On December 14 & 15, 2010 an important meeting is scheduled between the FDA and the Blood Products Advisory Committee(BPAC) to discuss stopping people who have Chronic Fatigue Syndrome(CFS) and Prostate Cancer(PC) from donating blood.  This comes in light to the fact that studies have shown the XMRV virus or now the new broader term Murine Leukemia Virus(MLV) can possibly be transmitted through blood products.  Some Countries have already taken this precautionary step.  For one, Canada has been deferring prostate cancer patients since 2003.  With all the recent debates this year as to whether or not CFS and PC patients have the virus or not and why the discrepancy in the findings, I am wondering what information is Canada hiding if they have deferred patients since 2003?

Following is an excerpt from the Meeting Summary:

December 14-15, 2010: Blood Products Advisory Committee Meeting Issue Summary

Topic: Murine Leukemia Virus (MLV) related human retroviruses and blood safety

Issue: FDA is seeking the advice of the Blood Products Advisory Committee (BPAC) on the deferral of donors based on a diagnosis of Chronic Fatigue Syndrome (CFS) or Prostate Cancer (PC) and testing for the newly identified MLV-related human retroviruses (that include XMRV) associated with CFS and PC that may pose a concern for blood safety.

Background
Murine Leukemia Viruses (MLVs) are gamma retroviruses belonging to the Retroviridae family. Gamma retroviruses are widespread in vertebrates and in animals they cause a wide range of diseases including cancers, immunodeficiency, and neurological disorders. Xenotropic murine leukemia virus-related virus (XMRV), the first gamma retrovirus known to infect humans, was originally identified in 2006 in prostatic tissue from patients with familial prostate cancer.

MLV-related viruses: Epidemiology and Disease Association

Prostate Cancer
Since the discovery of MLV-related human retroviruses, there have been several reports about their association with Prostate Cancer (PC) and Chronic Fatigue Syndrome (CFS) and other reports of a lack of association with these diseases. Using the viral sequence based array, XMRV sequences were identified in samples from 7/11 prostate cancer patients that were homozygous (QQ) for the R462 mutation for RNAse L which is an important molecule in the innate antiviral response [7]. A survey of an additional 86 PC tumors by RT-PCR specific for XMRV showed that 40% of QQ cases were positive for XMRV compared with 1.5% of heterozygous RQ and homozygous wild type RR cases. Subsequently an analysis of 334 consecutive prostate resection specimens using a quantitative PCR assay and immunohistochemistry showed that 6% were positive for XMRV DNA and 23% for protein expression. Taken together, these findings suggested an association of XMRV with prostate cancer [3]……

Chronic Fatigue Syndrome (CFS)
MLV-related human retroviruses have also been reported by a few laboratories in the blood of patients with Chronic Fatigue Syndrome (CFS), a disease of unknown etiology, known to affect several million people worldwide [4]. Other laboratories have failed to detect XMRV in blood samples from CFS patients. CFS is a clinically defined condition characterized by severe, debilitating fatigue and a combination of symptoms that prominently features self-reported impairments in concentration and short-term memory, sleep disturbances and muscle and joint pain and symptoms similar to those of infectious diseases [16]. A number of viruses, including human herpes virus-6 (HHV-6), Epstein-Barr virus (EBV), various enteroviruses, and the human T-lymphotropic virus type 2 (HTLV-2), have been cited as possible triggers of CFS; but, so far, no causative infectious agent has been conclusively identified [17]. Clinical diagnosis of CFS is largely a diagnosis of exclusion of other diseases………….

In a study reported in 2009 [4], DNA from peripheral blood mononuclear cells (PBMCs) of CFS patients and healthy controls from the US were tested for the presence of XMRV sequences. XMRV sequences were found in 68 out of 101 CFS patients (67%), as compared to 8 of 218 (3.7%) healthy US controls. Viral gene sequences identified in CFS patients clustered with sequences from PC, and both sequences were virtually identical. Further investigation using activated CFS patient PBMC co-cultured with susceptible PC cells (LNCaP) showed that virus could be transmitted by cells and supernatant, as indicated by protein expression and transmission electron microscopy, suggesting that the virus being detected by protein expression was infectious. Virus could also be transmitted in LNCaP cells from 10/12 CFS patient plasma samples. These studies suggested that both cell associated and cell-free transmission of XMRV is possible. Finally, antibodies to XMRV were detected in 9/18 CFS patients using a test based on the envelope of a closely related virus, spleen focus forming virus (SFFV).

Discussion Evaluation of Transfusion Risk

Transmission through blood transfusion of XMRV has not been shown, but is theoretically possible since XMRV virus has been detected in blood cells and there is evidence of cell-free virus………….

Donor Deferral for risk of MLV-related infection in patients with a diagnosis of CFS and PC

……..In the US, in June 2010, AABB (formerly known as the American Association of Blood Banks) published an Association Bulletin (10-03) which recommends as an interim measure that “blood collecting organizations make educational information available regarding the reasons why an individual diagnosed with CFS should not donate blood or blood components.” [33]. The AABB also developed donor education materials suitable for discouraging such donations. The AABB does not recommend adding a specific question to the donor history questionnaire. The Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) Association of America has a long-standing recommendation that individuals with CFS voluntarily not donate blood or organs based on both donor and recipient safety concerns which include low blood volume and infections common in CFS [34]. In May 2010, the HHS Chronic Fatigue Syndrome Advisory Committee (CFSAC) recommended to the Assistant Secretary for Health that blood collection facilities indefinitely defer donors with a history of CFS, or with active CFS, through a donor screening question specifically for CFS.
Currently, FDA does not have a policy for deferring donors based on a history of cancer and there is no scientific evidence that cancer can be transmitted through blood transfusions [35]. In regard to PC, results of a large survey conducted in Sweden and Denmark (SCANDAT) of 888,843 blood transfusion recipients without a prior cancer diagnosis at the index transfusion showed no increase in prostate cancer [36]. Furthermore, statistically significant decreased risk was observed in anatomic site-specific analysis for prostate cancer 2-4 years after transfusion. For these reasons, donor deferral on the basis of a history of PC has not been recommended in the US or other countries except in Canada, where since 2003, a policy of permanent deferral for prostate cancer patients has been implemented and prior donations are retrieved and destroyed.

Summary

The science of MLV related viruses in humans is still evolving. While many laboratories have detected MLV-related sequences in prostate cancer samples, others have not. The frequency of positive samples varies widely between laboratories. There is controversy about the detection of MLV-related sequences in CFS with the majority of laboratories failing to detect MLV sequences. There are ongoing studies to determine whether technical issues, such as extraction methods or primers and/or subject selection including clinical criteria and geographic issues might influence the detection of MLV sequences. Potential transmission through blood has not been demonstrated. There is no known causative relationship between MLV infection in humans and disease.

The BPAC session will include several presentations on MLV-related human retroviruses. The committee will hear presentations on the background of the issues to be discussed, an update of current research on epidemiology, disease association, animal transmission studies, ongoing validation studies of assays and panels for MLV related human retroviruses, and other relevant studies on the association of MLV-related viruses with CFS, prostate cancer and blood donors.

Based on the current scientific knowledge of MLV-related viruses in humans and their reported disease association, FDA is seeking recommendations from the BPAC on 1) indefinite deferral for blood and plasma donors with a diagnosis of CFS or PC, and 2) donor screening for MLV-related virus in absence of confirmed disease causation. FDA is also seeking the advice of the BPAC on the potential suitability of NAT and/or serology testing of blood donations as safeguards against transmission of MLV related viruses by blood transfusion.

To read the full article:

Blood Products Advisory Committee December 14-15, 2010: Blood Products Advisory Committee Meeting Issue Summary.

With the information in my last post, I have a feeling there will be a great shortage of blood and plasma in this world.  They will have to test your blood before you can donate.  The questionnaires are not enough anymore.  The costs will go up but it is the only way we can safeguard the blood supply.

Have a Great Day!!

Donna

Related Articles

• What’s Next for X (as in XMRV)? (blogs.wsj.com)
• New studies examine links between XMRV and human disease (eurekalert.org)
• Virus Linked to Chronic Fatigue Syndrome (webmd.com)
• Researchers Study Virus’ Link to Chronic Fatigue Syndrome (webmd.com)