OSU Update: All Good

I left sunny warm SoCal for cold and snowy Columbus, Ohio, but it was so worth it.

Labs remains stable with essentially normal red blood cells, white blood cells and platelet counts and differential, and boring blood chemistries.  Despite an small audience of student nurses, my bone marrow biopsy went well. It's harder to whine when it hurts if you have aspiring members of the healthcare team staring at your bottom and diligently taking notes. So let me take this opportunity in the privacy of my guest room to say OUCH now.

Results are weeks away.

Dr. Byrd is very happy with my progress, feels the slowed nodal shrinkage noted on my most recent CT scans last month is not a concern in anyway, and I am on a good trajectory.

After my clinic visit and biopsy, I had another interview and photo shoot with their very down to earth and professional marketing team at the James Hospital. This time I am really going to be the poster boy displayed smiling on 8 x 2 feet banners throughout the hospital and possibly at international meetings to promote the hematology and lymphoma clinical trials at OSU. It's a cause that I can fully endorse. As we have heard before, there has never be a better or more important time for a CLL patient to consider a clinical trial and OSU should be high on our list.

This modicum of "fame" allows me to join the ranks of my friend Terry in our local CLL support group who is already the international face and voice of RITUXAN. If this stardom trend continues for our members, our little OC group might need to have its own reality TV show soon.

Insurance issues are on track to be worked out quickly thanks to the hard work and co-ordinated efforts of several folks at OSU and Blue Shield of California today so I am happily leaving town tomorrow informed and consented and officially rolled over into the new continuation trial with a full 84 days of ibrutinib. Yeah. Goodbye Columbus for 12 full weeks.

Hard to believe it's been a year since I first started in this trial, and now that phase of my life has ended.

The next time I am back at OSU at the end of April, spring will be in the air and Dr. Byrd has promised me a much coveted tour of his lab. The marketing team says they may video or shoot photos for my blog- wouldn't that be sweet?

It's been hectic. Despite my nerves about presenting to a "specialists" audience, my lecture on sleep disturbed breathing and heart failure at UCSD last weekend went over well and now I am feverishly preparing my next lecture for the Nation Sleep Foundation in Washington due on Friday.

Life is crazy, but good.

ASH 2012: Dr Jeff Sharman interviewed about the new treatments in CLL

My friend and fellow CLLer, Andrew Schorr did a very nice and interesting interview of Dr. Jeff Sharman at ASH 2012.

Dr. Sharman brings up some new and provocative insights on how the researchers misstepped when searching for a specific genetic target in CLL similar to the famously fused Philadelphia chromosome of CML that Gleevec blocked and in doing so, produced low toxicity, durable remission. This breakthrough drug, this targeted oral therapy, revolutionized not just the management of CML, but the whole approach on how we treat or too often, wish we could treat cancer.

As you have heard many times, in CLL, it is more complicated. In CLL, it all about “turned on” pathways than need a brake applied rather than a specific genetic defect. However, as our knowledge of the activated cellular pathways of the cancerous B cell clone improves, so does our ability to intervene. That brings us to the new generation of small molecules including ibrutinib (PCI-32765), idelalisib (CAL-101 or GS-1101), AVL 292, ABT-199 and others in the pipeline.

He shares his experience of one of of his highly refractory patient finally responding to one of the new trial medications and another where idelalisib worked when ibrutinib failed.

He cautions us that it is way too soon to pick winners among the new molecules.

Some of Dr. Sharma’s tropes you have encountered before from the doctors I spoke with at ASH. It is good to witness the building consensus.

Some of you may know Dr. Sharman from his well-written, informative blog on blood cancers and lymphoma. Check it out if you haven't already. You should also know that he has been a pioneer in small molecule research and an energetic force in developing resources to get clinical trials done.  He talks about their paramount importance right now. He forecasts the end of the world of FCR as we know it. He reflects on how well these drugs work for even those with the worst prognostic markers.

Dr. Sharman asked me if I wanted to share the video. I am, of course, happy to get the word out however I can.

So enjoy and take heart.

Soon I will be posting my ASH interviews with Drs. Furman, Kipps, Wierda, and Wiestner.

On a personal note, I am home from a medical conference in San Francisco, but just for a few hours before I take off again to lecture in San Diego.

My health insurance has me in a ridiculous Catch 22. I can not get pre-authorized for my roll-over clinical trial at OSU that continues my lifeline of ibrutinib until I sign the informed consent, but I can't sign the consent until I am ready to roll-over into the new trial. All but two insurance companies that cover the myriad of patients from far away places that come to OSU for trials understand the fallacy of such a policy and do not insist on the signed consent, but mine is one of the two that makes it difficult.

That said, I am sure it will all work out (retroactively) with the help of some real kind, persistent, and hard working people at both OSU and Blue Shield. Just one more thing to worry about in the meantime.

On Monday I leave for cold Columbus to finish one trial and begin the new continuation trial. While there, I will be busy with a bone marrow biopsy, another photo shoot and interview. Guess which one I am not anticipating with joy. Hint: there there will be no camera or recorder involved, but there will be needles.

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 boring bone marrow biopsy and aspiration

When asked if I had had this procedure before, I just smiled my yes.

When asked how many times, I didn't know.

Becky, Dr. Kipps' NP was great, the pain was minimal during and after, though my blood pressure did shoot up a bit. I am convinced it more a matter of technique than strength, though I know this experienced oncology nurse worked hard to get the specimen. Thanks to G-d for lidocaine.

You want your bone marrow biopsy to be routine. Results in two weeks. That is the part that is hardest for me.

With no meds for pain, I was well enough to stop at my new favorite raw restaurant, Peace Pies in my old haunt, Leucadia. These guys are amazing and committed. Great introduction to raw food. And I love that old beachy still slightly hippy feeling of that stretch of Pacific Coast Highway.

Back home, after a desperately needed nap, I am back to the grind and cleaning up the house before my wife comes back tomorrow.

Making good progress on my to do list for the CLL but nothing is "completed" yet and life has a way of disrupting my plans. That's OK. It reflects an active engagement with the world.

Though the cat is fine company, I miss my wife who is out of town helping out with our 6 month old granddaughter. Amira's blog is much more more exciting and certainly more fun to look at than mine.

My most brilliant move today was to pick up "to go" a raw organic vegan "tuna sandwich" and a slice of "apple pie" for my dinner, so life is sweet.

A good day. Another ho-hum bone marrow biopsy and drive along the amazing California coast.

Bone marrow Biopsy and aspiration

It was about as painless as having two big bore needles put into your posterior superior iliac crest could be. Dr Kipps was great and the lidocaine worked its magic. Except for the transient but very weird and quite nasty feeling when my marrow was being sucked up into the syringe (I wish this experience on no-one), it was a non-event.

So nonplussed was I by the absence of the usual pain, I left without remember to get my blood drawn until we were 10 miles down the road in Leucadia enjoying a raw organic vegan lunch (wakame salad and a fantastic raw "burger") at the small but purposed raw eatery, Greenery Cafe .

No results on anything yet, but I should have the blood test back by tomorrow. Actually I should have had them today, so I am slightly put off. They are ready in 30 minutes at the most.'

And in typical Kipps fashion, the simple CBC (only 1 vial of blood he told me) turned into 8 with a retic count, a Coombs, chemistries and as those extras for his research.

He is obviously worried about my anemia. So am I. A little.

Kipps found my nodes in my neck have grown a bit, though most reamian small. Still my CLL may soon be demanding more attention. He did say it was OK to shift to MR to image my gut nodes as to avoid radiation exposure. We give up some accuracy, and may need a CT if Campath is part of the plan, but that is not likely soon.

Hopefully, nothing is likely soon.

The most recent results on the exciting breakthrough treatments such as CAL 101 have been more honest, and thus disappointing, but I remain hopeful that the silver bullet for CLL is being tested as I type.

If not ready when I need it, there is always transplant redux.

Still my CLL has been pretty tender and easy to nudge back, and most of my powder is still dry. Plus my counts, except for my very slight anemia, are super, so I have plenty of time to put my finger to the wind and judiciously choose my next crazy course of action.

I have now also waited a week for the path report on whatever is growing on my scalp (Those of us with CLL are experts at growing skin cancers). That too is overdue, but I am in complete denial that there could be any bad news brewing there. I vote for traumatic inflammation.

Now back to the difficult part, the waiting for all these results.

Not so bad

Another day, another bone marrow biopsy. I asked Dr. Forman, while doing the procedure, if I should have a DEXA test (a scan to check my bone density which can be adversely affected by a transplant and steroids and a bunch of other insults that are part of my past). He said he was doing one now.

What we meant was the bone was awful tough to penetrate with the needles for the biopsy and aspiration. I guess that's good.

That said while it was a pretty yucchy experience, especially that sucky feeling when he aspirated the marrow, it was not that bad. First he numbed up my back side pretty good, and the pain was minimal. Just some tenderness now.

Results in a few days. Last time 2.8%, this time.....

Here's hoping my CLL has been dawdling since my marrow was last assayed 6 months ago.

Drilling down

Bone marrow biopsy tomorrow morning and of course repeat lab at USCD with Dr. Kipps.

Ouch.

Overwhelmed with must dos. Let me connect some dots before I write anymore.

And the winner is...

My bone marrow biopsy was clean. No CLL.

FISH and engraftment studies are still pending.

CT scan in 3 days.

I worried for nothing. (So what else is new?)

Waiting for my bone marrow biopsy report

Is there any meaning in the lack of  results? Surely he would rush the good news to me.

I can easily get lost in this crazy thinking. The Talmud teaches that prophecy has been taken from prophets and given to fools and children. However, it does later adds, with typical twisted Talmudic logic, the wise to the prophetic group.

I just emailed Dr. Forman to ask if there any results back yet from my bone marrow biopsy.

In case you are new to my blog, I have a a freight train of trouble waiting for news.

Still I say it is an act of courage and optimism to push for my results.

Would you do the same? Live with the not knowing, or move up the time that the envelope gets torn open?

Of course, as in the rest of life, despite what the devotees of THE SECRET  believe, my writing the email will certainly have no effect on what the reply contains and in all likelihood on when it will arrive.

Yet I know that what I did was brave, but I was so nervous about doing it.

Be still my beating heart

Yesterday I had another bone marrow biopsy. Not too bad. As is my habit, I walk afterward to minimize the after pains. This time it was next to the rain swollen streams of Eaton Canyon, near City of Hope.  I listen as did Siddhartha for the laughter of the brook, loving the wildness of the place so close to the urbanity of Pasadena.

A great escape, but by bedtime, the anxious waiting for the results had begun.

This time I am not trying to stay calm about my chimerism results. Wouldn't it be great if I discovered that I had gone from 0% donor to, well, anything but 0%. That would be super and would make a pretty exciting story. When you're at zero, there is no concern that your level may have fallen in the latest test. It's going to be the same or better, so why worry.

Now my doctor and I are sniffing for the slightest hint of a relapse. The microscopy that can find 1 in 100 cancer cells may be back by the end of the week. The fancier flow cytometry that snoops out 1 in 10,000 may take a week longer. I am expecting good news. I feel well and honestly everyone tells me I look great.

This waiting part is always tough for me. You would think I would be an expert by now. The master of the here and now. 

Instead I have the unhealthy tendency of trying to seize the future instead of the day. I started to ask Dr. Forman one of my what if questions to which he wisely said "Why have a speculative discussion today when we can a specific one in two weeks".

He's right of course, but it means waiting the two weeks.

Between now and then is my CT scan.

My wife and I found another wonderful diversion to rescue me today.

Heard my long time friends and legendary jazzmen, Luther Hughes,  Tom Ranier, Paul Kreibich and Ron Eschete together as H.E.R.K. play some blow all your cares away and forget everything but the sweetness of this G-d given moment kind of music. All this plus I enjoyed a great meal with friends and drifted along with the beat.

It was perfect.

It's all perfect. Or darn close. And I can live with that.