Chronic GvHD occurs in 40-70% of long-term survivors of HSCT and is a multisystem disorder distinct from acute GvHD.
Mechanism cGvHD (simplified):
- Immunocompetent cells of donor tissue react with tissues of immunosuppressed graft recipient1
- Requires:
- Profound depression of recipient's cellular immune response
- Receipt of an allograft of immunocompetent cells
- Recognition by the allograft of foreign antigens in host tissue
- Pathogenesis:
- Donor T lymphocytes interact with recipient histocompatibility antigens to which they become sensitized which then mount an attack on recipient cells producing the clinical signs of GvHD
Increased risk of cGvHD:
Patients are at increased risk for cGvHD if they have a history of:
- Receiving transplants from human leukocyte antigen (HLA)-nonidentical donors
- Previous acute GVHD
- Being older than 20 years at the time of transplantation
- Transplant factors:
- Degree of HLA-match
- Type of GVHD prophylaxis administered
- Degree of acute GVHD
- Ongoing chronic viral infections
- Stem cell source:
- Recipients of peripheral blood stem cell transplants (PBSCT) were at increased risk for chronic GVHD.
cGvHD:
- Onset of cGvHD is after 100 days following HSCT, but can occur years later
- Presentation:
- Wide heterogeneity of clinical presentations
- Most closely resembles autoimmune / rheumatologic disorders such as Systemic Lupus Erythematosus, Sjogrens syndrome and Systemic Scleroderma
- Patients may be mildly (limited cGvHD) to severely (extensive cGvHD) affected
- Patients with extensive cGvHD are likely to experience very poor quality of life, ongoing medical care, and are at higher risk of mortality after a transplant because of effects of cGvHD
- cGvHD is very immunosuppressive itself and patients are at high risk of disseminated bacterial and viral infections
Notes on pathogenesis:
- Complex and poorly understood
- Partly explained by alloreactive donor-derived T-cells that react against the recipient tissues.
- Increasing recognition of the role of immune dysregulation and autoimmune effector cells such as T-cells and B-cells.
- Effector cells do not develop tolerance for the host and even for themselves, resulting in both an alloreactive (against the recipient) and autoreactive (against the graft) reaction.
