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.

Now a Word from the Creators: The Team who Designed and Synthesized the Molecule now called Ibrutinib

I was thrilled to the marrow to find the following email in my inbox.

I redacted two name as I do not yet have their permission to thank them personally.

I am hoping to talk to the team leader and post more on the history of the drug's birth and evolution. 

It takes more than a village to make a new drug and I am living in gratitude to so many, known and unknown.

Here's the first email (with very minor edits to protect identity):

Dear Dr. Koffman,

A former colleague just posted a link to your blog on his Facebook page. I'm happy to read of your positive response to ibrutinib.

Both of us were part of the team that discovered ibrutinib at Celera in 2005. One of my direct reports, Dr. X1, first designed and synthesized the molecule which we believed would be an inhibitor of Brutons Tyrosine Kinase (BTK). This enzyme plays a signaling role which we hypothesized is important in Rheumatoid Arthritis and cancer. Preclinical testing in animal models of RA and cancer cell culture looked very promising. Several months later, Celera shut down its pharmaceutical program and sold the rights to Pharmacyclics who subsequently advanced it into clinical trials.

My old team at Celera has since widely dispersed. Dr X1 is currently (teaching at a University in) China. Several others are no longer working in drug discovery due to massive lay-offs and changes in the US pharmaceutical industry. I am now with the National Cancer Institute and our former team leader (who posted the Facebook link) now works in Australia.

We are all thrilled to see that our molecule survived Celera's shutdown and has made it to the clinical setting. Words cannot express the joy we feel knowing that our work is positively impacting the lives of people like you. 

I hope for your continued recovery and will follow your blog with great interest.

Sincerely,

Paul

________________

Paul Grothaus, PhD

Bethesda, MD

Excepts from his follow-up email:

My former boss, Dr. X2, was the one who pointed me to your blog, he also told me that he had written to you as well. X2 was the one who coordinated the overall project and could best inform you about the drug's discovery and development at Celera. I was more directly involved in the chemistry rather than the biology of the compound. Of course, Pharmacyclics really deserves the credit for discovering its oncology applications and pushing it forward to the clinic. Development of any drug is really due to the work of many individuals, many of whom never really receive much credit or compensation. One doesn't go into this field expecting those, it's for the science and the hope that you find something useful. The dream of every medicinal chemist is to find a drug that makes it to the clinic and helps patients. We're all excited to have been part of that.

Best wishes for you and all cancer patients.

Paul

It is amazing to think that this molecule did not even exist in the universe until it was manmade only seven years ago, around the time that I was being diagnosed with CLL.

Like most breakthroughs, it began with a risky new idea and will only end with years of hard teamwork.

So many steps could have been missed. This molecule could have been less than a footnote to another company's shutdown and my story and that of so many others might be radically different and most likely less positive. Instead, through a path of fortuitous decisions, it is rapidly traveling forward to FDA approval for cancer treatment. I also hope I can learn more about from Pharmacyclics about how they moved the process on.

I am so lucky to have hitched a ride on part of this journey.

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.