BackgroundHemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that occur in many contexts and are often called by many names. They nevertheless can progress rapidly, and early identification and management are critical for preventing organ failure and mortality.ObjectivesThe purpose of this effort was to develop a series of ‘points to consider’ to assist clinicians at the earliest stages of evaluation and diagnosis, management, and monitoring of patients with HLH/MAS in order to improve patient outcomes.MethodsA working group of adult and pediatric rheumatologists (14), hematologist/oncologists (4), immunologists (2), infectious disease specialists (2), intensivists (3), allied health care professionals (1), and patients/parents (2) formulated relevant research questions for a systematic literature review (SLR). We then used the SLR results, Delphi questionnaires, and consensus methodology to devise and refine overarching and specific ‘points to consider’ statements.ResultsThe group arrived at six overarching statements and 24 specific points-to-consider relevant to early decision-making in diagnostics, initial management, and monitoring of HLH/MAS. Major themes included the a) need for prompt recognition, evaluation, and management of underlying triggers and conditions, b) multi-disciplinary/expert input, and c) early, tailored intervention with the goals of halting disease progression and preventing life- and organ-threatening immunopathologyConclusionThese 2022 EULAR/ACR Points to Consider provide guidance on the initial evaluation, management, and monitoring of patients during the initial consideration of HLH/MAS.Disclosure of InterestsBita Shakoory: None declared, Ashley Geerlinks: None declared, Marta Wilejto: None declared, Kate Kernan: None declared, Erkan Demirkaya: None declared, Angelo Ravelli: None declared, Rashmi Sinha: None declared, Raphaela goldbach-mansky Grant/research support from: SOBI, Novartis, Regneneron, IFM, Lilly, Pfizer, Fabrizio De Benedetti Consultant of: abbvie, sobi, novimmune, novartis, roche, sanofi, Grant/research support from: sobi novimmune novartis roche sanofi, Rebecca Marsh: None declared, Scott Canna Consultant of: Simcha Therapeutics, Grant/research support from: Immvention therapeutics, AB2Bio Ltd, Novartis

Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is characterized by high levels of EBV predominantly in T and/or NK cells with lymphoproliferation, organ failure due to infiltration of tissues with virus-infected cells, hemophagocytic lymphohistiocytosis (HLH) and/or lymphoma. The disease is more common in Asia than in the United States and Europe. While allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only curative therapy for CAEBV, its efficacy and the best treatment modality to reduce disease severity prior to HSCT is unknown. Here, we retrospectively assessed an international cohort of 57 patients outside of Asia. Treatment for the disease varied widely, although most patients ultimately proceeded to HSCT. Though patients undergoing HSCT had better survival than those who did not (55% v 25%, p<0.01), there was still a high rate of death in both groups. Mortality was largely not affected by age, ethnicity, cell type involvement, or disease complications, but development of lymphoma showed a trend with increased mortality (56% v 35%, p=0.1). The overwhelming majority (75%) of patients who died after HSCT succumbed to relapsed disease. CAEBV remains challenging to treat when advanced disease is present. Outcomes would likely improve with better disease control strategies, earlier referral for HSCT, and close follow-up after HSCT including aggressive management of rising EBV DNA levels in the blood.

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We describe five cases of children who completed chemotherapy for infantile acute lymphoblastic leukemia (ALL) and soon after were diagnosed with severe T-cell, non-HIV immunodeficiency, with varying B-cell and NK-cell depletion. There was near absence of CD3 + , CD4 + , and CD8 + cells. All patients developed multiple, primarily opportunistic infections. Unfortunately, four patients died, although one was successfully treated by hematopoietic stem cell transplantation. These immunodeficiencies appeared to be secondary to intensive infant ALL chemotherapy. Our report highlights the importance of the early consideration of this life-threatening immune complication in patients who received chemotherapy for infantile ALL.