1. CMV Working Group
Update to NAC April 2016

2. August 2014 Statement:
"The National Advisory Committee recommends that CMV safe and CMV IgG seronegative products be considered equivalent for the majority of patient populations including adult and pediatric Hematopoietic stem cell recipients, CMV seronegative patients who may require future transplant and immunodeficient patients.
Due to significant controversy and lack of evidence on the need for the provision of CMV seronegative products in addition to leukodepletion in the following 3 patient groups - intrauterine transfusion, neonates under 28 days of age and in elective transfusion of CMV seronegative pregnant women, NAC recommends to follow local policies".

3. October 2015 Recommendation
The National Advisory Committee recommends that CMV safe (leukoreduced) and CMV IgG seronegative products be considered equivalent.

4. Subcommittee discussions
During revision and refinement of white paper ( still in final stages), the subcommittee has had significant discussion and debate around the following two areas for the clinical scenario of Intrauterine transfusion:
Nucleic acid testing sensitivity / feasibilty
Applicability of the leukoreduction data in this patient group

5. Pathophysiology of Congenital CMV disease
Three routes of transmission have been identified with supporting studies in the literature:
1) Primary infection in non immunized pregnant woman causing primary infection of fetus.
2) Reinfection of seropositive pregnant woman with new strains of CMV.
3) Reactivation of latent virus in the pregant woman.
The first route has the highest risk but some studies suggest the non primary infections (routes 2 &3) have a higher risk of long term neurologic disease burden.

6. Leukoreduced versus CMV Seronegative
The first two routes would support avoidance of potential “window phase” infected individuals
However, nucleic acid testing may not be the answer…

7. No NAT?
Preiksaitis JK. Prevention of transfusion-acquired CMV infection: is there a role for NAT? Transfusion 2003 Mar; 43(3):302-5
Nucleic acid testing is NOT additive to determine the risk of disease transmission for the following reasons:
1) CMV NAT kits will detect free viral particles in plasma that are not disease related.
2) the current NAT testing methods that would be available for screening are insensitive and would need modification to be able to detect CMV reactivation in donors.

8. Summary of the Working Group
Due to significant advances in the leukoreduction process and practice pattern evidence from jurisdictions, both within Canada and internationally, in which CMV seronegative blood components are not considered standard of care for many of the indications suggested by the 2000 Canadian Consensus Guideline, the NAC recommends that all provinces and territories work to minimize unnecessary use of CMV seronegative blood components.

9. Summary of the Working Group (con’t.)
Recommendations for specific patient groups were discussed and agreed upon with NAC’s CMV working group. Clinical data supports the equivalency of leukodepleted product in all cohorts (e.g. stem cell transplants, solid organ transplants, pregnant women and neonates) EXCEPT for Intrauterine transfusions.

10. Summary of the Working Group (con’t.)
A revised recommendation suggested is to continue to provide CMV-seronegative units to all fetuses receiving an IUT but additionally recommend monitoring of their CMV status postnatally .
The rationale for monitoring is that fetal microchimerism is different compared to neonates, pediatric and adult patients. Transfusion associated microchimerism and the subsequent survival of leukocytes long enough for reactivation of latent virus has been documented in fetuses despite leukoreduction and may alter the CMV disease process in this population.  
However, monitoring would require resource implications outside of the realm of transfusion medicine

11. Next steps Finalization and approval of the position paper
? Publication of position paper versus letter to the editor regarding NAC recommendation and supporting points.