It's Been Nine Years Since my Diagnosis of CLL (Chronic Lymphocytic Leukemia)

Me (today, the 1st day of the Jewish NewYear 5775 or Sept 25, 2014)

It's been nine years since my diagnosis of CLL and am so happy to be alive and arguably in better health that I was when I received the life changing news in September of 2005.

When I was first told I had an aggressive version of an incurable cancer, I know little about CLL and what I quickly learned was discouraging.

Nothing back in 2005 had yet been shown to add a day to our lives. And the last few years alive with our disease were predicted to be full of misery.

Ibrutinib and idelalisib were just been being born in chemist's vials and were years away from first in human experiments.

I made appointment with our family lawyer to get my affairs in order almost sooner than I started my long term relationship with the wise and kind Dr. Tom Kipps.

I became a raw foodie but couldn't handle it and moved a bit closer to the center to become just a strict and mostly organic vegan. I cut back on my crazy workload and started to work out at the gym with weights for the first time in my life. I worry less and celebrate more.

I got no help with imbibing horrible tasting Chinese herbs that I brewed up myself or from a year of acupuncture. Nothing came of many other well intentioned but ultimately impotent alternative healing approaches, but I sure tried.

The cancer and its complications marched on.

Multiple hospitalizations for life threatening ITP, an emergency splenectomy where I lost half my blood, a failed clinical trial and bone marrow transplant, a move to Columbus, Ohio for the winter 2 and 1/2 years ago to get on an ibrutinib trial at OSU, and here I am, feeling better than ever.

I seen thousands of miles of travel in six continents, two daughters get married, my father's passing, and the birth of my first two granddaughters.

I have learned much from my mistakes and my fortunate choices, and I love to share what my experience, asking a lot of hard questions of the experts, and a ton of late night reading has taught me about surviving.

My hair is grey, my belly's flatter and I sure have learned a lot of hematology for a family doctor.

But best of all, I have met some of the most amazing people ever from all over the world, not despite, but directly because of my cancer.

My battle is hardly over, but I am still out there swinging.

Life is good.

Stay strong my friends. We are all in this together.

Celebrating My Two Year Anniversary Today on Ibrutinib for My CLL (chronic lymphocytic leukemia)

Much has happened in the last two years, most of it very good.

On a personal note, I swallowed my first 3 battleship grey capsules of PCI-32765 (it wasn't even called ibrutinib yet) on May 7, 2012 in a Phase I/II clinical trial at OSU with Dr. Byrd.

Two years later my lymph nodes have shrunk to less than 1/2 their size with the possibility that all that remains on the CT scans is the scarred shells of what used to be cancerous nodes.

Today, to find any CLL in my blood, you can no longer rely on the standard bloods test but must do the vey sensitive flow cytometry to find the < 0.3% of cells that are still clonal.

My latest bone marrow biopsy was 15 months ago in Feb. 2013 and even back then it showed only 4% CLL by flow cytometry down from between 10%-20% a year earlier.

I am clearly in a very deep and deepening remission.

I am very grateful.

On a community note, ibrutinib, the first in class signal blocker (BTK) for CLL, received breakthrough approval in the USA for anyone who has tried at least one prior therapy based on its outstanding safety and efficacy data in all patient groups, including those with 17p deletions and other hard to treat clones. But it is broadly available to any of us who have tried but not necessarily failed just one prior therapy.

Obinutuzumab, a potent 3rd generation monoclonal antibody (mAb) is now on the market and is getting complete remissions with the wimpy help of a touch of chlorambucil in clinical trials. Clearly it is this new mAB that is doing the heavy lifting.

Idelalisib, another  exciting targeted oral medication, should be approved later this year based on its stellar efficacy results in pivotal trials with few adverse events.

ABT-199 is proving to be perhaps the most potent oral agent yet in difficult to that patients.

ONO (ONO 4059) and Infinity (IPI 145) and others have very promising signal blockers well into development.

ROR1 trials are just beginning and should offer laser like focusing and very little off target damage.

CAR-T therapy has pulled a handful of patients from near death to deep remissions.

I was revising a 2012 CME (continuing medical education) on CLL program that I will be giving in Baltimore in June and realized just how far we (and I personally have) have come.

I am very grateful.

After  all, we are all in this together.

I think I''ll enjoy some  home made coconut milk yogurt to celebrate the amazing progress.

CLL: Eight years and counting

"The whole world is a very narrow bridge. The important thing is not be afraid."

Rabbi Nachman of Breslov

Walking 30 feet up on a telephone pole at the Cancer Advocate Leadership Conference at Miraval

Thank you Escape and Bag It

It was eight years ago on September 7th, 2005 that I received the lab results that changed my life forever and was handed the diagnosis of the incurable (and soon after the added adjectives of aggressive and complex) chronic lymphocytic leukemia.

I have riffed on these anniversaries before, but this one almost passed me by un-noted.

Why? Because recently my focus has shifted from my personal struggles to my efforts to increase awareness of how CLL therapy is changing.

Yes, my personal future is still unclear. Yes, my CLL is still hanging out in my mesenteric nodes and a small percentage of my marrow. Yes, it has evolved into a nastier dance partner over the eight years of this waltz. No, I am not cured, just very well controlled.

Though I would obviously prefer to get off the dance floor once and for all, or at least have a more benign partner who is not always trying to trip me up, I am just fine with living with a well mannered cancer. Fine enough to spend more of my energies in shining a light that might guide others to similar happy outcomes. Fine enough to teach and advocate and support.

I am in the process of putting together my non-profit and working with other not for profits to move forward on the mission of smarter care for all those with CLL and related B cell cancers.

Of course, when I was at XViwCLL 2013 in Cologne last week, I paid close attention to the news and research that might impact my health personally. But the bulk of my efforts in Germany were outward. Please understand that that is not an entirely selfless or strictly altruistic act, but as many have argued before me, a recognition of how much healthier it makes me to share and spread my good fortune. It is so much better for me personally to look to the needs of the whole CLL community as well as my own.

So I almost missed my "anniversary" because my focus was on the future, not the past.

Stay strong.

We are all in this together.

I am moving later  this week, so my posts may be a bit more sporadic over the next weeks or so.

Five Years Post "Failed" Hematopoietic Stem Cell Transplant

Granddaughter, Amira at the July 4th Parade

The last half of June and the first week of July are full of red letter days for me.

I had my hematopoietic stem cell transplant on July 1, Canada Day in 2008, a little over five years ago. I remember watching the fireworks on that 4th from the City of Hope hospital window on the 5th floor with my family and my IVs and my N95 mask.

About this time those five years ago, I was near the nadir for my blood counts and feeling about as healthy as a sticky asphalt road in Death Valley in a scalding August, with a convoy of overloaded 18 wheelers doing wheelies on my soft shoulder.

I ended up recovering quickly, but I never engrafted, and soon lost everything: the graft, my short lived MRD negative complete remission and any clarity that I ever had on what to do next.

My aggressive plan to deliver an early (first remission) knock-out punch to my CLL never even got cocked and ready.

But then again, it didn't knock me out either as it has done to so many others before. PC Venkat, my friend and the pioneering model for my shock and awe approach to CLL, passed away the day before I was admitted to City of Hope. That terrible news was both sad and sobering, but I went ahead with my plan to assault the same beachhead where he had fallen.

In hospital, I pushed to get ATG as part of my conditioning to cool my own immune system that never had been damaged by chemo or Campath. I failed and without it, my T cells at transplant time were still on active border patrol and as it turned out, more than up to the task of booting out the invading donor cells from my marrow. Later I pushed for more radical reinforcements, namely DLIs, but was told it would be too little too late. Either I should have a meaner and riskier second transplant, or.... Who knew.

Within six months, I had nearly simultaneously lost the graft and relapsed. Six months after that the ITP was back.

Not a good time.

But on the other hand, I have no graft versus host disease, because I have no graft. Actually the last check for my chimerism (measurement of more than one genetic fingerprint in an individual)  done years ago showed that I was still genetically in my marrow about 1% my wonderful Israeli donor (Yaakov). That is within the range of statistical error, but my wife swears it is Yaakov's lingering influence that has somewhat ameliorated my tone deafness.

Does that count as a partial remission?

My youngest son just visited him in Jerusalem. He is a gentle and generous young man.

Maybe losing the graft was for the best. GVHD (graft versus host disease) is tough and there can be worse, much worse outcomes. Only about half of those transplanted are still alive five years later to blog.

But I am doing well in my clinical trial and my life is most sweet these days. While it is possible that I might have been "cured" by today if I had been treated more aggressively those five years ago, it could just as easily been five years of misery with multiple hospitalization for some nasty mix of GVHD, sepsis, and relapse. Trading one disease, CLL, for another, GVHD.

I'll never know.

But it's hard to imagine a better life than the one I have now.

Sometimes it amazing how things work out and what looks like a disaster up close, from a distant turns out to be our saving grace.

I know how lucky that I am and for that I am deeply grateful.

Happy 4th!

Quick update: My talk to the San Diego CLL support group at UCSD yesterday was well attended and, I believe, well received. It was a great opportunity for me to meet others with my disease and share some of what I have learned over the last nearly eight years.

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.

Four Year Transplant Anniversary: A Request for your Help With CLL Research on Ibrutinib and More to Control and Cure CLL

I received this important email from John Byrd, my doctor at OSU, and one of the most innovative and patient friendly researchers in CLL in general and ibrutinib in particular. He is asking for your support in his fundraising efforts though Pelotonia.


Dr. Byrd is looking for ways to save lives without the risks and miseries of an allogeneic hematopoietic stem cell transplant or maybe even the use of the more toxic old school chemotherapy. 


In another email he said: The new trial that opened with Ibrutinib (Kami Maddocks PI) is being supported entirely by a 100,000 dollar grant from last years Pelotonia.  


He also wrote that the money raised is supporting the following studies that would not be happening without Pelotonia


1.  Post-doctoral fellow working on understanding role of autophagy in drug resistance in CLL
2.  PhD student working on an entirely new kinase inhibitor target for CLL 
3.  An idea grant from another lab (with us) looking at ATF3 as an immunosuppressive stromal factor in CLL


Four years ago today I had my transplant on Canada Day. It failed but I am still here.  Maybe it was a good thing that I never engrafted? I was spared the potential horrors of GVHD, but on the other hand maybe I would have been "cured" by now if it had taken. I will never know, but I do wonder.


Would I have made the same choice today with all the new options opening up?  The answer is probably not, but the data to help with that decision is far from being conclusive. We need to know more. It is so early in the research.


I am in the process of composing a post on the role of transplant in this nascent era of the new small molecules for CLL. It is an increasingly common question posed by patients and doctors alike.


If you can, please help Dr. Byrd and others in their research to get the answer to this and so many other cancer questions. Please consider clicking on the link to donate.


Thanks.


Please see Dr. Byrd's email below.


Dear Brian,

I am wrting to you because your help is needed.  I have decided to ride in Pelotonia and would greatly appreciate you to consider supporting me.  

Pelotonia is a grassroots bike tour with one goal: to end cancer. More than 10,000 supporters are expected to be a part of Pelotonia 12 on August 10-12, 2012. The ride will span two days and will cover as many as 180 miles. In its first three years, Pelotonia has attracted over 8,300 riders from 38 states, over 2,800 volunteers, hundreds of thousands of donors and raised $25.4 million for cancer research. In 2011 alone, a record $13.1 million was raised. Because operational expenses are covered by Pelotonia funding partners, 100% of every dollar raised is donated directly to life-saving cancer research at The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute. I am writing to ask you to help me raise funds for this incredible event. Large or small, every donation makes a difference.

What will your donation be used for?  The money derived from this race supports research to identify new drugs and also to perform clinical trials in cancer.  I am a leukemia doctor focused on curing a disease called chronic lymphocytic leukemia (CLL).  In the laboratory, Pelotonia is supporting idea grants to bring novel ideas that might translate into new therapies some day.  Additionally, it is supporting students and post-doctoral fellows to work on new antibodies (different from rituximab) and small molecules that could some day be therapies.  Addtionally, one of the trials that Pelotonia is supporting with money rasied from last year is with ibrutinib, a highly active bruton tyrosine kinase inhibitor that is very active in CLL.   We have seen this agent help many CLL patients and are delighted to have the support of Pelotonia to allow us how to use this medication better and along the way help patients with this disease.  Without Pelotonia, the trial with ibrutinib coul
d not happen.  I see Pelotonia as a way for us to move quicker to converting cancer to a chronic disease or one that is cured.   This is something I am passionate about supporting.  I hope you will contribute and remember no amount is too small.

When you follow the link below, you will find my personal rider profile and a simple and secure way to make any size donation you wish.

Think of this as a donation not to me, or Pelotonia, but directly to The OSUCCC-James to fund cancer research. Please consider supporting my effort and this great cause. My rider profile can be found at the following link: http://www.mypelotonia.org/riders_profile.jsp?MemberID=1227

Thanks for the support!

John

Control, Not Cure: A New Path Opens Up Four Years Later - Transplant Then, BTK Inhibitor (Ibrutinib) Now

Four years ago today, I was admitted to City of Hope for a first remission hematopoeitic stem cell transplant. It was and still is the only possible path to a cure for CLL.

The only way to say: "I used to have cancer."

At that time not only was CLL incurable outside of a high risk transplant, there were no options that had even been shown to prolong life.

Now we have proven that FCR can add years to our life. The same is probably (but not certainly) true for BR and perhaps other very effective chemo-immunotherapy cocktails.

But FCR is hard on the marrow and not a great choice if you are older or more frail or have an auto-immune history such as ITP (as I do) or AIHA or if you are 17 p deleted or otherwise F refractory.

As those or you who have followed me from the get-go know, I failed my transplant because I rejected the graft. I was too healthy from an immunity perspective. With no graft aboard, I never had any of the desired graft versus tumor effect. Within a year I had relapsed and needed treatment again for my ITP and later my CLL.

The transplant didn't cure me, but it didn't kill me either. What it did do was buy me time until the game changing new therapies showed up.

Because of the brave souls who entered into phase 1 trials of an unproven and radically different  approach to CLL, I was able to follow their trail into a more mature and certain trial for a tyrosine kinase inhibitor, in my case ibrutinib (formerly PCI-32765) that blocks a pathway that is jammed in the on position inside my cancerous clone. It keeps telling my cells to proliferate and never die.

Not a cure, but a promise of longterm control with a very manageable downside.

There are other similar small molecules and pathway blockers and promising new antibodies and immune modulators out there that are changing the way we will approach CLL in particular and cancer in general.

Four years after I entered hospital on my high stakes gambit to be rid of this cancer once and for all, I am shifting gears. My transplant failed and since I never engrafted, it is almost as if it never happened. All my benefits (and risks) were from my one week of high dose FCR conditioning.

Today I am amazingly healthy after seven years of a battle with a persistent and aggressive enemy, but  now I have a kinder gentler approach and it seems to be working. Let repeat today's theme: Control if not cure.

I have made the shift. I was lucky to be able to see how the paradigm was changing and make a move. 

I can now clearly envision a new future that was just a distant speck on the horizon four years ago.

I can live with that.

G-d willing, for a long, long time.

Two Year Anniversary

Today I celebrated, not only the birthday of the country of my birth, Canada, but the second anniversary of my hematopoietic stem cell transplant.

I am grateful to be here and so well. Others were not so blessed.

I have managed to avoid much of the grave toxicity of treatments which have knocked back my CLL and my fearsome complication of low platelets with a minimum of side effects using my most "unorthodox" approach as described by Dr. Kipps.

Yet I get tired of all this dancing around to avoid heavy duty chemo and still keep the CLL/ITP at bay. My maneuvering has bought me almost 5 years But it hasn't been enough time to find the cure. Not even close. How about an orthodox therapy that will save my life and that of so many friends? The only option out there is still a transplant, and I am more and more realizing how lucky I am to have had such a benign if failed course after mine.

We are all tired of the waiting for the magic bullet, our own Gleevec, a relatively non-toxic very focused small molecule that revolutionized care for our cousin disease, CML. CML used to top the list of transplants. Not anymore since Gleevec.

We are all tired of dancing and are looking for a more healing partner than old school chemo.

Will it be CAL 101 or Revlimid or ABT? I doubt it, but they are strong moves in the right direction. I have hope.

In the meantime, what choice do we have? We dance on. After all it is my rebirthday and I am deeply thankful to be alive and writing this note.