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A case of hemophagocytic lymphohistiocytosis with a significant response to baricitinib: a first report with review of literature

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Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a febrile disease with hyperinflammation characterized by activated macrophages with phagocytosis. The treatment strategy of secondary HLH has not been clearly established. Because of the high mortality rate and poor prognosis of HLH, alternative treatment strategies have been sought in treatment-resistant cases. Recently, there have been several reports that ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor, was effective against secondary HLH. Since the pathogenesis of HLH involves the overproduction of cytokines and JAK transmits a variety of cytokine signals, JAK inhibitors are thought to be effective in HLH. We herein report a case of HLH that was refractory to glucocorticoids, cyclosporine, and etoposide but responded to baricitinib. In the field of rheumatology, treatment-resistant cases of secondary HLH remain unmet needs. This is the first report to show that baricitinib was effective in a case of HLH. The accumulation of more cases in the future may prove that baricitinib is a potent agent for treating HLH.

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References

  1. Allen CE, McClain KL (2015) Pathophysiology and epidemiology of hemophagocytic lymphohistiocytosis. Hematol Am Soc Hematol Educ Program 2015:177–182. https://doi.org/10.1182/asheducation-2015.1.177

    Article  Google Scholar 

  2. Henter J-I, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S et al (2007) HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 48:124–131. https://doi.org/10.1002/pbc.21039

    Article  PubMed  Google Scholar 

  3. La Rosée P, Horne A, Hines M, von Bahr GT, Machowicz R, Berliner N et al (2019) Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood 133:2465–2477. https://doi.org/10.1182/blood.2018894618

    Article  CAS  PubMed  Google Scholar 

  4. Schram AM, Comstock P, Campo M, Gorovets D, Mullally A, Bodio K et al (2016) Haemophagocytic lymphohistiocytosis in adults: a multicentre case series over 7 years. Br J Haematol 172:412–419. https://doi.org/10.1111/bjh.13837

    Article  CAS  PubMed  Google Scholar 

  5. Rivière S, Galicier L, Coppo P, Marzac C, Aumont C, Lambotte O, Fardet L (2014) Reactive hemophagocytic syndrome in adults: a retrospective analysis of 162 patients. Am J Med 127:1118–1125. https://doi.org/10.1016/j.amjmed.2014.04.034

    Article  PubMed  Google Scholar 

  6. Parikh SA, Kapoor P, Letendre L, Kumar S, Wolanskyj AP (2014) Prognostic factors and outcomes of adults with hemophagocytic lymphohistiocytosis. Mayo Clin Proc 894:484–492. https://doi.org/10.1016/j.mayocp.2013.12.012

    Article  Google Scholar 

  7. Keenan C, Nichols KE, Albeituni S (2021) Use of the JAK inhibitor ruxolitinib in the treatment of hemophagocytic lymphohistiocytosis. Front Immunol 12:614704. https://doi.org/10.3389/fimmu.2021.614704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sin JH, Zangardi ML (2019) Ruxolitinib for secondary hemophagocytic lymphohistiocytosis: first case report. Hematol Oncol Stem Cell Ther 12:166–170. https://doi.org/10.1016/j.hemonc.2017.07.002

    Article  CAS  PubMed  Google Scholar 

  9. Ahmed A, Merrill SA, Alsawah F, Bockenstedt P, Campagnaro E, Devata S et al (2019) Ruxolitinib in adult patients with secondary haemophagocytic lymphohistiocytosis: an open-label, single-centre, pilot trial. Lancet Haematol 6:e630–e637. https://doi.org/10.1016/S2352-3026(19)30156-5

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wang J, Wang Y, Wu L, Wang X, Jin Z, Gao Z et al (2020) Ruxolitinib for refractory/relapsed hemophagocytic lymphohistiocytosis. Haematologica 105:e210–e212. https://doi.org/10.3324/haematol.2019.222471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hansen S, Alduaij W, Biggs CM, Belga S, Luecke K, Merkeley H et al (2021) Ruxolitinib as adjunctive therapy for secondary hemophagocytic lymphohistiocytosis: a case series. Eur J Haematol 106:654–661. https://doi.org/10.1111/ejh.13593

    Article  CAS  PubMed  Google Scholar 

  12. Ramos-Casals M, Brito-Zerón P, López-Guillermo A, Khamashta MA, Bosch X (2014) Adult haemophagocytic syndrome. Lancet 383:1503–1516. https://doi.org/10.1016/S0140-6736(13)61048-X

    Article  PubMed  Google Scholar 

  13. Akashi K, Hayashi S, Gondo H, Mizuno S, Harada M, Tamura K et al (1994) Involvement of interferon-γ and macrophage colony-stimulating factor in pathogenesis of haemophagocytic lymphohistiocytosis in adults. Br J Haematol 87:243–250. https://doi.org/10.1111/j.1365-2141.1994.tb04905.x

    Article  CAS  PubMed  Google Scholar 

  14. Osugi Y, Hara J, Tagawa S, Takai K (1997) Cytokine production regulating Th1 and Th2 cytokines in hemophagocytic lymphohistiocytosis. Blood 89:4100–4103. https://doi.org/10.1182/blood.V89.11.4100

    Article  CAS  PubMed  Google Scholar 

  15. Takada H, Ohga S, Mizuno Y, Suminoe A, Matsuzaki A, Ihara K et al (1999) Oversecretion of IL-18 in haemophagocytic lymphohistiocytosis: a novel marker of disease activity. Br J Haematol 106:182–189. https://doi.org/10.1046/j.1365-2141.1999.01504.x

    Article  CAS  PubMed  Google Scholar 

  16. Yang SL, Xu XJ, Tang YM, Song H, Xu WQ, Zhao FY, Shen DY (2016) Associations between inflammatory cytokines and organ damage in pediatric patients with hemophagocytic lymphohistiocytosis. Cytokine 85:14–17. https://doi.org/10.1016/j.cyto.2016.05.022

    Article  CAS  PubMed  Google Scholar 

  17. Chandrakasan S, Filipovich AH (2013) Hemophagocytic lymphohistiocytosis: advances in pathophysiology, diagnosis, and treatment. J Pediatr 163:1253–1259. https://doi.org/10.1016/j.jpeds.2013.06.053

    Article  PubMed  Google Scholar 

  18. Das R, Guan P, Sprague L, Verbist K, Tedrick P, An QA et al (2016) Janus kinase inhibition lessens inflammation and ameliorates disease in murine models of hemophagocytic lymphohistiocytosis. Blood 127:1666–1675. https://doi.org/10.1182/blood-2015-12-684399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Albeituni S, Verbist KC, Tedrick PE, Tillman H, Picarsic J, Bassett R et al (2019) Mechanisms of action of ruxolitinib in murine models of hemophagocytic lymphohistiocytosis. Blood 134:147–159. https://doi.org/10.1182/blood.2019000761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O’Shea JJ (2017) JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov 16:843–862. https://doi.org/10.1038/nrd.2017.201

    Article  CAS  PubMed  Google Scholar 

  21. Gatti M, Turrini E, Raschi E, Sestili P, Fimognari C (2021) Janus kinase inhibitors and coronavirus disease (COVID)-19: rationale, clinical evidence and safety issues. Pharmaceuticals (Basel) 14:738. https://doi.org/10.3390/ph14080738

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Rheumatology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, 1-9-6 Sendamachi, Naka-ku, 730-8619, Hiroshima, Japan

    Kensuke Irino, Shota Nakano & Takuya Sawabe

  2. Department of Hematology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan

    Fumiaki Jinnouchi

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  1. Kensuke Irino
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  2. Fumiaki Jinnouchi
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Correspondence to Kensuke Irino.

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Irino, K., Jinnouchi, F., Nakano, S. et al. A case of hemophagocytic lymphohistiocytosis with a significant response to baricitinib: a first report with review of literature. Clin Rheumatol 42, 1959–1963 (2023). https://doi.org/10.1007/s10067-023-06579-8

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  • DOI: https://doi.org/10.1007/s10067-023-06579-8

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