Chris just posted on how an OSU Medical Center Doc. manages CLL/SLL in which advice is given to avoid Zydelig/Idelalisib for patients with IBS or Irritable Bowel Syndrome due to the side effect of colitis seen in some patients. tinyurl.com/ojv8f3d
Here is an interesting article that underscores that advice and highlights the emerging field of micro biome importance study to our health. goo.gl/vM69F0
WWW
Hi WWW Am I reading the Doctors article correctly?
He seems to be advising "to avoid idelalisib use in patients with inflammatory bowel disease" (IBD)
Inflammatory bowel disease (IBD) is an uncommon condition. the condition term is mainly used to describe two conditions, ulcerative colitis and Crohn's disease. - NHS
NHS - " IBD is not the same as irritable bowel syndrome (IBS), which is a common condition that causes symptoms such as:
constipation
diarrhoea
abdominal pain"
NHS Choices about Inflammatory Bowel Disease (IBD) nhs.uk/conditions/inflammat...
NHS choices about Irritable Bowel Syndrome (IBS) nhs.uk/Conditions/Irritable...
Nick
I find it strange it isn't mentioned on the drug label yet... but perhaps this is new, although some bowel issues are blackboxed.. .time lag to update perhaps.
zydelig.com/include/media/p...
Thanks for this, Chris. Having started Zydelig/Idelalisib on the CALiBRe trial nearly 4 weeks ago, it's a sobering reminder of what can go wrong - and what to watch out for.
I've also noticed that this article recommends blood tests to be done every 2 weeks for the first 3 months of treatment, to check for hepatoxicity and neutropenia.
Hmm... On the CALiBRe trial, the schedule is that blood tests are done frequently for the first 4 weeks of treatment, then no more till 12 weeks (and every 12 weeks after that).
It's my 4 week appointment this Monday, and I'm going to question this...
Hi Paula
You need to be mindful that these are FDA approved uses...
Idelalisib (Zydelig) is FDA approved for secondline CLL, so the directions for follow-up etc. might be more different than a firstline trial...
Simply put... these patients have been treated once and relapsed, so closer follow might be recommended...
Also, it is FDA approved with Rituxan, which might add another dynamic
Hope your Monday results are terrific!
~chris
Ah... thanks Chris. That's very helpful - I hadn't thought of that. I'd been a bit taken aback by seeing those high proportions of people suffering adverse effects... But as you say, it will be different for those on CALiBRe trial - having Idelalisib as a first treatment and without Rituxan.
How's it going for you, with the Ibrutinib? I hope your results are looking terrific these days too...
Best wishes
Paula
CALiBRe trial allows for 2 Cohorts, Cohort A for treatment naive and Cohort B for relapsed patients needing treatment. I would expect the monitoring schedules to be identical.
Tricia
Thanks Tricia, that's very interesting. I would have thought that relapsed patients might need closer monitoring in the first few months of Idelalisib, than those having it as frontline. But maybe not.
My list of questions for tomorrow's appointment is growing...
I was doing very well for the first 3 weeks of my treatment, but just in this last week, I'm been getting some unexpected nausea and headaches. Hard to know if it's the Idela, or the Allopurinol or Aciclovir or antibiotics I was given at the same time. Or maybe none of these... could be completely unrelated I suppose...
I'm thinking that even if CALiBRe trial itself doesn't ask for any monitoring between 4 and 12 weeks, I will suggest that my own GP might do FBC and liver function tests in between those times. For my own peace of mind, if nothing else.
Best wishes,
Paula
Paula,
Nausea is a common AE (adverse event) with idelalisib. So is pneumonia, rash, diahrrhea, URI, elevated liver enzymes, etc. Dr. Susan Obrien has said that these AE are more predisposed to treatment naive because of a more intact immune system. That could be the explanation.
Jeff
Thanks Jeff. More factors to put into the equation... I'm on a steep learning curve in all this.
I suppose this is one of those rare situations when having an intact immune system doesn't work in our favour... But I think I'd rather have a better immune system that a knocked back one, even if it does predispose to "adverse effects". I just hope my doctors can work out what's causing what, and how best to deal with it.
Onwards and upwards,
Paula
Hi Paula
Which prophylactic antibiotic are you taking? I had to change antibiotics due to adverse effects and it made a big difference. Acyclovir made me nauseous to begin with but it passed eventually. Hope its not troubling you too much. Are you gaining weight now?
Tricia
Hi Tricia,
I'm taking Co-Trimoxazole (Septrin) One 400mg tablet, once a day. Which prophylactic antibiotic were you taking, that caused your problems?
Over the last couple of days, my headaches, brain fog and nausea have been MUCH worse, but I'm not sure if it's reaction to the tablets, or an infection of some sort. When I saw the haematologist yesterday and described the symptoms, he told me to stop the Allopurinol. (But to continue Co-Trimoxale and Acyclovir, as well as Idelalisib).
Since then I've been feeling worse, not better, but it's only been 24 hours since I stopped the Allopurinol - probaby too soon to judge.
My first 3 weeks of all these medications were fine - no adverse effects, so this has taken me by surprise. It's difficult to eat and drink much when feeling so nauseated, so I'm not surprised to see I'm not putting on weight as I'd hoped to. I'm now taking Metoclopramide for the nausea, but it doesn't seem to help much.
One unexpected aspect of having lost so much weight, is that the bones of my spine stick out very prominently. If I sit on a hard chair, it's like sitting on stones! In fact I thought I WAS sitting on a stone at first, till I realised that my own backbone was the "stone". I had to laugh when I realised my mistake 
Sorry - rant over...
Hope all is well with you these days,
Best wishes,
Paula
You must rant away, it'll help to get it out of your system. I was initially on Azithromycin which caused chaos with my insides, Doxycycline is a big improvement.
Allopurinol is important to protect our kidneys with all the extra work they are asked to do with this treatment. Am I right in remembering that you have reduced GFR? Is Allopurinol the right one to eliminate at this stage? I'm no expert but it never hurts to ask the question.
Also keep out of the sun (easy in the UK) and watch alcohol intake (harder to do!.)
Like you I had no problems in the first 3 weeks and felt the euphoria of initial success in the improving physical symptoms. But now I have thinning, drying hair and a strange skin reaction after SCIG which the Immunology consultant says is not from the blood product. Lots to discover on our journey.
Take care and keep in touch.
Tricia
Thanks Tricia. Yes I was a bit surprised when he told me to stop the Allopurinol, because my ALC is still 467. And you remembered rightly, that my kidney function isn't too great. (I have an eGFR that wobbles around between 47 and 54). So I think I will bring up the Allopurinol question with the doctor next time. If Allopurinal wasn't the culprit in causing my problems, it would be a shame to come off it unnecessarily and risk more kidney damage...
Interesting that like me, you had no problems in the first 3 weeks of Idelalisib... then things started to waver for both of us, and our phase of euphoria came to an end. Well, I had thought it was almost too good to be true.
Strange that you should get a skin reaction after SCIG, and the doctor says it isn't from the blood product. Did he/she suggest what might be causing it?
Pity about the thinning hair... Mine has been thinning a lot over the last year or so, and starting treatment certainly hasn't helped it... 
You're so right about avoiding sunshine. It was a sunny walk on the Cleveland Way that seemed to set off a lot of my problems last week, though I think I probably caught a bug later, that confused the picture. I read that Aciclovir can also cause photo-sensitivity, and I'm still taking that... So I think I'll just have to stay at home or walk in thick forests, when there's any chance of sun. Not easy for a hill-walker like me...
Hubby and I have had some brilliant night walks on hills though. We go out armed with torches, and if there's a full moon it helps a lot!
Anyway, I'm still glad to be on Idelalisib, but realise there will be some disadvantages and issues that need to be dealt with.
As you say, there's lots to be discovered on our journey... At least we've not alone...
Wishing you all the best,
Paula
Hi Paula;
As you know, I started a frontline trial at DFCI with Idelalisib (and later Ofatumumab) about the same time you did (mid August). During the first two weeks, my blood was tested weekly. From weeks three through at least eight, I have my blood tested twice a week to check on liver and kidney functions as well as CBC. This is part of the trial's standard testing protocol and not my personal kidney issues. I thought this information might be of use when you ask about more frequent testing.
John
Thanks John, that's helpful. You certainly are being monitored very carefully. The CALiBRe trial doesn't ask for any blood tests between week 4 and week 12, but my haematologist is now going to do blood tests a bit more often than the trial demands. I'm very glad of that.
Wishing you well,
Paula
Paula,
I looked at the schedule and found that I have twice a week blood draws through cycle 4 or roughly 16 weeks.
I'm sorry to hear that you have started to have some side effects. I hope they are transitory and you get back to feeling better
John
That's interesting, John. Twice a week blood draws seems very intense... I hope you live near your hospital!
I'm feeling much better today, thanks. Still rather weak and washed out, but a great improvement on yesterday. I'm beginning to think that some of my "flu-like" symptoms were a bug/virus and not side effects of the medications. But the picture got very confused with different factors.
I hope that you are keeping well., and still managing to avoid any side effects. It would be great if your kidney function continues to improve.
Best wishes,
Paula
HAIRBEAR -
I think you're right. IBS and IBD have 2 important letter differences.
The article didn't say how idelalisib interacted with IBD chemically, either.
The article on the Gut Bacteria was perhaps too simple to apply to humans. Bacterial balance has yet to be defined, though imbalance is getting more obvious. There may be more than one balance, and it may depend on genetic and diet factors.
To my knowledge, nobody has demonstrated that simple antibiotic therapy rebalances the gut in humans. Sometimes it does. Mostly, it doesn't. Also, an unbalanced gut is not as simple as having a single bad, identified bacteria. There are often hundreds or thousands of unknown and hard to characterize species involved. Plus there may be biofilm structures - pockets of bacteria, viruses, and DNA particles - that make it hard for antibiotics to do get in to do their job.
Age related decline has many factors. Consider that your thymus gradually decreases in size as you get older. It's the place where your T-cells learn what to recognize.
So my takeaway from the article is that if you don't get sick, you live longer, especially if you're a fly with unusual bacteria.
Hi HairBear,
My mistake but methinks too much may be made of the distinction between many disease names that indeed may have unique etiology but are in the main inflammatory in character. When I explore a drug and see that like Zydelig it is known to have a significant incidence of colitis and liver issues I would look for an alternative option if I already had an inflammatory issue, regardless of name, in either the lungs, liver or colon.
I was also rather surprised at the claim that an antibiotic could beneficially alter the gut micro biome without knowing the composition of the antibiotic or the critters it was killing off. The article was simplistic in suggesting the cause of trouble was solely overpopulation. In virology it has been observed that the same virus is not as virulent when confined to small numbers as it is when it is concentrated in large numbers. The same might be said of human beings
This issue logically applies to the controversy over differing results and claims for ingesting pro and pre biotics where some patients may benefit and others could be hurt.
The point of my post still stands: If I had any of a number of diseases or syndromes i.e. colitis, crohn's, diverticulitis, IBD, IBS, celiac, chronic diarrhea etc. I would be leery of taking Idelalisib/Zydelig with a demonstrated history of inflammatory side effects. Drug choice is still largely a crap shoot.
It will be most interesting to see where study of the gut micro biome may influence the future of our health and where it may intersect with various disease conditions to include CLL.
WWW
I experienced bloating, nausea, diverticulitis and multiple bouts of gastrititis before I found out about Monash University's FODMAP diet testing. My ALC's were steadily going up until I eliminated the biggest problem foods feeding the bacteria that were fermenting, plus some stress reduction. It could be coincidence, and ALC's are not precise measurement of overall tumor load - perhaps just tumor load in the blood. But my clones are fairly mature (IGHV mutated), so I kinda think it's a good measure for me. I'm still stage 0.
Even low levels of inflammation send out constant signaling molecules, such as IL7, that stimulate B-cell development:
ncbi.nlm.nih.gov/pmc/articl...
So lacking any CLL therapy during watch and wait, my strategy is to try to reduce infection and inflammation where I can. My allergies have steadily gotten worse the years, and are a source of inflammation, too. So I stopped mowing the lawn, and let my wife and kids do it, got a room air cleaner, and try to avoid dusting inside the house. There's also some indication that FODMAP and other foods can stimulate IgA, IgE, and IgG, which then stimulates further inflammatory signals in a vicious cycle. It's a shame my stomach can't tolerate even regular small doses of aspirin.
So lets just say, varied and interesting cuisine is a huge sacrifice I make to appease the gods and goddesses of CLL. I live in New Orleans, by the way.
I look forward to better biome analysis and targeted biome therapy in the next 10 years. I even did the American Gut Project, which is now also available in the UK and elsewhere:
humanfoodproject.com/americ...
fundrazr.com/campaigns/4sSf... British Gut - £75 for 1 person, £120 for 2.
I'm not a fan of Jeff Leach, though. I think he's a few cards shy of a scientifically verifiable deck. But I like citizen science. I support the Universities of Colorado and San Diego in their less flamboyant efforts to explore the biome.
Also, the biome testing has not even begun to address the virome - much trickier, and just as important.
Hi,
Can you expand a little about the Monash Univ. FODMAP Testing? Did you use the phone app? go and get tested?.... Thank you.
Steve
Steve -
I wouldn't recommend going it alone. The app is for use after you've been tested. Many people try to self-diagnose, and then concoct their own diet, and come to unscientific conclusions when it fails. You shouldn't just look up a food, and eliminate eating it without checking what it contains. There are some you can probably eat just fine. It's also not like an allergy where a tiny amount causes a huge reaction.
So find a dietitian certified in the FODMAP protocol:
ibs.about.com/b/2011/11/09/...
In my case, my gastroenterology clinic had hired a certified dietitian.
To start off the testing, I had to fast, go into her office, and drink a can a Coke (sweetened with high fructose corn sugar - that's important), and wait a half hour or so. Then she had me breathe into a gadget that checked for hydrogen or methane - none was found.
I had to wait a few days, and then did a fast again, and this time lactose was tested by drinking milk, waiting, and breathing into the gadget. On both occasions, no hydrogen was found.
The 2 breath tests easily prove or eliminate a wide variety of foods that ferment.
Then the hard part begins - the FODMAP avoidance diet for 6 weeks, while keeping a detailed food diary. Since the breath tests came out negative, I didn't have to avoid high fructose or lactose foods. The dietitian came up with a food plan, and recommended brands and specific fresh foods, and I looked at ingredients very carefully when I shopped. I noted any symptoms - particularly bloating, belching, nausea, pain, and bowel changes. After 6 weeks, I had no symptoms, but the menu was so boring! I really missed fresh bread ...
After 6 weeks, we started challenging a food from each of the remaining groups, and waiting at least 3 days between challenges. The challenge foods have to picked carefully, and noted in the diary.
blog.katescarlata.com/2014/...
A person can also be sensitive to a food content, and not have the bloating, in which case it's probably not a fermentation issue. Or a non-FODMAP food may cause belching and bloating. There's so many enzymes and other biome reactions that haven't been fully explored yet. I still have trouble with green bell peppers - always have. Sometimes it's a quantity issue - a slice of white bread doesn't bother me, but several in a day do.
The food diary, food challenge, and 3 day rule are really the tool that makes it happen. I found that most pre-biotic foods really cause me trouble - inulin or FOS - as do health food addititives like sorbitol, maltitol, and mannitol (polyols). I restricted alcohol - originally due to peptic ulcer, even though I tested negative for H. Pylori for years. But limited alcohol may be allowable:
lowfodmapdiets.com/ibs-and-...
Hoppy beers bother me more than ales - more nausea than bloating, though. I used to brew my own at home 20 years ago. I've always had trouble with wine and headaches, but a single glass is no problem. I like sake.
The digestive system is probably the most complex system in the body. There's more foreign organisms, lymph nodes, and neurons than any other place in the body. Well, the brain has more neurons - but the human gut has as many neurons as a cat. While the brain has the blood-brain barrier, the gut does not. It's sensing what you eat, and learning all the time.
Dear SeymourB,
Thank you so very much for your response. I truly appreciate the links and information as well as all the time you took to respond in such a comprehensive manner. I intend to look into the links and topic over the next few days and will talk with my DR. about an evaluation.
Thank you again.
Best regards,
Steve
Very interesting article on the micro biome study. I have posted before that Ultimate Flora 200 billion probiotic has helped bring my blood markers down to the high normal range. Also my digestive track is working perfectly again. I had lot's of issues and it turned everything around. I use it once a day in yogert and it couldn't be easier. Cost is minimal for the results and I am feeling better with more energy. It is really gentle and easy and all with no side effects. I think this article is on to something. Thank you for sharing so much information with us.
Kathy
Hi Kathy,
There is much to learn in the emerging field of micro biome study and health. Here is another article indicating the potential for benefit or harm studying the density of our micro biomes in the therapeutic context of cancer patients treated with chemo therapy. medicalnewstoday.com/releas...
This might be a way to cut down on serious infections that is a major cause of death among CLL patients. I have been remarkably free of infections on my CLL journey to include the time I was treated with chemo/mAb therapy and I have been a steady consumer of live bacteria yogurts, kefir and acidophilus/bifidus capsules. The cautionary note to balance the promise that micro biome tinkering holds, is that a portion of the patient population may have a compromised GI tract that could leak certain bacteria into the bloodstream causing a serious problem. That scenario could be created in some patients who respond to certain therapeutics (Idelalisib/Zydelig come to mind) that can cause inflammatory breakdown of the intestinal wall allowing leakage of bacteria into the bloodstream; not a good thing. Currently there is no way to test or know what comprises optimal density or makeup of GI tract bacteria. I would make a guess that given individual differences, optimal micro biomes would also differ. Meanwhile my bagel, to be enjoyed with Greek yogurt and fresh raspberries, is waiting for me to apply some Russian Kefir cheese spread. Bon appetit!
WWW
An Early Look at When CAR-T Therapy Fails Patients With CLL Canadian Study...treatment increases risk of secondary cancers in CLL
V & O combination therapyCLL INFORMATION - A developing reliable and current international list of CLL Information & Resources.WARNING to CLL patients about the UK shingles vaccination campaign - CLL patient's are immune compromised and should not be included.
