Hayden A, Park S, Giustini D, Lee AY, Chen LY (2016) Hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) in adults: a systematic scoping review. Blood Rev 30(6):411–420. https://doi.org/10.1016/j.blre.2016.05.001

Article  PubMed  Google Scholar 

Janka GE, Lehmberg K (2013) Hemophagocytic lymphohistiocytosis: pathogenesis and treatment. Hematol Am Soc Hematol Educ Program 2013:605–611. https://doi.org/10.1182/asheducation-2013.1.605

Article  Google Scholar 

Risma KA, Marsh RA (2019) Hemophagocytic Lymphohistiocytosis: clinical presentations and diagnosis. J Allergy Clin Immunol Pract 7(3):824–832. https://doi.org/10.1016/j.jaip.2018.11.050

Article  PubMed  Google Scholar 

Topalian SL, Taube JM, Anders RA, Pardoll DM (2016) Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer 16(5):275–287. https://doi.org/10.1038/nrc.2016.36

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kwok G, Yau TC, Chiu JW, Tse E, Kwong YL (2016) Pembrolizumab (Keytruda). Hum Vaccin Immunother 12(11):2777–2789. https://doi.org/10.1080/21645515.2016.1199310

Article  PubMed  PubMed Central  Google Scholar 

La Rosée P, Horne A, Hines M, von Bahr Greenwood T, Machowicz R, Berliner N et al (2019) Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood 133(23):2465–2477. https://doi.org/10.1182/blood.2018894618

Article  CAS  PubMed  Google Scholar 

Noseda R, Bertoli R, Müller L, Ceschi A (2019) Haemophagocytic lymphohistiocytosis in patients treated with immune checkpoint inhibitors: analysis of WHO global database of individual case safety reports. J Immunother Cancer 7(1):117. https://doi.org/10.1186/s40425-019-0598-9

Article  PubMed  PubMed Central  Google Scholar 

Ramos-Casals M, Brito-Zerón P, López-Guillermo A, Khamashta MA, Bosch X (2014) Adult haemophagocytic syndrome. Lancet 383(9927):1503–1516. https://doi.org/10.1016/S0140-6736(13)61048-X

Article  PubMed  Google Scholar 

Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D et al (2014) Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol 66(9):2613–2620. https://doi.org/10.1002/art.38690

Article  PubMed  Google Scholar 

Imashuku S, Morimoto A, Ishii E (2021) Virus-triggered secondary hemophagocytic lymphohistiocytosis. Acta Paediatr 110(10):2729–2736. https://doi.org/10.1111/apa.15973

Article  CAS  PubMed  Google Scholar 

Lehmberg K, Sprekels B, Nichols KE, Woessmann W, Müller I, Suttorp M et al (2015) Malignancy-associated haemophagocytic lymphohistiocytosis in children and adolescents. Br J Haematol 170(4):539–549. https://doi.org/10.1111/bjh.13462

Article  PubMed  Google Scholar 

Shah D, Shrestha R, Ramlal R, Hatton J, Saeed H (2017) Pembrolizumab associated hemophagocytic lymphohistiocytosis. Ann Oncol 28(6):1403. https://doi.org/10.1093/annonc/mdx113

Article  CAS  PubMed  Google Scholar 

Malissen N, Lacotte J, Du-Thanh A, Gaudy-Marqueste C, Guillot B, Grob JJ (2017) Macrophage activation syndrome: a new complication of checkpoint inhibitors. Eur J Cancer 77:88–89. https://doi.org/10.1016/j.ejca.2017.02.016

Article  CAS  PubMed  Google Scholar 

Liu P, Pan X, Chen C, Niu T, Shuai X, Wang J et al (2020) Nivolumab treatment of relapsed/refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in adults. Blood 135(11):826–833. https://doi.org/10.1182/blood.2019003886

Article  CAS  PubMed  Google Scholar 

Wang H, Xiong L, Tang W, Zhou Y, Li F (2017) A systematic review of malignancy-associated hemophagocytic lymphohistiocytosis that needs more attentions. Oncotarget 8(35):59977–59985. https://doi.org/10.18632/oncotarget.19230

Article  PubMed  PubMed Central  Google Scholar 

Cho J, Kim HS, Ku BM, Choi YL, Cristescu R, Han J et al (2019) Pembrolizumab for patients with refractory or relapsed thymic epithelial Tumor: an open-label phase II trial. J Clin Oncol 37(24):2162–2170. https://doi.org/10.1200/JCO.2017.77.3184

Article  CAS  PubMed  Google Scholar 

Bergsten E, Horne A, Arico M, Astigarraga I, Egeler RM, Filipovich AH et al (2017) Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood 130(25):2728–2738. https://doi.org/10.1182/blood-2017-06-788349

Article  CAS  PubMed  PubMed Central  Google Scholar 

Henter JI, 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(2):124–131. https://doi.org/10.1002/pbc.21039

Article  PubMed  Google Scholar 

Zoref-Lorenz A, Murakami J, Hofstetter L, Iyer S, Alotaibi AS, Mohamed SF et al (2022) An improved index for diagnosis and mortality prediction in malignancy-associated hemophagocytic lymphohistiocytosis. Blood 139(7):1098–1110. https://doi.org/10.1182/blood.2021012764

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ramos-Ruperto L, Busca-Arenzana C, Valdivieso J, López-Granados E, Robles-Marhuenda Á (2021) COVID-19 and Pembrolizumab-Induced secondary hemophagocytic lymphohistiocytosis: a Case Report. SN Compr Clin Med 3(6):1412–1415. https://doi.org/10.1007/s42399-021-00882-8

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu LL, Skribek M, Harmenberg U, Gerling M (2023) Systemic inflammatory syndromes as life-threatening side effects of immune checkpoint inhibitors: case report and systematic review of the literature. J Immunother Cancer 11(3):e005841. https://doi.org/10.1136/jitc-2022-005841

Article  PubMed  PubMed Central  Google Scholar 

Kalmuk J, Puchalla J, Feng G, Giri A, Kaczmar J (2020) Pembrolizumab-induced hemophagocytic lymphohistiocytosis: an immunotherapeutic challenge. Cancers Head Neck 5:3. https://doi.org/10.1186/s41199-020-0050-3

Article  PubMed  PubMed Central  Google Scholar 

Gordon SR, Maute RL, Dulken BW, Hutter G, George BM, McCracken MN et al (2017) PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature 545(7655):495–499. https://doi.org/10.1038/nature22396

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL (2011) How I treat hemophagocytic lymphohistiocytosis. Blood 118(15):4041–4052. https://doi.org/10.1182/blood-2011-03-278127

Article  CAS  PubMed  PubMed Central  Google Scholar 

Al-Samkari H, Snyder GD, Nikiforow S, Tolaney SM, Freedman RA, Losman JA (2019) Haemophagocytic lymphohistiocytosis complicating pembrolizumab treatment for metastatic Breast cancer in a patient with the PRF1A91V gene polymorphism. J Med Genet 56(1):39–42. https://doi.org/10.1136/jmedgenet-2018-105485

Article  CAS  PubMed  Google Scholar 

Brisse E, Wouters CH, Matthys P (2016) Advances in the pathogenesis of primary and secondary haemophagocytic lymphohistiocytosis: differences and similarities. Br J Haematol 174(2):203–217. https://doi.org/10.1111/bjh.14147

Article  CAS  PubMed  Google Scholar 

Henter JI, Aricò M, Egeler RM, Elinder G, Favara BE, Filipovich AH et al (1997) HLH-94: a treatment protocol for hemophagocytic lymphohistiocytosis. HLH study Group of the Histiocyte Society. Med Pediatr Oncol 28(5):342–347. https://doi.org/10.1002/(sici)1096-911x(199705)28:5%3C342::aid-mpo3%3E3.0.co;2-h

Trottestam H, Horne A, Aricò M, Egeler RM, Filipovich AH, Gadner H et al (2011) Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. Blood 118(17):4577–4584. https://doi.org/10.1182/blood-2011-06-356261

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dufranc E, Del Bello A, Belliere J, Kamar N, Faguer S (2020) TAIDI (Toulouse Acquired Immune Deficiency and Infection) study group. IL6-R blocking with tocilizumab in critically ill patients with hemophagocytic syndrome. Crit Care 24(1):166. https://doi.org/10.1186/s13054-020-02878-7

Article  PubMed  PubMed Central  Google Scholar 

Marsh RA, Allen CE, McClain KL, Weinstein JL, Kanter J, Skiles J et al (2013) Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab. Pediatr Blood Cancer 60(1):101–109. https://doi.org/10.1002/pbc.24188

Article  CAS  PubMed  Google Scholar 

Rajasekaran S, Kruse K, Kovey K, Davis AT, Hassan NE, Ndika AN et al (2014) Therapeutic role of anakinra, an interleukin-1 receptor antagonist, in the management of secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction/macrophage activating syndrome in critically ill children*. Pediatr Crit Care Med 15(5):401–408. https://doi.org/10.1097/PCC.0000000000000078

Article  PubMed  Google Scholar 

Fukaya S, Yasuda S, Hashimoto T, Oku K, Kataoka H, Horita T et al (2008) Clinical features of haemophagocytic syndrome in patients with systemic autoimmune Diseases: analysis of 30 cases. Rheumatology (Oxford) 47(11):1686–1691. https://doi.org/10.1093/rheumatology/ken342Epub 2008 Sep 9. PMID: 18782855

Article  CAS  PubMed  Google Scholar 

Lin TF, Ferlic-Stark LL, Allen CE, Kozinetz CA, McClain KL (2011) Rate of decline of ferritin in patients with hemophagocytic lymphohistiocytosis as a prognostic variable for mortality. Pediatr Blood Cancer 56(1):154–155. https://doi.org/10.1002/pbc.22774

Article  PubMed