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Hemophagocytic lymphohistiocytosis (HLH)

Hemophagocytic lymphohistiocytosis is a life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages



Age of Onset





Autosomal dominant


Autosomal recessive




X-linked dominant


X-linked recessive


5 Facts you should know



A life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages.



HLH clinically manifests with fever, enlargement of the liver and spleen, enlarged lymph nodes, yellow discoloration of the skin and eyes, and a rash.



It is classified as one of the cytokine storm syndromes.



Laboratory findings may include elevated triglyceride levels, low fibrinogen levels, transaminitis, and elevated ferritin levels.



The onset of HLH occurs under the age of one year in approximately 70 percent of cases.

Hemophagocytic lymphohistiocytosis (HLH)

Hemophagocytic lymphohistiocytosis (HLH)

HLH, hemophagocytic syndrome

What’s your rare IQ?

Abnormality in which organ is usually the first and most common sign of Hemophagocytic lymphohistiocytosis (HLH)?

Common Signs & Symptoms


Enlarged liver and/or spleen

Skin rash

Lymph node enlargement

Breathing problems

Easy bruising and/or abnormal bleeding

Kidney abnormalities

Heart problems

Increased risk for certain cancers

Top Clinical Trials

TitleDescriptionPhasesStatusInterventionsLocationsMore Information
Tocilizumab and Hemophagocytic Lymphohistiocytosis (HLH)This study seeks to determine the efficacy of tocilizumab (TCZ) in patients with hemophagocytic lymphohistiocytosis (HLH) and high cytokine levels (proteins involved in inflammation) in an attempt to decrease the damage caused by these proteins; and secondarily to assess its safety and impact on disease activity.Phase 2Active, not recruitingDrug: tocilizumabChildren's Hospital of Philadelphia, Philadelphia, Pennsylvania, United StatesMore Information
A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Emapalumab in Adult Patients With HLH Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on the background of several clinical conditions (e.g. autoimmune disease, infection, malignancy). Emapalumab (previously referred to as NI-0501) is a monoclonal antibody neutralizing interferon-gamma (IFN-gamma), a key cytokine driving the inflammation and tissue damage seen in HLH. The purpose of this study is to assess the efficacy, safety and pharmacokinetics of emapalumab in adult patients with HLH.
Phase 2|Phase 3Active, not recruitingDrug: Emapalumab-LzsgMD Anderson Cancer Center, Houston, Texas, United StatesMore Information
Use Of A Response-Adapted Ruxolitinib-Containing Regimen For The Treatment Of Hemophagocytic LymphohistiocytosisThis study is a multi-site Phase Ib/II, 2-arm non-randomized clinical trial to determine the efficacy and tolerability of a response-adapted regimen combining ruxolitinib, dexamethasone, and etoposide as Frontline therapy for patients with newly diagnosed hemophagocytic lymphohistiocytosis (HLH) or as Salvage therapy for patients with relapsed/refractory HLH.Phase 1|Phase 2RecruitingDrug: Ruxolitinib|Drug: Dexamethasone|Drug: EtoposideSt. Jude Children's Research Hospital, Memphis, Tennessee, United StatesMore Information
Alemtuzumab or Tocilizumab in Combination With Etoposide and Dexamethasone for the Treatment of Adult Patients With Hemophagocytic LymphohistiocytosisThe goal of this clinical research study is to compare the effect of adding either alemtuzumab or tocilizumab to the drug combination of etoposide and dexamethasone in controlling HLH. The safety of the drug combinations will also be studied.

This is an investigational study. Alemtuzumab, etoposide, tocilizumab, and dexamethasone are not FDA approved for the treatment of HLH. Etoposide is FDA approved and commercially available for the treatment of testicular cancer and lung cancer. Alemtuzumab is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia. Dexamethasone is a steroid used to reduce inflammation. Tocilizumab is FDA approved and commercially available for the treatment of arthritis. The combination of alemtuzumab, etoposide, tocilizumab, and dexamethasone to treat HLH is investigational. The study doctor can explain how the drugs are designed to work.
Phase 2RecruitingDrug: Alemtuzumab|Drug: Etoposide|Drug: Dexamethasone|Drug: Methotrexate|Behavioral: Phone Call|Drug: TocilizumabUniversity of Texas MD Anderson Cancer Center, Houston, Texas, United StatesMore Information
Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis The purpose of this study is to expand the knowledge on the efficacy and safety of emapalumab (previously known as NI-0501) as a treatment for primary haemophagocytic lymphohistiocytosis (HLH) patients, with special focus on long-term outcome and quality of life assessments. Emapalumab can be administered as the first-line therapy, to patients not previously treated with the current standard of care, or can be given to patients who have either failed or were unable to tolerate the available standard of care.Phase 3Active, not recruitingDrug: EmapalumabPhoenix Children Hospital, Phoenix, Arizona, United States|Children's Hospital Los Angeles, Los Angeles, California, United States|Children's Hospital Colorado, Aurora, Colorado, United States|Alfred I. duPont Hospital for Children - Nemours Center for Cancer and Blood Disorders - Division of Pediatric Hematology Oncology, Wilmington, Delaware, United States|Children's Healthcare of Atlanta, Atlanta, Georgia, United States|Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, United States|Spectrum Health Helen Devos Children's Hospital, Grand Rapids, Michigan, United States|Cincinnati Children's Hospital, Cincinnati, Ohio, United States|Texas Children's Cancer Center, Houston, Texas, United States|Seattle Children's Hospital, Seattle, Washington, United States|Hopital Ste-Justine Research Center, Montréal, Canada|Hospital for Sick Children, Toronto, Canada|Children's and Women's Health Centre of British Columbia, Vancouver, Canada|Universitätsklinikum Essen, Essen, Germany|Medical Center- University of Freiburg, Freiburg, Germany|Universitätsklinikum Eppendorf, Hamburg, Germany|Istituto Giannina Gaslini, Genova, Italy|Fondazione MBBM, Ospedale San Gerardo, Monza, Italy|Ospedale Pediatrico Bambino Gesu, Rome, Italy|Ospedale della Donna e del Bambino, Verona, Italy|Hospital Universitario Vall d'Hebron, Barcelona, Spain|Hospital Universitario Niño Jesús, Madrid, Spain|Karolinska University Hospital Huddinge, Stockholm, Sweden|University Children's Hospital Zurich, Zürich, Switzerland|Leeds Children Hospital, Leeds, United Kingdom|Great Ormond Street Hospital, London, United Kingdom|Royal Manchester Children's Hospital, Manchester, United KingdomMore Information
Immune Disorder HSCT Protocol This study hypothesizes that a reduced intensity immunosuppressive preparative regimen will establish engraftment of donor hematopoietic cells with acceptable early and delayed toxicity in patients with immune function disorders. A regimen that maximizes host immune suppression is expected to reduce graft rejection and optimize donor cell engraftment.
Phase 2RecruitingDrug: Transplant preparative regimen of alemtuzumab, fludarabine, thiotepa, and melphalanWashington University, Saint Louis, Missouri, United States|Methodist Heathcare, San Antonio, Texas, United StatesMore Information
Etoposide in Patients With COVID-19 Infection This is a randomized, open-label phase II study designed to evaluate the safety and efficacy of etoposide in patients with the 2019 novel coronavirus (COVID-19) infection. Randomization will be performed with a 3:1 allocation ratio. Treatment will be comprised of etoposide administered intravenously at a dose of 150 mg/m2 on Days 1 and 4 in patients with COVID-19 infection meeting eligibility criteria. Subsequent doses of etoposide will be allowed if the investigator and treating physician believe the patient had clinical benefit from etoposide therapy but subsequently has evidence of recurrent clinical deterioration. Subjects randomized to control will receive standard of care treatment. No placebo will be used.Phase 2Active, not recruitingDrug: EtoposideBoston Medical Center, Boston, Massachusetts, United StatesMore Information
Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation In this study, the investigators test 2 dose levels of thiotepa (5 mg/kg and 10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG) to determine the minimum effective dose required for reliable engraftment for subjects undergoing hematopoietic stem cell transplantation for non-malignant disease.Phase 1|Phase 2RecruitingDrug: Thiotepa--single daily dose|Drug: Thiotepa--escalated doseUF Health Shands Children's Hospital, Gainesville, Florida, United StatesMore Information
Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT The objective of this study is to evaluate the efficacy of using a reduced-intensity condition (RIC) regimen with umbilical cord blood transplant (UCBT), double cord UCBT, matched unrelated donor (MUD) bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) in patients with non-malignant disorders that are amenable to treatment with hematopoietic stem cell transplant (HSCT). After transplant, subjects will be followed for late effects and for ongoing graft success.Phase 2RecruitingDrug: Hydroxyurea|Drug: Alemtuzumab|Drug: Fludarabine|Drug: Melphalan|Drug: ThiotepaUPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United StatesMore Information
A Study to Evaluate Tabelecleucel in Participants With Epstein-barr Virus-associated DiseasesThe purpose of this study is to assess the efficacy and safety of tabelecleucel in participants with Epstein-Barr virus (EBV) associated diseases.Phase 2RecruitingBiological: TabelecleucelChildren's Hospital of Orange County (Pediatrics [up to 25 years old]), Orange, California, United States|University of California Davis Comprehensive Cancer Center (Adults and Pediatrics), Sacramento, California, United States|Emory University/Winship Cancer Institute (Adults [>= 16 years]), Atlanta, Georgia, United States|University of Michigan Rogel Cancer Center (Adults and Pediatrics), Ann Arbor, Michigan, United States|Washington University in St. Louis (Adults only), Saint Louis, Missouri, United States|Cleveland Clinic Taussig Cancer Center (Adults and Pediatrics), Cleveland, Ohio, United States|Medical University of South Carolina (Adults and Pediatrics), Charleston, South Carolina, United States|MD Anderson (Adults and Pediatrics), Houston, Texas, United States|Uniklinikum Salzburg Landeskrankenhaus (Adults only), Salzburg, Austria|Medizinische Universität Wien (Adults only), Wien, Austria|Hôpital Saint-Eloi (Adults only), Montpellier Cedex 5, France|Hôpital Universitaire Pitié Salpêtrière (Adults only), Paris, France|Hôpital Necker-Enfants Malades (Adults and Pediatrics), Paris, France|Hospital Universitari Vall d'Hebrón (Adults and Pediatrics), Barcelona, Spain|Hospital Universitario Ramón y Cajal (Adults only), Madrid, Spain|Hospital Universitario Viegen del Rocio (Adults and Pediatrics), Sevilla, SpainMore Information
Treosulfan and Fludarabine Phosphate Before Donor Stem Cell Transplant in Treating Patients With Nonmalignant Inherited Disorders This phase II clinical trial studies how well treosulfan and fludarabine phosphate with or without low dose radiation before donor stem cell transplantation works in treating patients with nonmalignant (noncancerous) diseases. Although effective in curing the patient's disease, many hematopoietic cell transplantation regimens use intensive chemotherapy and/or radiation which can be quite toxic, have significant side effects, and can potentially be life-threatening. Investigators are investigating whether a new conditioning regimen that uses less intensive drugs (treosulfan and fludarabine phosphate) with or without low dose radiation results in new blood-forming cells (engraftment) of the new donor cells without increased toxicities in patients with nonmalignant (noncancerous) diseases.Phase 2Active, not recruitingProcedure: Allogeneic Bone Marrow Transplantation|Biological: Anti-Thymocyte Globulin|Drug: Cyclosporine|Drug: Fludarabine Phosphate|Other: Laboratory Biomarker Analysis|Drug: Methotrexate|Drug: Mycophenolate Mofetil|Procedure: Peripheral Blood Stem Cell Transplantation|Drug: Tacrolimus|Radiation: Total-Body Irradiation|Drug: Treosulfan|Procedure: Umbilical Cord Blood TransplantationChildren's Hospital Colorado, Aurora, Colorado, United States|Oregon Health and Science University, Portland, Oregon, United States|Vanderbilt University/Ingram Cancer Center, Nashville, Tennessee, United States|Seattle Children's Hospital, Seattle, Washington, United States|Fred Hutch/University of Washington Cancer Consortium, Seattle, Washington, United States|Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United StatesMore Information

Top Treatments in Research

AgentClass/Mechanism of ActionDevelopment StatusCompanyCompany ContactClinical StudiesMore Information
Ruxolitinib (Jakafi)Ruxolitinib works by inhibiting the signalling of cytokines (small cell-signalling protein molecules) and growth factor receptors that use JAK1 and JAK2 for signalling. The drug restrains the growth of malignant cells and also controls cytokines that contribute to hypermetabolic state.Phase 1/2Incyte Corporation
n/aMore informationMore Information
Alemtuzumab (Lemtrada)
Alemtuzumab is a monoclonal antibody that selectively binds to CD52, highly expressed on lymphocytes (T and B cells), depleting these cells from circulation in the periphery. The mechanism by which LEMTRADA exerts its therapeutic effects is unknown.Phase 2This agent is being evaluated by M.D. Anderson Cancer Center. The agent was developed and is marketed by Genentech USA, Inc.Naval Daver, MD 713-794-4392 ndaver@mdanderson.org
More informationMore Information
Tocilizumab (Actemra)Tocilizumab is a novel monoclonal antibody that competitively inhibits the binding of interleukin-6 (IL-6) to its receptor (IL-6R). Inhibiting the entire receptor complex prevents IL-6 signal transduction to inflammatory mediators that summon B and T cells. Tocilizumab has a nonlinear pharmacokinetic profile.Phase 2This agent is being evaluated by M.D. Anderson Cancer Center. The agent was developed and is marketed by Genentech USA, Inc.Naval Daver, MD 713-794-4392 ndaver@mdanderson.org
More informationMore Information
Thiotepa (Tepadina)Thiotepa, as a conditioning regimen for allogeneic hematopoietic stem-cell transplantation, may have utility in improving outcomes in HLH. Thiotepa (and TEPA) form DNA crosslinks that lead to a reactive metabolite. The aziridine ring opens after protonation of the ring nitrogen. As an alkylating agent, thiotepa interferes with DNA replication and RNA transcription, ultimately leading to the disruption of nucleic acid function.Phase 1/2This agent is being evaluated by UF Health Shands Children's Hospital. Thiotepa is manufactured by Amneal Pharmaceuticals.Giselle Moore-Higgs, PhD 3522739050 mooregj@ufl.edu
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Tabelecleucel (Tab-cel)Tabelecleucel exhibits a consistent activation signature at the level of gene expression, T-cell receptor engagement (TCR), and secretion of factors associated with effective T cell responses.Phase 2Atara Biotherapeutics, Inc.Study Director 650-278-8930 ext option 1 clinicalstudies@atarabio.com
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