Canterbury DHB

Chronic GvHD (cGvHD)

Chronic GvHD has been more difficult to study than aGvHD and in an attempt to correct this the NIH has recently sponsored a chronic GvHD consensus project. Pavletic et al 2006 has summarised the work of the cGvHD working parties and this is a valuable source of cGvHD information. cGvHD may occur to some extent in up to 80% of patients in the 2 years following SCT. Risk factors for the development of cGvHD include: prior acute GvHD, mismatch or MUD SCT, and peripheral blood as the source of stem cells.

Clinical Features

• Acute GvHD may merge into cGvHD or cGvHD may arise de novo usually during the first 1-2 years post SCT. Day 100 is an arbitrary dividing line between acute and chronic GvHD. cGvHD may develop before this time.
• cGvHD may be mild and local eg skin or mouth and may only require local therapy. Any significant degree of cGvHD will lead to immunosuppression in its own right and the required treatment will also be immunosuppressive. These factors will both significantly increase the risk of infection.
• cGvHD typically affects the skin, mouth, eyes, GI tract, lungs, biliary tract, liver, genitalia and muscles and joints.
• Extensive chronic GvHD, and its associated treatment, increase the risk of infection, and are the leading causes of non relapse death occurring 2 years or more post SCT.
• By contrast there is good evidence linking the presence of cGvHD with a graft versus malignancy effect (GVM). The challenge is to control cGvHD while preserving GVM.

Pathogenesis

• Alloreactive, immunocompetent cells from the donor react against a number of defined tissues of the host. In general tissues at most risk for GvHD are the external surface tissues, as already indicated.
• Donor immuno-competent cells are primarily T cells and these expand within the recipient in response to host antigens.
• Tissues are attacked by a range of immunologic mechanisms – cytokine secretion, direct cytolysis, B cell activation and auto antibody production.

Diagnosis and Grading and Severity Assessment

See Pavletic 2006. The following criteria are based on the NIH Working Group recommendations:

cGvHD clinical features have been characterised as either diagnostic if they unequivocally indicate cGvHD or distinctive if they are merely suggestive of cGvHD.

The diagnosis of cGvHD should be made if there is one diagnostic manifestation of cGvHD or at least one distinctive manifestation with the diagnosis confirmed by biopsy, other lab tests, or radiology in the same or another organ.

The extent of cGvHD should be scored as follows:

Histology of cGvHD

See Shulmann et al for a recent review of the histological changes in cGvHD.

An algorithm for the diagnosis of liver GvHD has been developed to standardise reporting and help discriminate between GvHD and drug-related changes.

Topic Code: 9077