Graft-versus-host disease
Graft-versus-host disease is a complication of allogeneic hematopoietic stem cell transplantation in which donor T cells attack recipient tissues, classically the skin, liver, and gut in the acute form and multi-organ fibrosis in the chronic form. Diagnosis is clinical, supported by biopsy, and management is prophylaxis with a calcineurin inhibitor plus methotrexate and treatment with corticosteroids, escalating to agents such as ruxolitinib for steroid-refractory disease.
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What this article covers
- Overview
Definition: graft-versus-host disease (GVHD) is an immune complication of allogeneic hematopoietic stem cell transplantation (HSCT) in which immunocompetent donor T cells recognize and attack the genetically distinct recipient's tissues.
- Epidemiology
Occurs after allogeneic HSCT: a common complication despite prophylaxis; it does not occur after autologous transplantation.
- Risk factors
HLA mismatch: the strongest risk factor, from disparity between donor and recipient human leukocyte antigens (HLA); greater disparity increases risk.
- Pathophysiology
Donor T-cell activation: conditioning-related tissue damage releases inflammatory signals, and donor T cells recognize recipient alloantigens (major and minor histocompatibility antigens).
- Clinical features
Acute skin disease: a maculopapular rash, classically on the palms, soles, and ears, that can progress to blistering.
- Differential diagnosis
Drug eruption or drug-induced liver injury: rash or hepatitis from conditioning or other drugs rather than GVHD.
- Diagnosis
Diagnose clinically by the pattern of target-organ involvement after allogeneic transplant, supported by biopsy: GVHD is established by the characteristic skin, gastrointestinal, and hepatic findings…
- Management
First, prevent it with prophylaxis at transplant: a calcineurin inhibitor such as tacrolimus (about 0.03 mg/kg/day IV, then converted to oral to a target trough and continued for about 6 months…
- Complications
Life-threatening infection: from the disease and its immunosuppressive treatment, a leading cause of death.
- Prognosis
Variable by grade: mild acute GVHD often responds to steroids, while severe (grade III to IV) and steroid-refractory disease carries high mortality.
- Prevention
Standard prophylaxis at transplant: a calcineurin inhibitor (tacrolimus) plus methotrexate continued for about 6 months then tapered, or post-transplant cyclophosphamide-based regimens.
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