It's different in New York

This is a pretty technical post, so if you aren't part of the CLL crowd, you may want to skim it.

The lecture last night was refreshing and balanced. I even earned an hour of CME and ate mediocre steamed vegies on couscous.

Because it was accredited, the speaker was not pushing just a single product. Dr Weiss is from Sloane Kettering in NYC and he was a very good lecturer. With some very gutsy honest takes on some of the contradictions in results.

His take in the low response rate in the recent community based pentostatin study was that it was just a lousy study. As I suspected the wrong doses of both FCR and PCR and too many cycles of PCR resulted in increased toxicity.

His take on why MDACC gets such great results: They get healthier, younger patients. It is not that they cherry pick their patients. Their patients are young enough and rich enough to travel to see them. Their patients cherry pick them. Also in their first F study as a single agent they DID NOT DO BONE MARROW BIOPSIES TO ASSESS THE RESPONSE.  It is a lot easier to get a complete response with one eye closed. The blood is a much easier target than the marrow.

Finally he spoke about lenalidomide as a maintenance agent, using the lowest effective dose, instead of the  highest tolerated dose. He said it gets more effective the longer you use it.  That is so unlike most chemo in which the cancer sadly becomes increasingly resistant over time. CLL  is treated more like a chronic disease, like diabetes. Go slow and low and long. Tumor flare is a big issue when first starting, and can be fatal.

Finally, one last point. I was the only family doctor in a room of oncologists last night. Keep in mind that there are about 15,000 new cases of CLL a year and about 15,000 oncologists in the USA. That means your community cancer doctor is seeing one new case a year. Unfortunately that lack of experience showed around the room. See a CLL specialist, at least in consultation. Some of these very busy doctors are not up to date on CLL. How could they be with all the breast and colon and lung cancer they see? That is why, to their credit, they were there last night. To learn, and to get a free meal.

The latest news comes with a free meal

I am off to a free dinner lecture on latest trends in the management of CLL.

These can range from terribly proprietary, with the sponsor blatantly selling their drug in the guise of medical education, to excellent balanced and nuanced discussions of what is the present reality and what is in the pipeline that might shape the future with plenty of give and take.

Like tonight's presentation, they are often held at fancy restaurant that serves food a vegan would never eat. Ironically, the free meal that attracts many of the attendees, usually repels me.

The speaker tonight has published extensively on pentostatin. If he does discuss that, it will be interesting to see how he explains the recent negative results presented at ASH. I bet he blames the dosing.

With my wife out of town, I will enjoy the evening out. 

Before I finish, though I miss her like crazy, I realize how lucky I am to be well enough to be on my own for 4 days. That was not definitely in the cards when I was transplanted. It would have been unthinkable and even dangerous just a few months ago with my PICC and all my meds.

I am enjoying every moment, even the ones alone or at "questionable" meetings. That "questionable" is a double entendre.

"Oh teachers are my lessons done? Leonard Cohen

I cannot do another one.

They laughed and laughed

and said, Well child,

are your lessons done?

are your lessons done?

are your lessons done?

Leonard Cohen

My teaching on the abstracts from ASH went well. There was much lively discussion on why results in studies done at the fancy universities seem to have consistently higher response rates than those done in community based practices.

None of the answers are comforting. Are the big centers cherry picking their patients? Is care in the community inferior?  In truth, comparing one study to another is bad science. Doses and protocols may vary. Inclusion criteria and patient mix can make big differences in outcomes. Most older studies did not look at the new prognostic factors. Still it is worrisome. MDACC gets a 72% complete response rate and the community oncologists only help 17% of their patients to reach that desired goal with the same drug combo. Something is wrong here.

We also discussed the sad fact that there is still no evidence we are prolonging life in CLL, let alone curing it. Except maybe for a stem cell transplant. Which is why I made that choice. No regrets there. The new drugs reminded me of buying a house with lots of potential. They look so promising. So much potential. And yet the patients aren't living any longer. How's about some realization of all this potential.

HOW ABOUT A CURE!

That would be sweet. 

I will write some straight science soon from my take on ASH, but I will make it bite size and comprehensible.

For a tired guy on disability, I want to share with you just a tiny bit of the "work" I did this week. Forget the doctor's appointments and other commitments.

I reviewed a research project from 2005 on migraines, pulling up old data at the request of principal investigator.

I pulled and reviewed data on the epidemiology of cancer and transplants for my book.

I got copies of my old medical publications, again for my book to impress the potential agents. If they ask why the 30 year gap in publication, I will say I was busy.

I am preparing my writing sample and introduction for the book conference in early Feb.

I reviewed a proposal for a focus group to improve CME (continuing medical education) that I would moderate.

I researched second transplants in CLL. I can't find any papers!

I researched experts in second transplants and DLIs and CLL and began to try to make contact.

I reviewed a joint research proposal with Purdue University that may feature this blog.

I responded to medical questions online from everything from CLL to earwax to contraception. Honest!

I registered for two CME lectures for myself (CLL and gout).

I prepared the lecture for my colleagues in oncology, including getting copies of all the abstracts to them in advance of the meeting.

I also got a new cell phone (my old one died), a new external hard drive for backup (my old one misbehaved) and a new bluetooth speaker (my quite new one was DOA) for the car, all of which had some learning curves and set up hassle.

Who has got time to be sick? 

I may slow down again on the blog for a week as I need to finish some other writing, but I will be back.

"Tell me great hero, but please make it brief" Bob Dylan

I need to be  brief.

Tomorrow I am presenting to the local oncologists on what I took to be the most influential and exciting abstracts from the ASH meeting last month in San Francisco.

It is quite an privilege for me, a family doctor to get to lecture to his specialists colleagues. And even though they are all kind spirited, and I can be a bit cocky, the prospect is still intimidating. I am preparing carefully. For nearly every article I want to open for discussion with the group, I have a few more to compare and contrast. 

I so want to help them help their patients with CLL, and since my whole focus is on that single topic (well to be honest, also on transplants and ITP) I can tune out the thousands of other abstracts from ASH and dig deeper into the new stuff on CLL.

Over the next  few weeks I will review some of my thinking on what a few of the critical papers mean. For a few dear friends nearing decisions, these are not "abstract"  but will inform those difficult choices with the cold facts.

I saw Dr. Forman today.  The bone marrow biopsy (BMB) will soon be scheduled in about a month, the CT is on the calendar for Feb. 27. and my follow up appointments are in early March. 

For Dr. Forman, a donor leucocyte infusion (DLI) isn't even on the table. It's chemo, then transplant. I can find no medical literature on second allo-transplants in CLL. And I am info junkie as you well know. Dr. F. sees no chance for a bounce in my donor cells. He has never seen it recover from 0%. Bummer. But I could still have a very durable remission, even with me rejecting the graft.  The longer I stay minimal residual disease (MRD) negative, the better the chances that the brief flurry of donor T cell activity affected a cure.

Wouldn't that be great! I am hopeful. But sadly that is not a plan. The CT and BMB are the plan. And then crunch time if anything shows. 

Or not. I am betting I'll still be in CR (complete remission), MRD negative 

 

Back to my abstracts.

"It's a still life watercolor. Of a now late afternoon" Simon and Garfunkel

As the sun shines through the curtained lace

And shadows wash the room.

Simon And Garfunkel

I am moving very slowly through this times. Horse latitudes can make for bad attitudes.

I am waiting for the flurry of activity in late February and early March. Will the secrets be pulled out from the shadows of my ever churning gut? Will the nodes hold still long enough to be measured by the Computed cuts (Tomograms) made by millions of .25 cm. xray beams casting their shadows? Will the CT scanner read my internal tea leaves? (I drink enough of the stuff) It would not be unusual for my cancer to make its encore appearance deep in my belly, in my mesenteric nodes. What a stinker!

Or will a core of bone achingly sucked from my hip tell the tale? Hope not, because than would mean the a mere mortal, the pathologist aided only with a good microscope could see funny looking cells when he peers though his instrument. That means maybe 1% or more of the marrow is cancerous. That would mean it is doubling quickly. Lower levels of cancer are tough to catch with a microscope. But not for a laser beam and a computer, especially if the cells first have been tagged with 4 glow-in-the-dark antibodies. This four color flow cytometry can find one in 10,000 cancerous cells. If that is the only positive test, that means I have become MRD (minimal residual disease) positive. I was negative on December 1.

Let me clear on this. If I become MRD+, or if my nodes show growth, it does not mean my cancer has reoccurred. No, no no no. It means it was never gone. It was hiding at levels or places beyond our ability to probe. Not that that is a bad thing. If it wants hide for the next 40 years in some dark recess of my gut or some warm niche in my marrow, let it. It is only when it ventures out into the light of day that it causes problems. It doesn't play well with others.

Meanwhile, my life is on hold. If there is a trace of evidence of an unwelcome reappearance of the malcontent clone, then I headed into heavy therapy, likely a redo transplant. The only clarity achieved would be that treatment is definitely needed. There is still a deep fog surrounding what to do to deliver the coup de grace to these evil monsters. If on the other hand, March comes and goes like a lamb and shows no re-growth, I would like to plan my return to the visceral world of caring for patients. If my docs sign off.

So on one hand, a return to the world I love and miss, and on the other, I venture deeper into the dark side, fighting death with near death, and rebirth. 

This is bigger than the seventh game of the Stanley Cup. Heck, it's even bigger than the gold medal game in the Olympics.

Actually I am OK with either outcome. The call to action or the all clear.

I can't spend much time worrying about it. Better to live here than in the future. Here there is blissful ignorance of any changes in my bones or nodes since Dec 1. Enjoying the increased freedom and my few hours of good energy. Enjoying being alive. Now. 

It's all pretty sweet, like biking at the beach today. No snow here!

This will be my first and last jump through these three month hoops.  Waiting is not a life strategy that fits my temperament. It is nowhere as a long term approach. It makes senses for now, with so much craziness soon to be the air concerning my future. 

I have said before that the price of  freedom is eternal vigilance. I will be retested frequently, probably every three to six months. I don't want the Santa Ana winds blowing up a wild fire. I want to douse this when there is just a few embers. I want a pre-emptive attack. Again. That doesn't mean quietly waiting for the other shoe to drop. While I will be keeping one ear to ground, I will be rejoining the work world, knowing that I might need to leave to fight a few more rounds at a moment's notice. 

No reason to sit on the sidelines, even it you know there's a good chance you might be benched sooner than you want. 

"I have nothing to say but it's OK" The Beatles

Not one to sit idly by, with no news on my CLL front expected for several weeks, I am working feverishly on how to plan my next post transplant move, my presentation to the local oncologists on the important papers on CLL at ASH on Friday 1/23/09, my report for the medical group on improving physician charting and other compliance issues, and finally on editing material for my book. This is not easy for someone who needs his daily naps.

The book business is a a big deal. Like medicine or any other gig, the creative, personal side is just one piece of the puzzle that must fit into the whole industry machinery. Writing , like painting, is not nearly enough. There must be a business side or no-one will read what you wrote (or see what you painted). 

I knew this. I wasn't that naive. Maybe I underestimated the amount of work involved in the commercial side preparation. Now, with my scheduled meeting with three agents in early Feb, it is time for me to come out of my deep denial, and do what needs to be done to make this book more than a vanity.

"It won't be long" The Beatles

My hard drive is really on its way to the graveyard, and my warranty runs out real soon, so I have back up everything and printed out my plans for the next week. Tomorrow I will take my MAC to the not so Genius Bar at the Apple Store to get a new platter.

My son's old EMAC, after great trouble getting going (reminds me of an aging arthritic) finally booted up and will provide some access to email for the next week, but the blog will be a quiet for a day or two.

My book is moving along.  My research for my medical group is progressing. And my plans are tightening up for my "third opinion".  The letter to JAMA is on the back burner.

Tomorrow evening is a holistic comedy workshop with Melanie Chartoff (remember Fridays in the early 80s). If I am not signed by a major studio or offered my own sitcom or late night talk show, then I will return. Actually I am going to be cured, not famous.

Heck, I would return anyway.  I know nothing of TV (I still use bunny ears that don't get any stations well, but it doesn't matter cuz  I watch nothing ever). I feel more at home here on the internet, with readers who can write back. The scale is more human and more direct, even if the interface is a bit too digital for my liking.

"Forty thousand headmen couldn't make me change my mind" Traffic

But maybe fifty thousand could.

That how many "hits" this site has experienced since I began posting my journey pre-transplant.

Yesterday the 50,000th visitor lay their eyeballs on this blog.

I warned it would be a long haul on a mountainous road but I had hoped the fog would have cleared by now.

At least the breaks are still good, and I like the feel of the standard transmission. Gives me more control, and if you been with me for even a few miles, you know what a control freak I am.

Alright now. Here's a moment for silly diversion. What car does your mind's eye see this blogger coaxing up the hills and around the blind corners? Send me your vote as a comment.

See you at 1,000,000 visits. And the thousands of pit stops on the way.

Life is a journey.

"Tomorrow never knows" The Beatles

A friend reminded that when Jacob lay on his deathbed, he waited to speak a prophecy that he never got out. But his life and words still gave meaning without a vision of what was to come. You don't need to see the future to live it and influence it.

TomD in his comment suggests a backup for my backup. Reminds me of the Dr. Seuss book where the watcher watches another watcher watching yet another watcher and on and on and on.  His point is well taken.  When is enough, enough?

Let me respond. I have no need to see the future, but I do need to be ready to live in it. That means preparing for all the desired and all the less welcomed outcomes, and also having my feet under me if I am hit by the completely unexpected. 

How broad a stance you need to keep your balance in those winds of change is different for all of us.

For me it means a lot of reading about my opponent, and a good "Cut man" in my corner.

I know some of my readers are bothered by my violent images: boxing, warfare, hockey.

Think of it as tough love.

" I would be happy just to hold the hands I love Upon this winter night with you" Gordon Lightfoot

It has taken me too long to get around to Gordie's gold, as I have plowed through many more contemporary Canadian singer songwriters.

I doubt old Gordie had a walk at sunset at the water's edge in sunny Newport Beach in mind when he penned:

The fire is dying now, my lamp is growing dim

The shades of night are liftin'

The morning light steals across my windowpane

Where webs of snow are driftin' 

Still I love the still more empty winter. The summer is more visceral, more stimulating, and more participatory. The winter is more visual, more distant, more contemplative. Like Gordie's tune.

I have decided to get a third opinion. I will be asking another transplant expert to help me make the next call. The details and the dollars involved are yet to be worked out, but I would like to have my back up person in place, like the hockey goalie on the bench, dressed in all his equipment, ready to jump in and play for keeps on a moment's notice should the starter pulls a muscle or flubs an easy wrist shot. I am hoping this will be like packing extra medication when you travel. If you have it all ready, you are guaranteed not to need it, but if you aren't prepared, you can bet the unplanned occasion will arise. Would that reality was so easy to control with such simple and sweet paradoxical intentions! But it does give me that oh so necessary illusion of control.

I have decided to write JAMA (Journal of the American Medical Association) a letter about the mixed messages from the CDC and the heme-onc world on the zoster vaccines (see prior posts). My attack will not focus on the underlying studies, because there are none, but on the damage caused by the choir singing two songs at once. Makes me feel harmonious.

I have decided and already started doing some volunteer work to help my medical group with some policies and procedures to make our doctors better care givers. Makes me feel useful.

I have decided to push ahead with my book instead of looping around and around on word smithing the first few chapters. Makes me feel productive.

I have decided I have made enough decisions for awhile.  Makes me feel sleepy.

I need my nap.

"If you could see what I'm thinking" Pure Prairie League

This is a letter I wrote to some transplanters considering DLI. It may give you a glimpse of how I am slowly processing my decision. It assumes some basic understanding of the blood lingo but I suspect you can catch my drift with just skimming the content.

Friends,

Perhaps my story will be of some help. I welcome comments and advice.

I am joining the discussion a bit late, but I have been researching DLI as it looks like I am losing my graft. I had a RIC MUD 12/12 on 7/1/08 for CLL. My T cells never got over 65% and my myeloid lines about 28%. Now I am only 35% donor T cells and 0% B cells,  granulocytes, and monos.

My CLL appears to be in molecular remission. All my doctors say do nothing unless there is a relapse as any treatment is risky, and there is no need to treat falling chimerism in the absence of disease.

Where the RADICAL differences of opinion lies is in what to do if I relapse. Dr. Forman at City of Hope feels a DLI will either do nothing or could unleash severe GVH and perhaps aplastic anemia. That is a frequently fatal potential complication in which the donor T cells attack my host stem cells in my bone marrow, and since in my case there are no donor stem cells left, where are the stem cells to make my blood. He says I should do a second transplant, and skip the risky and futile DLI. Dr Castro as UCSD says there is nothing to lose with a DLI ( done with ATG to reduce the T cell attack), and it may save my graft, is very safe, and aplastic anemia is extremely rare. I am a MD and I am befuddled by the stark contrast in opinions.

I can say this: DLI are potentially fatally, usually from severe GVHD. They are also potentially life saving, especially in CML, but there is good literature in other blood cancers including CLL. Durable remissions even possible cures have followed DLIs. They are done most often with no immunosuppression and usually no chemo for the recipient so the immune attack on both the cancer and the patient can be quite profound. They are much easier on the donor, as they may not need to have the "shots" before to mobilize their stem cells. It is usual just done in less than a day. And it is way cheaper than a SCT.

If my myeloid lines were more donor, I would have a DLI in a heartbeat at the first whisper of a relapse, but the concerns of Dr. Forman (who did my transplant) give me pause. I  honestly don't know what I would do

I am happy to help however I can with questions about DLI. I have several articles on the subject, mostly related to CLL of course, I can forward if you contact me off list.

Be well

Brian, 57 yr family doc & father of 4, dx 9/05 with CLL del 11q  unmutated, CD38+, ITP 9/06 eventually failed steroids, IVIG , Rituxan and splenectomy  controlled w cyclosporin A  Rituxan combo.l CR. RIC MUD HSCT July 1/08  now CR but rejecting graft see http://bkoffman.blogspot.com/

"You say good bye and I say hello" The Beatles

The visit with Dr. Castro was illuminating but I am not crazy about what I saw. Nothing bad. Lots of encouraging information. In fact it was just what the doctor ordered. A second and very different opinion.

What I left UC San Diego with was more contradictory data points to add into a formula that would already give pause to a chaos theorist.

The bottom line is that Dr. Castro has radically opposite ideas to those of Dr. Forman on what to do next if my CT scan shows any progression. He favors a DLI and Forman rages against it.

I am still trying to find my middle path through what the Buddha in me whispers is just the illusion of a contradiction.

I will get back back to you when I achieve enlightenment or when I noodle my way around this twist in the road, whichever comes first.

My kids are visiting, so I  my posting  may be less frequent for another week or so.

Many blessings for the New Year. I have a good felling about 2009.