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Graft-Versus-Host Disease

Graft-Versus-Host Disease is a topic covered in the 5-Minute Clinical Consult.

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  • Tissue destruction in allogeneic hematopoietic stem cell transplant (HSCT) recipients is due to donor T cells responding to host (recipient) antigens.
  • Two types: acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD); classically defined by time from transplant (aGVHD <100 days and cGVHD ≥100 days). Current designation separates by clinical manifestations.
    • Overlap syndrome may occur; that is, “acute-on-chronic” graft-versus-host disease (GVHD)
  • aGVHD: Skin, liver, and gastrointestinal tract (GIT) are most commonly involved.
  • cGVHD: may involve any organ; pleomorphic presentation mimicking rheumatologic phenomena and characterized by clinical manifestations resembling collagen vascular disease


  • 25–50% of allogeneic HSCT recipients develop aGVHD, depending on disease, conditioning regimen, immunosuppressive therapy, and patient–donor specific factors. 80% have skin involvement, 50% have liver involvement, and 50% have GIT involvement.
  • 30–70% of allogeneic HSCT recipients develop cGVHD.
  • Half of patients diagnosed with cGVHD are diagnosed within 6 months of transplant.

Etiology and Pathophysiology

  • aGVHD: Antigen-presenting cells are activated by conditioning chemotherapy, radiation, and/or subsequent infections. This leads to activation of donor T-helper type 1 effector cells causing direct cytotoxicity via released cytokines.
  • cGVHD is poorly understood; chronic T-cell activation plays role.

Major histocompatibility complex determines degree of host–donor match; greater match leads to decreased risk of aGVHD and cGVHD.

Risk Factors

  • Following associated with greater risk of aGVHD
    • Human leukocyte antigen (HLA) discrepancy between host and donor
    • Unrelated (compared to related) donor
    • Peripheral blood stem cell source (rather than bone marrow source)
    • Type and remission status of disease
    • Conditioning regimen
    • Age of recipient
    • Sex disparity; highest risk = female donor to male recipient; risk increases for each pregnancy.
    • ABO blood group incompatibility
    • Prophylactic immunosuppressive medications
    • Cytomegalovirus (CMV) serostatus disparity
  • Risk factors for cGVHD
    • Antecedent aGVHD episodes
    • HLA disparity
    • Use of peripheral blood stem cells
    • Sex disparity; highest risk = female donor to male recipient; risk increases for each pregnancy.
    • Splenectomy

General Prevention

  • aGVHD
    • Specific prophylactic regimens vary by institution, donor characteristics, and other factors.
    • Immunosuppression with calcineurin inhibitor (CNI) such as tacrolimus OR cyclosporine plus short-course methotrexate or mycophenolate or sirolimus are standard.
    • CNI, mycophenolate, and posttransplant cyclophosphamide are used in haploidentical transplants.
    • Depletion of host alloantigens
    • Depletion of donor T cells (various ex vivo and in vivo strategies)
    • Emerging role for statins
  • cGVHD
    • No commonly accepted prophylaxis; limiting flares of aGVHD may minimize cGVHD.

Commonly Associated Conditions

  • Direct organ injury leads to various potentially life-threatening complications (liver failure, GI bleeding, dehydration, Stevens-Johnson–like physiology with disruption of cutaneous barrier, and others).
  • Secondary risks of infection due to GVHD and its treatment

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Stephens, Mark B., et al., editors. "Graft-Versus-Host Disease." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816824/all/Graft_Versus_Host_Disease.
Graft-Versus-Host Disease. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816824/all/Graft_Versus_Host_Disease. Accessed April 18, 2019.
Graft-Versus-Host Disease. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816824/all/Graft_Versus_Host_Disease
Graft-Versus-Host Disease [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 April 18]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816824/all/Graft_Versus_Host_Disease.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Graft-Versus-Host Disease ID - 816824 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816824/all/Graft_Versus_Host_Disease PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -