Graft-Versus-Host Disease
Basics
DESCRIPTION
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
- Graded from I to IV based on organ involvement, percent of body surface area involved (skin), volume of diarrhea (gut), and/or elevation of serum bilirubin (liver)
- Chronic:
- Develops 100 days after allogeneic HSCT
- Presents with diverse features resembling autoimmune syndromes; affects multiple organ systems
- Chronic subtypes
- Progressive: extension of acute GVHD
- Quiescent: after resolution of acute GVHD
- De novo: no prior acute GVHD
EPIDEMIOLOGY
- Acute GVHD (grades II to 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
- Use of total body irradiation
- Chronic GVHD specific
- Severity of acute GVHD
- Malignancy as indication for transplantation
- Gender mismatch (female donor, male recipient)
- Type of immunosuppressive prophylaxis
GENETICS
- 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 post-HSCT cyclophosphamide
- Donor T-cell depletion with anti–T-cell antibodies ex vivo in graft or in vivo in recipient
PATHOPHYSIOLOGY
- Acute GVHD: interaction of donor and host innate and adaptive immune responses
- Severity related to degree of HLA mismatch
- Three 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 alloreactivity, B-cell dysregulation, regulatory T-cell deficiency; marked collagen deposition in target organs and lack of T-cell infiltration
ETIOLOGY
- HSCT
- 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 one 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
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Citation
Cabana, Michael D., editor. "Graft-Versus-Host Disease." Select 5-Minute Pediatrics Topics, 7th ed., Wolters Kluwer Health, 2015. Medicine Central, im.unboundmedicine.com/medicine/view/Select-5-Minute-Pediatric-Consult/14101/1.0/Graft_Versus_Host_Disease.
Graft-Versus-Host Disease. In: Cabana MDM, ed. Select 5-Minute Pediatrics Topics. Wolters Kluwer Health; 2015. https://im.unboundmedicine.com/medicine/view/Select-5-Minute-Pediatric-Consult/14101/1.0/Graft_Versus_Host_Disease. Accessed October 6, 2024.
Graft-Versus-Host Disease. (2015). In Cabana, M. D. (Ed.), Select 5-Minute Pediatrics Topics (7th ed.). Wolters Kluwer Health. https://im.unboundmedicine.com/medicine/view/Select-5-Minute-Pediatric-Consult/14101/1.0/Graft_Versus_Host_Disease
Graft-Versus-Host Disease [Internet]. In: Cabana MDM, editors. Select 5-Minute Pediatrics Topics. Wolters Kluwer Health; 2015. [cited 2024 October 06]. Available from: https://im.unboundmedicine.com/medicine/view/Select-5-Minute-Pediatric-Consult/14101/1.0/Graft_Versus_Host_Disease.
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