The Trend is Our Friend: Living with Uncertainty with my CLL (chronic lymphocytic leukemia)

My lab test have shown a blip.

After a gradual but steady improvement in my tumor burden visit after visit at Ohio State University (OSU) during my last three years on ibrutinib (when I started it was then called PCI-32765), on my last visit my ALC (absolute lymphocyte count) rose the tiniest amount to about 2, but I didn't worry as it still was well within normal limits. It was just an unusual result for me. It hadn't been over 1.4 in a couple of years, now it was >2.

The rest of the CBC and the chemistry panel was all normal.

The next day back in California I was due for my IVIG and my repeat ALC was back down to around  1 again so I didn't think much of it. 

The fancy flow cytometry that checks for the small population of my clonal B cells, my CLL cells, is the test that really counts. That measures how many cancer cells that I still have and every test had shown fewer than the last. Both Dr. Byrd and I had predicted that already small number would continue to fall, but I would not yet be MRD negative.

What hubris!

When those results were not forthcoming in the weeks following my visit, I calmed my catastrophic flights of imaginations with reminders that when counts are too low, sometimes it hard to get an accurate result.

Then I got the news that I had a "small number of B cells" on the flow, within the expected variation seen from test to test. 

That is "doctor talk" for the fact that my count had bumped up a little, but the number was still within the expected margins of error of the test, or not significant different than the prior result. 

I still haven't seen my flow report nor do I know my absolute number. I will need to know that number at some point, but knowing it would make absolutely no difference today in what I do now, so I will try to be patient (not my best trait).

What I do know is that if the count had gone down, even just a little "within the expected margins of error" I would have been told and cheered on.

As we know that the only major group where we have seen a higher rate of relapse of their CLL on ibrutinib are previously treated patients with deletion 17p such as myself. They are the only group where < 1/2 are still progression free after less than 2 1/2 years. I have enjoyed being part of the happy minority on the Kaplan Meyer graphs.

But is this my personal start of a bad trend, the first stirrings of a tiny resistant clone that will only grow over time to become dominant? Is this the beginning of the end of my super duper run with ibrutinib?

Honestly I doubt it. 

Here's why I am honestly not worried.

A week later I received the wonderful news that my BTK and PLCG2 mutation test was negative and since nearly all CLL resistance to ibrutinib is related to a growing clone with either the BTK and PLCG2 mutation that prevents the ibrutinib from blocking signaling, odds are excellent that my lab result is nothing but a meaningless blip. Richter's Transformation (RT), the other common and more sinister cause of relapse on ibrutinib, tends to occur early in treatment and three years out is not early.  I don't have RT. No signs or symptoms.

So although I won't rest completely easy until I see my next flow cytometry results sometime after my next OSU clinic visit in August, odds are really with me on this one.

The trend is our friend, and as I have coached so many others, I now must heed my own advice: One lab test means nothing.

I will be traveling for a couple of weeks in Poland on a Jewish Heritage trip with my rabbi. One purpose of the trip is to forget all about CLL and our nonprofit CLL Society for a few days, but I will be busy in the evenings in Eastern Europe writing for the CLL Society website (some great stuff from the CLL Research Consortium or CRC Patient Empowerment and Education Meeting and from EHA coming soon) and more critically, for a peer reviewed medical journal on CLL due the beginning of August. 

I am alright with that crazy balancing act though I do worry what I will eat in Poland, not exactly a vegan's paradise.

Growing our Own: Family, Friends, Ibrutinib and Green Tea: Many Reasons to Give Thanks

Our flushing Camellia Sinensis (tea trees)

I have many reasons to celebrate my favorite secular holiday of the year, Thanksgiving. It is a good time to pause with family and friends, perhaps before the festive meal begins, and go around the table and have everyone reflect on all that brings us joy and purpose, all that makes us thankful.

I am blessed with a close and loving and expanding (through marriage and babies) family, amazing friends nearby and on the other side of the world, meaningful and rewarding work, year round access to, and better yet, the ability to grow our own tasty local organic vegan food (and soon make meaningful amounts of my own delicious green tea), the chance to travel and lecture in supposedly pedestrian towns that always turn out to be full of new experiences and friends, teachers and cultural opportunities that expand my vision, and maybe, just maybe, getting my health back, my chance to keep going, to do more, and to grow old.

I am so grateful for the opportunity to be a lab rat. Yes, I complain about the CT scans and all the travel, but honestly because of Clinical Trial NCT01217749 that gave me access to ibrutinib, I am here and well and celebrating with a mind that is not convulsed about my next treatment choice or about a looming unexpected twist in my health. I have a real shot at physical redemption. I am thankful for all the help I got from my case managers and my medical group (St Jude Heritage Medical Group), the entire medical and trial team at OSU, and my family, especially my wife for making this all  happen. 

It is possible to live in gratitude and sickness at once. Some of us with cancer must do this for long chunks of our lives, but it never easy and never the most desirable. Ghandi simply said: It is health that is real wealth and not pieces of gold and silver. While I have posted extensively on living with bad news and sickness, it has always been with an eye on the prize of getting better, of being well.

My next post will discuss the risks and benefits of clinical trials, both from my personal perspective and from what I learned at the Manhattan Beach Lymphoma Research Foundation Meeting a few weeks ago.

But first, I will enjoy a down day of turkey less vegan feasting with my family.

Ibrutinib (PCI 32765) Rapidly Improves Platelet Counts in CLL/SLL Patients and Has Minimal Effects On Platelet Aggregation

Apparently, judging by some of the emails that I received, my epistaxis (bloody nose) generated some general concern, so I am glad to be able to say that I am no longer walking around with a tissue at the constant ready, and more importantly, I have some reassuring research to share from an ASH 2012 abstract.

No less an expert than Dr. Mohammed Farooqui from the NIH did the study titled Ibrutinib (PCI 32765) Rapidly Improves Platelet Counts in Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL) Patients and Has Minimal Effects On Platelet Aggregation without any pharma support that looked at not only at platelet counts, but also how well they actually function or aggregate, a critical step in clot formation, and other measures of their activity. He found what yours truly had suggested in my last post.

Although grade 1 or 2 (mild or moderate and not dangerous or disabling) bruising is a known adverse event seen with an ibrutinib, Dr. Farooqui found in looking at 25 volunteers in the NIH trial who were taking 420 mg a day that " This preliminary report does not identify any significant ibrutinib effect on platelet function." Equally important, platelet counts rapidly improved. He concludes by saying something very similar to what I gathered from the old literature that I referenced in my last post:  A rough day: Bloody nose times two and a tender rash minutes before my CLL and MDS lectures in Chicago. I quote the last line of the ASH abstract: "The apparent functional tolerance of BTK inhibition in platelets is likely attributable to redundancy in the affected signaling pathways." What I said was "there are also clearly redundant pathways and signaling to get a healthy thrombus going in response to an arterial injury."  Like minded, except Dr. Farooqui has the lab data to support his finding.

Here's another thing I really liked about his abstract beside the reassurance on the platelet issue.


"This work was supported by the Intramural Research Program of NHLBI, NIH. We thank our patients for participating in these research studies." 

They not only funded the research themselves because they thought it was important, but they thanked the patients. That is so rare and so welcome. I would have to call Dr. Mohammed Farooqui and his team at the NIH (including my old friend, Dr. Wiestner) mensches (Yiddish for a good people).

Now you might argue that I should have read all the ASH abstracts that mention ibrutinib by now and you would make a good point. I am therefore most grateful to the reader who pointed me to this particular research after reading my last post. In my defense, I have been a tad busy with travel and teaching. I guarantee that all the ASH abstracts that mention CLL will be read with more than a few reviews presented here over the next few weeks.

As my more constant reader can perhaps tell from my upbeat tone, I am feeling much better with not only no more bloody noses or other issues with which to deal, but thankfully with a rested mind and body.

Nothing like a good night's sleep and being home again with my wife and cat.