tag:blogger.com,1999:blog-19490962.post115261063344227120..comments2023-12-10T10:06:41.979+00:00Comments on mutations of mortality: EBVTerry Hamblinhttp://www.blogger.com/profile/06346629921055055879noreply@blogger.comBlogger5125tag:blogger.com,1999:blog-19490962.post-1152692838521416022006-07-12T09:27:00.000+01:002006-07-12T09:27:00.000+01:00Actually, Steve, the Paul Bunnell test was a prett...Actually, Steve, the Paul Bunnell test was a pretty good test. Many patients did not even get that. It would be interesting if the tendncy to get severe could be traced to a polymorphism on the IL-15R alpha receptor. Whether this defect in T cell function would make people prone to CLL is difficult to say as there is no evidence that CLL is common in people with other forms of immunodeficiency. A recent paper in Blood suggests that familial tendenmcy to CLL may be related to defects in the ATM-CHK2-BRA2 pathway.Terry Hamblinhttps://www.blogger.com/profile/06346629921055055879noreply@blogger.comtag:blogger.com,1999:blog-19490962.post-1152670149532944612006-07-12T03:09:00.000+01:002006-07-12T03:09:00.000+01:00My experience with EBV started in 1973 where it wa...My experience with EBV started in 1973 where it was confirmed by the only test available at the time a Paul Bunnel test (I think this was the name, whoever he is?) I was told that there were many false negatives with this test but that I was positive.<BR/><BR/>Until this infection I was obscenely healthy, I was playing professional football and had just been selected to play for my state. I was never able to play competitive sport again and have had recurring symptoms of IM ever since (every 12-18 months)<BR/><BR/>I have been recently tested for CMV and declared negative.<BR/><BR/>Just my story that proves absolutely nothing but I thought I would share :)Steve Maddenhttps://www.blogger.com/profile/10284036509040132904noreply@blogger.comtag:blogger.com,1999:blog-19490962.post-1152652986284523952006-07-11T22:23:00.000+01:002006-07-11T22:23:00.000+01:00The poll on CLLForum is recording 11 out of 41 res...The poll on CLLForum is recording 11 out of 41 respondents being ill in bed with IM.<BR/><BR/>Of course people who know or think they had IM would vote where others may not.<BR/><BR/>So if we use the total membership of over 600 and 11 have had IM (resulting in bed rest)this is still vastly more than one would expect to see.<BR/><BR/>Using Chaya's 0.045% in the general community or 1 in 2200 we should expect to see this result if we had 24,200 members not 629.<BR/><BR/>Not at all scientific I realise but very interesting.Steve Maddenhttps://www.blogger.com/profile/10284036509040132904noreply@blogger.comtag:blogger.com,1999:blog-19490962.post-1152642112620133672006-07-11T19:21:00.000+01:002006-07-11T19:21:00.000+01:00Terry:I am delighted this topic has received the a...Terry:<BR/><BR/>I am delighted this topic has received the attention it has in the past few days, ever since the publication of our article "The enemy within" on www.clltopics.org . <BR/><BR/>I have received emails from 35 patients who have had clinically diagnosed infectious mononucleosis (IM) as kids or young adults. I have not counted in this number the patients who did not sound quite sure. These 35 cases had massive fatigue associated with them, and bed rest that stretched from a couple of weeks to a few months. I was intrigued that among these 35 cases of CLL with prior history of IM, there were 4 sets of familial CLL.<BR/><BR/>If one were to assume these 35 cases were indeed EBV driven infectious mononuclosis (your point on lack of quality control in IM diagnosis is well taken), then the incidence of IM in CLL patients is much higher than in the general population. <BR/><BR/>We estimate our article was read by about 1,500 people. Even if we assume each and every person who did not respond did not have IM in their past, this adds up to more than 2% of CLL patients with IM, versus 0.045% for the general public. It is reasonable that the 2% number is a tremendous underestimation, since many people who read our article and had IM in their past may not have bothered to write back. This was a "straw poll" on our website, not intended to be a scientific or rigorous survey.<BR/><BR/>My interest in IM stems from the observed increasing incidence of secondary aggressive lymphomas (Richeter's transformation) seen in CLL patients in recent years. EBV is clearly implicated in post transplant lymphomas (PTLPD), and situations where the patients have undergone very immunosuppressive therapies. <BR/><BR/>So, the million dollar question from patient's perspective is this: if the higher incidence of Richter's transformation is due to the advent of new and more aggressive therapy regimens that are likely to facilitate EBV reactivation, are CLL patients with a prior documented case of infectious mononucleosis more at risk from these therapies? <BR/><BR/>Making therapy choices is always a matter of balancing risks versus rewards. Very recently, we have learnt that there is not much point in putting 17p deleted patients through fludarabine therapy. They will not respond to the therapy, there is no bang for the buck in this situatin. We are also extra careful when administering Campath therapy to patients who are positive for cytomegalovirus (CMV) since a number of CMV reactivations have been documented following Campath therapy. Are we now on the threshold of learning that for patients with a potentially larger window of vulnerability to EBV (as demonstrated by prior IM) there is need to be extra careful about immne suppressive therapies, since this may give the old enemy (EBV) a chance to grow out of control? Richter's transformation carries a massive penalty, median survival is measured in months and not years.<BR/><BR/>Sometimes the choices CLL patients face are between the devil and the deep blue sea, and we cannot avoid therapies that may be dangerous but are necessary / essential to control a more immediate threat of CLL. But surely we need to take a closer look at patients with prior history of IM before signing them up for aggressive immune suppressive therapies as front-line first options? If regimens containing high doses of fludarabine, Campath or even high dose steroids are unavoidable, should we be developing "Best Practices" guidelines on how to protect particularly EBV-vulnerable patients as they go through these therapies? We have done that for CMV and Campath. Perhaps the time has come to see what needs to be done about protecting against EBV reactivation as well.<BR/><BR/>If any of the CLL researchers out there are willing and able to do a scientifically valid and statistically rigorous survey that sheds light on this issue, we at CLL Topics will support such an effort all the way. Heck, I am willing to go on record right now, we will even help fund and sponsor such an effort. No one has more at stake in learning about these issues than our patients, our very lives depend on it. I dount such an effort will get funding from drug companies!<BR/><BR/>Thank you for letting me use your soap box!<BR/><BR/>ChayaAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-19490962.post-1152638066288917362006-07-11T18:14:00.000+01:002006-07-11T18:14:00.000+01:00Terry,The CLL Forum poll is a straw poll, absolute...Terry,<BR/><BR/>The CLL Forum poll is a straw poll, absolutely unscientific. And, yes, memories can be deceiving. But maybe there is something there; the only way we patients have to gather this sort of information is anecdotally. <BR/><BR/>It is, of course, premature to draw conclusions. And the devil is always in the details.<BR/><BR/>But there is enough out there to make one at least take some pause. I think further serious study is warranted by those with the money and capability to take it on.<BR/><BR/>DavidDavid Arensonhttps://www.blogger.com/profile/13876562687586184006noreply@blogger.com