Development and Initial Validation of the Macrophage Activation Syndrome/Primary Hemophagocytic Lymphohistiocytosis Score, a Diagnostic Tool that Differentiates Primary Hemophagocytic Lymphohistiocytosis from Macrophage Activation Syndrome

Minoia, Francesca; Bovis, Francesca; Davì, Sergio; Insalaco, Antonella; Lehmberg, Kai; Shenoi, Susan; Weitzman, Sheila; Espada, Graciela; Gao, Yijin; Antón, Jordi; Kitoh, Toshiyuki; Kasapçopur, Özgür; Sanner, Helga; Merino, Rosa; Astigarraga, Itziar; Alessio, Maria; Jeng, Michael; Chasnyk, Vyacheslav; Nichols, Kim E.; Zeng, Huasong; Li, Caifeng; Micalizzi, Concetta; Ruperto, Nicolino; Martini, Alberto; Cron, Randy Q.; Ravelli, Angelo; Horne, AnnaCarin; Abinun, Mario; Aggarwal, Amita; Akikusa, Jonathan; Al‐Mayouf, Sulaiman M.; Apaz, María Teresa; Avčin, Tadej; Ayaz, Nuray Aktay; Barone, Patrizia; Bica, Bianca; Bolt, Isabel; Breda, Luciana; Cimaz, Rolando; Corona, Fabrizia; Cuttica, Rubén; Dāvidsone, Zane; Cunto, Carmen De; Arocena, Jaime de Inocencio; Demirkaya, Erkan; Eisenstein, Eli M.; Enciso, Sandra; Fischbach, Michel; Frosch, Michael; Gallizzi, Romina; Gámir, María Luz Gámir; Griffin, Thomas A.; Grom, Alexei A.; Hashad, Soad; Hennon, Teresa; Henter, Jan‐Inge; Horneff, Gerd; Huber, Adam M.; Ilowite, Norman T.; Ioseliani, Maka; Kapović, Agneza Marija; Khubchandani, Raju; Koné‐Paut, Isabelle; Oliveira, Sheila Knupp Feitosa de; Lattanzi, Bianca; Lepore, Loredana; Lipton, Jeffrey M.; Magni‐Manzoni, Silvia; Maritsi, Despoina; McCurdy, Deborah; Miettunen, Päivi; Mulaosmanović, Velma; Nielsen, Susan; Özen, Seza; Pal, Priyankar; Prahalad, Sampath; Rigante, Donato; Rumba-Rozenfelde, Ingrīda; Russo, Ricardo; Magalhães, Cláudia Saad; Sewairi, Wafaa Mohamed Saad; Silva, Clóvis A.; Staņēvicha, Valda; Sterba, Gary; Stine, Kimo C.; Sušić, Gordana; Sztajnbok, Flávio; Takei, Syuji; Trauzeddel, Ralf; Tsitsami, Elena; Ünsal, Erbil; Uziel, Yosef; Vougiouka, Olga; Wallace, Carol A.; Weaver, Lehn K.; Weiss, Jennifer E.; Wouters, Carine; Wulffraat, Nico; Zletni, Mabruka A; Aricò, Maurizio; Egeler, R. Maarten; Filipovich, Alexandra H.; Gadner, Helmut; Imashuku, Shinsaku; Janka, Gritta; Ladisch, Stephan; McClain, Kenneth L.; Webb, David

doi:10.1016/j.jpeds.2017.06.005

Cited by 54 publications

(40 citation statements)

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“…Haemophagocytic lymphohistiocytosis (HLH) is a rare syndrome with severe clinical sequelae that result from a dysregulated, hyperinflammatory immune response 112 and can present in a primary (inherited) or a secondary form 113 . Secondary HLH is thought to occur in the con text of an underlying immunological condition and, in the setting of autoimmune and inflammatory disorders, is often referred to as macrophage activation syndrome (MAS).…”

Section: Car T Cell Therapy-related Hlhmentioning

confidence: 99%

“…The diagnosis of HLH is made on the basis of the presence of mutations associated with primary HLH (such as mutations in PRF1, UNC13D, or STX11) and/or clinical and laboratory criteria, such as fever, cytopenias, hypertriglyceridaemia, hypofibrinogenaemia, elevated serum levels of ferritin and liver enzymes, haemophago cytosis, low or absent NK cell activity, and/or elevated soluble IL2 receptor levels 113 . Differentiation of primary HLH from MAS can be difficult, and distinction of sec ondary CAR T cell related HLH-MAS from CRS-CRES can be even more challenging owing to the overlapping symptoms associated with these conditions 16,29,37,112 . Future studies to define the role of genetic testing and functional analyses of NK cells might help identify patients who are at a disproportionately higher risk of this complication of CAR T cell therapy 30 .…”

Section: Car T Cell Therapy-related Hlhmentioning

confidence: 99%

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Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy

et al. 2018

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In 2017, an autologous chimeric antigen receptor (CAR) T cell therapy indicated for children and young adults with relapsed and/or refractory CD19 acute lymphoblastic leukaemia became the first gene therapy to be approved in the USA. This innovative form of cellular immunotherapy has been associated with remarkable response rates but is also associated with unique and often severe toxicities, which can lead to rapid cardiorespiratory and/or neurological deterioration. Multidisciplinary medical vigilance and the requisite health-care infrastructure are imperative to ensuring optimal patient outcomes, especially as these therapies transition from research protocols to standard care. Herein, authors representing the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Stem Cell Transplantation (HSCT) Subgroup and the MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program have collaborated to provide comprehensive consensus guidelines on the care of children receiving CAR T cell therapy.

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Section: Car T Cell Therapy-related Hlhmentioning

confidence: 99%

Section: Car T Cell Therapy-related Hlhmentioning

confidence: 99%

Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy

et al. 2018

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“…Depending on continued disease activity, further treatment modalities could be added: canakinumab, tocilizumab, tumor necrosis factor‐α (TNF‐α) inhibitor, methotrexate or leflunomide. The long‐term usage of corticosteroids should be avoided due to many potential adverse effects . Methotrexate is the most frequently used disease‐modifying anti‐rheumatic drug (DMARD), followed by cyclosporine A, leflunomide and so on .…”

Section: Introductionmentioning

confidence: 99%

“…The long-term usage of corticosteroids should be avoided due to many potential adverse effects. 2,5,6 Methotrexate is the most frequently used disease-modifying anti-rheumatic drug (DMARD), followed by cyclosporine A, leflunomide and so on. 7 Proinflammatory cytokines including interleukin (IL)-1, IL-6 and IL-18 play an important role in the pathogenesis of the disease.…”

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confidence: 99%

Prognosis, complications and treatment response in systemic juvenile idiopathic arthritis patients: A single‐center experience

et al. 2019

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Aim Systemic juvenile idiopathic arthritis (sJIA) is a distinctive subtype of JIA characterized by systemic features and poor outcome. We aimed to investigate demographic and clinical features, long‐term treatment response and disease complications in a large sJIA cohort. Methods Patients diagnosed with sJIA followed up at a pediatric rheumatology outpatient department from January 2003 to December 2017 were included. Demographic and clinical features, long‐term treatment response and disease complications were retrospectively collected. Results A total of 168 sJIA patients (51.8% female, 48.2% male) were included: 31.5% with monocyclic, 13.7% polycyclic and 54.8% with persistent clinical course. Corticosteroids were initially used in all patients. Methotrexate was used in 75% and cyclosporine A was used in 17.3% patients. Biological drugs were used in 42.8% patients; etanercept in 29.7%, anakinra in 16%, canakinumab in 16%, tocilizumab in 10% patients. Remission off medication was achieved in 82 (48.8%). Macrophage activation syndrome (MAS) was present in 11.9%, growth retardation in 11.3% patients. Eight percent (4/50) of patients had low bone mineral density. Three patients (1.78%) died due to MAS secondary multiorgan insufficiency and infection. Conclusion The disease is characterized with diverse clinical presentation and possibly severe complications. MAS complicated with multiorgan insufficiency is the major mortality factor. Corticosteroids represent the mainstay of the initial treatment. In patients resistant to classic treatment, biological drugs should be timely introduced.

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“…In developing the HScore, which was designed to distinguish reactive hemophagocytic syndromes in adults, Fardet et al included only 16 patients (5%) with either SLE or AOSD . Most relevant to this current discussion, the MH score, designed to distinguish MAS from familial HLH, was validated as a means to determine need for further functional and genetic testing, since it emphasizes age, degree of cytopenias, splenomegaly, and coagulopathy as distinguishing factors .…”

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confidence: 99%

To “Lump” or to “Split” in Macrophage Activation Syndrome and Hemophagocytic Lymphohistiocytosis

Nikiforow

Berliner

2019

Arthritis & Rheumatology

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Development and Initial Validation of the Macrophage Activation Syndrome/Primary Hemophagocytic Lymphohistiocytosis Score, a Diagnostic Tool that Differentiates Primary Hemophagocytic Lymphohistiocytosis from Macrophage Activation Syndrome

Cited by 54 publications

References 40 publications

Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy

Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy

Prognosis, complications and treatment response in systemic juvenile idiopathic arthritis patients: A single‐center experience

To “Lump” or to “Split” in Macrophage Activation Syndrome and Hemophagocytic Lymphohistiocytosis

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