In the past, chronic graft-versus-host disease (cGVHD) was characterized by time of onset. Generally speaking, any manifestation of GVHD after day 100 was termed cGVHD. The most recent NIH Consensus Working Group data suggests that clinical manifestations, and not the time to symptomatic onset after transplantation, determine if the syndrome is acute or chronic. In addition, a new scoring/grading system replaces the historical system of classifying a patient as having “limited” or “extensive” disease.

There is no consensus to the pathogenesis of cGVHD. T lymphocytes play a major role but evidence shows that in some patients there is coordinated B-cell and T-cell attack. In addition, there is data that suggests that cGVHD may be related to autoimmune reactions of the donor cells.

RISK FACTORS

Accepted Factors

• History of grade II or greater aGVHD

• Disparity at Class I or Class II human leucocyte antigen (HLA) loci

• Peripheral blood stem cells versus bone marrow source

• Patient diagnosis (chronic myelogenous leukemia [CML] and aplastic anemia)

• Female donor → male recipient (even greater if parous)

• Older recipient age

• Multiparous female donor

• History of acute inflammation, for example, TEN, Stevens Johnson, and others

• Non-T-cell-depleted source

• Donor lymphocyte infusion (DLI)

• Sun exposure

Possible Risk Factors

1. Cytomegalovirus (CMV) seropositivity

2. History of splenectomy

3. Corticosteroids as aGVHD prophylaxis

4. High number of CD 34+ cells in a peripheral blood stem cell infusion