Peter Flanagan

Establishment and operation of a Good Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease

Epstein‐Barr virus (EBV) is associated with several malignancies, including post‐transplant lymphoproliferative disorder (PTLD). Conventional treatments for PTLD are often successful, but risk organ rejection and cause significant side effects. EBV‐specific cytotoxic T lymphocytes (CTLs) generated in vitro from peripheral blood lymphocytes provide an alternative treatment modality with few side effects, but autologous CTLs are difficult to use in clinical practice. Here we report the establishment and operation of a bank of EBV‐specific CTLs derived from 25 blood donors with human leucocyte antigen (HLA) types found at high frequency in European populations. Since licensure, there have been enquiries about 37 patients, who shared a median of three class I and two class II HLA types with these donors. Cells have been infused into ten patients with lymphoproliferative disease, eight of whom achieved complete remission. Neither patient with refractory disease was matched for HLA class II. Both cases of EBV‐associated non‐haematopoietic sarcoma receiving cells failed to achieve complete remission. Thirteen patients died before any cells could be issued, emphasizing that the bank should be contacted before patients become pre‐terminal. Thus, this third party donor‐derived EBV‐specific CTL cell bank can supply most patients with appropriately matched cells and most recipients have good outcomes.

Donors with a rare pheno (geno) type

H. W. Reesink, C. P. Engelfriet, H. Schennach, C. Gassner, S. Wendel, R. Fontão-Wendel, M. A. de Brito, P. Sistonen, J. Matilainen, T. Peyrard, B. N. Pham, P. Rouger, P. Y. Le Pennec, W. A. Flegel, I. von Zabern, C. K. Lin, W. C. Tsoi, I. Hoffer, K. Barotine-Toth, S. R. Joshi, K. Vasantha, V. Yahalom, O. Asher, C. Levene, M. A. Villa, N. Revelli, N. Greppi, M. Marconi, Y. Tani, C. C. Folman, M. de Haas, M. M. W. Koopman, E. Beckers, D. S. Gounder, P. Flanagan, L. Wall, E. Aranburu Urtasun, H. Hustinx, C. Niederhauser, E. Massey, A. Gray, M. Needs, G. Daniels, T. Callaghan, C. Flickinger, S. J. Nance & G. M. Meny

Ultrio and Ultrio Plus non‐discriminating reactives: false reactives or not?

Background  The low, fluctuating levels of DNA characteristic of occult hepatitis B infection make its detection by nucleic acid testing (NAT) a challenge.

Factors affecting red blood cell storage age at the time of transfusion

Clinical trials are investigating the potential benefit resulting from a reduced maximum storage interval for red blood cells (RBCs). The key drivers that determine RBC age at the time of issue vary among individual hospitals. Although progressive reduction in the maximum storage period of RBCs would be expected to result in smaller hospital inventories and reduced blood availability, the magnitude of the effect is unknown.

Prevention of transfusion-transmitted cytomegalovirus (CMV) infection: Standards of care

L. Lieberman, D. V. Devine, H. W. Reesink, S. Panzer, J. Wong, T. Raison, S. Benson, J. Pink, G. C. Leitner, M. Horvath, V. Compernolle, P. S. Prado Scuracchio, S. Wendel, G. Delage, S. Nahirniak, X. Dongfu, T. Krusius, E. Juvonen, S. Sainio, J.-P. Cazenave, P. Guntz, D. Kientz, G. Andreu, P. Morel, E. Seifried, K. Hourfar, C. K. Lin, J. O’Riordan, E. Raspollini, S. Villa, P. Rebulla, P. Flanagan, D. Teo, S. Lam, A. L. Ang, M. Lozano, S. Sauleda, J. Cid, A. Pereira, B. Ekermo, C. Niederhauser, S. Waldvogel, S. Fontana, M. J. Desborough, R. Pawson, M. Li, H. Kamel, M. Busch, L. Qu & D. Triulzi

How should we assess risk behaviour when determining donor deferral? Reflections on the MSM deferral

Concerns are increasingly being raised in a number of countries in relation to the behavioural donor criteria and in particular the on-going permanent exclusion of men who have had sex with other men (MSM). The justification for this is broadly linked to the use of risk models. Generally current exclusion criteria are broadly defined and indirectly it might be argued that this leads to exclusion based on sexual orientation. Available data indicates compliance issues with the exclusion and recent reviews in Europe have recommended that further research in this area is needed before any change in the current permanent exclusion should be made. Lobby groups however promote a more targetted approach to behavioural criteria. Firm data to support this is however currently lacking. There are a number of possible approaches to assessing risk including the period since the activity took place, the number of partners in a given period, the type of sex act or a combination of these factors. Definition of an optimal approach will need to consider both the sensitivity and specificity of the intervention along with an assessment of ease and consistency of application.

In vitro comparison between gamma-irradiated cryopreserved and Day 7 liquid-stored buffy coat-derived platelet components.

Cryopreserved platelet (PLT) components stored at −80°C in 5% to 6% dimethyl sulfoxide (DMSO) demonstrate enhanced hemostatic activity. Alterations in PLT surface glycoprotein expression and release of procoagulant microparticles during the freeze/thaw cycle result in PLT activation. Nothing is known of the effect of gamma irradiation on the in vitro quality of reconstituted cryopreserved PLTs.

Use of anti-GOR testing in the screening of blood donors for hepatitis C virus infection

Sera from 12/1,155 (1%) anti‐HCV‐negative (Elisa) UK blood donors were found to be anti‐GOR positive. None out of 12 of those sera were positive for HCV RNA by the reverse transcriptase/polymerase chain reaction (RT/PCR). In a cohort of 316 anti‐HCV Elisa‐positive sera, 27/57 RIBA‐positive, and 1/188 RIBA‐negative sera were anti‐GOR positive, resulting in a sensitivity of 47% and a specificity of 99.5% for anti‐GOR as a marker for RIBA‐confirmed HCV infection. Four out of 71 (6%) of RIBA‐indeterminate sera were anti‐GOR positive. Donors with anti‐GOR reactivity were more likely to have antibodies against each of the individual HCV antigens represented in the RIBA, and those antibodies were of greater intensity, when compared to the anti‐GOR negative cohort. Twenty out of 36 (55.6%) of RT/PCR‐positive sera were anti‐GOR positive, compared to 1/7 (14.3%) of RT/PCR‐negative sera (p = 0.09). The usefulness of anti‐GOR testing of UK blood donors is discussed in the light of these results.

An international investigation into AB plasma administration in hospitals: how many AB plasma units were infused? The HABSWIN study: AB PLASMA UTILIZATION

Typical practice is to transfuse group‐specific plasma units; however, there are situations where group AB plasma (universal donor) is issued to group A, B, or O recipients. If demand for group AB plasma exceeds collections, there is potential for shortage. This project explored the patterns of group AB plasma utilization at hospitals around the world.

Changes in plasma unit distributions to hospitals over a 10-year period: PLASMA DISTRIBUTIONS TO HOSPITALS

There are many influences on a hospitals demand for plasma. Pharmaceuticals are now being administered for many indications instead of plasma, although trauma resuscitation now emphasizes increased and early intervention with plasma. This multinational study evaluated changes in blood center plasma unit distributions over a 10‐year period.