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Transfusion Rxn: GVHD

Transfusion-associated Graft-Versus-Host-Disease (Ta-GVHD) is a rare phenomenon that is distinct from the more common form of GVHD that occurs following stem cell transplant.

Definition: Transfusion-associated Graft-Versus-Host-Disease (Ta-GVHD) is a rare transfusion complication that occurs when viable T-lymphocytes are transfused to a new host (the recipient), engraft and multiply, and then attack HLA-presenting tissues in the host (recipient).

Pathogenesis: Ta-GVHD may occur with most transfusion products, including: whole blood, pRBCs, platelets, and plasma that has not been frozen. In affected individuals, the recipients immune system fails to destroy the transfusion lymphocytes either by lack of recognition or inability of the immune system to mount a defense.

Risk Factors: There are multiple disease states that place an individual at increased risk for developing Ta-GVHD, including: primary immunodeficiencies (ex. SCID, Wiskott-Aldritch syndrome), hematologic malignancy (Hodgkin’s lymphoma, Non-Hodgkin’s lymphoma, AML, CML, CLL), certain immunosuppressive drugs (fludarabine), and hematopoietic stem cells transplant. A particularly important risk factor for Ta-GVHD is partial-HLDA matching of transfusion products. In this situation, the recipient’s immune system fails to recognize the transfused lymphocytes due to recognition of some of the HLAs displayed by said lymphocytes. This mechanism is more common in genetically homogeneous populations.

Signs and Symptoms: Ta-GVHD is difficult to diagnose due to a varied, non-specific presentation. Donor cells may attack any tissue in the body, but classically attack the hematopoietic cells, intestinal epithelium, liver, and skin. Classically this may result in pancytopenia, hepatomegaly and/or transaminase elevation, diarrhea, rash, and fever. The disease typically presents within one week to one month of transfusion and often starts with rash. GI complaints can be serious and the typical diarrhea is high volume (7-8 L per day) and may result in electrolyte derangement.

Prevention/Treatment: The primary treatment for Ta-GVHD is prevention. This is accomplished primary by leukocyte irradiation of transfusion products for at risk populations. Practices vary by country, some of which provide universal leukocyte irradiation for their blood products.

Outcomes: The only effective treatment for Ta-GVHD is hematopoietic cell transplant, which is often not an option due to the rapid progression of the disease. Immunosuppression may mitigate disease affects, but is not a curative option.