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.

Dealing with "this mental roller coaster"

Here is what I believe is an important exchange between me and a friend with CLL.

I think it a critical teaching for anyone in a health crisis, including myself.

I am very grateful to the letter writer for allowing me to pause and formulate a response that I hope helps him and I know helps me.

This is looping around old themes, but sometimes I am a slow learner or I just forget what is important and what is not.

Brian

On a personal note - are you aware of any studies that have been done or help that may be available for those who have been on this mental roller coaster? When on "high alert" the other things of life tend to get shoved aside. Now that the alert level is lower it's as if I don't know how to behave.
The transitions between high alert stages and the low alert stages take too much mental energy. I need to find a middle ground to function in.
Any thoughts?

W

My response:

W

Boy oh boy do I hear you loud and clear. Shifting gears from crisis to normal is tough.

I bet there are studies. I just don't know the data.

If it's overwhelming, see your doc. He can help with counseling or even meds.

But I bet you can by with this plan:

My advice is to under react to everything, the high, the lows.

Don't get too excited by the good news and give yourself time to digest the bad news.

CLL is big actor is life's drama who may try to steal every scene, but it is not the lead performer.You are. You are also the director and the producer. You get to decide who gets the spotlight and the most attention. You can focus on the ones you love and the good works you do and your faith in a greater power and purpose. You can get lost in the joys of trivial pursuits or lofty projects. It's all OK.

You can't control the rascally CLL as much as you would like, but you can control how you react to its hamming it up. Believe me. I am dealing with a few very hard knocks myself these days, and I am just collecting the data, chatting with my friends using my support network of other CLLers and trusted confidants, and cooling my heels before I make a move. Under react.

Trust me on this. This is a great teaching I got from a very dear friend, a doctor who has fought and won a big cancer battle in his life. Under react. Take some time and get some distant. Let things digest. CLL is almost never urgent.

Love is urgent. Family is urgent. CLL is not urgent.

Stay strong

We are in this together

Brian

32,000

That was my platelet count today.

No way to sugar coat it. This is bad news. To say otherwise, to borrow for my last post would stink up the place with the powerful and obnoxious odor of mendacity.

Before I go into the details of what I see in my road ahead, I need to thank a few people.

The radiologist at St Jude triple booked my CT scan, the lab staff stayed late to redraw my blood (and give me a proud tour of their new facility), Dr. Sharma acted quickly and decisively to get the ball rolling, Dr. Forman weighted in and seconded the plan expeditiously by email, the nurses were all great getting the paperwork aligned, the scheduling staff at the hospital and at the clinic wrought miracles, and my wife was right there for me.

It will all be fine, just different and busier, but fine. Have no doubts. It will all be fine.

No panic, please. No big changes. I am just turning off the cruise control and driving myself, with a lot of help from my friends. I am still heading to a place of a healthy old age. And I still plan to have a hell of a time getting there. No stinking ITP is going to spoil my fun.

Lessons learnt but at what cost?

A letter I wrote to others with leukemia. This is an expansion on a recent post.

Friends,

I don't think anyone has posted on the sad news of the recent passing of my friend, Ron after a valiant struggles with an aggressive 17p del CLL, complicated by severe GVHD and recurrent infections after a transplant and DLIs at MDACC, Houston. He survived only 3 and 1/2 years from the time of diagnosis.

Ron was 48, a father of 5, a clean living, marathon running, church going sweetheart. I knew him from our local support group and he was a kind and generous intelligent man.

I don't share this bring you down, but to see what can be learnt from those who did not follow his blog.

I don't recall all the details of his therapy but I'll will tell you what I have gleaned.

First, while I am sure Ron lived longer because of his faith, his exercise, and his healthy lifestyle, sadly for most that is hardly enough.

Ron knew that and went quickly to Dr Khouri at MDACC. After a hard fought deep remission with different aggressive therapy combos , which included Campath. He chose to be aggressive with an earlier transplant .

He did well after FRC conditioning for his HSCT 1000s of miles from his Californian home because he had done his research. This is the same protocol I had 2 months later.

Ron's chimerism stayed mixed, and the CLL crept back. He kept going back to Houston for DLIs at escalating doses. they did nothing but he looked great. Ran a half marathon post transplant. The last DLI finally cleaned up his CLL, but at what a cost. He may have died freed of cancer, but he was soon back in Houston with severe GVHD. He was hospitalized longer for GVHD than his transplant .

At some point he made a decision to stop flying back to Houston, but there was never a clean handoff to a transplant team in SoCal.

The immunosuppressive drugs including steroids took their toll. Recurrent infections, bacterial and fungal, treated with antibiotics lead to toxic mixes. His kidneys shut down. Dialysis was started. Nausea led to weight loss and weakness.

The last infection was too much. He was only 48 years old with 5 kids.

So here's what I have learnt.

It may not matter to CLL how cleanly you live or how hard you work out or what a nice guy you are or who prays for you. (This is coming from someone who still believes in the power of all these).

You can do all the research and pick the top CLL guns and still have a lousy outcome.

There are risks in being aggressive, both with chemo and transplants and especially with DLIs ( Remember I am the guy who griped about NOT getting DLIs for my mixed chimerism)

The therapy can kill you as well as the disease. We all know this intellectually, but in Ron's case this burdensome fact is impossible to ignore.

There are risks in being treated a plane flight away, especially if you don't arrange in advance a clear and clean handoff to the appropriate local experts. Community oncologists will be the first to admit they are not transplant experts. Few doctors are. Few are CLL experts, truth be told.

Finally, this is a bloody rotten disease.

Victor Frankl (author of the life changing book, Man's Search for Meaning) said tragedy is suffering without meaning. I am look for meaning in this loss, but in a heartbeat i would throw away any lessons and any meaning to have my friend alive.

So sad.

Stay strong.

Brian

Bad news

Do you ever get an email you know you just don't want to open? Like when the phone rings at 3 AM and you don't know anyone who is expecting, so you anticipate bad news. Got that email today. A young friend with a younger family who had a transplant a few months before mine for his aggressive CLL lost his fight yesterday. His last supercharged DLI cleaned out all the CLL from his marrow and nodes. Ironically, he was cured of his cancer, but at what cost? Recurrent infections after endless months of severe GVHD and end stage renal failure beat him down to the point he just couldn't rise again.

He had what would seem to be a winning hand. A religious man. A spotless lifestyle. A marathon runner. Great insurance. Smart and willing to travel to get the best experts. Huge support network and a big safety net of loving family and friends. And a truly nice guy.

It made no damn difference. So sad. So very sad.

I will miss him.

And I'll admit it's scary too. The only two people I have met face to face who have had transplants for CLL are both dead, and I thinking of tempting fate again.

Ron and PC, this is a hard knock world. Thank you and your wives for sharing your struggles so others might learn from your courage and wisdom.

Best to know

The bone marrow biopsy showed 2.8% of the cells were CLL. The three lines of cell growth were adequate including the platelet precursors (megakarocytes) so the platelet problem is a return of my ITP, which is the better of the two possibilities, the other being cancerous shut down of the bone marrow.

So the CLL and the ITP are back in the nodes and in the marrow playing their nasty games with my life, though the blood may still be clean.

Not the news I wanted to hear, but not unexpected. For me it is always better to know the enemy you are dealing with. It certainly makes my present situation more clear. What to come and what to do is less clear.

I am busy tonight with McGill events and projects with my children, and broken electric gates and overdue paperwork, so more later.

The biopsy news is rather cold and stark, and so my response must match.

"When the world is running down, you make the best of what's still around" The Police

An' here I sit so patiently

Waiting to find out what price

You have to pay to get out of

Going through all these things twice.

Bob Dylan

I am still cancer free, but it looks like I may be rejecting my graft. My critical T cells fell to just over 50% donor down from 64% only 6 weeks ago, and my monocytes and granulocytes made in my marrow are all mine, 100%  recipient. No donors cells to be found. Looks like I needed to be hit with a bigger immunosuppressive hammer a the time of the graft. Looks like my own marrow and immune system were just too robust and beat back my invading donor. I was just too darn healthy at the time of transplant. I had this foreboding in hospital. It explains why I have had such an easy time of it and no (GVH) graft versus host disease.

This is bad news, no doubt, but the same blood test that showed the falling chimerism, also showed no CLL. So first I repeat the CT scan, repeat the bone marrow biopsy (BMB) and repeat all the lab test in 2 weeks and than I begin down a new path.

A donor leucocyte infusion (DLI) is possible, but not likely. Chemo is much more likely soon, and at sometime in the future almost for sure, a redo transplant, this time with a bigger chemo hammer. Could be real soon or years away. It could be never.

My leukemia sure took a dive with only 1 course of chemotherapy as it looks now like my remission was from the conditioning therapy (a common cocktail called FCR by its fans for its famed mix of the potent and poisonous fludarabine, cytoxan, and rituxan) and not  the much desired GVL (graft versus leukemia). Not really certain that is true. Not really certain of anything at this point. If it was the chemo, then it must be very sensitive which bodes well. And I feel well. And I look marvelous. Just ask my wife. All that is good.

I am off my anti-rejection drugs (tacrolimus and sirolimus) and my prophylactic antibiotics as of today. That may boost my donor T cells or maybe knock them out faster. Who knows?

I would say I won round one by a wide margin, but this will be a long fight. I was hoping for an early knock out, but I am dealing with a patient and wily, but weakened opponent. I remain certain of my ultimate victory. I'd be lying if I said this was a good day, but you would be mistaken if you thought I was going to be down for long.