Personal Update on my CLL: I am doing well with a near normal MR and no evidence of resistance to Ibrutinib at 42 months

I had MR imaging of my abdomen and pelvis earlier this week at St. Jude. The results were compared to my CT scans done on June 30, 2014 at Ohio State, about 16 months ago. 

I am now on my 42nd month on ibrutinib as part of the OSU clinical trial.

The abdomen showed no adenopathy. No abnormal nodes. None. No big nodes! 

WOW!

My pelvis did show one plump node in the left external iliac area (drains the lymph from the left side of GU tract) that was borderline enlarged and probably 2 millimeters bigger than it was before. 

Different techniques, different doctors, different times. I don't think the 2 mm. means anything and either does Dr. Byrd so I refuse to worry.

I switched to the less precise technique of MR to avoid the potential cancer causing risks of ionizing radiation of the many CT scans that are part and parcel of clinical trials.

When relapses happen with ibrutinib, they often start in the nodes. And that clearly is not happening in my case. And that is great news.

The other great news was that my blood tests done at OSU for the two common mutations that can lead to resistance to ibrutinib were negative, namely the downstream gain of function mutation of PLCγ2 or the C481S mutation at the BTK binding sites that prevents ibrutinib from irreversibly (covalently) binding. Either one of these mutations could turn back on the signaling. Blocking BTK signaling is the key to the success of ibrutinib in handling the CLL clone, so if the blockade is broken than will lead to resistance and eventually relapse

It is not a perfect test, but I had neither one at detectable levels.

Tomorrow I go for IVIG for my still dismal levels of immunoglobulins and to keep my auto-immune ITP at bay. I will also have routine labs drawn, but I am not expecting any surprises

A week later I am back at OSU for my 3 month check-up.

Flying to Ohio in the late fall and all winter is not predictable, but what I can predict is good care and what I can anticipate is more good good news as I am heading towards 4 years on ibrutinib.

UPDATE: My CBC at the infusion center Nov. 12, 2015 was basically normal. Hemoglobin was really normal at 14.5 so no anemia, platelets were very slightly above normal at 458,000 due to my splenectomy, ALC was at the low end of normal at 1.0 and that makes me most happy and my ANC was a healthy 8.1.  

All good. YEAH!

Hope to see you at our after ASH educational bash at City of Hope on Dec 12. Click here for the details.

The Risks of Too Much Testing in CLL

As those of you know who follow my chronicles know, I have been plagued by a cracking irritating noise in my right ear associated with a congested feeling for months now.

While steroids gave powerful if temporary relief, nothing has solved the problem. It seems each doctor who checks the ear sees something different. The diagnosis ranged from a serious infection to a completely normal tympanic membrane with a few stops in between at a dull and retracted eardrum.

Here I valued my family doctor’s evaluation more than that of the less experienced “ear-looker-at-er”, my CLL guru, and in the end, relied on the the findings of a otolaryngologist.

When we doctors look in your ear, we are using one eye therefore there is no depth perception. That can lead to a misreading of what the anatomical landmarks are telling us and as a consequence, a misdiagnosis. Minor findings seen on the otoscope can be over-interpreted and lead to unneeded therapies.

When I saw my ENT specialist, he told my ear looked great. So I asked “ Then why the crackly noises and stuffy feeling? ” He wasn’t sure but he also wasn’t worried. Often in medicine, it is much easier to tell a patient what they don’t have than what the do. We can reassure our patients and ourselves that the chest pain is not angina from the heart, but darned if we know what is the true cause.

This brings me to revisit another old theme.

Patients come to the office for two very distinct problems.

The first is that they want relief from the symptom- the pain or itch or nausea or depression or a thousands other “chief complaints.” Chief complaints or CC- that’s what we healthcare providers call them in your medical chart.

The second very different motivator that leads to a doctor visit is the need to know that the presenting symptom is not something serious. “ Doc, I don’t want you to remove that mole. It is not causing me any problems. Just tell me that it isn’t cancer.” Or  “ Is it normal to feel my heart beat in bed at night?” Or “ Why am I hearing this funny noise in my ear?” And a thousand more concerns and worries that need to be assessed and offered reassurance more than relieved.

These are disinct problems, and the wise practioner must recognize what the patient is asking for and meet that need or the encounter will not be satisfying for either party.

I wanted the reassurance. The noise itself is trivial, but was I missing a clue to a more occult issue?

Because of my CLL, my specialist did a tympanogram and demonstrated that my drums bilaterally were responding to changes in pressure in a normal and symmetrical way. That suggested no serious pathology. The big surprise was my hearing test. It was nearly perfect, at all frequencies, in both ears. This was a welcome and unexpected finding in a baby boomer. When I think of my teenage years when I stood inches away from the giant stage speakers at a Led Zeppelin or Janis Joplin concert, and woke up with ringing ears the next morning, I am truly amazed that I suffered no permanent damage.

The ears-nose-and-throat man can see where my internal auditory canal (IOC) ends at the eardrum with his otoscope and where it begins my looking up the nostril with a different specialized instrument, but he can not asses what is in between.

That is why he ordered an MRI of my IOC. With contrast to enhance any tumor.

And here is where my tale of too much knowledge gets interesting.

A few days ago after physical therapy, and before a memorial service where I gave the eulogy (see post Jennie Lynn Taylor) followed by a CLL support group meeting, and ending with packing for travel the next morning, I squeezed in my imaging test. The radiologist reading my study is an old pal, so he shared the results with me. Another of the unabashed perks of being a staff doctor.

My IOC was patent (open) with no tumor or inflammation or fluid.

Great news.

BUT…

My right mastoid that should be fully aerated and thus appear black on the scan as did the left side instead instead had a mottled appearance reflecting fluid and swelling in the air cells. It wasn’t subtle. It was obvious.

Mastoiditis he said! A dreaded infection, usually of children, that can lead to major surgery, nerve damage, hearing loss, and life threatening abscesses and brain infections. I have not seen a case since I worked on the ENT floor of St. Justine pour Les Enfants in Montreal as a med student at McGill.

Could my suppressed immune system allowed some weird organism to slip into my bone and take up a hostile and damaging occupation?  

This demanded action. Or did it?

Read my last post on worrying to see how I was coping.

You see it just didn’t add up. My ear was pain free and functionally normal. I wasn’t sick and hadn’t been sick recently. There was no tenderness or redness or warmth or fever.

I called to consult the doctor who had ordered the scan and they arranged an appointment later that same day on my way home from the memorial service.

He took one look at the MRI and reassured me (exactly what I needed) that is a non-event that he sees all the time. Sure the mastoid air cells are different on the right, but this could represent old minor damage from childhood infections or allergies or nothing.  Not a chance that it is some weird bug because there is no involvement of my ear canal and no free fluid. Why the right side only? Why has become symptomatic now? He has no idea, but he also has no worries, so I won’t either. 

Apparently MRIs are notorious for over diagnosing mastoiditis. Who knew? My ENT colleague gets too many calls from the ER or worried neurologists or family doctors about exactly this same non-issue.

So here’s my point, as I try to decide about whether to go ahead with my CT scans next week. Will they find another red herring on all those scans that will demand further workup to “rule-out” that it is nothing to worry about. Well I wouldn’t ever have worried if you hadn’t done the imaging to begin with. Much ado about nothing.

You order enough labs, x-rays, and other tests and sooner or later you are bound to find something, but does it mean something. As my pseudo-mastoiditis case revealed, often it doesn’t.

This is another cost of knowing too much, and too little at the same time.

Moreover as to my upcoming CTs, the size of my internal lymph nodes measured by the scan will make absolutely no difference in my own care. My suspicion is that it will also make little in any difference in the final study data as long as I get the exit CT scans and bone marrow biopsy in a brief three months from now. Others might disagree. The scan might find an unexpected non CLL growth or problem. While the yield on secondary cancers is small, it can be life saving for those few. I can count a half a dozen friends among those who are alive today with exactly this scenario.

My tendency is not to look for trouble. I am no diagnostic nihilist, but how many CTs do I need?  This recent brief scare with my MRI  “finding” is another reason to think twice about this testing.

Tests need to be reasonably expected to make an impact on how the patient or the disease will be managed. There is no role for curiosity, especially when we are talking about procedures that care some  small long term risk (see prior post on CT scans and secondary cancer).

In the big picture, the fact that I can focus in on such passing details such as the risk/ benefit of imaging is testimony to the fact that I am doing so well on the ibrutinib.

Labs are rock stable and energy is picking.

Life is good. Off  to Ohio in a few days to pick up more magic grey pills.

Fighting the hidden enemy- My big mesenteric CLL nodes force my hand

The disconnect between how well I might look and feel and the growing burden of cancer in my gut challenges my intuitions of how the world and leukemia works. Fighting the hidden enemies is my new imperative, one I can not ignore or wish away.

My doctors Forman and Kipps disagree on most everything, EXCEPT that I need therapy. Soon.

I will be spending the next 2 to 3 months deciding what to do next.

Doing nothing is not an option. Or at least not a very wise option, though it is certainly the most appealing in the short term.

I will not let this decision consume me, but will try as best I can to detach myself from the process and argue as I would for a friend or patient.

I will try to be calm in the face of imperfect choices and incomplete data.

I will try to look beyond the immediate horizons to the best possible future.

I will decide and move on.

I will, in the words of Jon Kabat-Zinn: Meditate, Act and Be Aware

You give me reason to live, you give me a reason to live, you give me reason to live!

My daughter and granddaughter in the California Redwoods

Patty and I went on one of our best trip ever. It wasn't exotic China, not romantic Italy, not Zen Japan, not super natural New Zealand, not historic Prague or musical Vienna or friendly OZ, not ancient Israel and Egypt, not the castled United Kingdom, not magical Peru, not the grand Grand Canyon, but gritty occupied Oakland because that's where my daughter, son-in-law, and granddaughter live.

That young lady with the pink bib in the picture is another reason to soldier on.

I have no bucket list. As I have said before, I have way too much joy in each day and way too many things left undone to imagine that a list of the top 10 or top 100 or 1000 checked off would signal it's OK to check out.

But seeing that four month old under the marriage chuppah might be a moment when I can say that I have seen enough.

Nah, make that holding my first great grandchild. I should be in my 90s or close. If I live long enough to see that baby's bat mitzvah, I would be around the century mark.

In any case, CLL would be a remote memory. What a blessing that would be.

But now CLL is front and center. Tomorrow I have my MRI to see if my CLL is trying to launch a sneak attack from inside enemy lines, my mesenteric or gut nodes. If they have grown too big despite another course of rituximab, I need to knock them back to size while I still can. If they become "massive" ( >10 cm) they become harder to kill. In these large niches, they have more supportive infrastructure such as nurse cells and they are just tricker to reach with what ever toxic cocktail I have planned for their last meal.

That means choosing a new treatment strategy that keeps one eye on my ITP, and another on my sleepy bone marrow and my third eye on a future transplant redux- probably my only chance to live long enough to see a fourth generation.

I wish there was another way, but I am not convinced. Kinase inhibitors such as CAL 101 or immunomodulators such as Revlimid might buy some time, but not a cure. They don't promise me another 30 years. Only a second transplant gives me a 50/50 shot at getting really old. But a transplant demands a big price for that shot of redemption and a second transplant demands even more.

I have been catching up on hours and hours of reading about my disease and transplant. CLL remains thankfully a hot research arena. Much is changing fast, but is it fast enough? I doubt it, at least for me and those of us who might need treatment soon.

Those who have followed me on some or part of my six year journey know this is a repetitive loop- my anxiety before a scan or bone marrow biopsy, my cogitation over my next move, my lament about the slow progress and the constricted choices, and my hunger for life.

Thanks for joining me on the trip. The CLL community and others facing similar challenges are among the many gifts in my life

I've got too many reasons to live and one very young, and beautiful new one.

Slight Progression

My MRI today produced fine crisp images that showed my nodes have grown slowly since the last CT in September and now the largest in the mesentery is 6.3 cm in its widest measurement.

What makes it more confusing is that the report from September was revised upward suggesting both that the response to the rituximab after the June CT was very much less than I had thought it was last fall, but on the other hand, the growth since has been quite slow.

But the growth may not have been linear, but rather a U curve with a early drop, and a recent growth spurt in node size.

Remember please that I had more rituximab since the last CT that likely shrunk the nodes (this was never documented and so is just my speculation) that are now rebounding. I will never know for sure, but it makes sense.

More later. Too tired to write tonight.

MRI tomorrow

What used to take a scalpel, then an x-ray, can now be done with a magnet.

Secret happenings in the deep source of growth of CLL, its proliferative centers, the lymph nodes in my gut and pelvis, not reachable by the longest fingers of the most expert palpating oncologist, will be revealed tomorrow.

Have they grown? How much? What does it all mean?

I am nervous. But I am ready.

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.