Hybrid Immunotherapy for Hemophagocytic LymphoHistiocytosis

2014-07-24 14:06:35 | BioPortfolio


Despite good progress during the last decade, hemophagocytic ymphohistiocytosis (HLH) remains difficult to treat. Two different treatment regimens have been used successfully. The first one, a treatment regimen based on two drugs called etoposide and dexamethasone, has been used worldwide. The second regimen, based on two drugs called Anti-thymocyte globulin (ATG) and prednisone, has been used mostly at one hospital in Paris, for over 15 years. With either regimen, about three quarters of treated children survive the most difficult time, the first two months after diagnosis. These two different regimens appear to work somewhat differently, and we suspect that combining them may give better results than either regimen alone. We are conducting this clinical trial to test the combination of ATG, dexamethasone, and etoposide for the treatment of HLH.

The purpose of this research study is to find out what effects (good and bad) this drug combination has on you and your HLH.


Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological disorder first recognized almost 70 years ago.(1) Genetic and animal studies have indicated that the familial form of HLH is clearly due to a deficiency of cytotoxic killing. Patients with HLH present with a potentially fatal syndrome of 'hyperimmunity.' These patients have severe inflammation, associated with cytopenias and variably severe bone marrow, liver, or CNS damage. Tissue damage and mortality appear to be due to hypercytokinemia related to persistent immune hyperactivation. An animal model of HLH and correlative human studies all suggest that excessive and abnormal activation of T cells drives the pathophysiology of this disorder, and that suppressing this excessive activation is critical for successful therapy of HLH. It is believed a combination of the two proven induction regimens for hemophagocytic lymphohistiocytosis (HLH) (anti-thymocyte globulin (ATG)- and etoposide-based) will result in response rates and overall survival rates at eight weeks which are comparable or better than the current standard of care (induction therapy per the HLH-94 protocol).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Hemophagocytic Lymphohistiocytosis


ATG, rabbit, Dexamethasone, Etoposide, Intrathecal Methotrexate, hydrocortisone


Cincinnati Children's Hospital Medical Center
United States




Children's Hospital Medical Center, Cincinnati

Results (where available)

View Results


Published on BioPortfolio: 2014-07-24T14:06:35-0400

Clinical Trials [1936 Associated Clinical Trials listed on BioPortfolio]

Treatment Protocol for Hemophagocytic Lymphohistiocytosis 2004

Without therapy HLH is often fatal, and often rapidly fatal. The treatment protocol HLH-94 has improved survival markedly as compared to the survival earlier. We now aim to improve surviva...

Etoposide in the First-line Treatment of Adult EBV-HLH

his study aimed to investigate the efficacy of etoposide as the first line therapy for adult Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.

L-DEP as an Initial Treatment for EBV-HLH

This study aimed to investigate the efficacy and safety of Pegaspargase together with liposomal doxorubicin, etoposide and high dose methylprednisolone (L-DEP) as an initial treatment for ...

Prospective Cohort for Adult Hemophagocytosis

This prospective study enrolls subjects who have clinical and laboratory manifestations related with hemophagocytic lymphohistiocytosis. The purpose of the study is to evaluate clinical an...

DEP-Ru Regimen as a Salvage Therapy for HLH

This study aimed to investigate the efficacy and safety of ruxolitinib together with liposomal doxorubicin, etoposide and methylprednisolone (DEP-Ru) as a salvage therapy for refractory/re...

PubMed Articles [1024 Associated PubMed Articles listed on BioPortfolio]

Hemophagocytic Lymphohistiocytosis in Cutaneous T-Cell Lymphoma.

Hemophagocytic lymphohistiocytosis (HLH) has been reported as a serious complication of cutaneous T-cell lymphoma (CTCL). Despite available diagnostic guidelines, it remains a diagnostic and therapeut...

Thrombotic thrombocytopenic purpura and hemophagocytic lymphohistiocytosis in an elderly man: A case report.

Thrombotic thrombocytopenic purpura (TTP) and hemophagocytic lymphohistiocytosis (HLH) are rare hematologic conditions and have high mortality. Both TTP and HLH result from deregulation of the immune ...

Hemophagocytic Lymphohistiocytosis Associated With Visceral Leishmaniasis.

This is the report of a 2-year-old boy who presented with fever, cytopenia, and splenomegaly. The patient was diagnosed with hemophagocytic lymphohistiocytosis (HLH) and treated with HLH-2004 protocol...

Establishment of a protein biochip to detect serum IgG antibodies against IL-2 and soluble CD25 in hemophagocytic lymphohistiocytosis.

Interleukin-2 (IL-2) and soluble CD25 (sCD25) are among the most important cytokines and diagnostic biomarkers in hemophagocytic lymphohistiocytosis (HLH). Detecting serum level of IL-2 and sCD25 is v...

Langerhans cell histiocytosis complicated with hemophagocytic lymphohistiocytosis in a boy with a novel XIAP mutation: A case report.

X-linked lymphoproliferative syndromes (XLPs) are rare, yet often fatal primary immunodeficiency diseases, which rarely manifest as Langerhans cell histiocytosis (LCH) complicated with hemophagocytic ...

Medical and Biotech [MESH] Definitions

A group of related disorders characterized by LYMPHOCYTOSIS; HISTIOCYTOSIS; and hemophagocytosis. The two major forms are familial and reactive.

A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.

Group of disorders which feature accumulations of active HISTIOCYTES and LYMPHOCYTES, but where the histiocytes are not LANGERHANS CELLS. The group includes HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; SINUS HISTIOCYTOSIS; xanthogranuloma; reticulohistiocytoma; JUVENILE XANTHOGRANULOMA; xanthoma disseminatum; as well as the lipid storage diseases (SEA-BLUE HISTIOCYTE SYNDROME; and NIEMANN-PICK DISEASES).

An anti-inflammatory 9-fluoro-glucocorticoid.

An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.

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