Graft-versus-host disease

Alloimmune complication of allogeneic transplantation where donor T cells attack the host's tissues, causing multi-organ inflammation (commonly skin, GI tract, liver).

• Major cause of transplant-related mortality (occurs in ~30–50% of allogeneic HSCT patients); high-yield because clinicians must balance preventing GvHD with preserving graft-versus-tumor effect.

• Acute GvHD (within ~100 days): maculopapular rash (often starting on palms/soles) with abdominal pain, nausea, severe diarrhea, and jaundice.
• Chronic GvHD (>100 days): features resemble autoimmune disorders (e.g. lichenoid or sclerodermatous skin changes, dry eyes/mouth from exocrine gland damage, obstructive lung disease like bronchiolitis obliterans).
• Transfusion-associated GvHD: ~1–2 weeks after a blood transfusion (especially from a relative or non-irradiated unit) with fever, rash, liver dysfunction, and pancytopenia (often fatal; prevented by gamma-irradiating blood products).

1. Prevention is key: allogeneic transplant recipients receive prophylactic immunosuppression (e.g. tacrolimus + methotrexate) to reduce GvHD; immunocompromised patients require irradiated blood products to prevent TA-GvHD.
2. Confirm the diagnosis with a biopsy of affected tissue (e.g. skin or colon): histology shows apoptotic host cells attacked by donor lymphocytes (e.g. apoptotic keratinocytes in skin or crypt cell apoptosis in gut).
3. Grade acute GvHD severity (I–IV) by extent of skin involvement, bilirubin elevation, and stool volume; higher grades correlate with worse prognosis and guide therapy intensity.
4. Always consider other causes for similar symptoms in post-transplant patients (e.g. drug rashes, infection) even as you evaluate for GvHD.

1. First-line for acute GVHD is high-dose corticosteroids (e.g. prednisone ~1–2 mg/kg/day); only ~40% of patients achieve a durable response.
2. Chronic GVHD is managed with prolonged immunosuppression (usually a corticosteroid taper ± calcineurin inhibitor or other agents).
3. Steroid-refractory GVHD: options include ruxolitinib (JAK inhibitor), extracorporeal photopheresis, and other immunosuppressants or biologics (no single standard; often used in combination).

• GvHD vs Rejection: GvHD is graft (donor T cells) attacking host, whereas rejection is host attacking graft.
• Always irradiate blood for at-risk recipients (immunosuppressed or HLA-matched donors) to kill donor lymphocytes and prevent TA-GvHD.

• Rapidly progressive skin rash with blistering, bloody diarrhea, and rising bilirubin in a post-transplant patient = severe GVHD emergency (high risk of shock/multi-organ failure).
• Never transfuse non-irradiated blood to immunodeficient or transplant patients—TA-GvHD causes pancytopenia and is often fatal.

1. Post-transplant patient with new rash or organ dysfunction → suspect GvHD.
2. Evaluate for other causes (infection, drug) but obtain skin or GI biopsy to confirm GvHD.
3. If acute GvHD is confirmed, start corticosteroids promptly (IV if GI involvement) and continue calcineurin inhibitor prophylaxis.
4. Grade the GvHD and escalate care if needed (e.g. add second-line immunosuppressants for steroid-refractory cases).
5. For chronic GvHD signs, initiate or adjust long-term immunosuppressive therapy (often a prolonged steroid taper ± steroid-sparing agents) with supportive care for affected organs.

• Allo-HSCT patient ~1 month post-transplant with painful rash on palms/soles, profuse diarrhea, and liver enzyme elevations → acute GVHD.
• Long-term transplant survivor with chronic dry eyes, oral ulcers, and tightening skin on hands (scleroderma-like) → chronic GVHD.