CLL Society Newsletter with Dr. Byrd on ACP-196 and Dr. Furman answering chronic lymphocytic leukemia questions and much more

The CLL Society’s 2nd newsletter is out at http://www.cllsociety.org/newsletter/.

There is a fresh interview with Dr. Byrd on his exciting ACP-196 data, Dr. Furman answers your questions, Dr. Sharman discussed antibodies, especially Gazyza, I review the basic anatomy of a lymph node in CLL, Terry Evans interviews Sheila Hoff, RN about being a clinical trial nurse, and most importantly fellow CLL patients write about compassion and nutrition and dealing with cancer and a transplant and much more.

Please take a look and let us know if you have any questions or even better if you want to write for us. Any feedback is welcome. 

We did 14 sets of interviews of live interviews with experts on CLL from ASH 2015 so please consider signing up for the alerts ( http://cllsociety.org/newsletter-sign-up/ ) so that you don’t miss any upcoming posting, but as always, all our content does not require your sign in. If you do sign up, we won’t share your data with anyone.

Stay strong.

We are all in this together.

Brian

http://cllsociety.org

ITP In CLL (Chronic Lymphocytic Leukemia): Personal And Clinical Reflections

Another great discussion courtesy of ONCLIVE with 4 top CLL experts, from left to right: Drs. Byrd, Furman, Ma, and Kipps.

This time they discuss immune thrombocytopenia (immune mediated low platelet count) or ITP.

ITP is where our immune system attacks our platelets. Just our luck, our wimpy inadequate immune system that can't alway respond to an infection or a vaccine or a secondary cancer, whips into high gear to attack its own cells.

In extreme cases it can lead to live threatening bleeding. It is well recognized complication of CLL occurring in < 5% of us, but as the doctors imply, I suspect many mild cases go unrecognized.

When the same process attacks our red blood cells, sometime leading to a dangerous anemia, it is called AIHA for the auto-immune hemolytic anemia. ITP is the platelet version of the same issue. Attacks on the neutrophils and multiple blood cells lineages also occur, but are more rare.

ITP is a subject near and dear to my heart.

About one year after my diagnosis with CLL, I remember being on call for my medical group and waking to the phone in the middle of the night. It was my exchange. I had asked my family doctor to order a CBC that morning because I had noticed some easy bruising and petechiae (tiny red dots caused by small hemorrhages often associated with low platelets) on my legs.

MEDICAL EXCHANGE: Dr. Koffman please.

ME: Yes. It's me.

MEDICAL EXCHANGE: We have a critical lab result ........ on Brian Koffman. A platelet count on 9.

ME: Thanks. I will definitely follow-up on this.

And I did. It was 6 they next morning and I was hospitalized for IVIG and steroids. It bounced up in 48 hours but because of my recurrently dangerously low platelets I would go on to five emergency admissions in the next year,  multiple outpatient infusions, and an urgent laparoscopic splenectomy where I lost half my blood. I failed steroids, rituximab, IVIG, cyclosporin and the splenectomy.

What finally worked post splenectomy was a combination of cyclosporin (an immune suppressing drug used today mostly to prevent rejection of kidney and other transplants) and rituximab that was recommended by Dr. Byrd. The combo's effects were nothing short of amazing, especially  considering that both drugs on their own had had no benefit in raising my counts. On the combo my platelets climbed from single digits to above normal (not uncommon when you have no spleen).

And the combination of cyclosporin and rituximab had the surprising and joyous bonus of reducing my bone marrow involvement with CLL down from 90% to 3%.

There are some case reports in the medical literature of cyclosporin having antileukemic activity, but it generally avoided due to the fact we are already immune suppressed and it can cause significant problems including renal disease, hypertension and aggressive gout.

It was my dangerous and refractory ITP more than my CLL that drove me to a first remission transplant.

That didn't work either, and my ITP was back one year post HSCT.

That were difficult times.

Despite the risks and side effects, it was only about none months ago, after almost two years on ibrutinib and with years of normal platelet counts under my belt, that I finally had the courage to taper off my cyclosporin. I feel it had helped save my life and I worried about stopping it.

But I did and I have done great since.

A few comments from one who's been there and done that. Yes, I know that one case is not data, but it can be a cautionary and instructive tale.

For obvious reason and because it is part of some of the guidelines, I would ask the doctors in the panel to add cyclosporin to their list of second line options for ITP. I would certainly use it well before the extremely immune suppressive alemtuzumab (CAMPATH) that knocks out both T and B cells for a very long time or splenic radiation that has a host of short and long term complications.

I would also remind us all that the surgery does not always go well, though laparoscopic is clearly the way to go. The research tells us that the best predictor of outcome is the experience of the surgeon. Though it didn't work for me, I have no regrets about my surgery.

I would also ask my colleagues to comment on just how difficult it can be to get us off steroids and not have the ITP return.

The data on ibrutinib is encouraging and makes sense from a biological point of view, but it is not 100% effective.

Overall, a very helpful and well considered discussion on a very important and scary topic. As we might expect, while there is much consensus, there is significant polite disagreement on how to proceed.



It is such a blessing to not have to live in fear of what my weekly or twice weekly blood test would reveal.  Showing up at the lab,  not  knowing whether I was OK or I was headed to the hospital.

That's all in my distant past now.

Still, as all of us with cancer know, we are always looking over our shoulder, wary of the return of our past tormentors,

Frontline therapies In CLL (Chronic Lymphocytic Leukemia)

In this lively ONCLIVE multi-part series of polite debates among four world class CLL experts (Drs. Byrd, Furman, Ma, and Kipps), I was struck by the conservative approach of the panelists to frontline therapy.

Almost all the discussion in this 13 minute segment is about chemo-immunotherapy (CIT).

Keep on mind that except for patients with 17p deletion where ibrutinib is approved, chemo-immunotherapy is all that is approved for frontline therapy. That said, we all know that many doctors including several on this panel would discuss with their patients other frontline options besides those they discuss on camera, namely FCR (fludarabine, cyclophosphamide and rituximab) or BR (bendamustine-rituximab) or chlorambucil and obinutuzumab.

Dr. Kipps points out the potential advantages of the chlorambucil and obinutuzumab in elderly patients with a less resilient bone marrow. This relatively gentle approach has achieved a 20% complete response rate and a 26.7 month mean progession free survival, much better than the other arms in the trial that lead to its approval. For the details of the study published in the NEJM please click on this link.

Drs. Byrd and Kipps talk glowingly about the very long term benefits of FCR in a small subset of patients with the best prognostic markers: mutated with no other bad prognostic indicators. This is a subject we have visited frequently visited in the past. Here Professor Hallek and I discussed this topic in this post in the context of the role of chemo-immunotherapy (CIT) way back at iwCLL 2013. I am still waiting for the published material on that low risk subgroup that is looking more and more as if they might be CURED!

In this ONCLIVE video, there is also debate on the need to complete all the cycles of FCR to get the full benefit. I fully agree with Dr. Kipps that the evidence suggests getting to MRD (minimal residual disease) negativity is what determines our prognosis and not the number of cycles it takes to get there. I quote from a Blood editorial by Sebastian Böttcher on the original research: "current investigation suggests that the number of treatment cycles also becomes irrelevant as long as MRD negativity can be attained." 
The full text of the original research is accessible here. The authors state in the abstract that:" MRD-negative patients had comparable PFS ( progression free survival) and OS (overall survival), independent of the number of courses received or interim staging. Early MRD eradication may be a desirable goal, prompting consideration of early discontinuation of treatment."

Dr. Furman hastened to point out the potential downside of chemo-immunotherapy and also that the group that did so well is a group that should do well with any therapy.

In this article from the British Journal of Hematology, we learn: "patients treated with purine nucleoside analogues (PNA) had a significantly increased risk of subsequent second LPD (5·2%) compared with patients who had not received PNA (1·9%; P = 0·008)"  PNA are drugs such as fludarabine and LPD are lymphoid cancers.  In fact, they go to stated that the only factor found to be associated with an increased risk of a secondary lymphoma for those us with CLL was prior treatment with chemotherapy.

That certainly does give one pause.

There is also some very interesting comparison of BR versus FCR, a subject that we extensively reviewed in this prior blog post with Dr. Jeff Sharman.  I appreciate Dr. Kipps' careful analysis of the different arms of the trial to ensure that we are really comparing apples to apples.

Give a listen and please share your comments.

Again, thank you ONCLIVE for bringing us this great panel discussion.

ASH 2013: Dr. Furman: Idelalisib in Fragile CLL (Chronic LymphocyticLeukemia) Patients

I am going to be busy posting several videos from ASH 2013 because some of the new data that I will be discussing from ASCO 2014, May 30-June 3 in Chicago will be the longer term follow-up data from the same studies.

Today is a short interview with Dr. Furman on his late breaking abstract presented at ASH 2013.

Dr. Furman was the lead investigator and author in this important NEJM article, arguably the world's  most prestigious medical journal. Dr. Furman, out of Cornell Weil, was deeply involved in the first in human trials of both ibrutinib and idelalisib. This important post from only one year earlier at ASH 2012 seems like ancient history as we have learned so much more about these game changing treatments. Worth reviewing to see just how far we have come in such a short time.

The study that we are discussing in the video (click here for the abstract) is pretty interesting for many reasons.

The first is the the particular population that was targeted.

I have blogged in the past about how we determine whom is fragile and whom is elderly. The CIRS score is one way to quantitate how sick we are besides having the obvious problem of CLL that needs treatment.

The group that was studied here was those of us who were likely not be able to tolerate a full course of chemo-immunotherapy due to our co-mordid conditions.

Turns out this group was also a tough group to treat too. 80% were unmutated and 45% had the dreaded deletion at 17p.  

This combo of fragile and tough to treat patients is a group that until very recently had few options and so I commend the researchers for looking to these neglected group.

The next interesting aspect of this trial was that it was placebo controlled. One arm was just single agent rituximab and isn't rituximab alone a pretty wimpy comparator? Dr. Sharman and I discussed this in some depth in a prior post. I recommend you review it. That way you will have the opportunity to hear from an important CLL researcher and also from the lead investigator about this same study.

And it did build in from the get-go a cross-over for those who progressed which for me mitigates much of the ethical problems with the trial design issue.

The adverse event profile is encouraging. One case of Richter's. As CLL is being better controlled, Richter's is becoming too often the cancer's escape route

Next, take a look at the data itself. It was very very impressive.

Finally, Dr. Furman gives his perspective on how this study and the other news out of ASH 2013 is influencing therapy choices for not just the fragile CLL patient, but for all of us.

Dr. Furman has been a pioneer and visionary in moving away from chemo based therapies of CLL. I am grateful for what he has done and even more so for the brave patients that have entered his and  others' clinical trials, especially the more risky early phase 1 trials. Without their courage, there would be no progress.



Much more to come soon.

I just learned that I will be lecturing on CLL to primary care providers at the Baltimore Convention Center on June 28. This is an introductory lecture with videos from interviews with Drs. Kipps and Wiestner and others. I'll be there June 26-29 and leave from there for Columbus, OH for every 84 day visit to Dr. Byrd in my CLL trial at OSU. Talk about having skin in the game. Please come, hear the lecture and visit. The day before I will be also speaking on gout and CAM. See this link below for my US lecture "tour"  schedule. This will be for CME, continuing medical education, that is intended mostly family doctors but many sophisticated patients find the presentations very helpful. And it's free. I would love if you could drop by and say hello.

Live From LRF (Lymphoma Research Foundation) Educational Forum

View from the Brooklyn Promenade

The weather in Brooklyn is wonderful and the view from the nearby Brooklyn Heights Promenade is iconic.

But I am spending most of the daylight hours indoors at the North American Lymphoma Research Foundation Educational Forum at the Marriott.

And I am happy to be here. LRF does strong work in several areas.

This Forum is an example of the kind of high quality education that it offers on lymphoma. For the approximately 500 patients and caregivers attending, the lectures are clear and comprehensive and certainly not simplistic. All the doctors (Rick Furman and Matthew Davids for CLL) are on top of their game and all volunteer their time.

They have excellent free disease specific publications and online webcasts and more.The website is our start, especially helpful if we are new to the diagnosis.

Another strengths of LRF is funding important research. A blue ribbon scientific advisory boards reviews the grant requests.

They offer support in many ways. One example is the buddy service that links us to someone else with the same diagnosis to share war stories.

The new mobile app is a must download for any with lymphoma.

And finally, they are involved in patient advocacy, from what I see, mostly at the government level, where they work with other advocacy organizations such as LLS (The Leukemia and Lymphoma Society).

The hot advocacy issues today I heard being discussed are research funding being affected by the current budget goings-on in congress, compassionate access, and oral parity.

So what actual educational tidbits have I learned? Please understand that this is not a meeting such as iwCLL or ASH where new research results are revealed, but rather where they are pre-digested and handed back to new and experienced patients in manageable bite size packets.

In the CLL breakout session, Dr. Rick Furman made it clear that the importance of many of the new prognostic factors is becoming more or less moot as we enter an era of small molecules because these new drugs are for the most part oblivious to them. They work well for the vast majority of patients.

However, the groundbreaking work by Dr. Rai on CLL staging published in 1975 still is helpful. One strong warning: you must completely ignore the average life expectancies attached to each stage. Pay no attention to the Kaplan-Meyer curves. Those were retrospective in 1975 and bear no relationship to the present reality with improved management and better therapies. We are all living longer.

And for those who are regular readers of my blog, this last item is hardly news: Dr. Furman sees the end of chemotherapy in CLL. I sure like that.

In the general session, Dr. Sonali Smith admitted to the need to revise the lymphoma staging systems to better reflect what we have learned in the last decades. I learned that in some cases disease burden trumps staging.

Dr. Hsi, a pathologist, said that most labs could perform the bulk of the fancier diagnostic tests on a paraffin specimen. There only a few circumstance where there is a need for the better DNA preservation offered by a frozen section.

Still, before any biopsy for possible lymphoma, I would always ask the surgeon to check with the pathologist to be certain the specimen will be properly handled to give you all the results that you need. A dear friend of mine was moving rapidly towards heavy chemo (and possible transplant) for Richter's Transformation (RT) until she got an outside pathology opinion that showed the biopsy from her enlarged node had a viral infection that was mimicking RT. Whew!

In the end, what is more valuable for me than the lectures at the Forum is the networking with old and new friends with CLL, and to their credit, the meeting planners built in enough time to make sure that happens. That's the upside of having cancer: the amazing people I get to meet and the experience and wisdom and and courage they have to share.

So, if you have never been to North American Lymphoma Research Foundation Educational Forum, plan to come, and if you been before, why aren't you here?

More from tomorrow sessions soon. But first I sleep.

Day 2:

I wish I could say there was much new to report, but what I would say is the take-away message is that the role of chemo-immunotherapy (think BR, FCR, FR, PCR and others) is either dying for all of us or most of us.

I could argue that for the small subgroup of patients (mutated with the appropriate cytogenetics) where it can be predicted in advance of starting therapy that FCR offers a very high chance of a durable remission (10 years or longer) and the hint of a cure (if you are MRD negative 14 years out, are you cured?), that for those of us and only those of us fitting into that tiny cohort, there might be a diminished but important role for chemo-immunotherapy (CIT). I personally would seriously consider the choice of 6 months and done of CIT if it really offered me a 90+% chance at being cured or at a minimum a 10 year remission.

My friend Wayne (WWW) points out there is also an age sweet spot for this therapy: too old and we can't tolerate the suppression of the bone marrow, too young and the risk of secondary cancers, especially MDS (myelodysplastic syndrome) is too high.

Others says just forget the chemo. Use one TKI such as ibrutinib or idelalisib or ABT-199 as long as you can, and if you develop resistance, switch to the next one coming down the pipeline.

Or maybe add a mAb or IMID to the TKI or combine two TKIs and go for the knock out punch.

Hard to argue with that vision of a chemo free future.

The doctors are split on how to proceed, but there are all shifting their stances in response to the  growing data supporting the new meds (TKIs and mAbs)

The world is changing fast. Stay tuned in.

ASH 2012: Dr. Richard Furman Discusses What is Known and What Isn't About the New Treatments in Trials

In the final part of Dr. Furman's interview from ASH 2012, the doctor who had the most early experience with GS-1101 (idelasilib) and ibrutinib discusses the still limited experience of disease progression with these new small molecules. He reminds of the real risks of bone marrow damage (MDS) and transformation to a more aggressive cancer (Richter's) and offers an interesting hypothesis on why Richter's might be found more often with these treatments.

He reviews the open pivotal for idelasilb (GS1101) and the associated crossovers, plus the trial for ibrutinib versus ofatumumab.

But there are other trials out there too that he didn't mention, especially for patients in special categories, such as 17p deletion or age  > 65.

So always remember to check what clinical trials might be a fit for you at http://clinicaltrials.gov when you are considering treatment. Don't count on your doctor to know all the latest. See my prior post on clinical trials.

Dr. Furman candidly outlines what is known and not known about how these drugs work.

What I really like is the strategy he outlines of using these drugs one after another as stepping stones to a normal life expectancy.



More to come from ASH 2012.

ASH 2012: Dr. Rick Furman Discussed the Very Early Experiences with Idelalisib and Ibrutinib

This video is a real treat as it shows us the recent history of the small molecules that are changing our future.

And the narrator, Dr. Richard Furman, the head of the CLL and Waldenstrom's Macroglobulinemia program at Weill Medical College was not only there at the beginning, he was the investigator for these phase 1 trials for ibrutinib and idelalisib.

He tells of the broken promises of a prior generation of small molecules. He reminds of the bravery of the volunteers who entered the unknown world of these new drugs with little more than hope that these pills would be different than all the rest that preceded them. He points out how the amazing changes that lead to the record fast accrual for the follow-up phase 2 trials. He explains why the climbing lymphocyte count was not a big concern and how it is so different than the rising counts encountered with the tumor flare seen with lenalidomide.

So much has changed in the last few years. What a brave new world we have entered. A place chock full of both hope and unknowns.

This was filmed at ASH 2012 in December.



I have nearly caught up on all my other non CLL medical writing so I can soon turn my attention to more on non-chemo answers for CLL, but this interview should help those looking more than my musical interludes when they tune in on my CLL adventure.

Part 2 with Dr. Furman to follow, then a long interview with my friend, Dr. Adrian Wiestner.

And I will be going to ASCO in May in Chicago though at this point it is uncertain whether I will be  bringing my video staff.

ASH 2012: 10 Minute Break from the Excitement of the End of the Chemotherapy Era in CLL

Since I last posted I have interviewed Dr. Wiestner and Byrd, two of the most important researchers in moving ibrutinib forward. I also taped a long discussion with Dr. Wierda about CAR-T therapy among other things. Dr. Furman who did the phase 1 ibrutinib trial is next, then meeting Dr. Jeff Sharman.

This afternoon more lectures on ibrutinib, lenalidomide, and the first one on CAR-T.

Squeeze in the poster sessions and exhibit halls. And a visit with my sister-in-law.

Let me just summarize the news from ASH on CLL. You may not have heard it here first, but let me shout it out loud and clear.

The days of chemotherapy for CLL are ending. 

Details to follow.

Dr. Richard Furman on Surprising Early Trial Results for Ibrutinib

We were all surprised, pleasantly surprised.

Dr. Furman did the first phase 1 study on ibrutinib. I remember him mentioning this trial to me years ago and it seemed to me such a long shot.

Not any more.

Thanks to those who had the courage to try something new. They were the real pioneers. We who are in the phase 2 and 3 trials are all in their debt.

And those who are eventually prescribed this drug or GS-1101 or others should look kindly on those of us who earlier make the decision, took a much lesser but still significant risk and entered a phase 2 or 3 trials.

To CT or not to CT: That is the question.

I saw Dr. Kipps for the first time in 6 months yesterday and the cold facts were good, in fact very good.

My lab remains perfect, and for the first time since transplant, my ALC is WNL. More importantly, my node exam by the meticulous Dr. Kipps and his magic fingers revealed nothing pathological. One small node in the neck was about it and it was around one cm. Nothing else found worthy of comment.

Based on my exam and routine lab, you would hard pressed to say I had CLL or had had a transplant.  Nearly four years out, and I am pretty unscathed to use the language of Dr. Rai.

Moreover the fact that my bone marrow cellularity was normal for my age at 40% told us that my blood making organ had bounced back very nicely from last year's toxic blast. My reserves may be down and may have a more difficult time rebounding from future treatments, but my marrow is doing great now.

In fact, when we look at the NOW, and what else is there to look at, it's all good. 

Sweet!

But Dr. Kipps had a different take on my CT report of my mesenteric lymph nodes doubling in size from 1.1 to 2.2 cm in just three months between the end of December and February.

He was incredulous. 

It doesn't fit with my healthy state and my clean as a whistle BMB.

He is another on a short but prestigious list of docs (Castro, Rai, Forman) to say that CLL doesn't come back in nodes. It likes to stop off in the BM first. Drs. Khouri and Keating might beg to differ. However, Kipps added this important caveat: the only time it relapses in the nodes is post Campath, and that sure isn't my case. And Khouri and Keating sure like their Campath.

Kipps just doesn't believe that last CT report. I told him that I had 4 different radiologist read it, and he still has his doubts.  He pontificated and I don't disagree that radiologist like to be pathologists and internist too.

Assuming these nodes have really grown (which is where I start), what the heck are they? 

Normal fluctuations? I have my doubts that normal fluctuations would have seen growth over three CTs spanning a full 6 months. But maybe.

An unknown viral culprit?  That could also explain my fatigue.  That would be more good news. Dr. Kipps believes that in that case IVIG might help my fatigue. It has a track record.

It could be telling us something worse. Post transplant lympho-proliferative disorder (PTLD)? This is the path that Dr. Furman suggested and Drs. Rai and Forman rejected out of hand. My lab work-up was negative, but that doesn't really rule it out. 

The dreaded Ritcher's transformation (RT). I am just too well for that, aren't I?

So the best way to tell according to Dr. Kipps, is to repeat the CT soon and see if they are growing. Or not.

If not, no worries. The nodes were nothing, or my vegan diet, Zeolite, digestive enzymes, and flaxseed oil has beaten them and with them any trace of my CLL into submission.

We can all relax, for a long time, G-d willing.

If yes, then the next step in a BMB to see if my CLL is still gone, gone, gone. 

If the BMB  still shows MRD-, and my nodes are still growing, that's where things get weird, and scary.

Maybe then Furman and Kipps are right. Maybe it isn't CLL in my nodes. And  many of the immuno-suppressive treatments used to treat CLL would make PTLD much worse. And wouldn't touch RT.

That means a none too easy mesenteric node biopsy because we need a sure diagnosis before we start a treatment. I am not liking the sound of this. That could lead to all kinds of risks and complications.

If both the nodes have grown and the CLL is back in the marrow, I know the story, and the story lines leads to transplant two. And I could ask myself, what advantage was served by forcing to expose my hidden cards earlier than needed in the game. Is my chance at a second CR improved? Probably, but at what cost?

Maybe that is why the wise Dr. Rai told me to tell Dr. Forman to stop with all the CT scans.

Here I am back in the usual CLL place: conflicting advice from world experts.

I think I am NOT going to think about it for awhile and wait to see if a light goes on or my hand is forced.

The best advice I got from Dr. Kipps, and we can all agree on this one:

Don't do anything stupid.

For me, that means sitting on my hands for awhile.

My rough thoughts

This is a rough draft of my notes to myself (and my wife), unedited and uncut to give you a sense of what goes on in my head as I try to sort out the best moves with this crazy thing called CLL.

First what do the nodes mean?

I have two growing nodes in my gut, maybe more. Other nodes are "plumper"

My CT scan shows definite growth. But is it the CLL?

Could it be nothing? Castro said it might be not important and Rai thinks it still might be fibrotic tissue that could grow.

Rai seemed to indicate the lack of any other nodes was particularly critical. At least he asked about it several times and examined me himself. Castro though that all the nodes should grow at once in CLL So does Kipps. Not Tam or Keating.

Steve Forman and the two radiologists say they are evidence of relapse. They offer nothing else to explain the change other than CLL on its way back.

Rick Furman goes in a different direction. He thinks my nodes are growing too fast for CLL and it is important to rule out PTLD, before any cytotoxic treatment. He said my disease is nodal. Acting like a lymphoma.

 

The next issue is the reason for the profound change in my nodes and for my bone marrow becoming and staying MRD negative after the transplant.

Castro and Rai think the T cells may have been a factor, though Rai also suspects that the chemo was definitive. He seemed to waver.

Steve Forman gave me a definite no to the transplant being any factor in my remission.It is all chemo effect. Rick Furman agrees saying that I couldn’t have formed T cells in the time the graft was aboard.

BTW, quoting Rai:” Losing the graft is bad, but it is not a death sentence” Another quote: “ I have gotten to this point remarkably unscathed” Forman:  “The news is good: You did get a complete remission (with the conditioning from transplant)”

 

Next monitoring, testing And the PTLD question.

Steve Forman wants to treat but not too soon and not too late. Not sure his definition of either point, except that the present is too soon. He plans to follow me with CT scans every 3 months for now and slightly less frequent BMB. That could all change after the next tests in June or July. Uninterested in other markers. Also said would treat like any other CLL, when it is time to treat, which is a bit different.

Castro would wait longer on the CT: 4-6 months. Also wants to track using CLU test. Forman does not trust CLU to make a treatment decision.

Rick Furman says B2M is of no use in my case and my CoH cytogenetics are suspect due to the fact they are stimulated tests and don’t capture the CLL cells. Prefers FISH.

Rick Furman wants a work-up for PTLD including EBV PCR (VCA?), monoclonal gammapathy?, T and B cells counts and ratio, mono-spot, peripheral blood gene rearrangement, CD4/CD8 counts, and others. Would biopsy before FRC or similar treatment, even if nodes continued to grow massively. Still could be PTLD. Dr. Furman thinks my CLL is behaving like a lymphoma.

PTLD didn’t come up with the radiologists, Steve Forman, or Castro. Or BTW with Keating or Tam or the German who did study on CT or any of the ASH crowd.

Rai says there is no tests on the blood that are certain for PTLD and besides this is not behaving like PTLD. No systemic symptoms. Would avoid biopsy, too risky and besides I might treat what I find when it is not needed. Rai: “If the biopsy doesn’t kill you, the treatment might”.

Rai said I should be tested less. CT in 2 years. No BMB needed.

 

So the big questions: When to treat and how?

Steve Forman is pretty clear, as mentioned above. When ready, he would do FCR, followed by what Rick Furman calls a “midi” transplant: Melphalan-Flu, hopefully from the same donor (which is unusual).

Rick Furman wants to connect with Dr. David Maloney out of the Hutch and get his take on a DLI. He is not big on transplants, but seeing as I have already had one and done well, then let’s get the most out of it.  He says he doesn’t know about the whole DLI issue and aplastic anemia that Steve Forman raised.

He would do nothing now or Lenalidomide 5 mg. They are doing a trial using Lenalidomide alternating with Thalidomide. Same action, but different toxicities. Thinks it might help GVL and is great for CLL. (BTW he says never stop the acyclovir due to risk of zoster) Test including biopsy before any treatment except Lenalidomide, which he says is so benign. Better treatments in the next few years, so hold off. Not keen on redo or any transplant.

Castro is still keen on the DLI, just not yet. Says it is never too late for DLI. Not worried about aplastic anemia. Not sure the nodes mean anything. Might consider Bendamustine.

Rai would wait until I was symptomatic. Would not test. Treat when B symptoms only, then treat hard Worried I might develop MDS which is very hard to treat with more therapy or a second transplant

Doesn’t like Lenalidomide. Too new, not sure how to use. Risk of getting T cells involved in tumor flare. Dismissive of any treatment, and especially mentioned Bexar and Zevilin as I am a candidate for both with a clean marrow, and they would wipe out the nodes, whatever they are, but they have risks too. He said" Let someone else worry about the nodes".

Kipps like Rick Furman, is biased against transplant. I haven't seen him since December, but he did not recommend treatment then and did not suggest any specific therapy when the time came. He is not keen on CTs and want to rely on his palpation of my nodes and discussed the radiation risk from CT scans.

All sharp caring doctors.

So the way I see it as of today March 25, 2009:

Back to watch and wait. Stop the CT scans every 3 months. Wait for any symptoms.(Maybe recheck in 6-12 months)

Here’s why.

I wanted a DLI. Dr Steve Forman said no despite my mixed chimerism as I was in complete remission MRD negative, so why take the risk.

We were watching carefully to see if I started to relapse; then time to pull the trigger on the DLI.

What happened is that the remission lasted longer than the donor cells. By the time I had relapsed and by Dr. Forman’s evaluation, needed a DLI, my donor cells were down to 0% and it was too late (again according to Dr. Forman).

I am not sure of the rationale to continue with the frequent CT scans.

The downside:

I could miss PTLD or even RT. Possible, but not likely.

My CLL could become more aggressive and harder to get a second complete remission. Recent data suggests that is important for transplant success.

My donor could not be available. The longer I wait, the more likely he won't be in a position to help again. I have only heard the one time from him.

I might have developed co-morbidities that would increase the risk of a second transplant or make it much more risky. I doubt it. I am pretty healthy, but you never know the future. I have sure learned that lesson.

Insurance or government enforced cost savings may make it more difficult to get the second transplant.

The upside:

Fewer CT scans and the radiation risk.

Less worry.

Possibly several long years of remission.

Better treatments. Experience with Bendamustine and Lenolidamide is growing. Humax CD will be approved pretty soon.

Better transplant protocols. The protocol for transplants are evolving. Even the PICC lines are better that 6 months ago.

Truth is that it likely won’t make that much if any difference when we start treatment as to the outcome of treatment.

It is the last one that really tips my hand. At least for now.