Graft Versus Host Disease: A TGH Special

During your time at TGH, you will likely encounter the entity of Graft Versus Host Disease (GVHD). It is  not a common disease; however, it is commonly seen at TGH due to our immune-suppressed patients, especially in transplanted patients. Let's first discuss the types of stem cell/bone marrow transplant (aka Hematopoietic cell transplantation).

Autologous: Hematopoietic cells are harvested from the bone marrow or peripheral blood prior to high-dose myeloablative chemotherapy/radiotherapy. The cells are then later reinfused back into the same patient during a period of prolonged bone marrow failure in order to help restore hematopoiesis. This type of transplant is used in lymphoma and myeloma, and has previously been used in patients with some solid tumors. 

Allogeneic: Stem cells are harvested from the bone marrow of healthy donors or newborn umbilical cord and are infused to reconstitute a host hematopoeitic system following myeloablative therapy. Allogenic stem cell transplants carry the same risks as autologous transplants, with the additional risk of graft-versus-host-disease.

Graft Versus Host Disease (GVHD)
GVHD occurs when donated lymphocytes attack normal host tissues because they are recognized as 'foreign.' GVHD is a common consequence of allogenic bone marrow transplantation, occurring in up to 40% of patients. It is a potential complication of all transplantation, including transfusion of blood products, but is particularly concerning in stem cell transplantations due to the inherent immune suppression of patient's undergoing stem cell or bone marrow transplantation. Due to their immune-suppressed nature, it is often difficult to differentiate infections from GVHD in patients who have received allogeneic transplants.

Risk Factors for GVHD
- Degree of HLA mismatching 
- Older age
- The use of peripheral blood/bone marrow samples instead of umbilical cord blood 

Sites Most Commonly Affected by GVHD
Skin - Lichen planus-like or morphea-like changes, sclerotic features. Diagnosis can be made without biopsy. 
Gut - Mucosal sloughing, severe cramps with secretory diarrhea. Diagnosis made on biopsy
Liver - Cholestatic hepatitis with nausea and vomiting.
Lungs - Bronchiolitis obliterans. Diagnosis made on biopsy.

Forms of GVHD
Acute
This form usually occurs before 100 days post-transplant and can present with a classic maculopapular or bullous rash, cholestasis with elevated bilirubin, nausea & vomiting, and abdominal cramps with diarrhea. Acute GVHD can occur more than 100 days after transplant, and is known as Late-Onset Acute GVHD.

Chronic
The chronic form more resembles other autoimmune disorders, presenting with arthritis, scleroderma-like skin changes or lichen planus, sicca syndrome, and chronic hepatitis with rising bilirubin. Patients may sometimes present with features of both chronic and acute GVHD, in which case they are labeled with an 'Overlap' syndrome.

Treatment
Because GVHD is immune-mediated, it is often treated with glucocorticosteroids. This therapy can be local (topical for skin, enteric for gut) or systemic (oral or IV). Other therapies include cyclosporine, MMF, and azathioprine. Complications related to the disease and its treatment must be monitored carefully.