Transfusion Associated Graft-Versus-Host Disease

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare complication that develops 4 to 30 days after the transfusion of cellular blood products (i.e. red blood cells, platelets, granulocytes). It can occur in both immunocompromised and immunocompetent patients, and recognition is often delayed because the nonspecific symptoms are attributed to the patient’s underlying diagnosis. TA-GVHD affects the transfusion recipient’s bone marrow and is nearly universally fatal, making prevention absolutely essential.

TA-GVHD is mediated by viable mature immunocompetent donor lymphocytes against the recipient’s antigen presenting cells. TA-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 certain settings. One is profound cell-mediated (T cell) immune deficiency, resulting from congenital, acquired, or iatrogenic causes. Another occurs when there is a specific type of partial Human Leukocyte Antigen (HLA) matching between the donor and recipient. HLA molecules are the primary means of distinction between self and non-self. If the donor HLA phenotype is homozygous and the recipient expresses the same HLA haplotype, it may mask donor lymphocytes from the recipient. The end result is engraftment and proliferation of mature donor T cells in the recipient’s bone marrow.

The donor T cells are then activated by mismatched HLA class I major antigens. This immunologic assault typically manifests clinically with fever and an erythematous, maculopapular rash which often progresses to generalized erythroderma. In addition to skin dysfunction, liver, gastrointestinal tract, and bone marrow symptoms are also common. The main laboratory findings of TA-GVHD include pancytopenia due to hypocellular marrow, abnormal liver function tests, and electrolyte abnormalities induced by diarrhea.

The differential diagnosis of TA-GVHD is broad. A more definitive diagnosis is suggested from skin biopsy which classically reveals vacuolization of the basal layer and a histiocytic infiltrate, and occasionally shows an almost pathognomonic finding — satellite dyskeratosis, which is characterized by single, dyskeratotic cells accompanied by lymphocytes. The definitive diagnosis of TA-GVHD relies in demonstrating that circulating lymphocytes have a different HLA phenotype from recipient APCs, proving that they came from the donor.

As mentioned above, TA-GVHD portends a high mortality rate and is poorly responsive to the available therapies; therefore prevention is of primary importance. Current strategies include gamma irradiation or leukocyte inactivation (i.e. pathogen reduction technology) of the blood products prior to transfusion to disable donor lymphocytes. Some of the more common indications for patients requiring irradiated blood products include those who are immunosuppressed, who have received a hematopoietic cell transplant, who are receiving blood components from a related donor, or who are given HLA-matched platelets. There is also evidence that transfusing older products decreases the risk of TA-GVHD due to the shortened lifespan of T cells within the products. In summary, TA-GVHD can occur in both immunocompetent and immunocompromised recipients, is mediated by donor T lymphocytes, and is almost always fatal.

For further reading, please see the review article by Kopolovic et al. A systematic review of transfusion-associated graft-versus-host disease. Blood. 2015;126(3):406-14.

 

Rogers

-Thomas S. Rogers, DO is a third-year resident at the University of Vermont Medical Center, a clinical instructor at the University of Vermont College of Medicine, and the assistant medical director of the Blood Bank and Transfusion Medicine service.

1 thought on “Transfusion Associated Graft-Versus-Host Disease”

  1. How can a resident (Dr. Rogers) be an assistant medical director of Blood Bank? This makes no sense as you need board certification (at least that is what I have always been told). Maybe the profile isn’t up to date, its just odd.

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