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Critical care management of patients with hemophagocytic lymphohistiocytosis

Sophie Buyse| Luis Teixeira| Lionel Galicier| Eric Mariotte| Virginie Lemiale| Amélie Seguin| Philippe Bertheau| Emmanuel Canet| Adrienne de Labarthe| Michaël Darmon| Michel Rybojad| Benoit Schlemmer| Elie Azoulay
Original
Volume 36, Issue 10 / October , 2010

Pages 1695 - 1702

Abstract

Objective

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition associated with multiple organ dysfunction. We sought to describe ICU management and outcomes in HLH patients meeting HLH-2004 criteria and to identify determinants of mortality.

Design

Retrospective study between January 1998 and January 2009.

Setting

Medical ICU of a teaching hospital.

Patients

Among the 72 patients fulfilling the HLH-2004 criteria, we report the 56 patients with complete follow-up and no missing data.

Interventions

None.

Measurements and main results

Clinical and laboratory data were abstracted from the medical records. Median SOFA score at admission was 6.5 (IQR, 4–8). At ICU admission, the number of HLH-2004 criteria was 6 (5–7). Sixty-six precipitating factors were found in 52 patients and consisted of 43 tumoral causes (8 Castleman’s diseases, 18 B cell lymphoma and 17 various malignancies), 13 non-viral infections and 10 viral infections. Underlying immune deficiency was present in 38 (67.8%) patients. Etoposide was used in 45 patients, corticosteroids in 31 and intravenous immunoglobulins in 3. Mechanical ventilation was required in 32 patients, vasoactive agents in 30 and renal replacement therapy in 19. Hospital mortality was 29/56 patients. By multivariate analysis, factors associated with increased hospital death were shock at ICU admission [OR, 4.33; 95% confidence interval (95% CI), 1.11–16.90; P = 0.03] and platelet count <30 g/l (OR, 4.75; 95% CI, 1.20–18.81; P = 0.02). B cell lymphoma [odds ratio (OR), 0.17; 95% CI, 0.04–0.80; P = 0.02] and Castleman’s disease (OR, 0.11; 95% CI, 0.02–0.90; P = 0.04) were associated with increased hospital survival.

Conclusions

Aggressive supportive care combined with specific treatment of the precipitating factor can produce meaningful survival in patients with HLH responsible for multiple organ failures. Survival is highest in patients with HLH related to Castleman’s disease or B cell lymphoma.

Keywords

References

  1. Wilson RF (1981) Etiology, diagnosis, and prognosis of positive blood cultures. Am Surg 47:112–115
    • View reference on PubMed
  2. Gauvin F, Toledano B, Champagne J, Lacroix J (2000) Reactive hemophagocytic syndrome presenting as a component of multiple organ dysfunction syndrome. Crit Care Med 28:3341–3345
    • View reference on publisher's website
    • View reference on PubMed
  3. Janka GE (2005) Hemophagocytic lymphohistiocytosis. Hematology 10(Suppl 1):104–107
    • View reference on publisher's website
    • View reference on PubMed
  4. Henter JI, Elinder G, Ost A (1991) Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society. Semin Oncol 18:29–33
    • View reference on PubMed
  5. Janka GE (2007) Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr 166:95–109
    • View reference on publisher's website
    • View reference on PubMed
  6. Castillo L, Carcillo J (2009) Secondary hemophagocytic lymphohistiocytosis and severe sepsis/systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation. Pediatr Crit Care Med 10:387–392
    • View reference on publisher's website
    • View reference on PubMed
  7. Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G (2007) HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 48:124–131
    • View reference on publisher's website
    • View reference on PubMed
  8. Creput C, Galicier L, Buyse S, Azoulay E (2008) Understanding organ dysfunction in hemophagocytic lymphohistiocytosis. Intensive Care Med 34:1177–1187
  9. Risdall RJ, Brunning RD, Hernandez JI, Gordon DH (1984) Bacteria-associated hemophagocytic syndrome. Cancer 54:2968–2972
    • View reference on publisher's website
    • View reference on PubMed
  10. Grom AA (2003) Macrophage activation syndrome and reactive hemophagocytic lymphohistiocytosis: the same entities? Curr Opin Rheumatol 15:587–590
    • View reference on publisher's website
    • View reference on PubMed
  11. Stephan JL, Kone-Paut I, Galambrun C, Mouy R, Bader-Meunier B, Prieur AM (2001) Reactive haemophagocytic syndrome in children with inflammatory disorders. A retrospective study of 24 patients. Rheumatology (Oxford) 40:1285–1292
    • View reference on publisher's website
  12. Strauss R, Neureiter D, Westenburger B, Wehler M, Kirchner T, Hahn EG (2004) Multifactorial risk analysis of bone marrow histiocytic hyperplasia with hemophagocytosis in critically ill medical patients–a postmortem clinicopathologic analysis. Crit Care Med 32:1316–1321
    • View reference on publisher's website
    • View reference on PubMed
  13. Stephan F, Thioliere B, Verdy E, Tulliez M (1997) Role of hemophagocytic histiocytosis in the etiology of thrombocytopenia in patients with sepsis syndrome or septic shock. Clin Infect Dis 25:1159–1164
    • View reference on publisher's website
    • View reference on PubMed
  14. Kaito K, Kobayashi M, Katayama T, Otsubo H, Ogasawara Y, Sekita T, Saeki A, Sakamoto M, Nishiwaki K, Masuoka H, Shimada T, Yoshida M, Hosoya T (1997) Prognostic factors of hemophagocytic syndrome in adults: analysis of 34 cases. Eur J Haematol 59:247–253
    • View reference on publisher's website
    • View reference on PubMed
  15. Dhote R, Simon J, Papo T, Detournay B, Sailler L, Andre MH, Dupond JL, Larroche C, Piette AM, Mechenstock D, Ziza JM, Arlaud J, Labussiere AS, Desvaux A, Baty V, Blanche P, Schaeffer A, Piette JC, Guillevin L, Boissonnas A, Christoforov B (2003) Reactive hemophagocytic syndrome in adult systemic disease: report of 26 cases and literature review. Arthritis Rheum 49:633–639
    • View reference on publisher's website
    • View reference on PubMed
  16. Imashuku S (2000) Advances in the management of hemophagocytic lymphohistiocytosis. Int J Hematol 72:1–11
    • View reference on PubMed
  17. Peigne V, Rusinova K, Karlin L, Darmon M, Fermand JP, Schlemmer B, Azoulay E (2009) Continued survival gains in recent years among critically ill myeloma patients. Intensive Care Med 35:512–518
  18. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22:707–710
  19. Francois B, Trimoreau F, Vignon P, Fixe P, Praloran V, Gastinne H (1997) Thrombocytopenia in the sepsis syndrome: role of hemophagocytosis and macrophage colony-stimulating factor. Am J Med 103:114–120
    • View reference on publisher's website
    • View reference on PubMed
  20. Yang K, Azoulay E, Attalah L, Zahar JR, Van de Louw A, Cerf C, Soussy CJ, Duvaldestin P, Brochard L, Brun-Buisson C, Harf A, Delclaux C (2003) Bactericidal activity response of blood neutrophils from critically ill patients to in vitro granulocyte colony-stimulating factor stimulation. Intensive Care Med 29:396–402
    • View reference on PubMed
  21. Delclaux C, Azoulay E (2003) Inflammatory response to infectious pulmonary injury. Eur Respir J Suppl 42:10s–14s
    • View reference on publisher's website
    • View reference on PubMed
  22. Azoulay E, Delclaux C (2004) Is there a place for granulocyte colony-stimulating factor in non-neutropenic critically ill patients? Intensive Care Med 30:10–17
  23. Le Tulzo Y, Pangault C, Amiot L, Guilloux V, Tribut O, Arvieux C, Camus C, Fauchet R, Thomas R, Drenou B (2004) Monocyte human leukocyte antigen-DR transcriptional downregulation by cortisol during septic shock. Am J Respir Crit Care Med 169:1144–1151
    • View reference on publisher's website
    • View reference on PubMed
  24. Oksenhendler E, Boulanger E, Galicier L, Du MQ, Dupin N, Diss TC, Hamoudi R, Daniel MT, Agbalika F, Boshoff C, Clauvel JP, Isaacson PG, Meignin V (2002) High incidence of Kaposi sarcoma-associated herpesvirus-related non-Hodgkin lymphoma in patients with HIV infection and multicentric Castleman disease. Blood 99:2331–2336
    • View reference on publisher's website
    • View reference on PubMed
  25. Scott D, Cabral L, Harrington WJ Jr (2001) Treatment of HIV-associated multicentric Castleman’s disease with oral etoposide. Am J Hematol 66:148–150
    • View reference on publisher's website
    • View reference on PubMed
  26. Fardet L, Coppo P, Kettaneh A, Dehoux M, Cabane J, Lambotte O (2008) Low glycosylated ferritin, a good marker for the diagnosis of hemophagocytic syndrome. Arthritis Rheum 58:1521–1527
    • View reference on publisher's website
    • View reference on PubMed
  27. Jones AE, Trzeciak S, Kline JA (2009) The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation. Crit Care Med 37:1649–1654
    • View reference on publisher's website
    • View reference on PubMed
  28. Azoulay E, Recher C, Alberti C, Soufir L, Leleu G, Le Gall JR, Fermand JP, Schlemmer B (1999) Changing use of intensive care for hematological patients: the example of multiple myeloma. Intensive Care Med 25:1395–1401
  29. Imashuku S, Hibi S, Ohara T, Iwai A, Sako M, Kato M, Arakawa H, Sotomatsu M, Kataoka S, Asami K, Hasegawa D, Kosaka Y, Sano K, Igarashi N, Maruhashi K, Ichimi R, Kawasaki H, Maeda N, Tanizawa A, Arai K, Abe T, Hisakawa H, Miyashita H, Henter JI (1999) Effective control of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis with immunochemotherapy. Histiocyte Society. Blood 93:1869–1874
    • View reference on PubMed

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