- Tissue destruction in allogeneic hematopoietic stem cell transplant (HSCT) recipients 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); defined by time from transplant (aGVHD <100 days and cGVHD ≥100 days) or clinical manifestations
- Overlap syndrome may occur; that is, “acute-on-chronic” 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 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 has less risk of aGVHD and cGVHD.
- Factors 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
- Age of recipient
- Sex disparity; highest risk = female donor to male recipient; risk increases with each donor 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 with each pregnancy.
- 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 (ex vivo and in vivo strategies)
- Emerging role for statins
- 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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Domino, Frank J., et al., editors. "Graft-Versus-Host Disease." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2020. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816824/all/Graft_Versus_Host_Disease.
Graft-Versus-Host Disease. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2020. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816824/all/Graft_Versus_Host_Disease. Accessed May 28, 2023.
Graft-Versus-Host Disease. (2020). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (27th ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816824/all/Graft_Versus_Host_Disease
Graft-Versus-Host Disease [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2020. [cited 2023 May 28]. 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 - Domino,Frank J, ED - Baldor,Robert A, ED - Golding,Jeremy, ED - Stephens,Mark B, 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 -