Canadian Coordinating Office for Health Technology Assessment LEUKOREDUCTION: the techniques used, their effectiveness and costs CCOHTA Report 1998: 6E Cite as: Canadian Coordinating Office for Health Technology Assessment. Leukoreduction: the techniques used, their effectiveness and costs. Ottawa: Canadian Coordinating Office for Health Technology Assessment (CCOHTA); 1998. Reproduction of this document for non-commercial purposes is permitted provided appropriate credit is given to CCOHTA. Legal Deposit - 1998 National Library of Canada ISBN 1-895561-60-4 Canadian Coordinating Office for Health Technology Assessment LEUKOREDUCTION: the techniques used, their effectiveness and costs Bernhard Gibis, MD, CCOHTA Research Fellow Jean-François Baladi, MBA February 1998 This report was commissioned by the Canadian Blood Agency. The opinions and conclusions reached, however, are those of CCOHTA. The Canadian Coordinating Office for Health Technology Assessment (CCOHTA) is a non-profit organization, funded by the federal, provincial and territorial governments. It was established to encourage the appropriate use of health technology by influencing decision-makers through the scientific evaluation of medical procedures, devices and drugs. The effectiveness and cost of technology and its impact on health are examined. Additional copies of Leukoreduction: the techniques used, their effectiveness and costs are available from CCOHTA. Vous pouvez aussi vous procurer la version française, La réduction leucocytaire : les techniques, leur efficacité et les coûts, à l’OCCÉTS. To obtain copies of publications please contact: CCOHTA Publications 110-955 Green Valley Crescent Ottawa, Ontario, Canada K2C 3V4 Telephone (613) 226-2553 Facsimile (613) 226-5392 E-mail [email protected] or download full text from http://www.ccohta.ca REVIEWERS Dr. Walter Dzik, MD Dr. Bernie O’Brien Director, Transfusion Medicine CCOHTA Scientific Advisory Panel Harvard Medical School subcommittee member Boston, USA Associate Professor, McMaster University Centre for Evaluation of Medicines, Dr. Sherill Slichter, MD St. Joseph’s Hospital Director, Division of Research and Hamilton, Ontario Education Puget Sound Blood Centre Dr. Murray Krahn Seattle, USA CCOHTA Scientific Advisory Panel subcommittee member Dr. Georges Andreu, MD Toronto Hospital Établissement de transfusion sanguine de Toronto, Ontario l’Assistance publique, Hôpitaux de Paris Paris, France This report was reviewed by external Dr. Andreas Laupacis reviewers and by members of a Chair, CCOHTA Scientific Advisory Panel subcommittee of CCOHTA’s Scientific Director, Clinical Epidemiology Unit Advisory Panel. These individuals Ottawa Civic Hospital kindly provided comments on drafts of Ottawa, Ontario this report. This final document incorporates most of the reviewers’ comments; however CCOHTA takes sole responsibility for its form and content. ACKNOWLEDGEMENTS CCOHTA would like to thank the Scientific Advisory Committee and staff members of the Canadian Blood Agency for their valuable input. i EXECUTIVE SUMMARY Leukocytes, as part of transfusions, can cause a variety of side-effects such as febrile reactions, platelet refractoriness, and transmission of viruses like the cytomegalovirus. In addition, transfused leukocytes may suppress the recipient’s immune response thereby increasing the risk of infection or malignancy. Therefore, reduction of leukocytes in blood and platelet transfusions may potentially reduce the frequency of these adverse events and save costs. Currently, third generation adhesion filters exist which can achieve a three log reduction of the original leukocyte load. This study examines the efficacy of various filtration techniques and compares their costs and their potential savings. More specifically, it compares the efficacy of various filtration techniques in reducing the leukocyte load of transfused blood components (apheresis platelets, pooled platelets and red blood cells), their cost, as well as the savings associated with a reduction in treating the adverse events related to transfused leukocytes. Adverse events examined include febrile reactions, platelet refractoriness following alloimmunization and immunomodulation. The efficacy of leukoreduction in reducing these adverse events was obtained from an extensive literature search of published literature complemented with a number of interviews with Canadian stakeholders. Level of evidence was assessed and is indicated throughout the report. Canadian resource use and cost estimates were obtained from a number of Canadian sources. A retrospective analysis of patient charts was conducted for estimating the cost of treating febrile reaction. The cost of platelet-refractoriness due to allo-immunization was estimated by a panel of experts. The cost of immunomodulation was estimated by assuming that immunomodulation increases the likelihood of surgical site infections. The use of blood products was based on the annual Red Cross statistical report and data obtained from the CBA. The analysis is conducted from the perspective of the Canadian health care and blood transfusion systems. The efficacy of leukofiltrating three blood components (apheresis platelets, pooled platelets and red blood cells) was examined at three possible stages: in a regional blood centre before storage of the blood component, in a hospital blood bank following storage and prior to delivering it to the requesting ward, and at a patient’s bedside just before the transfusion. Thus, nine filtration techniques are assessed, each one having its own clinical efficacy and its cost. Clinical Efficacy Non Hemolytic Febrile Transfusion Reactions: non Hemolytic Febrile Transfusion Reactions (NHFTR) are the most common leukocyte-related adverse effects of blood transfusions. Pre- or post-storage filtered transfusions prevent most febrile reactions to red blood cell transfusions and in this respect, the advantage of pre-storage filtration has not been proven in a randomized controlled trial. However, platelet transfusions are associated with a higher rate of adverse events, and post-storage filtration of platelets is not as effective as post-storage filtration of red blood cells. In the case of platelets, pre-storage filtration offers the advantage of preventing the production of some leukocyte mediated cytokines during the storage period. ii Infections: the risk of transmission of leukocyte born viruses such as the cytomegalovirus (CMV) via transfusion of red blood cells and platelets is markedly decreased by leukofiltration. Consequently, leukofiltration is increasingly accepted as an alternative to CMV screening of blood components. However, for other viral or bacterial/protozoal infections, we found no evidence that leukofiltration is an alternative to existing screening programs. Thus, apart from CMV, the impact of leukofiltration on the prevention of transfusion-related infections remains unknown. Platelet-refractoriness: To prevent thrombocytopenic bleeding due to high dose chemotherapy, prophylactic platelet transfusions are usually given. The ability of these transfusions to increase the platelet count can be inhibited if the recipient has an immune response due to prior HLA- alloimmunization to donor blood components, mainly leukocytes. Leukofiltration reduces the incidence of alloimmunization and therefore platelet refractoriness particularly in desensitized patients. However, despite several experimental and retrospective studies, no randomized controlled trial exists that has demonstrated an advantage of pre- over post-storage filtration. Immunomodulation: an immunomodulatory effect of blood transfusions in humans is still controversial. A recent meta-analysis of unconfounded randomized controlled trials concluded that any possible effect would be smaller than 25% (relative risk reduction of postoperative infection, cancer recurrence after surgery). At present, there is no evidence from clinical trials that the timing of filtration influences immunomodulation. Cost Comparison The cost of each of the nine filtration techniques was assessed in both single and multi- transfused patients. This cost included the cost of filters, the cost of related activities such as inventory management and overhead costs and the cost of treating adverse reactions. The cost of treating adverse events is itself dependent on the number of transfusions, the efficacy of the leukoreduction technique and the cost of treating the particular adverse reaction. We then calculated the cost impact for three main strategies, the first being filtering all blood components in a blood centre, the second, filtering all components in a hospital blood bank, and the third, filtering all blood components at the patient bedside. This analysis focused on the costs associated with filtration and does not take into account the cost of producing different blood components. Thus the cost of one apheresis platelet cannot be compared directly with the cost of one pooled platelet. In addition, health-related-quality-of-life under different techniques were not examined. Costs are presented in 1997 Canadian dollars and have been estimated from the perspective of the health care system. For the purpose of the cost comparison, the benefit of the doubt was given to pre-storage filtration. A higher efficacy for pre-storage was used than for post-storage filtration in reducing adverse events although this has not been proven in randomized controlled trials. It was assumed that leukofiltration can prevent alloimmunization