2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T5be,Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hematologic disorder characterized by unchecked immune activation and hyperinflammation, resulting in end-organ tissue damage and high mortality rates in untreated patients. Since the first description of this condition in 1939, our understanding of HLH has continued to deepen, with increasing appreciation of the differences and similarities between primary (familial) HLH and secondary (acquired) HLH. While primary HLH presents in the early years of life on the backdrop of inherited genetic mutations affecting cytotoxic immune cell function, secondary HLH more commonly presents in adults and is a heterogenous disorder with various potential triggers ranging from infections to malignancy, autoimmune disease, immunodeficiency, and medications. Yet, they converge in a common pathway of widespread systemic inflammation, which clinically manifests with fevers, organomegaly, cytopenias, laboratory derangements, and rapid development of multiorgan failure. As such, early recognition and intervention is critical to prevent irreversible organ damage and death in both primary and secondary HLH. In this review, we focus our attention on adult secondary HLH and explore the latest updates on the pathophysiology, precipitants, clinical presentation, diagnosis and management of this life-threatening condition. Note that primary HLH is reviewed separately as a companion article in this review series.31:T5cf,Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hematologic disorder characterized by unchecked immune activation and hyperinflammation, resulting in end-organ tissue damage and high mortality rates in untreated patients. Since the first description of this condition in 1939, our understanding of HLH has continued to deepen, with increasing appreciation of the differences and similarities between primary (familial) HLH and secondary (acquired) HLH. While primary HLH presents in the early years of life on the backdrop of inherited genetic mutations affecting cytotoxic immune cell function, secondary HLH more commonly presents in adults and is a heterogenous disorder with various potential triggers ranging from infections to malignancy, autoimmune disease, immunodeficiency, and medications. Yet, they converge in a common pathway of widespread systemic inflammation, which clinically manifests with fevers, organomegaly, cytopenias, laboratory derangements, and rapid development of multiorgan failure. As such, early recognition and intervention is critical to prevent irreversible organ damage and death in both primary and secondary HLH. In this review, we focus our attention on adult secondary HLH and explore the latest updates on the pathophysiology, precipitants, clinical presentation, diagnosis and management of this life-threatening condition. Note that primary HLH is reviewed separately as a companion article in this review series.32:T506,Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by severe hyperinflammation, leading to endorgan damage and death in the absence of treatments directed at suppressing the overactive immune system. The study of mouse models and human biospecimens has provided insights into disease pathophysiology and enabled investigations of novel therapeutic strategies. Nevertheless, clinical outcomes remain suboptimal. Additional research is required to further our understanding of this highly heterogeneous disease in order to develop improved diagnostic and prognostic tools and identify and implement targeted and less toxic treatments. In this article, written on behalf of the Histiocyte Society, we highlight six key areas of ongoing research, including the remaining questions in each area. We also outline the challenges of global dissemination and implementation of this research and call for the establishment of local, regional, and national cooperative groups aimed at providing education for physicians and targeted diagnostic and clinical guidelines. Finally, we discuss the role of international societies, including the Histiocyte Society, in nucleating this work to ensure coordinated efforts aimed at improving outcomes for patients with HLH worldwide.33:T517,Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by severe hyperinflammation, leading to endorgan damage and death in the absence of treatments directed at suppressing the overactive immune system. The study of mouse models and human biospecimens has provided insights into disease pathophysiology and enabled investigations of novel therapeutic strategies. Nevertheless, clinical outcomes remain suboptimal. Additional research is required to further our understanding of this highly heterogeneous disease in order to develop improved diagnostic and prognostic tools and identify and implement targeted and less toxic treatments. In this article, written on behalf of the Histiocyte Society, we highlight six key areas of ongoing research, including the remaining questions in each area. We also outline the challenges of global dissemination and implementation of this research and call for the establishment of local, regional, and national cooperative groups aimed at providing education for physicians and targeted diagnostic and clinical guidelines. Finally, we discuss the role of international societies, including the Histiocyte Society, in nucleating this work to ensure coordinated efforts aimed at improving outcomes for patients with HLH worldwide.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Hemophagocytic Lymphohistiocytosis: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Hemophagocytic Lymphohistiocytosis (condition). Clinician-written summaries and actionable practice insights. 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A TSAT-guided pathway directs workup toward HFE genotyping, hepatic MRI, or metabolic evaluation; the sTfR/log-ferritin index helps distinguish iron deficiency from anemia of inflammation, though sTfR is itself inflammation-sensitive.","limitations":"Narrative review design limits causal inference. The Valenti consensus on metabolic hyperferritinemia is only partially validated against clinical outcomes. Evidence for GLP-1 receptor agonists altering ferritin interpretation is insufficient in humans.","practice_takeaway":"Use a TSAT-guided pathway — not ferritin alone — to direct workup toward HFE genotyping, hepatic MRI, or metabolic evaluation. Document SGLT2 inhibitor use at every ferritin review, as it alters ferritin interpretation; apply adult-specific HLH criteria (HScore ≥169) rather than pediatric thresholds when HLH is suspected."}},{"doi":"10.1097/cmr.0000000000001120","pmid":"42495971","title":"Hemophagocytic lymphohistiocytosis and posterior reversible encephalopathy syndrome during BRAF/MEK inhibitor therapy following immune checkpoint blockade in metastatic melanoma: a case report","journal_title":"Melanoma Research","journal_issn":"0960-8931","published_at":"2026-07-23T00:00:00.000Z","url":"https://doi.org/10.1097/cmr.0000000000001120","source_score":1,"is_retracted":false,"is_open_access":null,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":false},"created_at":"2026-07-28T14:02:30.564Z","updated_at":"2026-07-28T14:02:30.564Z","tags":[{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"brand","value":"Mekinist","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"brand","value":"Opdivo","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"brand","value":"Tafinlar","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"brand","value":"Yervoy","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"condition","value":"Acute Kidney Injury","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"condition","value":"Disseminated Intravascular Coagulation","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"condition","value":"Hemophagocytic Lymphohistiocytosis","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"condition","value":"Metastatic Melanoma","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"condition","value":"Posterior Reversible Encephalopathy Syndrome","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"generic","value":"dabrafenib","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"generic","value":"ipilimumab","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"generic","value":"nivolumab","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"generic","value":"trametinib","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"modality","value":"BRAF Inhibitor","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"modality","value":"MEK Inhibitor","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"sample_size","value":"n=1","value_numeric":1},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"study_design","value":"Case Report","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"warning","value":"PRES diagnosis was based on neuroimaging findings; full clinical details of imaging are not provided in the abstract.","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"warning","value":"Single case report — findings cannot be generalized or used to establish causality between sequential therapy regimens and HLH.","value_numeric":null},{"paper_doi":"10.1097/cmr.0000000000001120","tag_type":"warning","value":"The relative contribution of EBV reactivation vs. drug-induced immune dysregulation to HLH onset is unclear from the report.","value_numeric":null}],"summaries":{"what_studied":"A 61-year-old woman with BRAF V600K-mutant metastatic melanoma (stage IV) who developed hemophagocytic lymphohistiocytosis (HLH) and posterior reversible encephalopathy syndrome (PRES) after sequential treatment with nivolumab/ipilimumab → nivolumab monotherapy → dabrafenib/trametinib.","key_result":"HScore of 234 (98% probability of HLH) was reached; the patient also developed hemolysis, DIC, acute kidney injury, EBV reactivation, and PRES with transient visual disturbances. With immunosuppressive and supportive therapy, inflammatory markers, coagulation, and renal function gradually improved; visual symptoms resolved within 2 days.","limitations":"Single case report limits generalizability; causal attribution between sequential therapy and HLH cannot be definitively established; long-term outcomes not reported.","practice_takeaway":"In patients transitioning from immune checkpoint inhibitors to BRAF/MEK inhibitors for metastatic melanoma, clinicians should maintain a high index of suspicion for HLH — especially when sepsis-like presentations are accompanied by cytopenias, coagulopathy, or EBV reactivation. Early HScore calculation and prompt interdisciplinary evaluation can be life-saving."}},{"doi":"10.1053/j.ajkd.2026.04.013","pmid":"42379468","title":"Hemophagocytic Lymphohistiocytosis and Fibroblast Growth Factor 23 (FGF23)–Induced Hypophosphatemia","journal_title":"American Journal of Kidney Diseases","journal_issn":"0272-6386","published_at":"2026-06-30T00:00:00.000Z","url":"https://doi.org/10.1053/j.ajkd.2026.04.013","source_score":6,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-23T07:33:07.836Z","updated_at":"2026-08-23T07:33:07.836Z","tags":[{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"condition","value":"Acute Lymphoblastic Leukemia","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"condition","value":"Cytokine Release Syndrome","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"condition","value":"Hemophagocytic Lymphohistiocytosis","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"condition","value":"Hypophosphatemia","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"generic","value":"fibroblast growth factor 23","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"modality","value":"CAR-T Cell Therapy","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"sample_size","value":"n=1","value_numeric":1},{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"study_design","value":"Case Report","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"warning","value":"Causation between HLH-driven inflammation and FGF23 elevation is proposed but not proven; alternative mechanisms were excluded by absence rather than direct testing.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"warning","value":"Sex of the patient is not reported in the abstract.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.04.013","tag_type":"warning","value":"This is a single case report (n=1); findings are hypothesis-generating only and should not be used to establish clinical protocols without further validation.","value_numeric":null}],"summaries":{"what_studied":"A case report examining severe, refractory hypophosphatemia with renal phosphate wasting in a patient with acute lymphoblastic leukemia and hemophagocytic lymphohistiocytosis (HLH), with clinical exacerbation following CAR-T cell therapy, focusing on FGF23 as a potential mechanistic driver.","key_result":"Markedly elevated FGF23 levels were identified in the absence of any known acquired or genetic causes of impaired FGF23 cleavage, suggesting HLH-associated inflammation as a novel mechanism for FGF23-induced renal phosphate wasting and hypophosphatemia in this setting.","limitations":"Single case report limits generalizability; causality between HLH-driven inflammation and FGF23 elevation cannot be established; no comparator group or FGF23 longitudinal data relative to HLH disease activity reported.","practice_takeaway":"In CAR-T or HLH patients with persistent hypophosphatemia despite standard supplementation, evaluate for renal phosphate wasting first, then measure FGF23 levels. Elevated FGF23 may point to an inflammation-driven mechanism requiring targeted management rather than simple repletion."}},{"doi":"10.1182/blood.2025030059","pmid":"41802111","title":"Immune-mediated side effects of cancer immunotherapies","journal_title":"Blood","journal_issn":"0006-4971","published_at":"2026-03-09T00:00:00.000Z","url":"https://doi.org/10.1182/blood.2025030059","source_score":12,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-20T13:25:06.776Z","updated_at":"2026-06-20T13:25:06.776Z","tags":[{"paper_doi":"10.1182/blood.2025030059","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"condition","value":"Cytokine Release Syndrome","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"condition","value":"Graft-Versus-Host Disease","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"condition","value":"Hematologic Malignancies","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"condition","value":"Hemophagocytic Lymphohistiocytosis","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"condition","value":"Immune Effector Cell-Associated Neurotoxicity Syndrome","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"condition","value":"Immune-Related Adverse Events","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"modality","value":"Allogeneic Hematopoietic Cell Transplantation","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"modality","value":"CAR T-Cell Therapy","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"warning","value":"Sex of study populations is not reported as this is a review article covering multiple conditions and trials.","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"warning","value":"The 'impact_flag' of practice_changing reflects the breadth of clinical guidance synthesized, not a single trial result.","value_numeric":null},{"paper_doi":"10.1182/blood.2025030059","tag_type":"warning","value":"This is a narrative review published in Blood; no original patient-level data or meta-analytic statistics are reported. Conclusions are expert synthesis, not graded evidence.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates the biological mechanisms, pathophysiology, and management strategies for immune-mediated toxicities arising from cancer immunotherapies — including allogeneic HCT (acute GVHD), CAR T-cell therapies (CRS, ICANS, IEC-HS, IEC-HT, LICAST), and immune checkpoint inhibitors (irAEs) — with a focus on the roles of myeloid and T cells, including tissue-resident T cells.","key_result":"Shared pathophysiologic mechanisms across acute GVHD, CAR T-cell toxicities, and irAEs — particularly involving myeloid and tissue-resident T cell dysregulation — provide a rationale for overlapping therapeutic strategies; approved, investigational, and potential future therapies targeting these commonalities are summarized.","limitations":"As a narrative review, it does not report original clinical trial data or pooled statistics. Evidence synthesis is qualitative, and the strength of recommendations for emerging therapies is not formally graded.","practice_takeaway":"Clinicians managing immune-mediated toxicities from GVHD, CAR T-cell therapy, or checkpoint inhibitors should recognize shared immune mechanisms that may allow cross-applicable treatment strategies. Awareness of both established and investigational therapies targeting myeloid and T-cell pathways can inform management of these overlapping toxicity syndromes."}},{"doi":"10.1182/blood.2025032352","pmid":"41779733","title":"How I treat HLH-like toxicities after immune effector cell therapy","journal_title":"Blood","journal_issn":"0006-4971","published_at":"2026-03-04T00:00:00.000Z","url":"https://doi.org/10.1182/blood.2025032352","source_score":12,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-30T13:22:51.300Z","updated_at":"2026-05-30T13:22:51.300Z","tags":[{"paper_doi":"10.1182/blood.2025032352","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/blood.2025032352","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/blood.2025032352","tag_type":"condition","value":"CRS With Multiorgan Dysfunction","value_numeric":null},{"paper_doi":"10.1182/blood.2025032352","tag_type":"condition","value":"Cytokine Release Syndrome","value_numeric":null},{"paper_doi":"10.1182/blood.2025032352","tag_type":"condition","value":"Hemophagocytic Lymphohistiocytosis","value_numeric":null},{"paper_doi":"10.1182/blood.2025032352","tag_type":"condition","value":"Immune Effector Cell-Associated HLH-Like Syndrome","value_numeric":null},{"paper_doi":"10.1182/blood.2025032352","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/blood.2025032352","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1182/blood.2025032352","tag_type":"modality","value":"Bispecific T-Cell Engager","value_numeric":null},{"paper_doi":"10.1182/blood.2025032352","tag_type":"modality","value":"CAR-T Cell Therapy","value_numeric":null},{"paper_doi":"10.1182/blood.2025032352","tag_type":"study_design","value":"Narrative Review / Expert Opinion","value_numeric":null},{"paper_doi":"10.1182/blood.2025032352","tag_type":"warning","value":"No sample size is applicable as this is not an original research study with a defined patient cohort.","value_numeric":null},{"paper_doi":"10.1182/blood.2025032352","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied cautiously — this article formalizes and operationalizes emerging consensus distinctions (IEC-HS vs. CRS-MOD) that are likely to influence clinical practice, though prospective validation is lacking.","value_numeric":null},{"paper_doi":"10.1182/blood.2025032352","tag_type":"warning","value":"This is an expert 'How I Treat' review; recommendations are based on collective clinical experience and should be interpreted as expert guidance rather than evidence-based guidelines from controlled trials.","value_numeric":null}],"summaries":{"what_studied":"This review describes the clinical approach to managing two CAR-T/bispecific T-cell engager-associated HLH-like toxicity syndromes — CRS with multiorgan dysfunction (CRS-MOD) and immune effector cell-associated HLH-like syndrome (IEC-HS) — including their differentiation, diagnostic workup, and evolving treatment strategies.","key_result":"IEC-HS is clinically and temporally distinct from CRS, typically emerging as CRS subsides or after resolution, while CRS-MOD features HLH-like manifestations that arise with worsening CRS and progress despite standard CRS-directed therapy; both are associated with poor outcomes.","limitations":"This is a narrative expert review ('How I Treat') without prospective data or controlled trials; recommendations reflect collective clinical experience rather than high-level evidence. No patient-level outcomes or comparative efficacy data are reported.","practice_takeaway":"Distinguish IEC-HS (post-CRS onset, HLH-like features) from CRS-MOD (concurrent with worsening CRS, progressive organ dysfunction) early, as each may require different interventions beyond standard CRS management. Early recognition and targeted intervention are emphasized given the association of both syndromes with poor outcomes."}},{"doi":"10.1111/pai.70282","pmid":"41540738","title":"HLA\n ‐\n DR\n +\n CD8\n + T lymphocytes as an alternative T‐cell activation marker in pediatric\n HLH\n : A real‐life study","journal_title":"Pediatric Allergy and Immunology","journal_issn":"0905-6157","published_at":"2026-01-16T00:00:00.000Z","url":"https://doi.org/10.1111/pai.70282","source_score":1,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-19","doi":"10.1111/pai.70282","days":"7","issn":"0905-6157","rank":"9","field":"Clinical Medicine","score":"1","category":"Allergy","categories":["Allergy"],"_categories":["Allergy"]},"pubmed":{"doi":"10.1111/pai.70282","title":"HLA-DR+ CD8+ T lymphocytes as an alternative T-cell activation marker in pediatric HLH: A real-life study.","journal":"Pediatric allergy and immunology : official publication of the European Society of 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It compiles data from animal models and human studies and outlines global implementation needs.","key_result":"In pediatric pHLH, HLH-94 (dexamethasone+etoposide) increased 5-year overall survival to 54% (from <10% historically), a recent retrospective series reported 3-year survival of 77% with etoposide-based frontline regimens, and emapalumab plus dexamethasone achieved 12-month survival of 73.4% in relapsed/refractory HLH; adults with malignancy-associated HLH had ~15% 5-year survival.","limitations":"This is a narrative society blueprint drawing largely on retrospective studies, with sparse prospective adult data and few trials in malignancy-associated HLH. Several diagnostic tools and anti-cytokine strategies referenced require prospective validation with standardized endpoints.","practice_takeaway":"For pHLH, HLH-94 (etoposide+dexamethasone) remains standard; if cyclosporine is used, avoid initiation before week 3 and target troughs of 120–150 μg/L. Use HLH-2004 criteria as the pediatric diagnostic benchmark and consider HScore in adults; anti-cytokine agents (emapalumab, ruxolitinib, anakinra) and HCT are options in defined contexts, while adult and malignancy-associated HLH need individualized, trial-guided care."}}],"initialOffset":8,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Hemophagocytic Lymphohistiocytosis"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Hemophagocytic Lymphohistiocytosis"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Hemophagocytic Lymphohistiocytosis"}}}]]

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