJ. Clinical pharmacology of systemic antifungal agents: a comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development. Adv Pharmacol 1998; 44: 343-500.
32. Ostrosky-Zeichner L, Marr KA, Rex JH, Cohen SH. Amphotericin B: time for a new “gold standard”. Clin Infect Dis 2003; 37: 415-425.
33. Skiada A, Lanternier F, Groll AH et al. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3). Haematologica 2013; 98: 492-504.
34. Walsh TJ, Anaissie EJ, Denning DW et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008; 46: 327-360.
35. Hamill RJ. Amphotericin B formulations: a comparative review of efficacy and toxicity. Drugs 2013; 73: 919-934.
36. Bassetti M, Aversa F, Ballerini F et al. Amphotericin B lipid complex in the management of invasive fungal infections in immunocompromised patients. Clin Drug Investig 2011; 31: 745-758.
37. Jessup C, Reyes G, Fothergill A et al. A head-on comparison of the in vitro antifungal activity of conventional and lipid-based amphotericin B: a multi-center study. J Chemother 2000; 12: 22-29.
38. Maertens J, Cesaro S, Maschmeyer G et al. ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother 2016; 71: 2397-2404.
39. Ljungman P, Boeckh M, Hirsch HH et al. Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. Clin Infect Dis 2017; 64: 87-91.
40. Ljungman P, Brand R, Hoek J et al. Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation. Clin Infect Dis 2014; 59: 473-481.
41. Schmidt-Hieber M, Labopin M, Beelen D et al. CMV serostatus still has an important prognostic impact in de novo acute leukemia patients after allogeneic stem cell transplantation: a report from the acute Leukemia Working Party of EBMT. Blood 2013; 122: 3359-3364.
42. Ljungman P, de la Camara R, Cordonnier C et al. Management of CMV, hhV-6, hhV-7 and kaposi-sarcoma herpesvirus(hhV-8) infectionsin patients with hematological malignancies and after SCT. Bone Marrow Transplant 2008; 42: 227-240.
43. Marty FM, Winston DJ, Rowley SD et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med 2013; 369: 1227-1236.
44. Chemaly RF, Ullmann AJ, Stoelben S et al. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation. N Engl J Med 2014; 370: 1781-1789.
45. Marty FM, Ljungman P, Papanicolaou GA et al. Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stemcell transplants: a phase 3, double-blind, placebo-controlled, randomised trial. Lancet Infect Dis 2011; 11: 284-292.
46. Erard V, Guthrie KA, Seo S et al. Reduced Mortality of Cytomegalovirus Pneumonia After Hematopoietic Cell Transplantation Due to Antiviral Therapy and Changes in Transplantation Practices. Clin Infect Dis 2015; 61: 31-39.
47. Boeckh M. The challenge of respiratory virus infections in hematopoietic cell transplant recipients. Br J Haematol 2008; 143: 455-467.
48. Martino R, Porras RP, Rabella N et al. Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respiratory tract infections by respiratory viruses in adult recipients of hematopoietic stem cell transplants for hematologic malignancies. Biol Blood Marrow Transplant 2005; 11: 781-796.
49. Seo S, Xie H, Campbell AP et al. Parainfluenza virus lower respiratory tract disease after hematopoietic cell transplant: viral detection in the lung predicts outcome. Clin Infect Dis 2014; 58: 1357-1368.
50. von Lilienfeld-Toal M, Berger A, Christopeit M et al. Community acquired respiratory virus infections in cancer patients-guideline on diagnosis and management by the Infectious Diseases Working Party of the German Society for haematology and Medical Oncology. Eur J Cancer 2016; 67: 200-212.
2. Passweg JR, Baldomero H, Bader P et al. Use of haploidenticalstem cell transplantation continuesto increase: the 2015 European Society for Blood and Marrow Transplant activity survey report. Bone Marrow Transplant 2017; 52: 811-817.
3. Styczynski J. Postępowanie diagnostyczne, profilaktyczne i terapeutyczne w powikłaniach infekcyjnych u dzieci z chorobami nowotworowymi. Standardy Medyczne Pediatria 2017; 14: 309-320.
4. Tomblyn M, Chiller T, Einsele H et al. guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 2009; 15: 1143-1238.
5. Bjorklund A, Aschan J, Labopin M et al. Risk factors for fatal infectious complications developing late after allogeneic stem cell transplantation. Bone Marrow Transplant 2007; 40: 1055-1062.
6. Martino R, Kerguelen A, Valcarcel D et al. Reduction of infection-related mortality after allogeneic PBSCT from HLA-identical siblings: longitudinal analysis from 1994 to 2008 at a single institution. Bone Marrow Transplant 2011; 46: 690-701.
7. Yang TM, Wang PN, Kao KC et al. Outcome of hematopoietic stem cell recipients who were mechanically ventilated and admitted to intensive care units. J Formos Med Assoc 2007; 106: 295-301.
8. Agarwal S, O’Donoghue S, Gowardman J et al. Intensive care unit experience of haemopoietic stem cell transplant patients. Intern Med J 2012; 42: 748-754.
9. Martin-Pena A, Aguilar-Guisado M, Espigado I et al. Prospective study of infectious complications in allogeneic hematopoietic stem cell transplant recipients. Clin Transplant 2011; 25: 468-474.
10. De Pauw B, Walsh TJ, Donnelly JP et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46: 1813-1821.
11. Chi AK, Soubani AO, White AC, Miller KB. An update on pulmonary complications of hematopoietic stem cell transplantation. Chest 2013; 144: 1913- 1922.
12. Kuzmina Z, Eder S, Bohm A et al. Significantly worse survival of patients with NIH-defined chronic graft-versus-host disease and thrombocytopenia or progressive onset type: results of a prospective study. Leukemia 2012; 26: 746-756.
13. Aguilar-Guisado M, Jimenez-Jambrina M, Espigado I et al. Pneumonia in allogeneic stem cell transplantation recipients: a multicenter prospective study. Clin Transplant 2011; 25: E629-638.
14. Chen CS, Boeckh M, Seidel K et al. Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation. Bone Marrow Transplant 2003; 32: 515-522.
15. Forslow U, Remberger M, Nordlander A, Mattsson J. The clinical importance of bronchoalveolar lavage in allogeneic SCT patients with pneumonia. Bone Marrow Transplant 2010; 45: 945-950.
16. Forslow U, Mattsson J, Ringden O et al. Decreasing mortality rate in early pneumonia following hematopoietic stem cell transplantation. Scand J Infect Dis 2006; 38: 970-976
17. Escuissato DL, Gasparetto EL, Marchiori E et al. Pulmonary infections after bone marrow transplantation: high-resolution CT findings in 111 patients. AJR Am J Roentgenol 2005; 185: 608-615.
18. Lass-Florl C, Resch G, Nachbaur D et al. The value of computed tomography-guided percutaneous lung biopsy for diagnosis of invasive fungal infection in immunocompromised patients. Clin Infect Dis 2007; 45: e101-104.
19. Georgiadou SP, Sipsas NV, Marom EM, Kontoyiannis DP. The diagnostic value of halo and reversed halo signs for invasive mold infections in compromised hosts. Clin Infect Dis 2011; 52: 1144-1155.
20. Pandey T, Maximin S, Bhargava P. Imaging of complications from hematopoietic stem cell transplant. Indian J Radiol Imaging 2014; 24: 327-338.
21. Heussel CP, Kauczor HU, Ullmann AJ. Pneumonia in neutropenic patients. Eur Radiol 2004; 14: 256-271.
22. Coussement J, Steensels D, Nollevaux MC et al. When polymerase chain reaction does not help: cytomegalovirus pneumonitis associated with very low or undetectable viral load in both blood and bronchoalveolar lavage samples after lung transplantation. Transpl Infect Dis 2016; 18: 284-287.
23. Franquet T, Rodriguez S, Martino R et al. Thin-section CT findings in hematopoietic stem cell transplantation recipients with respiratory virus pneumonia. AJR Am J Roentgenol 2006; 187: 1085-1090.
24. Gasparetto EL, Escuissato DL, Marchiori E et al. High-resolution CT findings of respiratory syncytial virus pneumonia after bone marrow transplantation. AJR Am J Roentgenol 2004; 182: 1133-1137.
25. Kowalczyk J, Stefaniak M, Kałwak K et al. Standardy postępowania diagnostyczno-terapeutycznego w inwazyjnej chorobie grzybiczej u dzieci: rekomendacje Polskiego Towarzystwa Onkologii i Hematologii Dziecięcej. Post Nauk Med 2016; 8: 528-533.
26. Maschmeyer G, Carratala J, Buchheidt D et al. Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Oncol 2015; 26: 21-33.
27. Maertens J, Marchetti O, Herbrecht R et al. European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3 – 2009 update. Bone Marrow Transplant 2011; 46: 709-718.
28. Styczyński J. Amfoterycyna B w kompleksie lipidowym na bazie polskich doświadczeń. Otomin, Asteria 2015.
29. Tissot F, Agrawal S, Pagano L et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 2017; 102: 433-444.
30. Klingspor L, Saaedi B, Ljungman P, Szakos A. Epidemiology and outcomes of patients with invasive mould infections: a retrospective observational study from a single centre (2005-2009). Mycoses 2015; 58: 470-477.
31. Groll AH, Piscitelli SC, Walsh TJ. Clinical pharmacology of systemic antifungal agents: a comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development. Adv Pharmacol 1998; 44: 343-500.
32. Ostrosky-Zeichner L, Marr KA, Rex JH, Cohen SH. Amphotericin B: time for a new “gold standard”. Clin Infect Dis 2003; 37: 415-425.
33. Skiada A, Lanternier F, Groll AH et al. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3). Haematologica 2013; 98: 492-504.
34. Walsh TJ, Anaissie EJ, Denning DW et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008; 46: 327-360.
35. Hamill RJ. Amphotericin B formulations: a comparative review of efficacy and toxicity. Drugs 2013; 73: 919-934.
36. Bassetti M, Aversa F, Ballerini F et al. Amphotericin B lipid complex in the management of invasive fungal infections in immunocompromised patients. Clin Drug Investig 2011; 31: 745-758.
37. Jessup C, Reyes G, Fothergill A et al. A head-on comparison of the in vitro antifungal activity of conventional and lipid-based amphotericin B: a multi-center study. J Chemother 2000; 12: 22-29.
38. Maertens J, Cesaro S, Maschmeyer G et al. ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother 2016; 71: 2397-2404.
39. Ljungman P, Boeckh M, Hirsch HH et al. Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. Clin Infect Dis 2017; 64: 87-91.
40. Ljungman P, Brand R, Hoek J et al. Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation. Clin Infect Dis 2014; 59: 473-481.
41. Schmidt-Hieber M, Labopin M, Beelen D et al. CMV serostatus still has an important prognostic impact in de novo acute leukemia patients after allogeneic stem cell transplantation: a report from the acute Leukemia Working Party of EBMT. Blood 2013; 122: 3359-3364.
42. Ljungman P, de la Camara R, Cordonnier C et al. Management of CMV, hhV-6, hhV-7 and kaposi-sarcoma herpesvirus(hhV-8) infectionsin patients with hematological malignancies and after SCT. Bone Marrow Transplant 2008; 42: 227-240.
43. Marty FM, Winston DJ, Rowley SD et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med 2013; 369: 1227-1236.
44. Chemaly RF, Ullmann AJ, Stoelben S et al. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation. N Engl J Med 2014; 370: 1781-1789.
45. Marty FM, Ljungman P, Papanicolaou GA et al. Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stemcell transplants: a phase 3, double-blind, placebo-controlled, randomised trial. Lancet Infect Dis 2011; 11: 284-292.
46. Erard V, Guthrie KA, Seo S et al. Reduced Mortality of Cytomegalovirus Pneumonia After Hematopoietic Cell Transplantation Due to Antiviral Therapy and Changes in Transplantation Practices. Clin Infect Dis 2015; 61: 31-39.
47. Boeckh M. The challenge of respiratory virus infections in hematopoietic cell transplant recipients. Br J Haematol 2008; 143: 455-467.
48. Martino R, Porras RP, Rabella N et al. Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respiratory tract infections by respiratory viruses in adult recipients of hematopoietic stem cell transplants for hematologic malignancies. Biol Blood Marrow Transplant 2005; 11: 781-796.
49. Seo S, Xie H, Campbell AP et al. Parainfluenza virus lower respiratory tract disease after hematopoietic cell transplant: viral detection in the lung predicts outcome. Clin Infect Dis 2014; 58: 1357-1368.
50. von Lilienfeld-Toal M, Berger A, Christopeit M et al. Community acquired respiratory virus infections in cancer patients-guideline on diagnosis and management by the Infectious Diseases Working Party of the German Society for haematology and Medical Oncology. Eur J Cancer 2016; 67: 200-212.