Battles Plans and Marching Orders

An internet friend with CLL and and a MD degree like me wrote to ask: so what is your plan?

This is my answer. Notice how it is all about CLL. ITP is for now in the background.

Here's my rough plan:

Staying on cyclosporine (CSP), but I am hoping to reduce the dose when I finish most of my travels in early Dec.

I am planning more rituximab, but my bone marrow biopsy (BMB) is first, this Wednesday with Kipps.

Clearly the response to rituximab is dose related. I would prefer to get 2,250 mg/M2 in a single dose as was done in O'Brien's trial of mono therapy, but short of that I will get 6 weeks of 375mg/M2. Clearly I am sensitive to it in combo with CSP.

If all stays good, then repeat another 6 weeks of R, than a CT and BMB 2 months later, so about in 6 months.

If my nodes are down more, just stay on a lower dose of CSP, and then probably FCR or BR to get a deeper remission and to wipe out the T cells and immediately onto transplant- likely using the same donor or one of his sibs if they agree and match. I have no other good options at this time. Likely at City of Hope (CoH) again.

If they are bigger, maybe lenalidamide + R or O to shrink them, then FCR or BR, then transplant.

I will see what Dr. Kanti Ray says when I see him in November. He likes DCR and that might also figure in.

I know Kipps is against more R, and Forman at CoH and my local oncologist like it.

My concern is that I need to go to transplant with as little disease as possible, and definitely with nodes less than 5 cm.

1: See how much deeper a remission can I get with more R
2: Not do too much while I will traveling all over this fall and early winter
3: Not blow a chance at a 2nd transplant by waiting too long. Big nodes scare me

Frankly, I don't see anything that is going to significantly help younger patients like us getting into our hands in the next few years, so I don't buy this treating CLL as a chronic disease patter from Furman and Kipps.

What do you think of my plan?

He wrote back (I made some small changes to hide his identity):

Your plan makes a lot of sense. I had planned to proceed to HSCT when the time came (I have a good match), but lately have felt a bit more reticent, given my horrendous journey after attempting FCR and the poor course of several people who have been posting about their recent transplants. I really don't know what I'll do when push comes to shove...my upcoming CT scan may influence how I proceed. My biggest concern is lack of data showing fantastic results beyond 2 or 3 years (or am I missing something?). If the upside were higher (more certainty of cure if you hurdle the first few months) I think that I'd be more certain of which path to take.

I wrote back:

There are no great answers.

Here's why I still prefer HSCT

A significant minority of transplants patients seem to do very well long term. The mortality curve is pretty shallow, but not flat after 5 years. Seems the important thing is try to join that select group by improving your odds going in: low disease burden, no co-morbid issues, and a good match.

On the other side without transplant, even if you get all the best therapies and pick the right trials, almost no-one with 11q does well after 7 years or so, especially if you are unmutated. Maybe that will change, but it hasn't yet.

So that's my story and I'm sticking to it.

For now. It could of course all change on a shekel.

More R, then more real chemotherapy as needed to get disease way down and beat back my T cells then a redo transplant next summer. Engraftment. DLIs as needed. GVL, GVHD, but manageable. GVHD burns out after a year or so. Vigilance forever. Big party on my 95th birthday.

What could be easier?

What to do, again? The same set of questions

Time to focus and bring my A game to the table. No more wishful thinking and pushing the tough issues aside. Lines are being drawn, and I better be aware of where I stand and what I must do.

It is always the same set of questions I must ask when staging my disease. Questions about when to keep my foot on the gas, when to brake, and when to change vehicles.

It helps me frame my plans if I lay them out here. This post will be of more interest to my CLL friends, as it is rather technical, though it does detail how I deconstruct my problems. And I always seem to get to the "big question" by the end.

In the next few days I will get my first CT scan in over a year and my latest of my many bone marrow biopsy, the last being in February.

Since that time I have had a reoccurrence of my ITP, controlled easily at first with just IVIG and nothing else for almost 10 months until June this year when my platelet count crashed again. Cyclosporin (CSP) and Rituximab (R) in about a week rescued my platelets from the 20,000s to the 300,000s.

Not surprisingly, my CLL was raising its ugly head at the same moment with the leukemic clone showing up for the first time in almost two years, the first time since my transplant. Not a welcomed repeat visitor to my blood stream. My palpable nodes were also slowly growing. The cancer was definitely back and on the march.

Today I am still on the same dose of cyclosporin (150 mg 2 x a day) that has raised my BP, made my muscles ache, and slightly challenged my renal function, but is doing its job. Last platelet count was 291,000.

I had rituximab 375/M2 six times between June 2 and July 8. My absolute lymphocytes that had risen just beyond the normal level to 4.8 when the flow cytometry showed my cancer before the R , quickly fell to 0.8 and my palpable nodes shrank to 1 cm at the most and have stabilized there.

It is now more than two months since my last rituximab, so it is time to check the marrow. R when it is effective, is still working its magic for at least two months after its last dose so I need to wait to assess its success.

Assess what? If I need more rituximab? If I should consider other therapy?

Here's how I see it.

If there is no evidence of disease, in other words, the marrow is no longer 5-10% CLL as it was seven months ago, but has become MRD neg, and more importantly the largest mesenteric cluster of nodes that was 3 cm a year ago and all its CLL friends have shrunk to less that 1 cm.

The odds of that are small, but not impossible. The last time I had my idiosyncratic CSP and R mixture my marrow went from 90% infiltrated to 3%, and my palpable nodes all shrank to nothing. Unfortunately I did not have a CT scan to measure the disease until months after my last R then and by the time I did, it revealed a 5 cm mesenteric node. Had it shrunk from much bigger to that size? Maybe. More likely it had both shrunk and re-grown. But how much and how fast? This time I am starting with a much lower disease burden, less work for the drugs, but has my CLL toughened up in the two years since my last encounter? R on its own is wimpy, but the CSP seems to add extra oomph in my case, especially in the marrow.

This is the result that I am hoping for. Praying for.

Another reason for no more R soon would be the other extreme. Many big mesenteric nodes well over 5 cm and/or heavy marrow involvement, say >70%. R on its own is not that great in cleaning out big nodes or the marrow. CSP has little track record and even less clinical data as a CLL drug.

I am not going there in my mind or heart, but that unlikely finding would mean time to move on to bigger guns and tougher questions. What to do when the R and CSP are losing their mojo? Likely Revlimid and Ofatuzamb, maybe FCR. That all means transplant redux in a year or so, but more about that later, G-d willing much much later.

Almost any finding in between those extremes, MRD neg. versus big tumor burden would seem to suggest more treatment with R. Not rituxan maintenance, another of my controversial trailblazing path, but more actual standard treatment. The distinction is not just a nicety for insurance reasons, but a considered plan to push back the CLL as far as possible.

My friend Chaya says I need to stop worrying about my ITP and pay attention to my CLL, especially the size of the mesenteric nodes. (I asked to have the CT of only the abdomen as that halves the radiation exposure and it is the mesenteric nodes that have always been where I have the worst disease.) Let's examine what Chaya calls my opportunity cost. If my nodes are too big, then waiting or fussing around with more R makes little sense and might actually be ill advised. Because if they get too big, getting them down to size will be very difficult with fewer option. Getting them down to size will always be crucial in insuring the success of my next transplant.

I face the identical questions about node size that I did a over two years ago. Say my nodes are the same or a touch bigger than a year ago. Surely they were even bigger before I started CSP + R in June. After all, my palpable nodes shrunk so my gut nodes must have followed suit. Yet I had no palpable nodes and a hidden 5 cm mesenteric node pre-transplant, so there is no tight guarantee. Never is.

I will have the CT scan next Friday with my own medical group in Fullerton so I'll have my results within minutes, all this just a few hours before the call of Kol Nidre. The bone marrow biopsy is a week from Tuesday with Dr Kipps at UCSD, so results will only be available some three weeks later. Waiting, again, one of my weakness.

Truth be told, the big drama is next Friday.

Will I be sealed in the book of life?

I am asking this same question for the fifth time since my diagnosis. I am thrilled and grateful to be here and able to pose it.

I plan to be asking it for decades to come.

Battle Plans and Diversions

Botero

My failure to post has not been due to lack of news, but rather lack of focus.

On the CLL front, after some advanced noodling, my battle plans are being drawn up for what I am certain will be the final successful struggle with this deadly foe.

Sun Tzu will be my general.

He orders:

Attack him where he is unprepared, appear where you are not expected.

And,

In war, then, let your great object be victory, not lengthy campaigns.

And finally,

Though we have heard of stupid haste in war, cleverness has never been seen associated with long delays.

What does this means?

It means on to chemo, likely in the next 60 days, likely FCR or PCR, then on to a second transplant.

Honestly, I sense all these forces moving at a distant, they are not in focus yet.

Why not?

I have been having too much fun is why.

Let me share as best I can an emotionally towering experience. Hearing and seeing John Adams at the Disney Hall, sitting behind the orchestra, right above the tympani for THE DHARMA AT BIG SUR.

Magical to watch the conductor/composer moving the giant engine of the orchestra together as a transcendent unit, to a place unique in time. From our unusual vantage point we saw when JA had called for one of the percussionists to slap his stool with a wooden stick or draw a violin bow across his xylophone. There is music is everything. The sounds and sights are lingering still.

Then another trip back to the 60s, this time aboard the PIRATE RADIO battleship moored off the coast of an uptight England, in a wonderful period piece with revolutionary music, reminiscent characters, and rad clothes. This must see movie captures much of the joy and some of the sickness of a time that seems so far out, it is hard to believe it really happened. Did it happen?

Did I mention our second trip to be thrilled and tutored at the same time by the neo-Baroque art of Botero and the Latin American exhibit at the Bowers? Botero sees it all and tells it like it is.

And the cultural pinnacle: Two King's game, where my battered team wins both in shootouts. And one of them was a gift to two sweet suite seats. (Say that fast three times) And at the other, every fan in attendance received a bobble-head Luc Robitaille doll. Life doesn't get much better. Go, Kings, go.

Add to that a raw holiday food prep class, numerous walks on the beach, Balboa Island, and the back bay, home visits with dear friends recovering from various hospital adventures, shopping for Hanukkah, and finishing SKINNY LEGS AND ALL, a slap in the face book of what I though I knew about the root of Judaism by my favorite author, Tom Robbins.

You can see why my focus on CLLL has been blurred.