Diagnosis and treatment of haemophagocytic lymphohistiocytosis

Czech version

Authors: J. Starý
Authors‘ workplace: Klinika dětské hematologie a onkologie 2. LF UK a FN Motol, Praha
Published in: Transfuze Hematol. dnes,30, 2024, No. 3, p. 143-150.
Category: Review/Educational Papers
doi: https://doi.org/10.48095/cctahd2024prolekare.cz12

Overview

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome induced by excessive activation of lymphocytes and macrophages producing a cytokine storm. The result may be life-threatening organ damage. HLH develops in patients with genetic abnormalities, haematological malignancies, chronic inflammatory conditions, or infections. The most frequent clinical and laboratory features are fever, cytopenia, splenomegaly, hyperferritinemia, and transaminitis. Early identification of a HLH trigger, such as malignancy or viral infection, is crucial for improving patient outcomes. Treatment has to be frequently started before the diagnosis of a predisposing condition. The treatment of first choice in such situations may involve the combination of corticosteroids and anakinra. Patients with primary HLH require intensive therapy consisting of corticosteroids and etoposide followed by allogeneic hematopoietic stem cell transplantation.

Keywords:

diagnosis – therapy – primary haemophagocytic lymphohistiocytosis – secondary haemophagocytic lymphohistiocytosis

Sources

1. Canna SW, Cron RQ. Highways to hell: Mechanism-based management of cytokine storm syndrome. J Allergy Clin Immunol. 2020; 146: 949–959.

2. Hines MR, von Bahr Greenwood T, Beutel K, et al. Consensus-based guidelines for the recognition, diagnosis, and management of hemophagocytic lymphohistiocytosis in critically ill children and adults. Crit Care Med. 2022; 50: 860–872.

3. Canna SW, Marsh RA. Pediatric hemophagocytic lymphohistiocytosis. Blood. 2020; 35: 1332–1343.

4. La Rosée P, Horne AC, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019; 133: 2465–2477.

5. Henter JI, Horne A, Arico M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007; 48: 124–131.

6. El-Mallawany NK, Curry CV, Allen CE. Haemophagocytic lymphohistiocytosis and Epstein-Barr virus: a complex relationship with diverse origins, expression and outcomes. Br J Haematol. 2022; 196: 31–44.

7. Kumar A, Cournoyer E, Naymagon L. Inflamed-HLH, MAS, or something else? Hematology Am Soc Hematol Edu Program. 2023; 1: 31–36.

8. Löfstedt AH, Jäderssten M, Meeths M, et al. Malignancy-associated hemophagocytic lymphohistiocytosis in Sweden: incidence, clinical characteristics and survival. Blood. 2024; 143: 233–242.

9. Zoref-Lorenz A, Murakami J, Hofstetter L, et al. An improved index for diagnosis and mortality prediction in malignancy-associated hemophagocytic lymphohistiocytosis. Blood. 2022; 139: 1098–1110.

10. Bloch C, de Saint-Basile G, Hermine O, et al. A predictive score based on cytokines, CD4/CD8 ratio and age predicts hematological neoplasm-associated hemophagocytic lymphohistiocytosis. Blood. 2023; 142 (Suppl 1): 1164.

11. Shakoory B, Geerlinks A, Wilejto M, et al. The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Ann Rheum Dis. 2023; 82: 1271–1285.

12. Fardet L, Galicier L, Lambotte O, et al. Development and validation of the HScore, a score for the diagnosis of hemophagocytic lymphohistiocytosis in adult and pediatric patients. Am J Clin Pathol. 2016; 145: 862–870.

13. Triggianese P, Vitale A, Lopalco G, et al. Clinical and laboratory features associated with macrophage activation syndrome in Still’s disease: data from the internationl AIDA network Still’s disease registry. Int Emergency Med. 2023; 18: 2231–2243.

14. Bloch C, Jais JP, Gil M, et al. Severe adult hemophagocytic lymphohistiocytosis correlates with HLH-related gene variants. J Allergy Clin Immunol. 2024; 153: 256–264.

15. Hines MR, Knight TE, McNerney KO, et al. Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. Transpl and Cellular Therapy. 2023; 29: 438.e1–438.e16

16. Zoref-Lorenz A, Ellis M, Jordan MB. Inpatient recognition and management of HLH. Hematology Am Soc Hematol Edu Program. 2023; 1: 259–266.

17. Ehl S, Astigarraga I, von Bahr Greenwood T, et al. Recommendations for the use of etoposide-based therapy and bone marrow transplantation for the treatment of HLH: consensus statements by the HLH steering committee of the Histiocyte society. J Allergy Clin Immunol Pract. 2018; 6: 1508–1517.

18. Böhm S, Wustrau K, Pachlopnik Schmid J, et al. Survival in primary hemophagocytic lymphohistiocytosis 2016-2021: etoposide is better than its reputation. Blood. 2024; 143 (10): 872–881.

19. Verkamp B, Zoref-Lorenz A, Francisco B, et al. Early response markers predict survival after etoposide-based therapy of hemophagocytic lymphohistiocytosis. Blood Adv. 2023; 7: 7258–7269.

20. Allen CE, Chandrakasan S, Jordan MB, et al. Real-world treatment patterns and outcomes among patients with secondary hemophagocytic lymphohistiocytosis treated with emapalumab in the United States: The real-HLH study. Blood. 2023; 142 (Suppl 1): 3909.

21. Ehl S, Greenwood TB, Bergsten E, et al. Is neutralization of IFN- g sufficient to control inflammation in HLH? Ped Blood Cancer. 2020; 68: e28886.

22. Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Ann Rev Med. 2012; 63: 233–246.

23. Ravelli A, Minoia F, Davi S, et al. 2016 classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Ann Rheum Dis. 2016; 75: 481–489.

24. Parodi A, Davi S, Pringe DAB, et al. Macrophage activation syndrome in juvenile systemic lupus erythematodes: a multinational multicenter study of thirty eight patients. Arthritis Rheum. 2009; 60: 3388–3399

PODĚKOVÁNÍ

Za pomoc při přípravě manuskriptu děkuji Aleši Lukšovi, za fotografii hemofagocytujícího makrofágu MUDr. Eleně Vodičkové.

ČESTNÉ PROHLÁŠENÍ

Autor práce prohlašuje, že v souvislosti s tématem, vznikem a publikací tohoto článku není ve střetu zájmu a vznik ani publikace článku nebyly podpořeny žádnou farmaceutickou firmou.

Do redakce doručeno dne: 8. 2. 2024.

Přijato po recenzi dne: 29. 2. 2024.

prof. MUDr. Jan Starý, DrSc.

Klinika dětské hematologie a onkologie

2. LF UK a FN Motol, Praha

e-mail: jan.stary@lfmotol.cuni.cz