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Transfusion-associated graft-versus-host disease

INTRODUCTION

Graft-versus-host disease (GVHD) is a rare, although increasingly reported, almost always fatal complication of a blood transfusion. It occurs much more commonly after bone marrow transplantation, a setting in which it is less severe — mortality rate of 20 to 25 percent following transplantation versus 80 to 90 percent when associated with a transfusion [1].

GVHD results from an attack by viable immunocompetent donor lymphocytes on the recipient's lymphoid tissues. This immunologic assault is manifested clinically by dysfunction of the skin, liver, gastrointestinal tract and bone marrow. The effect on the bone marrow distinguishes transfusion-associated GVHD (ta-GVHD) from transplantation-associated disease. With bone marrow transplantation, the marrow cells in the recipient are of donor origin and are therefore exempted from attack. Thus, bone marrow aplasia, which is the primary cause of death in ta-GVHD, is an infrequent complication after bone marrow transplantation [2].

PATHOGENESIS AND INCIDENCE

GVHD does not occur after most transfusions because the donor lymphocytes are destroyed by the recipient's immune system before they can mount a response against the host. However, this protective response does not occur in two settings: when the recipient is immunodeficient; and when there is a specific type of partial HLA matching between the donor and recipient.

Immunodeficient states — Transfusion-associated GVHD was first described in 1965 in a cohort of immunodeficient children [3]. Over the next 15 years, 38 cases were reported in a number of different immunodeficient states, including newborns with erythroblastosis fetalis, Hodgkin's and non-Hodgkin lymphoma, and acute and chronic leukemia [4]. Other patients at risk include those with solid tumors who are immunosuppressed because of chemotherapy (eg, purine analog therapy) or radiation and severe congenital or acquired immune deficiency [5-7].

By 1980, the incidence of ta-GVHD was estimated at 0.1 to 1.0 percent in patients with hematologic cancers or lymphoproliferative disorders. With the increased use of irradiation and leukoreduction of blood products in the 1990s, as well as a decreased use of fresh blood and directed donations, the incidence of ta-GVHD has fallen considerably. As an example, the incidence of ta-GVHD was approximately 0.15 percent in Japan between 1981 and 1986, whereas there were no cases reported in Japan during 2000 or 2001 [5].
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