TRANSFUSION ASSOCIATED GRAFT VS. HOST DISEASE AND IRRADIATED BLOOD COMPONENTS

Darrell J. Triulzi, M.D., Assistant Medical Director, Patient Transfusion Services

INTRODUCTION

Graft vs. host disease is a rare complication of transfusion.  The disease results from transfusion of immunocompetent T cells capable of engrafting and initiating an immune response against recipient antigens.  The most susceptible patient groups are those who are severely immunocompromised or are the recipients of directed donations from first-degree relatives.  Transfusion associated graft vs. host disease (TAGVHD) can be prevented by gamma irradiation of cellular blood components (red cells, platelets, granulocytes).

CLINICAL PRESENTATION

TAGVHD has the same features as graft vs. host disease occurring in other settings such as allogeneic bone marrow transplantation.  It typically occurs 3-30 days after transfusion of non-irradiated cellular products.  The initial manifestations are often a high fever and an erythematous skin rash.  Bone marrow aplasia and pancytopenia are also characteristic findings in TAGVHD.  Other organs which may be involved include the gastrointestinal tract and liver.  The diagnosis is made on the basis of a constellation of clinical features and can be confirmed by biopsy of the skin or other involved organs.  This form of GVH has an extremely poor prognosis; the mortality rate approaches 90%.  Unfortunately, there are no current effective therapies.

pathogenesis

TAGVH occurs when immunocompetent T cells are transfused into a host incapable of eliminating these foreign lymphocytes.  The donor T cells initiate a cell mediated immune response directed at a host tissue antigens.  The recipient’s inability to eliminate these donor lymphocytes may result from severe immunoincompetence or an inability to immunologically recognize the transfused cells as foreign.  An example of the former is a bone marrow transplant recipient who immune system has been ablated by the chemotherapeutic regimen.  The latter case is exemplified by reports of the occurrence of TAGVHD in immunoceompetent patients.  HLA studies have confirmed that TAGVHD occurs in this setting as a result of donor homozygosity for an HLA haplotype in the recipient (e.g., A19, B7, B57).  Thus, donor T cells recognize the recipient antigens (A19, B57) as foreign but the recipient does not recognize the donor T cells as foreign (A2 and B7 are “self” antigens). 

Directed donations from first degree relatives and transfusion of HLA matched platelets increase the risk that this situation will occur.

irradiation of blood products

Only cellular blood components contain viable lymphocytes capable of causing TAGVH.  Gamma irradiation abolishes the proliferative activity of the lymphocytes.  Blood irradiators are capable of delivering 15-30 Gy over 1-5 minutes per unit; this dose effectively inactivates immunocompetent T cells.  Gamma irradiation does not affect in vivo red cell, platelet, or granulocyte survival or function, but slightly decreases the ability of red cells to tolerate storage.  For this reason, it is recommended that irradiated red cells not be stored for more than 28 days.  Irradiation does not eliminate leukocytes and thus is ineffective in preventing febrile transfusion reactions.  Fresh frozen plasma and cryoprecipitate do not contain viable lymphocytes and thus do not need to be irradiated.

indications for irradiated blood products

The American Association of Blood Banks requires that the following patients receive irradiated cellular blood products:

1)      fetuses requiring intrauterine transfusions.

2)      Recipients of directed donations from first degree relatives

3)      Selected immunoincompetent recipients.

It is recommended that the latter group include the following: bone marrow transplant recipients, patients with congenital immunodeficiency syndromes (i.e. DiGeorge syndrome, Wiscott Aldrich, SCID), and neonates receiving exchange transfusion for hemolytic disease of the newborn.  Irradiated blood products may be considered for premature neonates, patients with leukemia, lymphoma, or Hodgkin’s disease, recipients of HLA matched platelets, or recipients of solid organ transplants.

The need for irradiated blood products has not been demonstrated in AIDS patients, term newborns, renal transplant recipients, or patients with nonhematologic malignancies treated with chemotherapy or irradiation.

Copies of the Transfusion Medicine Update can be obtained by contacting Deborah Small at (412) 209-7320 or
by e-mail:  dsmall@itxm.org.