Pediatric Graft Versus Host Disease Medication

  • Author: Phillip Ruiz, Jr, MD, PhD; Chief Editor: Harumi Jyonouchi, MD   more...
 
Updated: Dec 13, 2011
 

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.

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Methotrexate (Folex PFS)

 

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

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Cyclosporine (Sandimmune, Neoral)

 

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

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Methylprednisolone (Solu-Medrol)

 

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

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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.

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Sirolimus (Rapamune)

 

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

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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.

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Mycophenolate mofetil (CellCept)

 

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.

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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 similar to 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.

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Contributor Information and Disclosures
Author

Phillip Ruiz, Jr, MD, PhD  Professor of Pathology, Department of Pathology and Surgery, Miller School of Medicine, University of Miami

Phillip Ruiz, Jr, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American Society for Clinical Pathology, American Society of Nephrology, American Society of Transplant Surgeons, American Society of Transplantation, Clinical Immunology Society, Florida Medical Association, New York Academy of Sciences, Pan American Medical Association, Southern Medical Association, and United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Coauthor(s)

Yaxia Zhang, MD, PhD  Resident Physician, Department of Pathology, Jackson Memorial Hospital, University of Miami School of Medicine

Disclosure: Nothing to disclose.

Shoib Sarwar, MD, MPH  Fellowship in Cytopathology and Immunopathology, Department of Pathology, Jackson Memorial Hospital, University of Miami Miller School of Medicine

Shoib Sarwar, MD, MPH, is a member of the following medical societies: American College of Healthcare Executives, American Medical Association, American Society for Clinical Pathology, American Society of Cytopathology, College of American Pathologists, and United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Specialty Editor Board

Ann O'Neill Shigeoka, MD †  Former Clinical Associate Professor, Department of Pediatrics, Division of Immunology-Rheumatology, University of Utah School of Medicine

Ann O'Neill Shigeoka, MD † is a member of the following medical societies: American Federation for Medical Research, Clinical Immunology Society, Pediatric Infectious Diseases Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

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.

John Wilson Georgitis, MD  Consulting Staff, Lafayette Allergy Services

John Wilson Georgitis, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American College of Chest Physicians, American Lung Association, American Medical Writers Association, and American Thoracic Society

Disclosure: Nothing to disclose.

David Pallares, MD  Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville School of Medicine

David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD  Associate Professor, Division of Pulmonary, Allergy/Immunology, and Infectious Diseases, Department of Pediatrics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Mucosal Immunology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Mustafa Suterwala, MD, to the development and writing of this article.

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Pathophysiological pathways and mechanisms of acute GVHD.
This boy developed stage III skin involvement with acute graft versus host disease (GVHD) in spite of receiving prophylaxis with cyclosporin A. The donor was an human leukocyte antigen (HLA)-matched sister; however, the sex disparity increased the risk for acute GVHD. Image courtesy of Mustafa S. Suterwala, MD.
This photo depicts the same boy who has progressed to grade IV graft versus host disease (GVHD). Both cyclosporin A and methylprednisolone had been administered in high dose intravenously. He later died with chronic pulmonary disease caused by chronic GVHD. Image courtesy of Mustafa S. Suterwala, MD.
Autologous graft versus host disease (GVHD) involving the skin of a patient's arm shortly after showing signs of engraftment after an autologous peripheral blood stem cell transplant for ovarian cancer. Image courtesy of Romeo A. Mandanas, MD, FACP.
Acute graft versus host disease (GVHD) involving desquamating skin lesions in a patient following allogeneic bone marrow transplantation for myelodysplasia. Image courtesy of Romeo A. Mandanas, MD, FACP.
Oral mucosal changes in a patient with chronic graft versus host disease (GVHD). Note the skin discoloration (vitiligo), which can result from GVHD. Image courtesy of Romeo A. Mandanas, MD, FACP.
Acute graft versus host disease (GVHD). Hematoxylin-stained and eosin-stained tissue shows dyskeratosis of individual keratinocytes and patchy vacuolization of the basement membrane. A moderate superficial dermal and perivascular lymphocytic infiltrate is also seen in this case. Image courtesy of Melanie K. Kuechler, MD.
 
 
 
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