Seven Years Ago Today CLL Entered My Life

Seven years ago my wife and I were happily planning the home wedding for my oldest daughter. Now that marriage has given us our number one granddaughter who applauds her own first time success at standing up. Today. It is so good to be alive. Seven years ago, odds were not looking so good that I would reach this day. I am one lucky soul.

Seven years ago, it started so innocently. Some lumps at the back of my neck at the hairline. Soft, mobile, not tender. The symbol for cancer is the crab, with its pincers grabbing and invading. A tenacious rough visitor who clings to its hard won territory and gets ready to expand its reach. This felt nothing like that. These were smooth and rubbery, but persistent. I was overdue for lab work so I ordered blood work on myself (one of the advantages of being a doctor)  including the usual lipid panel and blood chemistries and a CBC on September 7, 2005.

The next day, Sept 8, 2005, seven years ago today, rocked my world. I remember being happy that  my cholesterol was so good, and that my chemistries were are fine. What did that matter when my white count was way too high and it was all lymphocytes?

While it would be more than a week before the final diagnosis was confirmed, that day everything changed. A disease enters our life when we decide we have had enough of the worry or the uncertainty or the pain or the itch or the whatever. The limit of tolerance or the limit of anxiety has been exceeded and we need relief, but it comes with a price tag. We seek help. We consult a doctor who makes a diagnosis. Many of these labels,  a sprain or bronchitis or a migraine are temporary. Many are not. Professor Ian McWhinney, the father of family medicine in Canada, and one of my mentors laid the groundwork of this understanding about how a word, a disease comes to our lives. Some maladies are amorphous, nameless and usually evanescent. All the bad one ones have names. and if it is compounded, it's usually really bad. Get scared if it's three words long and the first word isn't benign.

My three letter monster, CLL or chronic lymphocytic leukemia has been my traveling companion since that fateful day seven years ago. No, that's not right, because more than once it has been the driver, grabbed the steering wheel and heading us over a cliff until I could wrench back control. The first time was when another three letter hitchhiker, ITP squeezed into the front seat and sent us careening towards the rocks over and over again.

Cancer patients talk about pre and post diagnosis as different universes, as an epic paradigm shifts  whether we want one or not . We talk about "the new normal". We talk about altered priorities, lost trivialities, and new imperatives.

A cancer diagnosis has the opportunity to be a crash course in everything.

I quoted before from the late great Gilda Radner who said about her cancer: If it wasn't for the downside, everyone would want it.

But what a downside! Let us be honest. It comes with the real risk of intractable pain, increasing disability, bankrupting expenses, unimaginable inconvenience and stolen time, overwhelming fatigue, annoying side effects, unknown fears and of course death too soon, too soon, too soon.

The upside too is amazing. Life becomes purposeful, more focused, more urgent, more timely. The junk melts away. New friends and challenges and interests and opportunities appear. A brave new world. A chance to make a difference, a chance to beat the odds, blaze new trails and drags others with us on the road to, dare. I say it, a cure.

It seems possible now. The accepted wisdom is that the only possible path to cure for CLL is a transplant. Maybe that is changing. My transplant failed, as it does for about half of those who go that route. And it kills and mains too many.

Maybe the ibrutinib or GS1101 or GA101 will buy me and others the time needed for the CLL gurus to perfect the CAR-T or the next winning cocktail to get us to the promised land of no more leukemia, forever.

Much has changed in the seven years since my diagnosis. Then they was no therapy even shown to slow down the disease or add a day to survival. Options were limited to toxic drug combos or  the go for broke transplant.

With my nasty mix of 11q deletion, complex karyotype, CD38+, elevated B2M. strongly positive ZAP 70, 100% unmutated, aggressive ITP, and the recent addition of the worst or the worst, 17p del, I have more than beaten the odds.

I should be long gone. But instead, I am feeling stronger than ever with less fatigue, with blood counts near normal and nodes that are getting harder to find.

Seven years out and I am charging ahead to see how I help more CLLers get the best possible care and push the scientists to not take their feet off the accelerator. We aren't there yet and our path is not yet clear, but we are closer and the palliative options are increasingly gentle and effective. This is all good.

Although there are no guarantees and everything could chance in a heartbeat, and moreover, G-d forbid, I don't wish to invite trouble through trumpeting my good fortune, but the truth is that seven years out and my life has never been better and my hopes for all us CLLers have never been higher.

I am so grateful to all of you who follow along here and elsewhere and who share your stories.

The best is yet to come. Please stay the course. Our future is bright.

My granddaughter stands up for the first time and applauds herself. Does it get any better.

I see where President Clinton stole my best line at the Democratic convention.

But I stole it first.

WE ARE ALL IN THIS TOGETHER.

We WON

ME HOISTING THE FLAG AT GAME 6 OF THE STANLEY CUP FINALS

The ibrutinib is working. I am working on a post detailing shrunken nodes and healthy blood counts and improved energy.

Honest I am but I have my priorities straight. 

That good news pales in comparison to the sheer joy of being at the game where the Kings and their patient fans finally got to hoist Lord Stanley's Cup. Been a loyal fan for 22 or their 45 year wait.

I buy season tickets so I can go the playoffs. My cancer trial made me miss going to all but two games in their amazing record breaking Stanley Cup run. 

But those two games were thunderingly joyful.

 Game 3 in LA -where they won 4-0 and tonight at home where they won it all.

They could have clinched in game 4 when I was in Ohio or game 5 when they were in Jersey and I was in Orlando.

But as it turned out,  they waited until I was back in SoCal to claim the big prize. And in such amazing style. 6-1. Three goals scored on the major penalty in the first period.

I am so happy. People were crying at Staples Center.

Sometimes delays are good.

Sometimes we get a lucky bounce.

Sometimes things just workout.

I am feeling like such a lucky man tonight. I am getting my health back, I have love in my life, and the Kings won the Stanley Cup.

I CAN'T STOP SMILING!

Celebrating with a organic vegan muffin and raw vegan coconut milk "ice cream".

GO KINGS GO!

Part 2 Is there a doctor on the plane?

It has too busy with travel and treatment and lectures and the Stanley Cup Finals (GO KINGS GO) to blog. I should be able to catch up more with lots of good news about me and ibrutinib from rainy Orlando real soon


But first when I last left you, I was walking to the back of the plane to see who needed medical attention.


To see if I could help?


To see if was putting myself at risk/


What I found in the last  row was a man in his early 50s acutely short of breath with an oxygen mask on, very afraid for his life.


Less than a minute after arrived, t was being asked should we divert  the plane to Las Vegas. (What power. I should have said that Hawaii was a better choice).


I took a brief medical history. Turns out my patient suffered from chronic inflammatory demyelinating polyneuropathy (CIDP). I had had one patient with that rare disorder years ago. It is a bit like MS in that the sufferers develop an auto-immunity against their own myelin sheaths so the nerves, especially the motor nerves getting weaker and weaker. If CIDP involves the respiratory muscles, life threatening shortness of breath is a rare but real possibility. Pneumonia can also occurs with a decrease cough reflex.


He denied chest pain. No calf swelling or tenderness. No cough or fever. No new new meds or foods. No history of asthma or severe allergic reactions. No other major medical issues.


I used the emergency stethoscope that the steward provided. I could hear no air moving in and out. A very very bad sign. Then I listen to the heart. Again I heard nothing. But my patient had a normal pulse.  And he was not turning blue or had any altered mentation. In fact there was none of the classic signs of respiratory distress- nasal flaring, using accessory muscles, tracheal tugging. Maybe the CIDP was obscuring them? I retrieved my own stethoscope from my seat. Still nothing. Then I listen to my own heart. Nothing. The problem of course was the volume of the ambient noise, not that my patient had no air entry into the lungs and that his heart had ceased beating. I didn't asked if they could turn the engines off for a few minutes so I could listen in the quiet, but the thought did cross my mind for a moment.


He had an infusion of IVIG the day before and was worried about the effect of flying so soon afterward. Now I have great personal familiarity with flying right after IVIG. I have done it dozens of time without a blink or blip. I plan my long foreign trips around my IVIG and try to get it just before I leave for  exotic lands. He was very reassured by this.
.
We chatted more. He was able to talk without gasping or halting. He was felling better, less air hungry. We walked up to first class. His gait was weak and his hands shaky. CPID has devastated his muscles.


No need to divert the plane.


We talked about his family, my leukemia, his treatment. The oxygen mask came off. He was smiling, relaxed, feeling OK again. I gave him my contact information.


His panic attack was over. I still had the paramedics meet the plane and take over his care. After all I had yet to really auscultate his lungs. I could have missed a pulmonary embolism or a cardiac issue or....


That afternoon back home at last, I got a call from a dear friend, a fellow family doctor with CLL living in Canada just admitted to the neuro-ICU with chronic inflammatory demyelinating polyneuropathy. Was it related to the weird immune system us CLLers share? Was it totally unrelated? Seeing as no-one knows the cause of CIDP, it is anyone'e guess.


What are the odds? Two cases of an exceedingly rare disorder on the same day. 


Synchroncity? Where is Dr. Jung when I need him?


I had done my doctorly thing. It ended well. I could talk to my Canadian friend with some fresh knowledge of CIDP from the research I did after I landed.


The steward asked for my frequent flier number as I was leaving the plane. Maybe I will even get some miles out of just doing what I do.


One last puzzle piece. When I got down to baggage claim, another doctor who was on our flight walked up to me too thank me for jumping in. He was being treated for cancer and didn't want to take the risk of offering to help due to his lowered immunity. 


Don't be judgmental.


We all make decisions. If the patient that I had found at the back of the plane had not had a panic attack on top of a rare neuromuscular disorder, but was suffering from a much more common condition such as severe asthmatic bronchitis, putting anyone such as me or the more reluctant doctor at grave danger and with little to offer in the way of help, his decision would have been the correct one, not mine.


It is good to be lucky.


I promise more lucky news soon from my ibrutinib trial at OSU.

Very bad and irrelevant news: Ibrutinib (PCI-32765)

Soon after I first arrived here, I hinted at some bad news that I needed some time to digest.


As circumstances developed, I didn't see Dr. Byrd for several weeks to get the proper perspective and then I had to digest what he said.


The good thing about CLL is even with bad news, you almost always have time to analyze your circumstances, adjust to the new realities, under react, and move forward. 


I also wanted to wait to share with you until I had more distant from the shock


Let me set up the story.


Just before I came to see Dr. Bryd at OSU to assess whether I was a good candidate for his trial, I had a bone marrow biopsy with Dr. Kipps to show that I  had recovered my CD20+ after all my rituximab, an inclusion requirement for the clinical trial with ofatumumab and ibritinib and to assess my status.


That bone marrow biopsy done two months early showed slightly less than 10% CLL (with CD 20 positivity), and my old friend 11q deletion back in 11.5% of the the cells analyzed. The marrow was pretty healthy. No big surprises.


I tried to talk them out of another biopsy at OSU, but they insisted. 


It told a different story.


They use mitogens or stimulants that makes cells divide and thus make it easier for the pathologist to find genetic abnormalities.


And they sure did.


The FISH testing found over 50% of my cells as being 11q deleted.


For the first time 13q14.3 (D13S319) and l-3q34 (LAMP) were both positive.


And:


17p1-31 (TP53) which should be 0-6% of the background population was positive at 7.3%. Not a strong signal, but not a signal I wanted to see at all.


And worse yet, the cytogenetic studies showed that I had not one but two evil clones with "complex karyotypes" that confirmed the FISH findings and re-enforced my bad prognostics and suggested likely resistance to most therapy.


My cancer apparently consisted of two clonal populations, both nasty and both pretty bizarre. Bizarre is bad. Bizarre is aggressive and unresponsive. 


This was very dark news indeed. 17p deletion is usually a clarion call for a transplant. Nothing else reliably stops its often furious and fast fatal march. Complex cytogenetics may make any decision, transplant or other therapy more problematic. Clonal evolution is itself a very poor prognostic indicator. Zap 70 +,  unmutated, CD38+.  I had just about every bad omen.


Things were not looking good.


Now before I proceed, I must point out that comparing the sudden change to a much more aggressive and hard to treat cancer in the 60 days between Kipps' and Byrd's biopsies is not fair because the two labs were using very different techniques.


The mitogens employed by the team at OSU are used precisely because they powerfully stimulate cell division, and thus can demonstrate and some would say artificially inflate genetic abnormalities.


The two methods are looking at very different raw material. Comparing apples and rabbits. Static and active. Most research and data you see in the journals and at conferences still asses their findings the way Kipps' lab did with the static FISH studies. That is the existing standard when a paper says that 20% of the patients were risk risk 17p or 11q. 


So there may be much less change in the 60 days than the numbers suggest.


But the realist in me, says it is still some kind of devolution.


And Dr. Byrd said that these low level findings may not be accurate, as the 17p is the most difficult probe to nail against the background noise. It may mean nothing. It may be a false positive.


The skeptic in me says it must mean something.


Moreover, Dr. Byrd (and Dr. Keating agreed) reassuringly stated that he has seen these low levels of 17p disappear. 


The worrier in me wonders if they are really gone or just hiding? 


But what makes all this speculation and grim foreshadowing and ruminating moot and irrelevant is that I am responding to the ibrutinib.


The proof is in the pudding.


It's working. 


IT'S WORKING!


Some data generally suggests that, at least at first, low levels of 17p del are not as a important factor in response to most therapies as are high levels.


Most importantly, as I have posted before, there is little difference in the response to ibrutinib of 17p deleted patents compared to this with those with more favorable FISH. The depth or durability of the drug's activity seem blind to 17p deletion status. And there are theoretical reasons to believe that being the usual lousy ZAP70 + as I am might be actually be an advantage as PCI-32765 blocks B cell signaling and ZAP70 is all about signaling.


It is all irrelevant as long as the pills work their magic. So far, so good.


What it does tell me, is that it was one of my more prescient and fortuitous moves to push to get into this trial when I did. It's closed now.


If I had not, I would not  had a second biopsy and would not have known of my clonal evolution and the sinister loss of a 17p. 


When it came time (sooner rather than later)  that I needed treatment, my options would have been very limited as most therapies are inactive or pretty toxic or both when you don't have a working P53 pathway (usually found on my missing 17p) to tell the cells to die. Making matter worse, many trials with ibrutinib or other tyrosine kinase inhibitors would exclude me because of my prior transplant.


Of course, there still exists a few scary "what ifs" and "what nexts". Planning for them has become much more difficult and constricted. But that can wait.

Right now, the overwhelming sense I have moment to moment and week to week is just I how fortunate I am to have made the jump to Columbus, Ohio when I did.


I am very lucky and very blessed and very thankful to be here. Now.

Another letter from a patient on faith, hope, fighting, planning, and luck

As a relatively successful basketball coach and teacher, if there is only one thing that I have learned it is this:  Out plan, out work, out rehearse, out scout and out practice your opponent and you will place yourself in a situation where you are controlling as many variables as you can.  Hope is wonderful and motivating but hope without preparation is mind fluff.  Luck is a variable.  Luck or the lack of luck can never be discounted in the human condition but as John Wooden so accurately said, “…luck is more often than not a byproduct of hard work…”.

 

Faith is essential as it confirms and embraces our efforts but it still comes down to fighting the good fight each and every day.

 

Keep fighting as I want to see you back at work soon.

"Relatively successful" My friend is being modest: Teacher of the Year in Orange County, many time champion coach, world class safari guide, and just a great guy. 

I think I will let my patients do more of the writing for me.