Comment

THE EARLY DESCRIPTION O f graft-versus-host disease (GV H D) as a secondary syndrome in a transfused patient who received an allogeneic bone marrow graft was confirmed by many investigators.'.2 G V H D is now recognized as a rare complication of modern blood transfusion practice. The affected patient usually is immunosuppressed and develops G V H D when given blood products containing viable donor lymphocytes. After a latent period of about I week, affected patients develop a characteristic syndrome usually presenting with a skin rash, progressing to gut, liver, and bone marrow involvement. Study of posttransfusion G V H D has been hampered by the difficulty of its identification in the face of other disease-associated clinical problems, its infrequent occurence. and the fact that many of these cases have a fatal outcome. G V H D as a posttransfusion event is thought to be a preventable complication of blood transf~sion. ' .~ Most investigators recommend irradiation of allogeneic blood components to be transfused to susceptible recipients. Although controlled trials have not documented the efficacy of this approach, irradiation of blood products is commonly performed for recipients thought to be at highest risk. Since GVHD is a rare complication, other patients with a potential risk are not likely to be studied on a prospective basis. lrradiation of blood is a simple procedure with the proper equipment. The high cost of blood irradiators has led to questioning of the efficacy of this procedure for small groups of patients. Leitman and Holland' attempted to answer some of these questions in the previous article. They provide the reader with a thorough review of the pathophysiology of G V H D and its prevention. The authors established a list of patient groups at risk for posttransfusion GVH D and presented a formulation of guidelines for the appropriate use of irradiated blood products. Another published review by Brubaker' attempted to accomplish similar functions. Despite the excellence of these two scholarly efforts, controversies remain concerning the clinical settings in which irradiated blood is a real versus theoretical need, the dosage and type of irradiation that is optimal for G V H D prevention. the effect of irradiation on other cellular elements, and the potential long-term effect of transfusion of irradiated blood products. The recommendations of Leitman and Holland regarding who should receive irradiated blood are generally accepted. Certainly recipients of allogeneic or autologous bone marrow transplants and patients with congenital immune deficiency syndromes should receive irradiated blood as a standard adjunct t o their therapy. However, based upon our review of the literature, we also would include infants receiving intrauterine transfusions and subsequent transfusions after birth in this initial category. Our list of relative indications also would include children with neuroblastoma on chemotherapy regimens that cause severe marrow ablation: It must be recognized that the low incidence of G V H D makes prospective randomized studies both difficult and expensive to perform. As chemotherapy becomes more ablative and as new T-cell depletion methods are established, the indications for irradiated blood are likely to expand. Two potential clinical applications involve patients receiving antithymocyte globulin (ATG) or thymosin alpha-], and patients with osteogenic sarcoma and other hematological malignancies undergoing combined extensive irradiation and chemotherapy. Recipients of solid organ transplants, such as kidney, heart, or liver, receiving transplant immunosuppression may belong t o another group that warrants irradiated products. The extent and timing of ablative therapy and coincidence with transfusion might warrant the use of irradiated blood products in certain solid tumors cases. Future indications should be based upon the documentation of presumed risk (severe immunodeficiency) but cannot safely await reports of G V H D in patients a t risk. Part of our dilemma concerns establishing irradiated blood as a requirement for managing patients. Most patients a t risk for G V H D are treated at tertiary care hospitals where irradiated blood products are required for some patients. As leukemia therapy and intensive neonatal medicine become more common in rural areas, the need for hospitals t o provide irradiated blood products increases in these areas. Is the large technologic investment justified to help only a small group of patients? If irradiation equipment is already available, it becomes reasonable to expand the clinical indications for more speculative cases. A better understanding of the factors that make patients susceptible to G V H D after transfusion also will assist in determining which patients will benefit from receiving irradiated blood. Histocompatibility similarities between donor and recipient may be one f a ~ t o r . ' . ~ The number of immunocompetent cells transfused per unit time during maximal immunosuppression is a n ~ t h e r . ~ Certain undetermined factors, such as type of chemotherapy, also may be important. Since it is difficult to quantitate the immunosuppressive effects of various chemotherapeutic agents, it is difficult t o assess how the type of chemotherapy may affect the likelihood of GVHD. The age of the patient may be another factor; G V H D is associated with a higher