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Home > Disclaimer > BM Transplant

Acute Graft Versus Host Disease (aGVHD)

 

Occurs because alloreactive T-cells from the donor recognize foreign tissue of the host.

Classically occurs within first 100 days of transplant.  Now recognized to occur even later in some patients as a distinct clinical entity from chronic GvHD.

Three primary organ systems are affected by aGvHD:

• Skin
• Gastrointestinal Tract
• Liver

 

Figure:  Acute Stage 3 Skin GvHD

 

Figure: Acute Stage 4 Skin GvHD with desquamation of skin.  This severe aGvHD is of similar severity to a burn victim.

 

 

Combined immunosuppression is used after transplant for prophylaxis against aGvHD.  Multiple regimens exist.  Classic aGvHD prophylaxis regimens use combinations of

• Cyclosporin (a T-cell inhibiting calcineurin inhibitor)
• Short courses of lower dose methotrexate
• Corticosteroids 

• Other regimens use tacrolimus (another T-cell inhibiting calcineurin inhibitor) and mycophenolate mofetil.

Despite prophylaxis some patients still develop aGvHD and need to be treated.

aGvHD (particularly when severe) is a major contributor to transplant related mortality and morbidity.

 

Each of the three primary organ systems are staged to reflect their relative severity:

Stage	Skin Rash	Gastrointestinal	Liver (Total Bilirubin)
I	< 25% BSA	Diarrhea 5-10 mL/kg/day or persistent nausea	32.2-64.4 mmol/L
II	25-50% BSA	Diarrhea 10-15 ml/kg/day	64.4-102.6 mmol/L
III	50-100% BSA	Diarrhea >15 mL/kg/day	102.6-256.6 mmol/L
IV	Desquamation of Skin and Bullae Formation	Severe abdominal pain and ileus	> 256.6 mmol/L

Stages of aGvHD for the three major organ systems are then combined to provide an overall grade of aGvHD:

• Grade I: Mild aGvHD (requires no treatment)
• Grade II: Moderate aGvHD (requires treatment)
• Grade III: Severe aGvHD (requires treatment)
• Grade IV: Life-Threatening aGvHD (requires treatment and aggressive supportive care)

 

Treatment of aGvHD:

Moderate doses of systemic corticosteroids are first line therapy (e.g. Methylprednisilone 2 mg/kg/day IV divided q12 hour).

Patient remains on corticosteroids until a response is determined and then steroids are tapered over weeks.

If after 5 days there is no response or progression to higher grades, second line agents for treatment of aGVHD are initiated.

Second-Line Treatments for steroid-refractory aGvHD:

• Many options exist.  Little literature to support one over another.
• Examples of second line agents include:
  • Anti-thymocyte globulin (ATG)
    • monoclonal antibody that selectively depletes T-cells
  • Campath-1H
    • monoclonal antibody that depletes a number of mononuclear cell types
  • Etanercept (TNF-a receptor antagonist)
  • Infliximab (TNF-a antagonist)
  • Sirolimus
  • Mycophenolate Mofetil
  • Extracorporeal Photopheresis

Experimental studies are showing good promise in infusing mesenchymal stem cells (MSCs) as therapy for steroid-refractory aGvHD.

MSCs can be harvested from bone marrow of alternative donors (e.g. from a parent) and isolated.  MSCs have immunomodulating properties that suppress alloreactive T-cells causing aGvHD.