Lymphohistiocytosis (Hemophagocytic Lymphohistiocytosis) Medication

Updated: Feb 26, 2021
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Medication Summary

This life-threatening hyperinflammatory syndrome is difficult to treat. [54] Initial therapy in patients with hemophagocytic lymphohistiocytosis (HLH) consists of etoposide and dexamethasone for 8 weeks in varying doses as described below. [55] In the HLH-2004 protocol, cyclosporine is added in the beginning. Intrathecal methotrexate is used only with persistently abnormal cerebrospinal fluid (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 intravenous (IV) infusions, dexamethasone pulses, and oral cyclosporine is instituted at week 9 from the start of initial treatment. [50]

Emapalumab, a monoclonal antibody that binds and neutralizes INF-gamma, was approved by the FDA in 2018. It is indicated for primary HLH in adults and children with refractory, recurrent, or progressive disease or who are intolerant to conventional HLH therapy. [49]

Alemtuzumab may be an effective salvage agent for refractory HLH, with retrospective trials needed to define optimal dosing. [54]

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.



Class Summary

Elevated interferon-gamma (INF-gamma) is thought to be part of the pathogenesis that causes the hyperinflammation associated with HLH. Controlling the inflammation helps maintain organ function while preparing for hematopoietic stem-cell transplant (HSCT).

Emapalumab (Gamifant, emapalumab-lzsg)

Human monoclonal antibody that binds to and neutralizes interferon-gamma (IFN-gamma). It is indicated for primary HLH in adults and children (newborn and older) with refractory, recurrent, or progressive disease or who are intolerant to conventional HLH therapy.


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%).