The Role of UV Radiation in the Prevention of Human Leukocyte Antigen Alloimmunization

Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma, and even poliomyelitis. The early studies were carried out by several physicians in USA and published in the American Journal of Surgery. However, with the development of antibiotics, the use of UBI declined and it has now been called “the cure that time forgot.” Later studies were mostly performed by Russian workers, and in other Eastern countries, and the modern view in Western countries is that UBI remains highly controversial. This review discusses the potential of UBI as an alternative approach to current methods used to treat infections, as an immune-modulating therapy and as a method for normalizing blood parameters. Low and mild doses of UV kill microorganisms by damaging the DNA, while any DNA damage in host cells can be rapidly repaired by DNA repair enzymes. However, the use of UBI to treat septicemia cannot be solely due to UV-mediated killing of bacteria in the bloodstream, as only 5–7% of blood volume needs to be treated with UV to produce the optimum benefit, and higher doses can be damaging. There may be some similarities to extracorporeal photopheresis (ECP) using psoralens and UVA irradiation. However, there are differences between UBI and ECP in that UBI tends to stimulate the immune system, while ECP tends to be immunosuppressive. With the recent emergence of bacteria that are resistant to all known antibiotics, UBI should be more investigated as an alternative approach to infections, and as an immune-modulating therapy.

Improvements in the availability and quality of platelet transfusions have markedly reduced the morbidity and mortality associated with intensive myelosuppressive therapy. Alloimmunization and refractoriness to platelet transfusion remains a significant clinical problem, although the incidence of alloimmunization may be declining due to more widespread use of leucocyte depleted products. Alloimmunization can be distinguished from other causes of poor post transfusion increments by the measurement of lymphocytotoxic or antiplatelet antibodies. In addition to medical approaches to reduce the risk of bleeding in individual patients, identification of histocompatible donors can usually be accomplished by HLA matching of donor and recipient, platelet cross matching or a combination of both techniques. There are a number of selection strategies which can be utilized and optimal patient management requires close cooperation and communication between clinicians and blood centers.

Blood components are modified to meet the clinical requirements of specific patient populations. The clinical indications for some well-established components have narrowed with the development of new technology. Leukoreduced blood components are being considered for a variety of clinical applications. Published data support the use of leukoreduced components to prevent febrile nonhemolytic transfusion reactions. The routine use of such components for other indications should be considered experimental, and the cost effectiveness of experimentally validated indications should be evaluated.

We studied the value of leukocyte depletion of platelet transfusions for the prevention of secondary human leukocyte antigen (HLA)-alloimmunization in patients with a high-risk of prior immunization induced by pregnancies. Seventy-five female patients with hematologic malignancies (mostly acute leukemia) and a history of pregnancy were randomized to receive either standard random single-donor platelet transfusions (mean leukocytes, 430 × 10⁶ per transfusion) or leukocyte-depleted random single-donor platelet transfusions, Leukocyte depletion to less than 5 × 10⁶ leukocytes per platelet transfusion (mean leukocytes, 2 × 10⁶ per transfusion) was achieved by filtration. Of the 62 evaluable patients, refractoriness to random donor platelets occurred in 41% (14 of 34) of the patients in the standard group and in 29% (8 of 28) of the patients in the filtered group (P = .52); anti-HLA antibodies developed in 43% (9 of 21) of individuals in the standard group and 44% (11 of 25) of cases in the filtered group. The time toward refractoriness and development of anti-HLA antibodies was similar for both groups. We conclude that leukocyte depletion of random single-donor platelet products to less than 5 × 10⁶ per transfusion does not reduce the incidence of refractoriness to random donor platelet transfusions because of boostering of anti-HLA antibodies.

Many of the risks and discomforts associated with blood transfusion may be avoided by removing the contaminating leukocytes from cellular blood components. Leukocyte reduction prevents many febrile reactions that occasionally occur following red cell transfusion and prevents some febrile reactions following platelet transfusion. Prophylactic use of leukocyte-reduced components may prevent primary HLA alloimmunization, which is a principle cause of the refractoriness to platelet transfusion seen in many multiply transfused, thrombocytopenic patients. Leukocyte-reduced components are equally effective in the prevention of CMV as seronegative blood.