Graft-vs.-host disease (GVHD)

Graft-vs.-host disease (GVHD) results from introduction of sufficient HLA-incompatible and immunologically competent donor lymphocytes into a recipient who is sufficiently immunodeficient that the incompatible donor cells cannot be destroyed. The donor lymphocytes proliferate and attack tissues of the new but incompatible host. There are two clinical types, organ transplants (represented here by bone marrow transplant) and blood transfusion. In bone marrow grafts the donor lymphocytes are in the graft. Current reports indicate that 60%-70% of patients with bone marrow grafts from HLA-compatible siblings (not identical twins) develop some degree of GVHD symptoms, and 10%-20% of marrow transplant patients die from it.

Graft-vs.-host(GVH) transplant disease can be acute or chronic. In bone marrow transplants, the acute type clinically begins about 10-28 days after transplantation; the first symptom usually is a skin rash. This is a somewhat longer time interval than onset in transfusion-related GVHD. About 20%-50% of HLA-compatible marrow transplant patients develop some degree of acute onset GVHD. Chronic GVHD occurs in 25%-45% of longer-term marrow transplant survivors; it typically appears 100 days or more after transplantation, but it can occur as early as 50 days or as late as 15 months. Persons under age 20 years have a relatively good chance of escaping or coping with GVHD, while those over age 50 have the worst prognosis. Marrow transplant patients develop B-lymphocyte lymphoproliferative disorders (benign, premalignant, or malignant lymphoma) in about 0.6% of cases. This is often associated with evidence of Epstein-Barr viral infection.

In the other clinical category of patients, transfusion is the usual cause. Patients at risk are those receiving intrauterine or neonatal exchange transfusions, and in congenital immunodeficiency syndromes, malignancy undergoing intensive chemotherapy (especially when combined with radiotherapy), and aplastic anemia. Incidence of posttransfusion graft-vs.-host syndrome in these conditions is not known with certainty but varies from 0%-8%, depending on the disease, therapy, and institution. The highest incidence appears to be in malignant lymphoma. In classic cases the syndrome develops 1-2 weeks (range 3 days-6 weeks) after transfusion and consists of fever, severe diarrhea, pancytopenia, hepatitis, and skin rash. Up to 90% of patients with a transfusion-related full-blown syndrome die, usually from infection. Both transplant and transfusion syndromes can be prevented by gamma radiation treatment of the blood product being transfused, in doses sufficient to affect lymphocytes but not other blood cells (usually 25 Gy = 2,500 rads). The AABB recommends radiation for all donors related by blood to the recipient. The greatest incidence of GVHD from blood-related donors is from first-degree blood relatives. RBC transfusion itself has immunologic effects on the recipient. It has been shown that random-donor blood transfusions before renal transplant decrease the incidence of graft rejection. Some institutions use RBC transfusion for this purpose. It is reported that transfusion therapy depresses natural killer cell function in these patients but the T4/T8 cell ratio remains normal. In addition, some studies report a somewhat greater incidence of recurrences or decreased overall survival in colon cancer patients who had multiple transfusions compared with those without transfusion, although this is disputed by other investigators.