Recent advances in the treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome.
Journal
Current opinion in allergy and clinical immunology
ISSN: 1473-6322
Titre abrégé: Curr Opin Allergy Clin Immunol
Pays: United States
ID NLM: 100936359
Informations de publication
Date de publication:
01 12 2022
01 12 2022
Historique:
pubmed:
8
10
2022
medline:
1
11
2022
entrez:
7
10
2022
Statut:
ppublish
Résumé
The approach to treating patients with hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) has shifted in recent years with the aim to limit exposure to genotoxic agents, such as etoposide, yet dampen hyperinflammation by targeting the activity of specific HLH/MAS-associated cytokines. In this review, we discuss recent efforts to reduce the dose of etoposide and/or incorporate cytokine-targeted therapies for the treatment of HLH/MAS. There is emerging evidence that reduced-dose etoposide and/or cytokine-targeted therapies, including agents that neutralize or inhibit signaling induced by interferon gamma, interleukin (IL)-1, IL-18, and IL-6, can effectively ameliorate the clinical and laboratory manifestations of HLH/MAS and improve overall outcomes. The application of novel regimens containing lower doses of etoposide and/or cytokine-directed agents to treat HLH/MAS holds potential to dampen inflammation while minimizing therapy-associated toxicities. Nevertheless, further research is needed to better understand, which patients represent the most appropriate candidates to receive cytokine-targeted therapies, elucidate the optimal timing and dose of these therapies, and decipher whether they should be administered alone or in combination with conventional HLH-directed therapies, such as dexamethasone and standard-dose or reduced-dose etoposide.
Identifiants
pubmed: 36206094
doi: 10.1097/ACI.0000000000000865
pii: 00130832-202212000-00005
doi:
Substances chimiques
Etoposide
6PLQ3CP4P3
Cytokines
0
Interferon-gamma
82115-62-6
Interleukin-1
0
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
364-370Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Références
Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr 2007; 166:95–109.
Henter JI, Elinder G, Söder O, et al. Hypercytokinemia in familial hemophagocytic lymphohistiocytosis. Blood 1991; 78:2918–2922.
Meyer LK, Verbist KC, Albeituni S, et al. JAK/STAT pathway inhibition sensitizes CD8 T cells to dexamethasone-induced apoptosis in hyperinflammation. Blood 2020; 136:657–668.
Yang SL, Xu XJ, Tang YM, et al. Associations between inflammatory cytokines and organ damage in pediatric patients with hemophagocytic lymphohistiocytosis. Cytokine 2016; 85:14–17.
Moshous D, Briand C, Castelle M, et al. Alemtuzumab as first line treatment in children with familial lymphohistiocytosis. Blood 2019; 134: (Supplement_1): 80.
Trottestam H, Horne A, Aricò M, et al. Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. Blood 2011; 118:4577–4584.
Bergsten E, Horne A, Aricó M, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood 2017; 130:2728–2738.
Horne A, von Bahr Greenwood T, Chiang SCC, et al. Efficacy of moderately dosed etoposide in macrophage activation syndrome-hemophagocytic lymphohistiocytosis. J Rheumatol 2021; 48:1596–1602.
Padmanabhan A, Connelly-Smith L, Aqui N, et al. Guidelines on the use of therapeutic apheresis in clinical practice - evidence-based approach from the writing committee of the american society for apheresis: the eighth special issue. J Clin Apher 2019; 34:171–354.
Yuan YH, Zhang H, Xiao ZH, et al. Efficacy of plasma exchange in children with severe hemophagocytic syndrome: a prospective randomized controlled trial. Zhongguo Dang Dai Er Ke Za Zhi 2022; 24:249–254.
Rademacher JG, Wulf G, Koziolek MJ, et al. Cytokine adsorption therapy in lymphoma-associated hemophagocytic lymphohistiocytosis and allogeneic stem cell transplantation. J Artif Organs 2021; 24:402–406.
Bottari G, Murciano M, Merli P, et al. Hemoperfusion with CytoSorb to manage multiorgan dysfunction in the spectrum of hemophagocytic lymphohistiocytosis syndrome in critically ill children. Blood Purif 2022; 51:417–424.
Ceruti S, Glotta A, Adamson H, et al. Hemoadsorption treatment with CytoSorb® in probable hemophagocytic lymphohistiocytosis: a role as adjunctive therapy? Case Rep Hematol 2021; 2021:5539126.
Binder D, van den Broek MF, Kägi D, et al. Aplastic anemia rescued by exhaustion of cytokine-secreting CD8+ T cells in persistent infection with lymphocytic choriomeningitis virus. J Exp Med 1998; 187:1903–1920.
Jordan MB, Hildeman D, Kappler J, Marrack P. An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder. Blood 2004; 104:735–743.
Pachlopnik Schmid J, Ho CH, Chrétien F, et al. Neutralization of IFNγ defeats haemophagocytosis in LCMV-infected perforin- and Rab27a-deficient mice. EMBO Mol Med 2009; 1:112–124.
FDA approval of emapalumab. Available at: https://www.fda.gov/drugs/fda-approves-emapalumab-hemophagocytic-lymphohistiocytosis .
Locatelli F, Jordan MB, Allen C, et al. Emapalumab in children with primary hemophagocytic lymphohistiocytosis. N Engl J Med 2020; 382:1811–1822.
Emapalumab clinical trials for MAS. Available at: https://clinicaltrials.gov/ct2/show/NCT05001737 . [Accessed 26th July 2022].
Das R, Guan P, Sprague L, et al. Janus kinase inhibition lessens inflammation and ameliorates disease in murine models of hemophagocytic lymphohistiocytosis. Blood 2016; 127:1666–1675.
Maschalidi S, Sepulveda FE, Garrigue A, et al. Therapeutic effect of JAK1/2 blockade on the manifestations of hemophagocytic lymphohistiocytosis in mice. Blood 2016; 128:60–71.
Albeituni S, Verbist KC, Tedrick PE, et al. Mechanisms of action of ruxolitinib in murine models of hemophagocytic lymphohistiocytosis. Blood 2019; 134:147–159.
Keenan C, Nichols KE, Albeituni S. Use of the JAK inhibitor ruxolitinib in the treatment of hemophagocytic lymphohistiocytosis. Front Immunol 2021; 12:614704.
Zhang Q, Zhao YZ, Ma HH, et al. A study of ruxolitinib response-based stratified treatment for pediatric hemophagocytic lymphohistiocytosis. Blood 2022; 139:3493–3504.
Joly JA, Vallée A, Bourdin B, et al. Combined IFNγ and JAK inhibition to treat hemophagocytic lymphohistiocytosis in mice. J Allergy Clin Immunol 2022; doi: 10.1016/j.jaci.2022.07.026. [Epub ahead of print].
doi: 10.1016/j.jaci.2022.07.026.
Triebwasser MP, Barrett DM, Bassiri H, et al. Combined use of emapalumab and ruxolitinib in a patient with refractory hemophagocytic lymphohistiocytosis was safe and effective. Pediatr Blood Cancer 2021; 68:e29026.
Arnold DD, Yalamanoglu A, Boyman O. Systematic review of safety and efficacy of IL-1-targeted biologics in treating immune-mediated disorders. Front Immunol 2022; 13:888392.
Shakoory B, Carcillo JA, Chatham WW, et al. Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome: reanalysis of a prior phase III trial. Crit Care Med 2016; 44:275–281.
Bami S, Vagrecha A, Soberman D, et al. The use of anakinra in the treatment of secondary hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2020; 67:e28581.
Phadke O, Rouster-Stevens K, Giannopoulos H, et al. Intravenous administration of anakinra in children with macrophage activation syndrome. Pediatr Rheumatol Online J 2021; 19:98.
Charlesworth JEG, Wilson S, Qureshi A, et al. Continuous intravenous anakinra for treating severe secondary haemophagocytic lymphohistiocytosis/macrophage activation syndrome in critically ill children. Pediatr Blood Cancer 2021; 68:e29102.
Kavirayani A, Charlesworth JEG, Segal S, et al. The Lazarus effect of very high-dose intravenous anakinra in severe nonfamilial CNS-HLH. Lancet Rheumatol 2020; 2:e736–e738.
Eloseily EM, Weiser P, Crayne CB, et al. Benefit of anakinra in treating pediatric secondary hemophagocytic lymphohistiocytosis. Arthritis Rheumatol 2020; 72:326–334.
Kostik MM, Isupova EA, Belozerov K, et al. Standard and increased canakinumab dosing to quiet macrophage activation syndrome in children with systemic juvenile idiopathic arthritis. Front Pediatr 2022; 10:894846.
Takada H, Nomura A, Ohga S, Hara T. Interleukin-18 in hemophagocytic lymphohistiocytosis. Leuk Lymphoma 2001; 42:21–28.
Shimizu M, Nakagishi Y, Inoue N, et al. Interleukin-18 for predicting the development of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Clin Immunol 2015; 160:277–281.
Geerlinks AV, Dvorak AM. XDT Consortium. A case of XIAP deficiency successfully managed with Tadekinig Alfa (rhIL-18BP). J Clin Immunol 2022; 42:901–903.
Dufranc E, Del Bello A, Belliere J. Ts group. IL6-R blocking with tocilizumab in critically ill patients with hemophagocytic syndrome. Crit Care 2020; 24:166.