Rearranging deck chairs on the Titanic

I finished the workup of my leukemic relapse, having had a bone marrow biopsy and PET/CT over the last week and a half and in 2 days visit my oncologist to learn the results and find out what the next treatment regimen is. I had to have another RBC and platelet transfusion last week, less than a week after the last. These have become more frequent making me wonder if my anemia and thrombocytopenia are due to more than bone marrow failure, perhaps hypersplenia, which my oncologist has mentioned as a possibility in the past. Adding to this possibility is that I can now feel a very firm mass in my left upper quadrant that is probably spleen (confirmed by internist last week on routine followup visit, see below). I would think our first step would be to treat the leukemia and see how my counts respond to get a better idea about whether drug-induced marrow failure and/or hypersplenism are contributing to my significant and worsening transfusion dependence. My last count was Hgb 7.6, WBC 57K, and platelets a dangerously low 8K, see photo of my arm from a routine blood test, demonstrating how much we all need platelets.

So I also saw my internist this past week as routine follow-up, primarily on mild hypercholesterolemia and a previous slightly raised PSA. I was very worried about the latter since it could mean I had early prostate cancer, something I certainly did not want to deal with given my leukemia relapse. Thankfully the value this time was normal. My LDL (bad) cholesterol was low and I also had low testosterone (which is funny since one of my company's clients is the maker of a testosterone replacement product). I complained of my quite painful nighttime leg cramps and the doc said to either try CoQ10 (a borderline alternative product found in vitamin aisle that is not cheap) and/or stop my statin since my cholesterol never that high and have no significant or personal family history of heart problems. I asked about testosterone replacement but had to admit any symptoms of lack of energy, sexual interest, etc were more likely due to the leukemia. My doc actually had me laughing (?gallows humor) when he said these problems he was managing were like rearranging the deck chairs on the Titanic. I think that this is no doubt true and now can just focus on getting better with the next treatment, God willing.  

Here is what my internist meant, the leukemia is my main problem and I could be going down, but I am here to tell you, NOT WITHOUT A FIGHT!

T-Cell Chimeric Antigen Receptor pilot trial at Penn

Saw Dr Porter at Penn today, for a second opinion for the first time, thinking I may be interested in the chimeric antigen receptor in vitrio genetically modifying T-lymphocyte pilot trial (I know that is a mouthful, see here for explanation). I have been needing both platelet and RBC transfusions almost every 2 weeks since I finished my 6 cycles of bendamustine-rituximab at the end of March. My last WBC count showed a rising lymphocyte count and I have noticed that some of my lymph nodes have started to increase in size a bit. Dr Porter felt, as does my regular oncologist at Hahnemann/Drexel, that I need to have my bone marrow checked again as well as repeat CT scans, to better determine if my low counts are due only to the leukemia coming back or perhaps in part also bone marrow failure as a treatment-related adverse event, maybe even myelodysplasia.... He suggested that the next treatment could be ofatumumab (a monolclonal antibody supposedly more effective than rituximab) or either rituximab or alemtuzumab (Campath) with high dose methylprednisolone, stating that Campath is not so effective by itself. The response to this therapy would help to determine whether my marrow is showing just leukema or some underlying dysplasia. Stem cell transplant may be an option if it looks like my marrow is not performing well, but it would have to be from an unrelated donor (see prior post - unless I can get my brother to help me out), but If my marrow seems to be OK than an option would be this T cell tiral or perhaps one of the small molecule tryosine kinase inhbitors under development. Time will tell, but not having a good response to B-R after 3 prior treatments with fludarabine shows my disease is advancing.....

Finished 6 cycles of Treanda/Rituxan...only PR

My last treatment with Treanda (bendamustine) and Rituxan (rituximab) was late March, at that time, prior to the infusion, my CBC showed total WBC 22K. Hb 7.8 and platelets 22K. A month later the CBC = 8K total WBC, 8.7 Hb (after weekly Procrit and one transfusion) and 36K platelets, the only normal value being the white cell count. Since then the total WBC peaked at 30 and then down to 16K last week but both Hgb and platelets sliding slowly downward to 6.4 and 16K respectively, leading to another RBC and platelet transfusion last week... Bottom line: My markedly enlarged lymph nodes have decreased significantly in size but my marrow is not yet cleared AND/OR still recovering from bendamustine suppression.... 

 So my oncologist has suggested I look into consultation with Dr Porter at U Penn who a few months ago published a study in which genetically engineered T cells led to good results in 3 patients with CLL (see article or for any layfolk reading this), so I have an appointment in early July (maybe sooner if my medical record and request for stat consult for a fellow MD are heeded) 

 My doc has talked also about using another monoclonal antibody Campath (alemtuzumab) which is good for ongoing bone marrow disease but hard on one's immune system, particularly T cells. One has to get weekly checks of CMV reactivation with the aim to treat if this bad virus comes back with a very expensive drug, worth it if one wants to avoid retinitis!

 New drugs in the pipeline that have gotten a lot of press are oral tyrosine kinase inhibitors, now in phase III trials (see this) but these trials may not work for me, because I have had Rituxan 3 times already:

• for GS-1101, the active arm is Gs-1101 and Rituxan vs placebo and Rituxan
• for  ibrutunib (PCI32765) it would be the drug vs  ofatumumab (a CD 20 Monoclonal not necessarily any better than Rituxan

there is an earlier phase trial for a drug similar to ibrutinib (AVL-292) that has a small phase I trial that I could go to NYC for but would need to have a platelet count over 30K

I tried to get into Revlimid phase II trials but in the spring of 2011 my disease was not advanced sufficiently and in the fall I failed to qualify because my platelet count was under their criteria. Phase III trials are drug vs placebo + BR which I have just completed with only partial remission so not for me..

So I am running out of options, and need to think about stem cell transplant also. My brother who matches me well has stopped communicating with me and may not be  interested in saving my life, but I will keep trying....

Halfway through 6 cycles of Treanda/Rituxan

So my lymph nodes everywhere are at least half the size they were before treatment, my WBC total is down to 17K from over 70K, and my platelets have rebounded from treatment-related low of 20K to close to where I started. On the downside I had the one hospitalization for fever with borderline neutropenia, 1 platelet transfusion, and 4 PRBC transfusions. Still have anemia, last Hb 7.1 but getting weekly Epogen. Hope to tolerate the drugs better in the next 3 cycles, with the help of pretreatment Decadron and post-treatment Neulasta. Even more I hope for normalization of my lymphocyte count and continued shrinkage of nodes. Will I get a prolonged remission? Should i consider a second opinion at U Penn, should I look into a maintenance trial if available? Time will tell....

O'Brien on oral tyrosine kinase inhibitors

Dr. Susan O'Brien on kinase inhibitors, interview with Andrew Schoor --

Bottom line:
CAL-101 (now known as GS-1101) and PCI-32765 have shown great results with little myelosuppression. Moving quickly to later phase trials as monotherapy or in combo with chemo and or immunotherapy. Dr O is excited, the FDA is excited as am I if and when my next relapse occurs.....

Doing well after my second round of bendamustine/rituximab

I am now almost 3 weeks from my second round of bendamustine/rituximab (BR) and am happy to report good progress. At the beginning of treatment I had very large lymph nodes and a WBC of 75K. My nodes shrank considerably after the first round and some more after the second. My WBC has gotten as low as 2.9K (fortunately with the help of Neulasta half of those WBC are neutrophils). I have had side effects though, as expected, as platelets got as low as 20K (got one platelet transfusion) and anemia with hemoglobin to 6.2 twice (got transfusions of packed RBCs twice).

I had shaking chills without fever and then fever during my Rituxan infusion on the second cycle, despite stopping the infusion, giving steroids and Benadryl, I only got 1/3 of the whole Rituxan dose. This was odd as I have had Rituxan many times before without effect. But it is possible to have an allergic reaction any time from the second to the one millionth exposure (this is what I often told my patient's parents when they developed drug allergy after tolerating their amoxicillin many times before). With these complicated biological molecules there may even be an infusion reaction on the very first exposure, the molecule somehow setting off a cytokine storm of sorts. My wife, a recent nursing school grad (yay! congrats over and over!) and I speculated while I was recovering from the shakes that maybe there was an antibody against mice protein in the packed RBC I had gotten a week and a half prior. Packed RBCs have a small amount of plasma and this could contain antibodies or antibody-antigen complexes (for example see http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/BloodSafety/ucm095556.htm). If there were antibodies against mouse protein that could explain my reaction, in that rituximab is a chimeric mouse-human protein.

The fever persisted after treatment and even though I had 1.4K neutrophils I was admitted for several days for observation and antibiotics. The fever subsided by day 2 after last Bendamustine and 3 days afte aborted Rituximab. The plan for next round of BR is to preload me with steroids and antihistamines. Here's hoping I don't have to go through the fever part again.

My hemoglobin has run between 8.4 and 7.7 after the second transfusion, and since I am in good cardiovascular shape, having trained for a half marathon this summer, I can tolerate this level, getting a bit winded only when going up hill with my dogs or doing a few staircases. That said, my oncologist is contemplating starting me on erythropoietin to get my hemoglobin up into a more tolerable range.

I will continue to post on my experience, and maybe even a semi-scholarly exposition on bendamustine since I have a week and a half off from my job with the Christmas holidays...

Forget the Revlimid, pass me the Treanda with a side of Rituxan...

Thought I'd update you on where I am at with my CLL. Sadly it has advanced rapidly. Not just a big increase in node size but my bone marrow is involved with the cells to the point where my peripheral WBC is at 56K and I have low red cells and platelets. I have to wonder about my bad luck because you may recall I could not qualify for a great trial with the up and coming oral med, Revlimid,  in the spring because my nodes were not big enough. This time as my nodes increased and the leukemia came back I tried to get in the trial again but I found out this past Wednesday that my platelets were too low to go on the trial! Oh well instead I am to get what we knew was Plan B (but could just as easily been Plan A) - a well established chemo drug called Treanda along with the usual monoclonal antibody Rituximab. (a similar cocktail-- Fludarabine/Rituxan-- has worked well twice in the last 5 years, we are just switching out the chemo drug). I will get 28 day cycles up to 6, starting next week. So I have high hopes...


Instead of posting a semi-scholarly review of Revlimid in CLL (I had downloaded almost 20 articles covering clinical trial results and possible mechanisms of action as well as experts view of how Revlimid could fit in to the CLL armamentarium)...look in coming days for a similar analysis of Treanda (bendamustine)