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Transfusion Associated Graft Versus Host Disease

Transfusion associated graft versus host disease (TAGVHD) occurs when viable donor T lymphocytes engraft and multiply in a recipient incapable of eliminating them. Donor T cells initiate a cell mediated immune response directed at recipient tissue antigens. The recipient’s inability to eliminate these donor lymphocytes may result from severe immunodeficiency or an inability to immunologically recognize the transfused cells as foreign.  An example of the former is a bone marrow transplant recipient whose immune system has been ablated by high dose chemotherapy. The latter situation occurs in immunocompetent patients who receive directed donations of red cells from first degree relatives or HLA matched platelets. It seems to occur when the donor is homozygous for one of the recipient’s HLA haplotypes. For example, if a donor is homozygous for an HLA haplotype (e.g. HLA A2 A2, B7, B7) and a recipient is heterozygous (HLA A2, A19, B7, B57) the recipient would not recognize donor lymphocytes as foreign, but donor lymphocytes would recognize recipient lymphocytes as foreign. As seen in the following table, relative risk of TA-GVHD varies with the relationship of donor and recipient.


Donor Relationship Relative Risk of TAGVHD
Parent/Child 7.2
Second Degree Relative 4.1
Sibling 3.9
First Cousin 2.6
Second Cousin 1.4
Unrelated 1.0


The National Healthcare Safety Network (NHSN) hemovigilance protocol has published the following case definition of TAGVHD: A clinical syndrome occurring from 2 days to 6 weeks after cessation of transfusion characterized by:

  • Erythematous, maculopapular rash that develops centrally and spreads to extremities
  • Diarrhea
  • Fever
  • Hepatomegaly
  • Liver dysfunction
  • Marrow aplasia
  • Pancytopenia
  • Characteristic histological appearance of skin or liver biopsy.

Response to therapy is poor and mortality is 90%. Most patients die from severe pancytopenia and infection. TAGVHD can be prevented by gamma irradiation (2500 cGy per unit for 1 to 5 minutes) of cellular blood components to inactivate lymphocytes. Leukocyte reduction by filtration does not remove sufficient numbers of lymphocytes to prevent graft versus host disease. 

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