Update on the Use of Irradiated Blood Components for Transplantation

by Laurie J. Sutor, MD, MBA, VP of Medical and Technical Services

Irradiation of blood is done to prevent graft-versus-host disease (GVHD) in susceptible patients getting transfusion. Current practice in U.S. blood banks tends to use one of two types of dedicated blood component irradiators: the traditional cesium source irradiator which emits gamma rays, or the x-ray irradiator which has been growing in popularity. Both will inactivate the lymphocytes in the components and prevent their proliferation and attack on recipient tissues after transfusion. Leukocyte reduction filters are NOT considered adequate to remove enough white cells to guarantee prevention of GVHD. GVHD is 90 to 100% fatal when caused from transfusion (as opposed to the GVHD a patient gets following a hematopoietic stem cell transplant). Pathogen reduction technology (now available for platelet components but not often used in our area) can also inactivate lymphocytes and prevent GVHD without irradiation.

So which patients need irradiated blood? This question is a never-ending source of debate. Some patients are clearly at risk and are outlined in references such as the AABB Technical Manual. They include fetuses, premature infants, some with congenital immunodeficiencies, some solid tumors, hematopoietic stem cell transplants, those getting HLA matched components, patients getting restricted donations from relatives, patients getting purine analogue drugs (e.g. fludarabine), and patients with Hodgkin disease. Less clear are other patients with cancer, especially leukemia’s and lymphomas. Unresolved questions seem to be whether irradiated blood is ever indicated for solid organ transplant patients, and when exactly to start and possibly stop use of irradiated blood in hematopoietic stem cell transplant (HSCT) patients who successfully engraft.

I did a review of current literature to see if there have been any changes to recommendations for use of irradiated blood, or especially if there were any published studies to support an evidence-based medicine approach to practice.

A very useful article that I found was by Treleaven et al in the British Journal of Haematology in 2010. These authors did an extensive review of the English literature from 1950 to 2009 on blood irradiation and transfusion-associated GVHD and did an evidence-based grade of each article on the strength of its recommendations. They found articles to support that if chronic GVHD is present after HSCT, or if immunosuppression is required, irradiation should be continued indefinitely. Also, if an allogeneic donor will be required for the HSCT patient, and their harvest occurs within 7 days of transplant, they should also
get irradiated blood if transfusion is necessary. The same goes for autologous HSCT donors needing transfusion within 7 days of freezing their product. Otherwise, if all goes well with the transplant, autologous HSCT patients should receive irradiated blood from the time of conditioning treatment until 3 months post-transplant (or 6 months if total body irradiation was used). Hodgkin disease patients should receive irradiated blood for life, as should patients receiving purine analogue drugs. Patients with leukemia, not undergoing HSCT, do not need irradiated blood unless getting HLA matched components. This article did
not comment on organ transplant or solid tumors.

Another interesting article was by Kopolovic et al in Blood in 2015. This article looked at 348 cases of known transfusion-associated GVHD from 6 databases. 34.8% of the cases occurred in patients that should have gotten irradiated blood but didn’t (e.g. high risk patients). Five cases of TA-GVHD in this study got GVHD despite getting irradiated blood, raising the question of whether it was done correctly. The other cases were apparently immunocompetent patients with no known risk factors under our current guidelines. Of all the cases, 89.7% died at a median of 24 days.

The newest publication I found was a May 2018 article in Archives of Pathology and Laboratory Medicine by Bahar and Tormey. This article did specifically say that organ transplant patients do not need irradiated blood. They cited old evidence that kidney transplant patients getting non-irradiated blood actually do better than those getting irradiated blood (Opelz and Terasaki 1978). Finally, they state that any GVHD in this group has been found to be from passenger lymphocytes from the organ, not the transfusions (Triulzi et al 2001).

 Finally, I did a survey of local hospitals to see what regional practice is for irradiation in the transplant population. Few conclusions could be drawn, other than once a patient gets irradiated blood, the blood bank flags the patient’s chart and continues to give irradiated blood until told not to. The practices for using irradiated blood for organ transplant patients varied significantly from place to place, as did whether to use irradiated blood for leukemia and lymphoma patients and solid malignancies. Every place surveyed that has HSCT patients replied that they never stop giving irradiated blood to that group.

 In summary, although there have been some slight changes in recommendations in recent years, much remains unresolved as to our transplant and cancer population and the use of irradiated blood, but there is evidence that many facilities probably overuse irradiated blood in an effort to be safe rather than sorry.

 References
Prevention of transfusion-associated graft-versus-host disease with blood product irradiation. The past, present, and future. B Bahar and CA Tomey. Arch Pathol Lab Med 2018 142(5):662-7.
Survey of irradiation practice for the prevention of transfusion-associated graft-versus-host disease. AE Pritchard and BH Shaz. Arch Pathol Lab Med 2016
140(10):1092-7.
A systematic review of transfusion-associated graft-versus-host disease. I Kopolovic, J Ostro, H Tsubota, Y Lin, CM Cserti-Gazdewich et al. Blood 2015
26(3):406-14.
Guidelines on the use of irradiated blood components prepared by the British Committee for Standards in Haematology blood transfusion task force. J
Treleaven, A Gennery, J Marsh, D Norfolk et al. Brit J Haematol 2010 152:35-51.
Microchimerism, GVHD, and tolerance in solid organ transplantation. DJ Triulzi and MA Nalesnik. Transfusion 2001. 41(3):419-26.
Improvement of kidney graft survival with increased numbers of blood transfusions. G Opelz and PI Terasaki. N Engl J Med 1978 299(15):799-803.