Transfusion of CMV Seronegative T-Deplete Allogeneic Stem Cell Transplant Recipients with CMV Unselected Blood Products Confers a Zero Risk of CMV Transmission in the Era of Universal Leucodepletion: A UK Single-Centre Experience

Infection with cytomegalovirus (CMV) remains a major cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). Primary CMV infection may follow infusion of stem cells or blood products from a seropositive (or actively infected) donor. CMV negative SCT recipients, especially those receiving T-deplete grafts, are particularly at risk and have routinely only received blood products from CMV negative donors. Previous studies suggest a low rate of CMV transmission with the use of leucodepleted but CMV unselected blood products. These studies belong to an era where techniques used to detect CMV infection (culture, serology or antigen testing) had limited sensitivity. A small number of studies in recent times have attempted to address this issue using nucleic acid testing to detect CMV infection, once again confirming the safety of this approach. Of note, none of these studies specify the proportion of patients receiving a T-deplete graft. We report our experience using a highly sensitive qPCR assay in CMV seronegative allogeneic SCT recipients, predominantly receiving an intensely T-depleted graft at a single, large UK transplant center.

Universal leucodepletion to <5 x 10⁶ white cells per unit has been in routine use for blood components in the UK since 1999. Its effectiveness as a strategy to prevent CMV transmission in SCT remains uncertain. Prior to April 2013, CMV seronegative SCT recipients at our center received CMV negative blood products and had no routine CMV PCR monitoring post transplant if the graft was from a seronegative donor. In April 2013, in response to the UK advisory committee on the safety of blood, tissues and organs (SaBTO) position statement (2012), we switched to CMV unselected blood products for all transplant patients and introduced routine weekly blood CMV PCR monitoring.

We set out to establish the frequency of CMV transmission in CMV seronegative patients prior to and since the change in transfusion policy at our center. Patients with <100 days post transplant follow up were excluded. Between April 2013 and April 2104, 24 CMV seronegative recipients underwent allogeneic SCT (index group) at the University Hospital Birmingham and received CMV unselected but leucodepleted blood products. Weekly CMV PCR monitoring was performed in these patients, using a highly sensitive qPCR assay (sensitivity of 200 copies /ml whole blood), until a minimum of 100 days post-transplant. We analyzed 24 sequential CMV seronegative allogeneic SCT patients who received a transplant prior to the change of policy and received leucodepleted, CMV negative products as a matched control group. In this group, CMV PCR monitoring was performed routinely only in patients receiving a graft from a CMV seropositive donor. Testing was otherwise performed only if there was clinical suspicion of infection.

Mean age of patients in the index group was 41.2 years at time of transplant. All patients received peripheral blood stem cells with the donor source being sibling in 9 (37.5%), unrelated in 14 (58.3%) and cord blood in 1. Twenty-one patients (87.5%) in the index group and 17 (70.8%) in the control group received intense T-depletion with in vivo alemtuzumab or anti-thymocyte globulin. Six patients in each group (25%) received graft from a CMV seropositive donor. Patients in the index group were transfused a total of 129 red cell and 103 platelet units. In comparison, patients in the control group received more transfusions (314 red cell and 245 platelet units). This difference may be partly attributable to an excess of lymphoma patients in the index group who may have a lower transfusion requirement compared to patients with myelodysplasia or acute leukemia. In addition follow-up was longer in the control group (535 days compared to 306 days). There were no CMV transmissions or symptomatic CMV infections in either group.

With a total of 232 units of leucodepleted, CMV unselected blood products transfused we find no evidence of CMV transmission using a highly sensitive qPCR assay in a uniform population of high risk CMV seronegative patients receiving an allogeneic SCT, predominantly with intense T cell depletion. Our data provides strong evidence supporting the safety of this approach and if confirmed in a larger, prospective UK study, could form the basis for discontinuing routine CMV PCR monitoring in this setting with significant cost savings.