FAQs
Is Leukocyte Reduction Equivalent to CMV-seronegative Products for Prevention of Transfusion-transmitted CMV?
This question is really a loaded one! The answer, for most people, is "Yes", but the long answer is a little more complicated.
Problem: Cytomegalovirus (CMV) is a white blood cell-based DNA virus that causes a mild, transient illness in people that have normal immune systems. Over 50% of the US population has been infected at some point (more in lower socioeconomic areas). In patients with a compromised immune system, however, CMV infection can be devastating, often with lethal consequences. Traditionally, blood banks tested donors for antibodies to CMV to try to prevent transmission to immunocompromised patients, but blood bankers believe that CMV transmission can also be accomplished through removal of CMV's host: White blood cells.
Leukocyte reduction is accomplished either through the use of specialized filters or as part of the processing of blood on an apheresis machine. Either way, about 99.99% (4 "logs") of the WBCs originally present in a particular product are removed (this means that a unit of red cells that starts out with 100,000,000 WBCs ends up with about 10,000 WBCs after leukoreduction). The use of leukocyte reduction to prevent CMV transmission is based on the knowledge that the virus is cell-based and doesn't float around free in plasma. As a result, removal of the vast majority of white cells is proposed to reduce the risk by lowering the total amount of residual CMV to below infectious levels.
In 1995, a group from Seattle published the first large study (Blood, Vol 86, No 9, 1995: pp 3598-3603) which directly compared CMV-seronegative products with filtered products for CMV prevention in bone marrow transplant recipients. The study (known commonly as the "Bowden Study") concluded that there was no significant difference in CMV transmission between the two CMV seronegative and the filtered groups. This study's methods have been called into question somewhat in the years since, but the disagreements seem to be mostly with the mechanics of the study and the wording and scope of what was said, rather than with the basic point that leukocyte reduction reduces the risk of CMV transmission.
Since the Bowden study, many other investigators have examined the issue, and here is the best summary I can give: The data is mixed. There are some studies that show that checking the CMV antibody status of the donor is superior to leukoreduction, while others show them to be essentially equal. As a result, some clinicians will only accept CMV-seronegative products for their at-risk recipients, while others accept leukoreduced products as "CMV-safe."
Here's the problem as I see it: Testing a donor for anti-CMV antibodies does not give us a definite answer of whether or not he is currently infected! New data seems to indicate that there may actually be a viremic (plasma-based) infectious period for CMV, prior to seroconversion. As a result, there will always be a small number of CMV-seronegative individuals that are acutely infected and may pass along the virus despite being seronegative (there is also, of course, the possibility of a false-negative antibody test in someone with a more established infection). When you think about it, those are the exact same products (with plasma-based viremia) on which leukoreduction would have no effect! As a result, there is a fairly well-defined failure rate for both CMV-seronegative and leukoreduced blood products of between 1% and 4% . So, unfortunately, when comparing leukocyte reduction to antibody testing, it is important to recognize that neither method is fail-safe.
At this point in the discussion, someone usually raises the obvious question: "Why not do both? If leukocyte reduction and CMV antibody testing both reduce the risk, should doing both reduce it even more?" If the argument above is indeed true (that the at-risk products would probably be unaffected by either method), then doing both probably wouldn't change anything. The data seems to support that argument, as studies have not shown a significant difference when both methods are used. As it turns out, in modern US blood banking practice where basically every product is leukocyte reduced, choosing to give a patient CMV-seronegative blood will, by default, use both strategies.
These discussions led to a 2002 AABB Association Bulletin (Bulletin #02-4, member access only) that was a little bit noncommittal, but concluded in general that if leukocyte reduction was done properly (and prior to storage of the product, so-called "pre-storage leukocyte reduction"), it yielded a product which is considered equivalent to a CMV-seronegative product for preventing CMV transmission, a so-called "CMV-safe" product.
The policy I use is simply this: If a clinician specifically requests CMV-seronegative blood (especially in neonatal transfusions), I will try to accommodate that request whenever possible. I won't hesitate, however, to have a conversation with the clinician and recommend the use of what I consider equivalent leukoreduced products. This is a situation that is best discussed thoroughly with clinicians prior to the time of the transfusion, however, so that both the blood bank and the clinician know what to expect when a request for "CMV-safe" blood is made.
Updated January 2011.