Intensive Care Medicine

, Volume 41, Issue 2, pp 296–303 | Cite as

Prognosis of neutropenic patients admitted to the intensive care unit

  • D. MokartEmail author
  • M. Darmon
  • M. Resche-Rigon
  • V. Lemiale
  • F. Pène
  • J. Mayaux
  • A. Rabbat
  • A. Kouatchet
  • F. Vincent
  • M. Nyunga
  • F. Bruneel
  • C. Lebert
  • P. Perez
  • A. Renault
  • R. Hamidfar
  • M. Jourdain
  • A.-P. Meert
  • D. Benoit
  • S. Chevret
  • E. Azoulay



The prognosis of critically ill cancer patients has improved recently. Controversies remain as regard to the specific prognosis impact of neutropenia in critically ill cancer patients. The primary objective of this study was to assess hospital outcome of critically ill neutropenic cancer patients admitted into the ICU. The secondary objective was to assess risk factors for unfavorable outcome in this population of patients and specific impact of neutropenia.


We performed a post hoc analysis of a prospectively collected database. The study was carried out in 17 university or university-affiliated centers in France and Belgium. Neutropenia was defined as a neutrophil count lower than 500/mm3.


Among the 1,011 patients admitted into the ICU during the study period 289 were neutropenic at the time of admission. Overall, 131 patients died during their hospital stay (hospital mortality 45.3 %). Four variables were associated with a poor outcome, namely allogeneic transplantation (OR 3.83; 95 % CI 1.75–8.35), need for mechanical ventilation (MV) (OR 6.57; 95 % CI 3.51–12.32), microbiological documentation (OR 2.33; CI 1.27–4.26), and need for renal replacement therapy (OR 2.77; 95 % CI 1.34–5.74). Two variables were associated with hospital survival, namely age younger than 70 (OR 0.22; 95 % CI 0.1–0.52) and neutropenic enterocolitis (OR 0.37; 95 % CI 0.15–0.9). A case–control analysis was also performed with patients of the initial database; after adjustment, neutropenia was not associated with hospital mortality (OR 1.27; 95 % CI 0.86–1.89).


Hospital survival was closely associated with younger age and neutropenic enterocolitis. Conversely, need for conventional MV, for renal replacement therapy, and allogeneic hematopoietic stem cell transplantation (HSCT) were associated with poor outcome.


Neutropenic patients ICU Mechanical ventilation Neutropenic enterocolitis Dialysis HSCT Prognosis 


Conflicts of interest


Supplementary material

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  1. 1.
    Recher C, Coiffier B, Haioun C, Molina TJ, Ferme C, Casasnovas O et al (2011) Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet 378:1858–1867PubMedCrossRefGoogle Scholar
  2. 2.
    Vogelzang NJ, Benowitz SI, Adams S, Aghajanian C, Chang SM, Dreyer ZE et al (2012) Clinical cancer advances 2011: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol 30:88–109PubMedCrossRefGoogle Scholar
  3. 3.
    Zuber B, Tran TC, Aegerter P, Grimaldi D, Charpentier J, Guidet B et al (2012) Impact of case volume on survival of septic shock in patients with malignancies. Crit Care Med 40:55–62PubMedCrossRefGoogle Scholar
  4. 4.
    Azoulay E, Mokart D, Rabbat A, Pene F, Kouatchet A, Bruneel F et al (2008) Diagnostic bronchoscopy in hematology and oncology patients with acute respiratory failure: prospective multicenter data. Crit Care Med 36:100–107PubMedCrossRefGoogle Scholar
  5. 5.
    Vincent F, Hospital MA, Lemiale V, Bruneel F, Darmon M, Gonzalez F et al (2012) Therapeutic of respiratory manifestations at the early phase of acute myeloid leukaemia. Rev Mal Respir 29:743–755PubMedCrossRefGoogle Scholar
  6. 6.
    Legrand M, Max A, Peigne V, Mariotte E, Canet E, Debrumetz A et al (2012) Survival in neutropenic patients with severe sepsis or septic shock. Crit Care Med 40:43–49PubMedCrossRefGoogle Scholar
  7. 7.
    Mokart D, van CT, Lambert J, Textoris J, Brun JP, Sannini A et al (2012) Prognosis of acute respiratory distress syndrome in neutropenic cancer patients. Eur Respir J 40:169–176PubMedCrossRefGoogle Scholar
  8. 8.
    Mokart D, Azoulay E, Schnell D, Bourmaud A, Kouatchet A, Pene F et al (2013) Acute respiratory failure in neutropenic patients is associated with a high post-ICU mortality. Minerva Anestesiol 79:1156–1163PubMedGoogle Scholar
  9. 9.
    Vanneman M, Dranoff G (2012) Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer 12:237–251PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Maschmeyer G, Carratala J, Buchheidt D, Hamprecht A, Heussel CP, Kahl C et al (2015) 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 26:21–33Google Scholar
  11. 11.
    Maschmeyer G, Beinert T, Buchheidt D, Cornely OA, Einsele H, Heinz W et al (2009) Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients: guidelines of the infectious diseases working party of the German Society of Haematology and Oncology. Eur J Cancer 45:2462–2472PubMedCrossRefGoogle Scholar
  12. 12.
    Mokart D, Textoris J, Ettori F, Chetaille B, Blache JL (2011) Acute respiratory distress syndrome (ARDS) in neutropenic patients. In: Azoulay E (ed) Pulmonary involvement in patients with hematological malignancies. Springer, Berlin Heidelberg, pp 477–490Google Scholar
  13. 13.
    Zafrani L, Azoulay E (2014) How to treat severe infections in critically ill neutropenic patients? BMC Infect Dis 14:512PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Azoulay E, Mokart D, Pene F, Lambert J, Kouatchet A, Mayaux J et al (2013) Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium—a groupe de recherche respiratoire en reanimation onco-hematologique study. J Clin Oncol 31:2810–2818PubMedCrossRefGoogle Scholar
  15. 15.
    Vincent JL, de MA, Cantraine F, Moreno R, Takala J, Suter PM et al (1998) Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med 26:1793–1800PubMedCrossRefGoogle Scholar
  16. 16.
    Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET et al (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649–655PubMedCrossRefGoogle Scholar
  17. 17.
    Charlson ME, Sax FL, MacKenzie CR, Braham RL, Fields SD, Douglas RG Jr (1987) Morbidity during hospitalization: can we predict it? J Chronic Dis 40:705–712PubMedCrossRefGoogle Scholar
  18. 18.
    Azoulay E, Mokart D, Lambert J, Lemiale V, Rabbat A, Kouatchet A et al (2010) Diagnostic strategy for hematology and oncology patients with acute respiratory failure: randomized controlled trial. Am J Respir Crit Care Med 182:1038–1046PubMedCrossRefGoogle Scholar
  19. 19.
    Mourad M, Chow-Chine L, Faucher M, Sannini A, Brun JP, de Guibert JM et al (2014) Early diastolic dysfunction is associated with intensive care unit mortality in cancer patients presenting with septic shock. Br J Anaesth 112:102–109PubMedCrossRefGoogle Scholar
  20. 20.
    Mourad M, Chow-Chine L, Faucher M, Sannini A, Brun JP, de Guibert JM et al (2013) Early diastolic dysfunction is associated with intensive care unit mortality in cancer patients presenting with septic shock. Br J Anaesth 112(1):102–109PubMedCrossRefGoogle Scholar
  21. 21.
    De PB, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T et al (2008) 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 46:1813–1821CrossRefGoogle Scholar
  22. 22.
    Resche-Rigon M, Azoulay E, Chevret S (2006) Evaluating mortality in intensive care units: contribution of competing risks analyses. Crit Care 10:R5PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Darmon M, Azoulay E, Alberti C, Fieux F, Moreau D, Le Gall JR et al (2002) Impact of neutropenia duration on short-term mortality in neutropenic critically ill cancer patients. Intensive Care Med 28:1775–1780PubMedCrossRefGoogle Scholar
  24. 24.
    Pene F, Aubron C, Azoulay E, Blot F, Thiery G, Raynard B et al (2006) Outcome of critically ill allogeneic hematopoietic stem-cell transplantation recipients: a reappraisal of indications for organ failure supports. J Clin Oncol 24:643–649PubMedCrossRefGoogle Scholar
  25. 25.
    Azoulay E, Thiery G, Chevret S, Moreau D, Darmon M, Bergeron A et al (2004) The prognosis of acute respiratory failure in critically ill cancer patients. Medicine (Baltimore) 83:360–370CrossRefGoogle Scholar
  26. 26.
    Buchner T, Berdel WE, Wormann B, Schoch C, Haferlach T, Schnittger S et al (2005) Treatment of older patients with AML. Crit Rev Oncol Hematol 56:247–259PubMedCrossRefGoogle Scholar
  27. 27.
    Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R et al (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242PubMedCrossRefGoogle Scholar
  28. 28.
    Thieblemont C, Coiffier B (2007) Lymphoma in older patients. J Clin Oncol 25:1916–1923PubMedCrossRefGoogle Scholar
  29. 29.
    Rhee CK, Kang JY, Kim YH, Kim JW, Yoon HK, Kim SC et al (2009) Risk factors for acute respiratory distress syndrome during neutropenia recovery in patients with hematologic malignancies. Crit Care 13:R173PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Karlin L, Darmon M, Thiery G, Ciroldi M, de Miranda S, Lefebvre A et al (2005) Respiratory status deterioration during G-CSF-induced neutropenia recovery. Bone Marrow Transplant 36:245–250PubMedCrossRefGoogle Scholar
  31. 31.
    Berghmans T, Paesmans M, Lafitte JJ, Mascaux C, Meert AP, Jacquy C et al (2002) Therapeutic use of granulocyte and granulocyte–macrophage colony-stimulating factors in febrile neutropenic cancer patients. A systematic review of the literature with meta-analysis. Support Care Cancer 10:181–188PubMedCrossRefGoogle Scholar
  32. 32.
    Hohenberger P, Buchheidt D (2005) Surgical interventions in patients with hematologic malignancies. Crit Rev Oncol Hematol 55:83–91PubMedCrossRefGoogle Scholar
  33. 33.
    Badgwell BD, Cormier JN, Wray CJ, Borthakur G, Qiao W, Rolston KV et al (2008) Challenges in surgical management of abdominal pain in the neutropenic cancer patient. Ann Surg 248:104–109PubMedCrossRefGoogle Scholar
  34. 34.
    Cronin CG, O’Connor M, Lohan DG, Keane M, Roche C, Bruzzi JF et al (2009) Imaging of the gastrointestinal complications of systemic chemotherapy. Clin Radiol 64:724–733PubMedCrossRefGoogle Scholar
  35. 35.
    Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM et al (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871PubMedCrossRefGoogle Scholar
  36. 36.
    Ferrer R, Artigas A, Levy MM, Blanco J, Gonzalez-Diaz G, Garnacho-Montero J et al (2008) Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA 299:2294–2303PubMedCrossRefGoogle Scholar
  37. 37.
    Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA et al (2011) Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 52:427–431PubMedCrossRefGoogle Scholar
  38. 38.
    Canet E, Zafrani L, Lambert J, Thieblemont C, Galicier L, Schnell D et al (2013) Acute kidney injury in patients with newly diagnosed high-grade hematological malignancies: impact on remission and survival. PLoS One 8:e55870PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Munker R, Hill U, Jehn U, Kolb HJ, Schalhorn A (1998) Renal complications in acute leukemias. Haematologica 83:416–421PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2015

Authors and Affiliations

  • D. Mokart
    • 5
    Email author
  • M. Darmon
    • 15
  • M. Resche-Rigon
    • 1
  • V. Lemiale
    • 1
  • F. Pène
    • 2
  • J. Mayaux
    • 3
  • A. Rabbat
    • 4
  • A. Kouatchet
    • 6
  • F. Vincent
    • 7
  • M. Nyunga
    • 8
  • F. Bruneel
    • 9
  • C. Lebert
    • 10
  • P. Perez
    • 11
  • A. Renault
    • 12
  • R. Hamidfar
    • 13
  • M. Jourdain
    • 14
  • A.-P. Meert
    • 16
  • D. Benoit
    • 17
  • S. Chevret
    • 1
  • E. Azoulay
    • 1
  1. 1.Saint-Louis HospitalParisFrance
  2. 2.Cochin HospitalParisFrance
  3. 3.Pitié-Salpétrière HospitalParisFrance
  4. 4.Hôtel Dieu HospitalParisFrance
  5. 5.Polyvalent Intensive Care Unit, Department of Anesthesiology and Critical CareInstitut Paoli CalmettesMarseille Cedex 09France
  6. 6.Centre Hospitalier Universitaire HospitalAngersFrance
  7. 7.Avicenne HospitalBobignyFrance
  8. 8.Victor Provo HospitalRoubaixFrance
  9. 9.Mignot HospitalVersaillesFrance
  10. 10.Montaigu HospitalLa Roche Sur YonFrance
  11. 11.Brabois HospitalNancyFrance
  12. 12.Brest HospitalBrestFrance
  13. 13.Albert Michallon HospitalGrenobleFrance
  14. 14.Salengro HospitalLilleFrance
  15. 15.Nord HospitalSaint-EtienneFrance
  16. 16.Institut Jules BordetBrusselsBelgium
  17. 17.Ghent University HospitalGhentBelgium

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