Graft-Versus-Host Disease

Graft-Versus-Host Disease is a topic covered in the Select 5-Minute Pediatrics Topics.

To view the entire topic, please or purchase a subscription.

Medicine Central™ is a quick-consult mobile and web resource that includes diagnosis, treatment, medications, and follow-up information on over 700 diseases and disorders, providing fast answers—anytime, anywhere. Explore these free sample topics:

Medicine Central

-- The first section of this topic is shown below --



Graft-versus-host disease (GVHD) is a multiorgan inflammatory process that develops when immunologically competent T lymphocytes from a histoincompatible donor are infused into an immunocompromised host unable to reject them. Divided into acute and chronic, historically based on time of presentation but best delineated by clinicopathologic findings.

  • Acute: develops within 100 days after allogeneic hematopoietic stem cell transplant (HSCT); affects skin, GI tract, and/or liver
  • Chronic: develops 100 days after allogeneic HSCT; presents with diverse features resembling autoimmune syndromes
  • Chronic subtypes
    • Progressive: extension of acute GVHD
    • Quiescent: after resolution of acute GVHD
    • De novo: no prior acute GVHD


  • Acute GVHD (grades II–IV): 10–80% of patients receiving T-cell–replete HSCT
    • 35–45% for human leukocyte antigen (HLA)–identical related donor bone marrow
    • 60–80% if 1-antigen HLA-mismatched unrelated donor bone marrow or peripheral stem cells
    • 35–65% if 2-antigen HLA-mismatched unrelated umbilical cord blood
  • Chronic GVHD: most common cause of late morbidity and mortality of allogeneic HSCT
    • 15–25% if HLA-identical related marrow
    • 40–60% if HLA-matched unrelated marrow
    • 54–70% if HLA-matched unrelated peripheral stem cells
    • 20% if unrelated umbilical cord blood
  • Flare-ups triggered by infection (usually viral)

Risk Factors

  • HLA disparity (both major and minor antigens)
  • Older donor or recipient age
  • Stem cell source and dose
    • Highest risk: with peripheral stem cells
    • Lowest risk: with umbilical cord blood
  • Donor leukocyte infusions
  • Reactivation of viruses (e.g., HHV-6, CMV)
  • T-cell depletion decreases incidence.
  • Acute GVHD-specific
    • Higher intensity conditioning regimen
    • Prior pregnancies in female donors
    • Gender mismatch
  • Chronic GVHD specific
    • Severity of acute GVHD
    • Malignancy as indication for transplantation
    • Use of total-body irradiation
    • Type of immunosuppressive prophylaxis


  • HLA gene complex on chromosome 6; inherited as haplotype
  • Full siblings: 25% chance HLA identical
  • Minor histocompatibility antigen differences likely account for GVHD in HLA-identical sibling stem cell transplants.

General Prevention

  • Transfusion: irradiation of all cellular blood products for patients at risk
  • Stem cell transplantation
    • Selection of a histocompatible donor
    • Immunosuppression (gold standard): cyclosporine or tacrolimus with a short course of methotrexate
    • Other options: corticosteroids, sirolimus, mycophenolate mofetil, and low-dose cyclophosphamide
    • Donor T-cell depletion with anti–T-cell antibodies ex vivo in graft or in vivo in recipient


  • Acute GVHD: interaction of donor and host innate and adaptive immune responses
    • Severity related to degree of HLA mismatch
    • 3 phases ending in “cytokine storm”
      • Tissue damage by conditioning regimen
      • Priming and activation of donor T cells
      • Infiltration of activated T cells into skin, GI tract, and liver resulting in apoptosis
  • Chronic GVHD: findings similar to autoimmune disorders: donor T cells directed against host antigens, donor T-cell autoreactivity, B-cell dysregulation, regulatory T-cell deficiency; marked collagen deposition in target organs and lack of T-cell infiltration


  • Hematopoietic stem cell transplantation
  • Transfusion of nonirradiated blood products to immunodeficient hosts: caused by viable donor lymphocytes engrafting in the recipient
  • Transfusion of nonirradiated blood from a donor homozygous for 1 of the recipient’s HLA haplotypes (1st- or 2nd-degree relative)
  • Intrauterine maternal–fetal transfusions and exchange transfusions in neonates
  • Solid organ grafts: contain immunocompetent T cells, into immunosuppressed recipient

-- To view the remaining sections of this topic, please or purchase a subscription --