Pediatric Graft Versus Host Disease Medication

Updated: Aug 23, 2021
  • Author: Phillip Ruiz, Jr, MD, PhD; Chief Editor: Harumi Jyonouchi, MD  more...
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Immunosuppressive agents

Class Summary

Methotrexate is a folate antagonist and a potent inhibitor of the cell-mediated immune system. Selective inhibitors of T-cell lymphocytes (eg, cyclosporine) suppress early cellular response to antigenic and regulatory stimuli.

Traditionally, high-dose steroids were thought to be lympholytic, but recent studies have suggested that steroids may inhibit T-cell proliferation and T-cell dependent gene expression of cytokines. They produce nonspecific anti-inflammatory effects and anti-adhesion effects that contribute to immune suppression.

Methotrexate (Trexall)

Prevents T-cell proliferation. Acts on purine and pyrimidine synthesis and has been employed as an immunosuppressive agent.

Cyclosporine (Sandimmune, Neoral)

Inhibits calcineurin activity. A serine-threonine phosphatase whose activity is essential for T-cell cytokine transcription.

Methylprednisolone (Solu-Medrol, Depo-Medrol, Medrol)

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Tacrolimus (Prograf)

Previously known as FK506. Macrolide immunosuppressant produced by Streptomyces tsukubaensis. Reported to prolong survival of the host and transplanted graft in some animal transplant models.

Sirolimus (Rapamune)

Inhibits lymphocyte proliferation by interfering with signal transduction pathways. Binds to immunophilin FKBP to block action of mTOR.

Mycophenolate mofetil (CellCept, Myfortic)

The 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent. Inhibits purine synthesis and proliferation of human lymphocytes. Prolonged survival of allogeneic transplants has been demonstrated in experimental animal models.

Antithymocyte globulin, rabbit (Thymoglobulin)

Purified concentrated gamma-globulin (primarily monomeric IgG) from hyperimmune horses immunized with human thymic lymphocytes. Mechanism of action is thought to be its effect on lymphocytes responsible in part for cell-mediated immunity and lymphocytes involved in cell immunity.

Immunosuppressive action generally is like other antilymphocyte preparations. However, they may differ qualitatively and/or quantitatively in extent to which they produce specific effects, in part because of factors such as source of antigenic material used, type of animal used to produce antiserum, and method of production.

A hematologist or another physician with extensive experience must be involved in the administration and monitoring of antilymphocyte serum because of the many complications and adverse effects of this therapy. Dose and duration of therapy vary with different investigational protocols.


Monoclonal Antibodies

Alemtuzumab (Campath)

Monoclonal antibody against CD52, an antigen found on B cells, T cells, and almost all CLL cells. Binds to the CD52 receptor of the lymphocytes, which slows the proliferation of leukocytes.


Kinase Inhibitors

Ruxolitinib (Jakafi)

Kinase inhibitor inhibits Janus Associated Kinases (JAKs) JAK1 and JAK2. JJAK-STAT signaling pathways play a role in regulating development, proliferation, and activation of several immune cell types imperative for GVHD pathogenesis. It is indicated for treatment of steroid-refractory acute GvHD in adult and pediatric patients aged 12 years or older.

Belumosudil (Rezurock)

Belumosudil is the first approved kinase inhibitor targeting Rho-associated coiled-coil kinase 2 (ROCK2). This signaling pathway modulates inflammatory response and fibrotic processes. It is indicated for the treatment of chronic GvHD in patients 12 years and older who failed at least 2 prior systemic therapies.