Graft-Versus-Host Disease

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Basics

Description

  • 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

Epidemiology

Incidence
  • 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.

Genetics
Major histocompatibility complex determines degree of host–donor match; greater match has less risk of aGVHD and cGVHD.

Risk Factors

  • 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.
    • 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 (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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