THE PLAN: More of the same

So here's the plan.

As of today. It could change tomorrow.

This is mostly a medical post, so those who aren't CLL or transplant aficionados might want to skim it quickly or skip to the last few paragraphs.

As you know from my spotty posting, my status has been delightfully boring with little new to report.

To understand what I am planning to do, it is important to see it for what it is: more of the same.

Let's go back to last spring when I started down this very smooth path.

Allow me to briefly summarize my journey over the last 12 months.

Almost two years post transplant, my platelets had fallen again, this time over four weeks from 242,000 to 32,000 in May 2010 despite low dose IVIG infusions (30 grams) twice a month.

With the platelet crash I was re-staged to be sure it was ITP.

It was.

My CT scan showed the largest cluster of nodes was way too big: 6.4 x 3.4 cm. on the right side of my mesentery. The flow cytometry showed CLL was back in my peripheral blood again. My ALC was normal but my atypical lymph count had reached 12%. Red cells were fine and I could feel some small palpable nodes in my neck, but nothing worrisome.

So besides the ITP, it was all too clear that the CLL was stealthily but forcefully on the move again.

Yucch.

That's when it was decided to go back to what had worked so well before my transplant, the unusual but magic mix of ciclosporin (CSP) 150 mg twice a day and some heavy cycles of rituximab (R) at 500/M2 weekly x 6. And continue the IVIG unchanged.

It worked quickly. My platelets jumped up immediately and were soon a non-issue again.

As of now, my ITP as measured by my platelet count seems to be stable or even trending upward with numbers often well above the amazing level of 400,000, and never below 270,000 for almost a year now. The therapy is working great for ITP!

After the first cycle of rituximab, my follow up CT scan in September 2010 showed my largest node was 3.8 x 1.7 cm, still much too big, but also much better. My ALC was low to low-normal ranging from 0.52 to 0.79, likely from the R wiping out all my B cells. My bone marrow showed about 5-10% CLL on the biopsy and 3% by flow cytometry.

Not just my ITP, but my CLL was responding to this non-chemo therapy as it had done before.

So I did a second round of 6 weekly doses of rituximab starting in October and finishing late in November. During this time, I also had to reduce the CSP because of its well known nasty side effects when my uric acid jumped to 9.4 (really should be less than 6 but we can accept as high as 8) and when my blood pressure shot up. Thankfully renal function (creatinine and eGFR) stayed in the normal range this time, unlike my last CSP scare.

I eventually readjusted my BP meds and halved the CSP to 75 mg twice a day, which is my present dose. Uric acid is fine again, creatinine has climbed a touch but is still normal, and my BP is great to high normal. It depends on who is checking it. It is always great at my office and alway borderline at the cancer center.

Not a perfect portrait, but not bad. I can't imagine what these renal parameters would be if I wasn't vegan. I do believe my anti-inflammatory diet moderates some of the toxicity of my disease and its treatments.

My ALC is now up to normal ranging from 0.7 to 1.2.

My Hgb has dipped as low as 12.7 but last week was a robust 15. It fluctuates between a bit low and low normal. My red cells are always slightly too big or macrocytic, but it is not progressive.

The few tiny nodes that never went away in my neck after the first round of R therapy didn't change much with the second hit of monoclonal antibody, but they were tiny.

The bone marrow biopsy on March 30 showed 3% CLL on flow, and < 5% on the biopsy. Even better than 6 months earlier. It also showed some mild hypocellularity (30%), which means it may have been beaten up more than I realize with the transplant. FISH studies for the usual suspects for MDS and CLL were negative. All in all a very good result.

The next important piece of the puzzle is the imaging.

Here there is a new wrinkle in the strategy. I am switching to MR. My hospital has just installed a new more powerful machine, and although the details won't be as precise as on a CT, it will be good enough for a new baseline. Truth is that I don't need to know if my nodes are 1.9 or 2.2 cm but I do need to know if they are 2 or 4 cm. All future imaging will be on this same machine, and hopefully this will eliminate the Morton's fork of too much radiation or not enough information. The scan will be in mid June.

What I do know is that my palpable nodes are definitely growing very slowly. Kipps agrees. Is it because of the reduction of the CSP as the nodes seemed to enlarge after the last drop in dosage, or is that the R finally wearing off (it has been 6 months since the last infusion), or is it just what it is.

Unless the MR finds the bad or good extreme of either massive nodes or no nodes, I will be doing 6 weeks of R again in late June through early August. 6-12 weeks later I will repeat the MR.

During this time I will continue on the same dose of CSP and then try to stretch out the IVIG to three weeks between treatments which will also spare my veins, which are getting a little inflamed from years of abuse by the IV nurses.

I hope to make only one change at a time so I can monitor the effect.

After that, I will try to reduce the CSP to 50 mg twice a day, but I am nervous about going lower than that. Rai is not keen on my stopping the ciclosporin, ever.

After that more R again in 6 months and another BMB and MR scan somewhere in there, depending on how things go this summer.

If this is smelling a lot like rituximab maintenance with the every six month dosing, it might be.

But I believe it is more than that because clearly the CSP has anti-leukemic properties proven in the test tube and a few published cases and at least twice in this little body of mine. It is a novel low toxicity combination therapy that probably should be better studied.

I believe this approach is using CSP and R to treat to goal, to shrink those mesenteric nodes.

Maybe I will need to add something like AMD3100 or CAL 101 to get the B cells out of the nodes, but I will cross that bridge if and when I need to.

Imagine no chemotherapy and getting a complete remission!

The plan:

More R, slowly reduce the CSP, and stretch out the IVIG, but don't totally stop either, and watch the nodes in the gut with a MR instead of a CT.

So I can avoid more chemo.

So I can feel well longer without damaging my marrow or likely making my cancer more aggressive or resistant and only mildly mangling my immunity.

So I can stay out of the 5th floor of City of Hope for a second transplant a little longer .

So I can wait out a possible cure without burning too many bridges.

So I can hug and hold my first grandchild, a girl due in July without dreading every cough or drool.

"Please understand I never had a secret chart to get me to the heart of this or any other matter" Leonard Cohen

Not much punch to this post. And certainly no punch line. Only the sober business of making choices.

These are my crib notes for tomorrow's appointment. Possibly the most important doctor's appointment in my short life so far. 

Or maybe not.

Dr. Forman Dec 15, 2008

Ask what he plans to do and shut up and listen:

If he recommends wait and see with a repeat CT and maybe BMB early in the new year then I must get across two points

1: Why not an urgent DLI?

As he is well aware, if I lose the graft or don’t have a second transplant my chances of living to 65 are negligible. I must make difficult choices, and not be guided by wishful thinking, but by the reality of my circumstances.

Without a new immune system, my brand of CLL is universally fatal. GVHD from a DLI can be too, but much less often.

When I relapse which odds are will be sooner rather than later, based on the medical literature for pts with 11q del and unmutated status, plus my personal disease history of quick growth when not getting treatment, I will then quite possibly be Fludara refractory with a very small chance of another CR (under 20% in most studies), so my likelihood of a second long remission are slim, and diminish with each subsequent treatment. More importantly my best chance for a cure with a second transplant is with a deep remission.

2: If CT or BMB do show any hint of relapse how seriously is he considering a second transplant?

If he is noncommittal, I argue that my indications are even more cogent for a second transplant soon than they were for my first transplant, as I have a lower disease burden, likely present access to the same well-matched donor, and my good health in a particularly nasty disease that definitely will reoccur without a new immune system.

If he recommends more FRC

Same argument. Even if I get a lengthy remission, which is very unlikely based on the literature with my 11q- and my unmutated status say 3 years, then what do I do? Also O’Brien and Keating did not recommend it, and the literature suggests once you have reached MRD- status, not much advantage in going further. I need to plan several moves ahead.  By doing more FCR now, I may be playing a card that I might need later to get into a complete remission for transplant if  the changes on the CT scan are not getting worse and I do remain in CR for a long period. I think this is not likely, but is possible.

     If he recommends a DLI

I need to ask if it doesn’t work, does that jeopardize the risk of a second transplant? What dose to start?

            If he recommends a second transplant,

Discuss finishing FRC first and what conditioning he plans.

Finally: Insurance forms, FU appointments and testing

"If I listened long enough to you" Tim Hardin

"If I gave you time to change my mind

I'd find a way just to leave the past behind

Knowing that you lied straight-faced while I cried

Still I'd look to find a reason to believe"

Tim Hardin

This post is pretty straight ahead medical. I will share some of my emotional and intellectual twisting in the wind later this week.

As you may recall we left me, our protagonist on a quest for more information.

When the experienced pathologist peered through his microscope at my bone marrow on the first of the month, when the hematology section of the lab went further and dug deeper using the fancy flow cytometry to search for one in 10,000 cancerous cells, they came up empty. No cancer. Nada! Rien de tout!

When they did my CT scan, the rad (the in term for radiologist), found rock solid stability in my cervical, axillary (armpits), inguinal, mediastinal (chest) nodes, BUT he discovered to our mutual dismay that my mesenteric (gut) nodes were "plumper".  True, I am trying to bulk up, but not nodally. Today I got a second opinion and had the digital files (x-ray on actual films are so 90s) reviewed by another rad. He found some growth not only in size, but also in number. Subtle. He called it suspicious. I call it bad news.

At ASH ( the 20,000 strong Hematology conference) I got a plethora of conflicting takes from the transplant and CLL gurus. More on my reflections on ASH later.

I met some wise doctors who were most generous with their time, and I asked very specific questions, about what matter most to me, that being me.

Question: Can CLL reoccur in the nodes with a clean marrow after transplant? 

Answer: Very rarely, OR " you betcha" especially with my risk factors, maybe a 1/4 of the time.

Question: Is the change in node size significant or are there benign causes for the fluctuation?

Answer: Maybe in the neck or groin, but you just don't see those changes in the gut OR they are still so small I wouldn't worry about it.

My best guess?  You must call them the way you see them, not the way you wish they were. Not much else would cause my nodes to swell. I assume it is the CLL, but I also think it is safe to wait 6 week to confirm with a follow up CT scan to be for sure for sure. There is much at stake. One CLL expert from Australia said I might be cured by the processes I have already been through. It was a minority opinion, but maybe he's right.

Question: Should I get a DLI (donor leucocyte infusion where I get donor white cells injected into my blood stream with no immunosuppression in a daring attempt to save my graft and knock out any residual cancer, but at a high risk of  GVHD or graft versus host disease)?

Answer: Most everyone said yes, but I better hurry. My doctor was not convinced as of Sunday, but he planned to get more opinions. I hope he's changed his mind.

Question: Should I complete the course of chemo with 3 more sets of FCR (the top chemo cocktail out there to treat CLL and the one that was heavily fortified for use in my pre-transplant preparation or conditioning)?

Answer: Finally a consensus: Don't do it. Turns out that a MRD- (minimal residual  disease negative) remission is just as predictive of good outcome no matter if the test is able to uncover only 1/1,000 cancer cells or 1/100.000. That would seem to suggest that striving for an even deeper remission once I've hit that sweet spot of being MRD-  by dousing me with more chemo wouldn't add much except more toxicity and immunosuppression. My doctor doesn't necessarily agree.

Here's my plan as of 12/8/2008 at 23:28:47. It could change 10 times in the next 10 days. Or ten seconds.

I want a DLI if possible, but it must be soon. If no DLI, then a second transplant now (now really means in 6-8 weeks in all probability if donor and insurance line up). I am also fine with waiting up to two months, but not longer and if the CT scan or bone marrow biopsy then shows any hint of a problem, cue the transplant music again. Details of that particular dance will be the thrust of another post. If I remain disease free, I just need close follow-up, every 90 days or so. That's a lot of rads (not the cool term for radiologists, but the hot term for absorbed cancer causing radiation energy), but I don't see much choice. You can't fight what you don't know

What I won't do is more chemo unless it is the first step of a two step process, with step two being transplant. Makes no sense to me.

But if I gave you time to change my mind....