Over nine years of blogging since transplant for CLL (chronic lymphocytic leukemia) on July 1, 2008

This picture, painted by son William, launched by blog and was originally painted as a way to remember me after I was gone. Now it just serves to reminds us of a more challenging time.

My story telling all started here in this blog.

On July 1, I celebrated nine years since my allogeneic hematopoietic stem cell (bone marrow) transplant. There are a ton of posts around that time pre and post about my ups and downs.

In May, it was five years since I started in a phase 1 trial of PCI-32765, now better known as ibrutinib to control by advancing chronic lymphocytic leukemia and avoid another set of death threats from plunging platelets due to my auto-immune dysfunctions or ITP (immune thrombocytopenic purpura). Lots of post sharing my inner processes and fears and triumphs.

Next September, it will be 12 years since my CLL diagnosis when I felt some lumps on the back of my neck and my blood test showed too many lymphocytes.

It's been almost 11 years since my first of five hospitalizations for crashing platelets culminating in losing half my blood after an urgent splenectomy.

I am lucky to be alive.

I am just darn lucky, but as others have said, we can at least to some extent, make our own luck as I have tried to do by becoming an expert patient and an advocate for myself and others with CLL.

And the last dozen years has had more than its share of rewards.

During these times, I have written my will, but I have not made any concrete funeral plans. I don't believe I am going soon and will likely change my ideas for the best memorial as I age. Plus I am too busy and alive.

I have walked two daughters down the aisle, and been blessed with 3 granddaughters. 

I have outlived by father of blessed memory. That was not likely when I has first diagnosed.

I have attended too many funerals of other CLL patients and a few friends who helped me on this journey.

I have held in my arms euthanized pained and sick cats and dogs as they breathed their last.

I have moved my home several times, quit work as a family doctor because I was too sick, fatigued and immune suppressed, and now returned to my medical practice, still sick, fatigued and immune suppressed, but making it work, making a difference in my patients' lives.

My blog tells much of the story until about two years ago, when it fell almost silent, mostly just echoing what was happening with my new love, the nonprofit CLL Society Inc. http://cllsociety.org.  

It happened because it became clear that my chronological tale of my own failed transplant, brushes with death, hard decisions and my life saving move to Ohio for an experimental treatment, while cathartic for me, and helpful for many, was not the best way to share what I had fought hard to learn over the last decade.

I set up the nonprofit CLL Society Inc. http://cllsociety.org which is much bigger than my particular story and is as wide as it is deep in CLL knowledge and wisdom because many others pour their experience into it.

There we are saving lives. There we are changing how CLL is treated. 

But it all started here.

It has been amazingly rewarding as I have traveled the world talking to CLL doctors and patients and industry about the patients' perspective. I have friends wherever I  go around this small globe: doctors, researchers, patients, advocates, and caregivers, that know me or the CLL Society or this humble blog.

But setting up a nonprofit, especially one with a ferocious appetite for new material and research that yours truly produces nearly every week, one that does its own research and advocacy and teaching and consulting, all with a amazing but tiny staff and wonderful volunteers,  plus practicing family medicine again where the burnout rate is soaring, keeping pace with the rising bureaucratic demand of medicine, and being an an available husband, father, grandfather and friend doesn't leave much time for blogging.

The blog has been neglected, given short shrift. Like the wayward husband who leaves his true love who stood by him for years for a younger trophy wife, I make the excuse that I have outgrown it.

But I haven't. 

I still need it.

And I believe that it still fills a need for others.

Despite my years of benign neglect, it was just rated as one of the top 10 leukemia blogs and has had over 1,100, 000 page views.  Over 1,100 posts since I started in April, 2008.

I am not promising that I will be posting daily again soon. In fact I am sure that I won't, but I did post this one and that's a start. 

I have other burning issues that would be best shared here as a good place to noodle about my concerns and decisions. 

So...

Stay tuned.

Stay strong.

We are all in this together.

Brian

http://cllsociety.org
http://bkoffman.blogspot.com

If the CLL Society has helped you or a loved one, please consider making a contribution.

Another CLL (Chronic lymphocytic leukemia) Patient Dies Disease Free from Complications of Her Treatment

I lost another friend to CLL: a kind and powerful woman who so loved her life filled with friends and strong family support and love. She was an important and passionate member of our local support group.

Too young, too alive to be gone so soon.

She was treated at the end at one of the world's best CLL centers, but that transfer of care from a community oncologist might have come too late.

When she passed on, her CLL was nowhere to be found, but her uncontrollable GVHD (graft versus host disease) from her transplant (her sister was the donor) killed her. GVHD can be so unpredictable and so relentless.

Yet another death by treatment.

Transplant is a very blunt tool with huge collateral damage, but when the disease is on the march again and has wised up from former chemotherapy so that it can no longer be lulled back to sleep with the usual drug combos, transplant may be the only option left that offers us another chance. I am glad it's available. It can be a life saver. Or not. Remember that I opted for one for myself almost 6 years ago. That's how this whole blog started.

The issue, however, is not knocking back the CLL. That we can do most of the time. The issue is healing the patient. That is where we fall short.

That is why I am pushing for new therapies.

That is why I am looking at preserving our immunity and our marrow.

That is why we need research to rebuild our damaged B and T cells.

The pain of these losses motivates what I do here on the blog and out there in the community. Most of the time, I feel so lucky to be able to do blog and share my story and ideas and interviews.

But sometimes, like today, it just reminds me of how vulnerable that we all are and how raw are our  wounds .

Right now, once again, I will just want to stop and stoop my head and say a prayer for her family.

I am so sad.

I hate this cancer.

Flashback: I meet my Donor in 2009

This page, recently sent to me by a CLL friend  who lives across the country, is from the 2009 Annual Report of Ezer Mizion, a not for profit charity that among other good works, helped me find my bone marrow donor and a new friend in Israel. Ezer Mizion has a huge international bone marrow donor registry. All recruits  of the Israeli Defense Force are screened. in 2009 they found 642 matches and 138 transplants were done around the world.

We raised a lot of money that day in Manhattan. Yaakov and I have stayed in touch. We visited in Israel and my son, Will just met with Yaakov in Jerusalem last month.

I later spoke to the rabbi in Leeds, England that had lead the campaign to raise the money that ended up screening Yaakov and hundreds of others. They failed to find a donor for their congregant in need, but they found my donor. We never know the results of any kind act. We never know whom we might touch when we reach out our hand to give. Or to take.

And even though I never engrafted and it was not the cure that I hoped for, it did buy me enough time to make it to my present life changing clinical trial.

The months before my transplant was like crossing a minefield blindfolded, the months after, like tramping through a quagmire with no sleep, but all that is in the past, and today and the future are bright.

I am grateful for the friends that I have met along the way and especially to the selfless contribution of my blood brother, Yaakov.

As to my comments below, I am happy to report that I have not only met my first two grandchildren, I now plan to live long enough to meet their children.

By the way I got back the rest of my lab and even my IGG level after 6 weeks with no refilling of the tank, was still in the normal range, albeit barely. Looks like the 6 weeks between infusions is about as far as I dare stretch. 

Vitamin D3 level was high normal, just where I want it. I need to take 10,000 a day to get it there. Zinc level wasn't done. Lab error. Not worried.

Here's the article.

YAAKOV MEETS BRIAN

Cancer survivor, Dr. Brian Koffman (56) of California, spoke eloquently at an Ezer Mizion event of his bout with cancer. "It's great to be here," he began. "In fact for me it is great to be anywhere.
“I had been diagnosed with a particularly virulent form of cancer with a short leash and a tight grip. All my knowledge as a medical doctor offered no protection or control over the disease. It was like being on a roller coaster ride without the safety bar. My daughter recently got married. Would I be around to see my grandkids?
"Because of Ezer Mizion's efforts, I am alive. One thing I learned at the school that no one wants to attend: You need the right team. I was stretching out my arm as far as I could and Ezer Mizion reached across the ocean and gripped my fingertips and pulled me to safety."
Unknown to Dr. Koffman, waiting in the audience was Yaakov Fabian (24), the donor whose bone marrow donation had saved his life. An emotional meeting ensued between the two ‘blood brothers' and their spouses, who remained at each other's side for the rest of the evening.
This lifesaving transplant was made possible thanks to the generous sponsorship of the Leeds Jewry Donor Pool at Ezer Mizion’s Registry.

The Perfect Stranger: Meeting Wanda's Hematopoietic Stem Cell Transplant (HSCT) Donor

Aaron, Wanda, and me, Newport Beach, 2013

My friend, Wanda had a particularly nasty form of CLL. I say had, because she has been disease free for long time, all because of the kindness of a stranger who is a stranger no more.

But I am getting ahead of myself.

Wanda had had a difficult time with her cancer. Her leukemia had resulted in multiple hospitalizations include at least twice for near death experiences with septic shock, recurrent disabling and painful infections despite heavy duty prophylaxis and an aggressive CLL clonal evolution of the dreaded 17p deletion. And I am leaving out huge chunks of her travails.

Clearly when she looked at her options a few years ago, it was apparent that she couldn't keep going much longer without more therapy, but her fragile immunity couldn't have tolerated the blows from the chemotherapy that she needed.

This has just before our awareness of the promise of the emerging TKIs such as ibrutinib (PCI-32765) and idelalisib (CAL-101) in CLL and at that time, her options were mighty limited.

Wanda bravely elected for an allogeneic stem cell transplant, but wisely chose one where there was no chemo! A transplant and CLL researcher that I knew, Dr. David Miklos at Stanford had an innovative small but growing successful series of outpatient allo-transplants for CLL using only very low dose radiation and high dose ATG (anti -thymic globulins) to briefly knock out the recipient's T cells just long enough to sneak the donor cells into the marrow. No immune suppressing chemo is used, not that all the animal antibody of the days of ATG and radiation to the gut is a risk free or pleasant experience.

Still it was perfect option for Wanda, as her dangerous period of immune suppression would be both of shorter duration and lower intensity.

Steeling her nerves, all in, ready to go for the move up to Palo Alto for the months of therapy and follow-up, her difficult to find perfect 10/10 donor backed out at the very last minute.

Emotionally sucker punched, Wanda's knees may have buckled, but ever the fighter that she is, she just got ready to face what ever would be thrown at her in the next round of her cancer battle.

Enter the perfect stranger. Or at least a nine out of ten donor. A match made in in heaven. Her transplant hopes were rebooted.

More than a year after the HSCT, she found out that this genetic near doppelgänger was a rock solid sweet family man from a small town two hours north of Houston, Texas.

Her transplant path since has had its share of scares and joys, but Wanda is CLL and infection free these days. She is living big and is always ready to be more than generous and thankful for the chances she has been offered.

Earlier this week, it was my great privilege to join Wanda and her family and friends to celebrate her donor and savior, Aaron and his wonderful young family in her backyard.

For those few of us who have had that opportunity to meet and thank the perfect stranger from miles away who's selfless actions have saves our lives, it is one of life's magic moments. We meet someone we probably would never have met. Someone whose whole upbringing and life experiences make have no common points of connection with ours. A path we might never have crossed and a hand we might never have shaken if it wasn't for their random act of kindness that mades us blood brothers.

Knowing that we truly are all in this together can change everything. It makes the world bigger and brighter.

I am still in frequent contact with my Israeli donor, Yaakov and living in gratitude for his painful and selfless efforts to help a stranger. I remember so well the tears of thanks and the tidal wave of emotion when we first met.

The world is a better place because of the work of doctors such as David Miklos (and let me share this celebratory moment with my doctor, Steve Forman, at City of Hope), true heroes such as Aaron (and my donor Yaakov), and survivors such as Wanda.

I am lucky to be able to share in these celebrations.

Yaakov and me meeting in NYC, 2009

My blog started all about my transplant adventure and has subsequently morphed more into my editorials and interviews on blood cancers, and I will write again soon about CLL and other malignancies including the still important role of transplants, but I haven't forgotten my original vision for this blog. Even though my transplant failed, it bought me the time to get to the game changing treatment with ibrutinib that I am enjoying now. If it weren't for Yaakov, my story might have ended years ago.

ASH 2012: Dr. Pagel discusses transplants for CLL and the Role of Radioimmunotherapy

In the final short segment of my ASH 2012 interview with Dr. John Pagel, he discusses the approach to hematopoietic stem cell transplants (HSCT) or what were once only bone marrow marrow transplants in CLL. Now, we more often harvest the primitive blood stem cells from the peripheral blood after they have been mobilized. Much easier for the donor who doesn't need multiple bone marrow aspirations.

What Dr. Pagel talks about the real possibility of cure for some patients, especially those who go in to transplant with their disease in a deep remission.

The news is that using a drug such as Zevalin (ibritumomab tiuxetan), a radioimmunotherapy (a radiolabeled monoclonal antibody) or RIT in high doses is getting the necessary deep remissions and improving the odds of that cure. Ibritumomab is similar to rituximab in that it latches onto and destroys any and all CD 20+ B cells (cancerous or not), but it differs in that it carries a radioactive payload to those cells and thus destroys not just the cell, but its nearby homeys. This is especially helpful in shrinking bulky cancerous nodes, but can be dangerous if there are too many B cells left in the marrow as the local radiation delivered can cause lingering damage to the future home of the new donor stem cells. Still, it is a lower dose, more "surgical" way in many settings to get the radiation precisely  to the desired sites (at the cellular level) than is an external ionizing radiation source, no matter how focused. And most CLL, at least to start out, is exquisitely sensitive to radiation, although it always come back, and often comes back meaner. 

There are significant expense and turf issues in the medical world that explain why RIT is a very much underused therapy. Briefly, it is very costly per treatment, but is usually used only once or sometimes twice, so the total cost is comparable to a full course of say FCR. More tricky is the role of the doctors administrating it. It can mean transfer of care from the medical to the radiation oncologist and many doctors are loathe to give up control of their patients. We can argue that it needs the services of both a medical and radiation oncologist and their support teams of pharmacists, nurses, and technicians. More turf issues.

But I digress. RIT is a great choice if we need a transplant and we can get buy in from our doctors and insurance.

And the other news is that the mortality curve seems to plateau around 3, not 5 years. After 3 years, we stop relapsing. The CLL doesn't come back.

In other words, if we can make it three years out with no evidence of the cancer returning, we can be pretty confident that we are, dare I say it, cured.

Transplants are risky business, but are a sensible option for those who are young with aggressive disease, who may not have the time or the option to wait for one of the new magic pills. And they can absolutely be curative.

You can't say that about any other CLL therapy. At least not yet.

Here is Dr. Pagel. Enjoy.

Novel Therapies and Their Integration into Allogeneic Stem Cell Transplant for Chronic Lymphocytic Leukemia Biol Blood Marrow Transplant 18:S132-S13

Dr. John Byrd is the lead investigator on the clinical trial NCT01217749 that is the reason I am flying to Columbus hoping to enroll to procure this exciting new therapy.

Anticipating the future, Dr. Byrd co-authored an important article (Novel Therapies and Their Integration into Allogeneic Stem Cell Transplant for Chronic Lymphocytic Leukemia Biol Blood Marrow Transplant 18:S132-S13) that articulate how the trial drug- PCI-32765 and other promising novel therapies may effect the time and place of transplants in CLL. It is a clear, thoughtful and accessible discussion that I strongly recommend.

On the eve of my departure for Ohio, I sent Dr. Byrd an email expressing how the uncertainty about the durability of the response to these new promising agents might be a good thing

Please tell me what you think.

Dear John,

Thank you for your thoughtful review of this important topic.

Implicit in your review of the evolving therapeutic paradigm for novel therapies and RIC HSCT in CLL is a shift in the calculation that each doctor and each patient must make when dealing with aggressive CLL .

Before the bloom of these new treatment options, an informed patient or hematologist could make a good faith calculation on what gives the better chance of PFS in five or ten years. Although it is always dangerous to compare data from one trial to that in another, and even more so to assume that statistics that are applied to a group can predict what happens to an individual, one could still study the Kaplan-Meier curves for a HSCT and any particular therapy and make at least a partially informed choice.

Now with the promise of the new treatments, the decision to consider a transplant has become more tricky for some. The K-M curves are known on the transplant side of the equation, but what the novel therapies will yield is based on extrapolation of very thin data. We are comparing a known to an unknown. Ironically, with the survival rates so poor for F refractory or 17p del disease, this "unknownness" is a source of hope for some patients and another reason for others with the aggressive or refractory CLL to consider a clinical trial over a more conventional route starting with chemotherapy and moving to transplant.

Thanks again.

Brian

What is implicit but not explicit in my letter to Dr. Byrd is how I myself employed precisely this hopeful calculus in my decision of the known versus the unknown.

As I leave tomorrow, I will keep you informed every step on the way.

Wish me luck.

It calls for snow in Columbus tomorrow.

Borrowing a New Immune System from your Family

One of the problems with a hematopoietic stem cell transplant (HSCT) is that what you want is the new immune soldiers to march in, destroy ALL the bad guys and all their children and their children's children, then go home. It also helps if they bulldoze some of their favorite hiding places. All this and please no civilian casualties.

The problem is that if you successfully engraft (sadly not my story), then the soldiers (the new 100%  donor T cells and their allies)  are with you forever and these are trained fighters, and you, Mr. or Ms. Recipient, look like a prime target to rape and pillage. So while they might wipe out any strangling insurgents, they may also cause your life to be miserable with graft versus host disease (GVHD).

Comes along a fine study by Veronika Bachanova, MD, PhD  that uses natural killer cells harvested from a parent or child or sibling to do the search and destroy work. Since they are only a halploid (1/2) match your body rejects them after several weeks. 

In that time, they have shrunk your nodes and cleaned out your blood, marrow and spleen (if you still have one, that is) of any leukemia.

Great idea.  An elite force that attacks, then disappears into the night. Pretty non-toxic.

Especially makes sense if you are heading to a transplant, but can't shrink down some pesky nodes with FRC or OFAR or whatever.

Or if you can't find a donor that is a close enough match.

Also may be a real option for cleaning up residual disease. Like in my  gut nodes. Could it do a thorough enough job, like its big diploid (full match) sister, a HSCT, to be curative?  Way to early to tell.

Truth is that the only way be are ever going to cure this disease is through clinical trial, and if you think as I do that an immunological approach is a good place to bet your  money or your life, take a look-see at:  http://clinicaltrials.gov/ct2/show/NCT00625729

Natural Killer Cells With Rituximab In Patients With CD20 Positive Relapsed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia
(MT2007-12)

ClinicalTrials.gov Identifier: NCT00625729

Clinical Trials Office – Masonic Cancer Center at University of Minnesota
Phone: 612-624-2620, 612-273-2800, or toll free 888-601-0787

Principal Investigator: Dr. Veronika Bachanova
Phone: 612-624-0123

What I have given you is a gross oversimplification.

Chaya Venkat has a more detailed and referenced review of the study, and I thank her  (again) for her tireless work, sponsorship, and the great material on her web site:  http://clltopics.org/SponsoredProjects/NKCellTherapy.htm

The PI is a wonderful and kind person. Contact her if you are seriously considering the trial, or email me at BkoffmanMD@gmail.com and we can chat.

For myself,  while I am not flying off to Minnesota next week, I am definitely keep this study on my shelf in easy reach should  the need arise.