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Lymphohistiocytosis (Hemophagocytic Lymphohistiocytosis) Medication

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
Updated: May 18, 2016

Medication Summary

This life-threatening hyperinflammatory syndrome is difficult to treat.[42] Initial therapy in patients with hemophagocytic lymphohistiocytosis (HLH) consists of etoposide and dexamethasone for 8 weeks in varying doses as described below. In the HLH-2004 protocol, cyclosporine is added in the beginning. Intrathecal methotrexate is used only with persistently abnormal CSF or progressive neurologic symptoms. Resolved nonfamilial hemophagocytic lymphohistiocytosis does not require continuation of the therapy regimen unless disease reactivation occurs after completion of the initial therapy or unless patients are undergoing bone marrow transplantation (BMT). For the remaining children with persistent nonfamilial disease or familial disease, continuation therapy with etoposide IV infusions, dexamethasone pulses, and cyclosporine PO is instituted at week 9 from the start of initial treatment.[38]

Alemtuzumab may be an effective salvage agent for refractory HLH, with retrospective trials needed to define optimal dosing.[42]

Hemophagocytic lymphohistiocytosis associated with malignancies demands prompt therapy directed at the neoplasm.


Antineoplastic agents

Class Summary

These agents interfere with cell reproduction. Some agents are cell cycle specific, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not phase specific. Cellular apoptosis (ie, programmed cell death) is also a potential mechanism of many antineoplastic agents.

Etoposide (Toposar, VePesid)


Also called VP-16. Inhibits topoisomerase II and results in DNA strand breakage causing cell proliferation to arrest in late S or early G2 portion of the cell cycle.

Methotrexate (Trexall)


Antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA synthesis and cell reproduction in malignant cells. Satisfactory response observed 3-6 wk following administration.

Adjust dose gradually to attain satisfactory response.



Class Summary

These agents elicit anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Dexamethasone (Decadron, Hexadrol)


Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability. Postulated mechanisms of action of corticosteroids in tumors include reduction in vascular permeability, cytoxic effects on tumors, and inhibition of tumor formation.


Immunosuppressant agents

Class Summary

These agents may be used in combination with corticosteroids and immune globulin in patients at low risk.

Cyclosporine (Sandimmune, Neoral)


Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease for various organs.

In children and adults, base dosing on ideal body weight.


Immune globulins

Class Summary

Immune globulin is a purified preparation of gamma globulin. It is derived from large pools of human plasma and is comprised of 4 subclasses of antibodies, approximating the distribution of human serum.

Immune globulin, intravenous (Carimune NF, Gamumex, Gammagard)


Neutralizes circulating myelin antibodies through anti-idiotypic antibodies. Down-regulates proinflammatory cytokines, including INF-γ. Blocks Fc receptors on macrophages. Suppresses inducer T and B cells and augments suppressor T cells. Blocks complement cascade. Promotes remyelination. May increase CSF IgG (10%).

Contributor Information and Disclosures

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Steven K Bergstrom, MD Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland

Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, Children's Oncology Group, American Society of Clinical Oncology, International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Kathleen M Sakamoto, MD, PhD Shelagh Galligan Professor, Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine

Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Nicole L Lacz, MD, and Franklin Desposito, MD, to the original writing and development of this article.

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A lymph node biopsy is performed. Note that a marking pen has been used to outline the node before removal and that a silk suture has been used to provide traction to assist the removal.
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