MMW - Fortschritte der Medizin

, Volume 160, Supplement 4, pp 12–17 | Cite as

Wichtige Differentialdiagnosen von Lungeninfiltraten bei hämatologischen Patienten

  • Igor-Wolfgang BlauEmail author
  • Werner J. Heinz
  • Stefan Schwartz
  • Hans-Peter Lipp
  • Philippe Schafhausen
  • Georg Maschmeyer



Pulmonale Komplikationen treten bei hämatologischen Patienten häufig auf.


In einer Übersichtsarbeit wird das Ergebnis einer Diskussion zusammengefasst, die während eines Expertentreffens zum Thema Lungeninfiltrate stattfand.

Ergebnisse und Schlussfolgerungen

Die häufigsten Ursachen von Lungeninfiltraten bei hämatologischen Patienten sind bakterielle Infektionen, aber auch Virusinfektionen verursachen, zum Teil mit relevanter saisonaler Schwankung, einen wichtigen Anteil pulmonaler Infiltrate. Für beide Erregergruppen stellt die mikrobiologische Untersuchung von Materialien des Respirationstrakts (möglichst bronchoalveoläre Lavage, BAL) die wichtigste Diagnostik dar. Insbesondere bei länger anhaltender (> 7 Tage) Neutropenie steigt die Wahrscheinlichkeit, dass Infiltrate durch Pilzinfektionen bedingt sind. Nichtinfektiöse Ursachen, z. B. durch Medikamente bedingte Infiltrate, sind differentialdiagnostisch grundsätzlich zu berücksichtigen, dürfen jedoch eine schnelle Diagnostik und adäquate antimikrobielle Therapie nicht verzögern.


Galactomannan Glucan Bildgebung Leukämie Lymphom Myelom 

Pulmonary infiltrates in haematological patients


Pulmonary complications are frequent in haematologic patients.


This review article summarizes the outcome of a discussion that took place during an expert meeting on the subject of pulmonary infiltrates.

Results and Conclusions

The most common causes of pulmonary infiltrates in haematologic patients are bacterial infections. Viral infections are subject to relevant seasonal variations, but they may also cause an important proportion of pulmonary infiltrates. Microbiological examination of respiratory tract material (if possible, bronchoalveolar lavage, BAL) is the most important diagnostic procedure. Particularly in the case of prolonged (> 7 days) neutropenia, the likelihood of infiltrates being caused by fungal infections increases. For a differential diagnosis, however, also non-infectious causes, e.g. drug-induced infiltrates, have to be taken into consideration. The diagnostic workup, however, should not delay a timely start of an adequate antimicrobial therapy.


galactomannan glucan imaging leukaemia lymphoma myeloma 


  1. 1.
    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(1): 21–33.CrossRefPubMedGoogle Scholar
  2. 2.
    Maschmeyer G, Donnelly JP. How to manage lung infiltrates in adults suffering from haematological malignancies outside allogeneic haematopoietic stem cell transplantation. Br J Haematol 2016; 173(2): 179–189.CrossRefPubMedGoogle Scholar
  3. 3.
    Garcia JB, Lei X, Wierda W, et al. Pneumonia during remission induction chemotherapy in patients with acute leukemia. Ann American Thorac Soc 2013; 10(5): 432–440.CrossRefGoogle Scholar
  4. 4.
    Kim T, Lee K, Chung M, et al. Nonspecific interstitial pneumonia with fibrosis: high-resolution CT and pathologic findings. Am J Roentgenol 1998; 171(6): 1645–1650.CrossRefGoogle Scholar
  5. 5.
    Kubo K, Azuma A, Kanazawa M, et al. Consensus statement for the diagnosis and treatment of druginduced lung injuries. Respir Investig 2013; 51(4): 260–277.CrossRefPubMedGoogle Scholar
  6. 6.
    Neumann S, Krause SW, Maschmeyer G, Schiel X, von Lilienfeld-Toal M. Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematological malignancies and solid tumors: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 2013; 92(4): 433–442.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Atilla E, Atilla PA, Bozdag SC, Demirer T. A review of infectious complications after haploidentical hematopoietic stem cell transplantations. Infection 2017; 45(4): 403–411.CrossRefPubMedGoogle Scholar
  8. 8.
    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.CrossRefGoogle Scholar
  9. 9.
    Nandhagopal R, Khmeleva N, Jayakrishnan B, et al. Varicella zoster virus pneumonitis and brainstem encephalitis without skin rash in an immunocompetent adult. Open Forum Infect Dis 2014; 1(2): ofu064.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Chamilos G, Luna M, Lewis RE, et al. Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989-2003). Haematologica 2006; 91(7): 986–989.PubMedGoogle Scholar
  11. 11.
    Kume H, Yamazaki T, Togano T, et al. Epidemiology of visceral mycoses in autopsy cases in Japan: comparison of the data from 1989, 1993, 1997, 2001, 2005 and 2007 in Annual of Pathological Autopsy Cases in Japan. Med Mycol J 2011; 52(2): 117–127.CrossRefPubMedGoogle Scholar
  12. 12.
    Herbrecht R, Bories P, Moulin JC, Ledoux MP, Letscher-Bru V. Risk stratification for invasive aspergillosis in immunocompromised patients. Ann N Y Acad Sci 2012; 1272: 23–30.CrossRefPubMedGoogle Scholar
  13. 13.
    Maertens JA, Nucci M, Donnelly JP. The role of antifungal treatment in hematology. Haematologica 2012; 97(3): 325–327.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Walsh TJ, Skiada A, Cornely OA, et al. Development of new strategies for early diagnosis of mucormycosis from bench to bedside. Mycoses 2014; 57 Suppl 3: 2–7.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Poschenrieder F, Stroszczynski C, Hamer OW. Drug-induced interstitial lung diseases: often forgotten. Radiologe 2014; 54(12): 1180–1188.CrossRefPubMedGoogle Scholar
  16. 16.
    Abdel-Rahman O, Fouad M. Risk of pneumonitis in cancer patients treated with immune checkpoint inhibitors: a meta-analysis. Ther Adv Respir Dis 2016; 10(3): 183–193.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Barr PM, Saylors GB, Spurgeon SE, et al. Phase 2 study of idelalisib and entospletinib: pneumonitis limits combination therapy in relapsed refractory CLL and NHL. Blood 2016; 127(20): 2411–2415.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Bashey A, Medina B, Corringham S, et al. CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation. Blood 2009; 113(7): 1581–1588.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Brown JR, Byrd JC, Coutre SE, et al. Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110delta, for relapsed/refractory chronic lymphocytic leukemia. Blood 2014; 123(22): 3390–3397.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Haustraete E, Obert J, Diab S, et al. Idelalisib-related pneumonitis. Eur Respir J 2016; 47(4): 1280–1283.CrossRefPubMedGoogle Scholar
  21. 21.
    Lampson BL, Kasar SN, Matos TR, et al. Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity. Blood 2016; 128(2): 195–203.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Nishino M, Sholl LM, Hodi FS, Hatabu H, Ramaiya NH. Anti-PD-1-Related pneumonitis during cancer immunotherapy. N Engl J Med 2015; 373(3): 288–290.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Sehgal S, Velcheti V, Mukhopadhyay S, Stoller JK. Focal lung infiltrate complicating PD-1 inhibitor use: A new pattern of drug-associated lung toxicity? Respir Med Case Rep 2016; 19: 118–120.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Wormanns D, Hamer OW. Glossary of terms for thoracic imaging — German version of the Fleischer Society Recommendations. Rofo 2015; 187(8): 638–661.CrossRefPubMedGoogle Scholar
  25. 25.
    Stanzani M, Battista G, Sassi C, et al. Computed tomographic pulmonary angiography for diagnosis of invasive mold diseases in patients with hematological malignancies. Clin Infect Dis 2012; 54(5): 610–616.CrossRefPubMedGoogle Scholar
  26. 26.
    Stanzani M, Sassi C, Lewis RE, et al. High resolution computed tomography angiography improves the radiographic diagnosis of invasive mold disease in patients with hematological malignancies. Clin Infect Dis 2015; 60(11): 1603–1610.CrossRefPubMedGoogle Scholar
  27. 27.
    Heinz WJ, Buchheidt D, Christopeit M, et al. Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol 2017; 96(11): 1775–1792.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Martin-Mazuelos E, Ruiz-Santana S, Loza A, et al. Beta-D-glucan and Candida albicans germ tube antibody in ICU patients with invasive candidiasis. Mycoses 2015; 58(Suppl 4): 147.Google Scholar
  29. 29.
    Gonzalez M, Sanchez C, Posada Velez V, et al. Presence of (1-3) Beta-D-Glucan in patients at risk for invasive fungal infections. Mycoses 2015; 58(Suppl 4): 112.Google Scholar
  30. 30.
    Arikan-Akdagli S. Aspergillosis, mucormycosis, and other mould infections: the role of the mycologists. Mycoses 2015; 58(Suppl 4): 28.Google Scholar
  31. 31.
    Son HJ, Sung H, Park SY, et al. Diagnostic performance of the (1-3)-beta-D-glucan assay in patients with Pneumocystis jirovecii compared with those with candidiasis, aspergillosis, mucormycosis, and tuberculosis, and healthy volunteers. PLoS ONE 2017; 12(11): e0188860.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    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(12): 1813–1821.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Chong GM, Maertens JA, Lagrou K, Rijnders BJA. Diagnostic performance of galactomannan antigen in cerebral spinal fluid in patients with cerebral aspergillosis. Mycoses. 2015; 58(Suppl 4): 105.Google Scholar
  34. 34.
    Lora V, López G, Pérez ML, Bonifaz A, Velasco C. Galactomannan antigen detection as a biomarker for invasive mycosis in immunosuppressed pediatric host. Mycoses 2015; 58 (Suppl 4): 175.Google Scholar
  35. 35.
    Eigl S, Prattes J, Reischies FM, et al. Galactomannan Testing and Aspergillus PCR in same-day bronchoalveolar lavage and blood samples obtained from patients with hematological malignancies at risk for invasive mould infection. Mycoses 2015; 58(Suppl 4): 157.Google Scholar
  36. 36.
    Bergeron A, Porcher R, Sulahian A, et al. The strategy for the diagnosis of invasive pulmonary aspergillosis should depend on both the underlying condition and the leukocyte count of patients with hematologic malignancies. Blood 2012; 119(8): 1831–1837; quiz 956.CrossRefPubMedGoogle Scholar
  37. 37.
    Koo S, Bryar JM, Baden LR, Marty FM. Prognostic features of galactomannan antigenemia in galactomannan- positive invasive aspergillosis. J Clin Microbiol 2010; 48(4): 1255–1260.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Bustin SA, Thornton CR, Shannon M, et al. Immuno PCR-based assays for the early detection of Aspergillus species. Mycoses 2015; 58(Suppl 4): 28.Google Scholar
  39. 39.
    Imbert S, Gauthier L, Palous M, et al. Performance of an Aspergillus fumigatus real-time PCR assay using serum for the diagnosis of invasive aspergillosis in neutropenic and non-neutropenic patients. Mycoses 2015; 58(Suppl 4): 44.Google Scholar
  40. 40.
    Millon L, Herbrecht R, Grenouillet F, et al. Detection of circulating Mucorales DNA for early diagnosis and monitoring of mucormycosis. Mycoses 2015; 58(Suppl 4): 44.Google Scholar
  41. 41.
    Springer JU, Lackner M, Heinz WJ, et al. Non-invasive detection of mucorales DNA in serum by mucorales specific real-time PCR assay. Mycoses 2015; 58(Suppl 4): 98.Google Scholar
  42. 42.
    Lehmann LE, Hunfeld KP, Emrich T, et al. A multiplex real-time PCR assay for rapid detection and differentiation of 25 bacterial and fungal pathogens from whole blood samples. Med Microbiol Immunol 2008; 197(3): 313–324.CrossRefPubMedGoogle Scholar
  43. 43.
    Chong GM, van der Beek MT, von dem Borne PA, et al. PCR-based detection of Aspergillus fumigatus Cyp51A mutations on bronchoalveolar lavage: a multicentre validation of the AsperGenius assay(R) in 201 patients with haematological disease suspected for invasive aspergillosis. J Antimicrob Chemother 2016; 71(12): 3528–3535.CrossRefPubMedGoogle Scholar
  44. 44.
    White PL, Barnes RA, Springer J, et al. Clinical performance of Aspergillus PCR for testing serum and plasma: a study by the European Aspergillus PCR Initiative. J Clin Microbiol 2015; 53(9): 2832–2837.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Buchheidt D, Reinwald M, Hofmann WK, Boch T, Spiess B. Evaluating the use of PCR for diagnosing invasive aspergillosis. Expert Rev Mol Diagn 2017; 17(6): 603–610.CrossRefPubMedGoogle Scholar
  46. 46.
    White PL, Wingard JR, Bretagne S, et al. Aspergillus polymerase chain reaction: systematic review of evidence for clinical use in comparison with antigen testing. Clin Infect Dis 2015; 61(8): 1293–1303.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    de Jong E, van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016; 16(7): 819–827.CrossRefPubMedGoogle Scholar
  48. 48.
    Schütz P, Mueller B. Procalcitonin in critically ill patients: time to change guidelines and antibiotic use in practice. Lancet Infect Dis 2016; 16(7): 758–760.CrossRefGoogle Scholar
  49. 49.
    Brodöfel H, Vogel M, Hebart H, et al. Long-term CT follow-up in 40 non-HIV immunocompromised patients with invasive pulmonary aspergillosis: kinetics of CT morphology and correlation with clinical findings and outcome. Am J Roentgenol 2006; 187(2): 404–413.CrossRefGoogle Scholar
  50. 50.
    Vehreschild JJ, Heussel CP, Groll AH, et al. Serial assessment of pulmonary lesion volume by computed tomography allows survival prediction in invasive pulmonary aspergillosis. Eur Radiol 2017; 27(8): 3275–3282.CrossRefPubMedGoogle Scholar
  51. 51.
    Segal BH, Herbrecht R, Stevens DA, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis 2008; 47(5): 674–683.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    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(9): 2397–2404.CrossRefPubMedGoogle Scholar
  53. 53.
    Maschmeyer G, Helweg-Larsen J, Pagano L, Robin C, Cordonnier C, Schellongowski P. ECIL guidelines for treatment of Pneumocystis jirovecii pneumonia in non-HIV-infected haematology patients. J Antimicrob Chemother 2016; 71(9): 2405–2413.CrossRefPubMedGoogle Scholar
  54. 54.
    Postow MA. Managing immune checkpoint-blocking antibody side effects. Am Soc Clin Oncol Educ Book 2015: 76–83.CrossRefGoogle Scholar
  55. 55.
    Cohen N, Dubnow S, Paskovaty A, Seo SK. Antifungal prophylaxis in high-risk oncology patients. Clinical Oncology News 2010(Feb 2010): 1–15.Google Scholar
  56. 56.
    Cornely OA, Aversa F, Cook P, et al. Evaluating the role of prophylaxis in the management of invasive fungal infections in patients with hematologic malignancy. Eur J Haematol 2011; 87(4): 289–301.CrossRefPubMedGoogle Scholar
  57. 57.
    Gerber B, Koppel J, Paul M, et al. Efficacy of antifungal but not anti-bacterial prophylaxis in intensive primary AML therapy: A real-world, retrospective comparative single-centre study. Swiss Med Wkly 2014; 144: w13985.PubMedGoogle Scholar
  58. 58.
    Kontoyiannis DP. Antifungal prophylaxis in hematopoietic stem cell transplant recipients: the unfinished tale of imperfect success. Bone Marrow Transplant 2011; 46(2): 165–173.CrossRefPubMedGoogle Scholar
  59. 59.
    Zimmerli S, Bialek R, Blau IW, Christe A, Lass-Florl C, Presterl E. Lichtheimia infection in a lymphoma patient: case report and a brief review of the available diagnostic tools. Mycopathologia 2016; 181(7–8): 561–566.CrossRefPubMedGoogle Scholar
  60. 60.
    Groll AH, Castagnola E, Cesaro S, et al. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation. Lancet Oncol 2014; 15(8): e327–e40.CrossRefPubMedGoogle Scholar
  61. 61.
    Mousset S, Buchheidt D, Heinz W, et al. Treatment of invasive fungal infections in cancer patients — updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 2014; 93(1): 13–32.CrossRefPubMedGoogle Scholar
  62. 62.
    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(3): 433–444.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Verweij PE, Ananda-Rajah M, Andes D, et al. International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus. Drug Resistance Updates 2015; 21-22: 30–40.CrossRefPubMedGoogle Scholar
  64. 64.
    Muñoz P, Valerio M, Vena A, Bouza E. Antifungal stewardship in daily practice and health economic implications. Mycoses 2015; 58 Suppl 2: 14–25.CrossRefPubMedGoogle Scholar
  65. 65.
    Agrawal S, Barnes R, Brüggemann RJ, Rautemaa- Richardson R, Warris A. The role of the multidisciplinary team in antifungal stewardship. J Antimicrob Chemother 2016; 71(Suppl 2): ii37–ii42.CrossRefPubMedGoogle Scholar
  66. 66.
    Aguado JM, Silva JT, Bouza E. Conclusion and future perspectives on antifungal stewardship. J Antimicrob Chemother 2016; 71(Suppl 2): ii43–ii4.CrossRefPubMedGoogle Scholar
  67. 67.
    Vento S, Cainelli F, Temesgen Z. Lung infections after cancer chemotherapy. Lancet Oncol 2008; 9(10): 982–992.CrossRefPubMedGoogle Scholar
  68. 68.
    Miyakoshi S, Kami M, Yuji K, et al. Severe pulmonary complications in Japanese patients after bortezomib treatment for refractory multiple myeloma. Blood 2006; 107(9): 3492–3494.CrossRefPubMedGoogle Scholar
  69. 69.
    Ohnishi K, Sakai F, Kudoh S, Ohno R. Twenty-seven cases of drug-induced interstitial lung disease associated with imatinib mesylate. Leukemia 2006; 20(6): 1162–1164.CrossRefPubMedGoogle Scholar
  70. 70.
    Salmasi G, Li M, Sivabalasundaram V, et al. Incidence of pneumonitis in patients with non-Hodgkin lymphoma receiving chemoimmunotherapy with rituximab. Leuk Lymphoma 2015; 56(6): 1659–1664.CrossRefPubMedGoogle Scholar
  71. 71.
    Sakurada T, Kakiuchi S, Tajima S, et al. Characteristics of and risk factors for interstitial lung disease induced by chemotherapy for lung cancer. Ann Pharmacother 2015; 49(4): 398–404.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  • Igor-Wolfgang Blau
    • 1
    • 7
    Email author
  • Werner J. Heinz
    • 2
  • Stefan Schwartz
    • 3
  • Hans-Peter Lipp
    • 4
  • Philippe Schafhausen
    • 5
  • Georg Maschmeyer
    • 6
  1. 1.Medizinische Klinik für Hämatologie, Onkologie und Tumorimmunologie, Leitender Oberarzt KnochenmarktransplantationCampus Virchow Klinikum der Charité — Universitätsmedizin BerlinBerlinDeutschland
  2. 2.Medizinische Klinik und Poliklinik IIUniversitätsklinikum WürzburgWürzburgDeutschland
  3. 3.Medizinische Klinik für Hämatologie, Onkologie und TumorimmunologieCampus Benjamin Franklin der Charité — Universitätsmedizin BerlinBerlinDeutschland
  4. 4.Universitätsklinikum TübingenTübingenDeutschland
  5. 5.Zentrum für Onkologie, II. Medizinische Klinik und PoliklinikUKE HamburgHamburgDeutschland
  6. 6.Klinik für Hämatologie, Onkologie und PalliativmedizinKlinikum Ernst von Bergmann gemeinnützige GmbHPotsdamDeutschland
  7. 7.Klinik für Hämatologie, Onkologie und TumorimmunologieCampus Virchow Klinikum der Charité — Universitätsmedizin BerlinBerlinDeutschland

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