Next treatment planned

So, I saw Dr Porter at U Penn this past Friday and found out my marrow was still 95% lymphs, so still in relapse (enlarging nodes also confirm this). Porter was worried that there were few if any normal cell precursors so I may also have drug- induced (from prior chemo) myelodysplasia which would explain my now year-long transfusion dependence. I may indeed be better off with transplant than CAR T-cell therapy since doing CAR with a lousy marrow makes no sense. I do have 2 matches tentatively from unrelated donor search, hooray!

The next treatment to try and clear the leukemia is to be high-dose methylprednisolone, HDMP, (a corticosteroid, NOT compounded in NE, that's for sure ;-) ) along with Rituxan, to start Jan 7, since it's 5 days of HDMP with Rituxan the first day also....should that not clear up CLL in marrow, the next step would be Campath, which may be needed anyway as preliminary consolidation before transplant.

here is link to study on my next treatment, reasonable results if only 30+ % complete remission, perhaps I'll get some good luck in 2013!

Here is a portrait of the blogger's huge nodes in neck (note trying to grow full beard since with low platelets I should keep away from razor.,,)

Not going in the preferred direction, but trying for a positive attitude

So this past weekend I had no energy, and left the residual fallen leaves alone. I just lounged around watching college and pro football, and eating. Found out Monday my Hemoglobin was only 5.7 so got 2 units of packed cells and felt somewhat better. Still with arm pain and am beginning to thnk it may be related to a recent increase (sadly not a decrease....) in the lymph nodes in both axillae (under-arms). I also have a newly enlarged node in my neck on the right. All of these changes have come in about a week, here when I was supposedly improving and on the maintenance phase of my second treatment course in a year. Although my total white blood cell count is still normal these nodes suggest yet another relapse.

Am to get a bone marrow biopsy next week and to see my new oncologist at Penn, Dr Porter the week after. He had mentioned trying another treatment since clearly not completely cleared of leukemia/lymphoma with the ofatumumab course, with high dose steroids and Campath (alemtuzumab) being high on the list. Campth is yet another story that makes pharma look bad, taking it off the market so can sell smaller quantities to patients with MS, but leaving it available for CLL patients on a free, compassionate basis. Hope the U Penn oncos can get the drug for me, even though it has major immunosuppression and is better for marrow disease than nodes, hopefully with high dose steroids I can get some response. I did another search for small molecule TKI clinical trials but they all want a functional marrow which clearly I don't have, being transfusion dependent now for almost a year.....We shall see...

I will be finding out soon I hope if I have a match on the unrelated donor search, for a stem cell transplant. Thing is have to be somewhat clear of disease to even contemplate a transplant.. I tried one last time to reach out to my brother (who matches me) but have had no response, giving up on him....see envelope screen shot below, tried to make it obvious I REALLY needed his help.

 

 



 

It may be getting time for me to get going on a living will and health care proxy stuff....

Four days in hospital for culture-negative febrile neutropenia

My onco and the infectious disease specialist who saw me in hospital think the migratory bone and or muscle pain was part of the illness that reached to a new height last week with fever to 102 and general malaise necessitating hospitalization for the routine IV antibiotics to cover the usual suspects.  Had chest CT again as cough got a bit worse and was productive; it didn't show much different from the last - some nodular peribronchial thickening not pathognomonic (I love this typically high brow med word which means characteristic of ...) of any cause of lung disease or pneumonia.

The fever vanished after the first few hours, the cough got more prominent but not really any different than my usual and my arm pain gradually decreased. Blood cultures were negative, the docs presumed virus (not the flu though as they checked for that) and so went home yesterday.

Have today to rest up, help my wife clean and cook for T-day (her daughter, son-in-law and grandkids coming from upstate NY) maybe even attack the leaves if my pain stays under control ...it is a beautiful day outside....of course it could be miserable weather and still better than being in hospital ...

Marrow still sluggish, need to find out why, and a new wrinkle in my travails

I got my first of 4 monthly planned maintenance Arzerra infusions earlier this week but the week before was crazy. I woke up middle of night Thursday with severe left upper arm pain, and wondered if this was heart attack. But no chest pain and pulse normal so decided to wait it out, it disappeared mostly in several hours, but when awoke in AM had what I thought was bone pain in both upper arms and right leg. Discussed with onco fellow and they thought it was my leukemia acting up, I of course along with a fellow employee/doc also a pediatrician had hopes it bespoke of marrow recovery, similar to how those getting Neupogen for stem cell harvest get bone pain. Pain got worse not responding that well to Tylenol and Tramadol but I went to upstate NY with wife to wedding and to see our granddaughters.  Next day needed a cane to walk as right leg pain was worse and more localized to my knee (which had acted up after treatments before).  I stared my pretreatment steroids (before Arzerra) a bit early to see if helped the knee pain, and there was some effect. Pain in upper arms seemed to be more in the joint also..Had to use platelet-poisoning naproxen or ibuprofen as well to touch the pain, rated as high as 8/10 at times, both drugs which of course could exacerbate bleeding with my usual low platelet count. Very frustrating as the weather was beautiful and I have so many many leaves to rake up around our property but no way I could use a rake or even the tractor pulled lawn sweeper with my pains and aches. Forced to watch college and NFL football in family room on couch all weekend, don't ask how my teams did ;-(

Saw my onco team the Monday AM and with the even higher dose of Decadron the night and morning prior I had no pain in arms or legs or findings on exam...they ran a few tests for arthritis, and had me use oxycodone/acetaminophen rather than an NSAID (to protect my platelets). I had continued pain off and on and decided to keep on Decadron until tests back.  Will talk with them again tomorrow. Is it some kind of inlammatory process in my joints due to disease or treatment? Time will tell I guess.

Saw Dr Porter at U Penn yesterday. I have, after all, been needing both red cells and platelets weekly and he is still thinking my marrow may be bothered by treatment effect (even a myelodysplasia almost) as much as a stubbon to respond leukemia. At least my spleen is down and nodes no bigger and WBC counts were running low until the pretreatment Decadron may have pushed them up (and or the crazy inflammatory thing in my joints).  Porter wants to do another bone marrow test so we scheduled for next month and we will start looking for unrelated donor. If marrow seems unable to recover as leukemic cells continue to be controlled by maintenance Arzerra. I will need a transplant but Porter would rather I get into to the CAR CD19 trial as a preferrence but not if I have a sick marrow.....

Dare I hope that my marrow is recovering?

I ended up needing several platelet and one packed RBC transfusions in the last several weeks, but my counts this week were good enough to skip both until the coming Monday, yay!  My total WBC remains low, only 6K this week, but I did not see the differential. My hemoglobin was good as it usually gets at day 6 after last red cell transfusion - 8.7.   The bottom line here is that I may be experiencing some recovery of my bone marrow, but probably I am jumping the gun. My count early next week will probably show the need for platelets but maybe not RBC.  At any rate I have not seen a platelet count over 20K since May this year, about the time of my last Treanda-Rituxan treatment. If only my marrow would start doing its job, then I could be enrolled in a clinical trial somewhere.....

Of note is that despite getting a unit of platelets the day before the Mohs surgery on my scalp, I bled badly and did not stop until almost an hour of intermittent direct pressure the evening of the surgery. I had to go to a local hospital where they used Surgicel (absorbable plant-derived cellulose pledgets that are hemostatic, learn more) to help stop the bleeding and rechecked my platelet count. It was 14k so I got another unit of platelets. My wife the RN and I were both annoyed that the dermatologists were not more concerned about my bleeding risk and should have aimed to get my plt count higher before the surgery. This is what the US and UK guidelines recommend. I suspect though that the fact I had Mohs surgery near my ear on my face a few months before with a similar starting platelet count (and a day after transfusion) the docs and I were lulled into a false sense of security. Another aspect of this is that once again there is this tendency for docs to allow a doc patient to make his own choices and be on top of all the medical issues, which is clearly not optimal.

Continued hints of progress and one more weekly Arzerra infusion

My last blood count, 2 days ago, showed a total WBC of 3.0K and again platelets of only 14K so got some platelets to hold me over the weekend. My onco decided to go for that last weekly Arzerra so would get the whole course of 7 full doses. I hope the low WBC represents continuing death of bad lymphocytes but of course no doubt also includes significant neutropenia.....

On another note the biopsy of the skin lesion on my scalp showed basal cell cancer so now I have to have my third Mohs surgery in 5 years (see this explanation on MayoClinic.com). One squamous and two basal cell skin cancers. I guess I should have worn hats more when younger...but of course CLL is a risk factor for skin cancer and then my mother suffered horribly from multiple skin cancers. Oh well the CLL in relapse is the real beast I have to deal with.

Going to try to reach out to my brother again re: possible stem cell transplant.

Maybe some progress

So its a quiet sunny warm Saturday morning and as I sit at our kitchen island eating a mid-morning snack after a walk in the Wharton State Forest behind our house with our 4 dogs and Cynthia,  I decided to go online and update this blog.

My total WBC count was up a bit this week, around 10 but this week I only needed platelets as my hemoglobin stayed above 8. On Monday I got my 6th dose of ofatumumab as an outpatient without any reaction and so this coming Monday (Columbus Day, an actual holiday at work!) I get my last (#7) of weekly doses of ofa.  I did bring up the fact I had a two week hiatus due to the leg infection and only about a quarter of the first (because of wheezing and shakes during attempted outpatient infusion)  full 2000 mg of ofa so if my onco thinks it is worth it and the insurance company approves perhaps I could get an 8th weekly infusion of ofa; we shall see. ...

I see Porter again in mid November, after I get my first of monthly ofa, most likely.  One can hope that by that time there will be some evidence of marrow recovery.

Maybe some progress, but still don't know about marrow

Some good news, maybe. I saw Dr Porter at U Penn 10 days ago (have been remiss with timely posting).  He thought my spleen was smaller, in fact hard to palpate and that some of my nodes were smaller. These findings along with a total WBC count of 7.3 led him to believe I was responding to ofatumumab. 

On the other hand, my ongoing transfusion requirement (including the need for both platelets and red cells the next day after visit) are concerning. Dr Porter (and I) are worried about marrow dysplasia as a consequence of the fludarabine X3 and bendamustine. Copy of my records given to the Penn team showed my last bone marrow cytogenetics to be a bit screwy - a 13q- deletion (which is said to be good prognostic sign if present early and by itself but sadly I had other abnormalities including several cell lines with an extra X chromosome!  Porter thought this was evidence for possible marrow damage and that he would like to do another marrow exam once off weekly ofatumumab to see how the marrow looks with some (hopefully!) control of leukemia. We shall see.

I continue to need weekly RBC transfusions and often biweekly platelets. My total WBC count was down to 5.4 three days ago, so my leukemia seems to continue to respond. Since I had two in-hospital ofatumumab infusions without reaction, my onco group is going to try to do the last two weekly infusions as an outpatient, with the next treatment in two days....crossing fingers, etc.

Finally got through an Arzerra infusion without reaction! And some musings on medical rationing...

So last Friday I was once again admitted for my ofatumumab infusion but fortunately this time around I had no reaction, and left the hospital about 8:30 PM for home.  I did not need any platelets or RBCs either since I had been transfused on last admission with RBC a week ago and platelets 2 days prior. But total WBC was 33.4K and I had only 3% neutrophils. It should be noted that my WBC count a week ago, also after whopping loading dose of dexamethasone (known to increase WBC) was 79.9K so maybe my marrow is starting to respond. Next count is tomorrow so we'll see. Am to visit Dr Porter at Penn for followup in 2 days. 

The cellulitis on left leg is finally healing so looks like I won't need a skin graft. What we thought was dead tissue was probably just a lot of blood under the skin because of my low platelets.

Anyway, onward and upward.....I posted a link to an interesting NYT editorial Beyond Obamacare on Facebook and will share here as well. It is all about the need to ration limited resources in the Medicare age group. I believe it is true but at the same time the need to control costs may directly affect those of us with CLL lucky to get to Medicare age. 

Here is what I wrote on FB about this:

Rationing is inevitable, we should do it rationally, taking a page from UK NICE, and using QALY of around $50K as yardstick - I may be shooting myself in the foot with this,as my leukemia may require quite expensive treatment in the years to come....I am currently in the middle of a 12-infusion course of a second generation monoclonal Ab, which reportedly costs $9K for each infusion....If I can get 2 years remission with this, would meet the NICE criteria....

Wishful thinking re a long remission? Perhaps, since I got very little long-term response from Bendamustine-Rituximab....time will tell. I know that a clinical trial somewhere is in my future.... 

Home from hospital. long road ahead....

I went home 2 days ago (in August) as the infectious disease docs thought with negative cultures including fungal that I had had enough IV antibiotics but with my alterred immune system would need another 10 days of oral antibiotics. Still with much pain when standing or walking, but no significant spread of inflammation at least of the skin area involved.Only a bit of redness at the edges. The central necrotic (dead) area has not increased and I noted a bit of discharge after a shower yesterday.

Two days before going home I finally understood why my leg hurts so much, an MRI showed "Inflammation and fluid collection in the subcutaneous tissues and posterior muscles in lower leg consistent with clinically suspected cellulits and myositis."  That was the first time the involvelment of calf muscles ie myositis was used. Not sure if my treatment team had suspected.that but they did note calf pain, previously having ruled out a deep vein thrombosis with an ultrasound.

I am to see my onco in 2 more days, and infectious disease in 1-2 weeks.  They held my Arzerra treatment again because, I think, I had continued neutropenia and the lesion basically blossomed after my last Arzerra treatment. I had my laptop in hosptial so did a PubMed search for necrotic cellulits and myositis due to Arzerra or Rituxan, and found nothing. So final working diagnosiss is cellulitis/myosits probably bacterial and secondary to inital trauma of unknown etiology.along with neutropenia.

I was distressed to hear from one of the nurses in casual conversaton that my primary onco, Dr T, is not at Hahnemann except rarely and is instead at a Cancer Treatment Center of America hospital in North Philly. I was never told this and along with not knowing I had neutropenai the week before admission I have decided to transfer all my onco care to U Penn even in the middle of this damn leg infection and the courses of Arzerra. I sent an email to the intake nurse asking to be plugged in there. We shall see.

Warning: I am going to show how bad my leg is but to spare those who don't want to bring up a recent meal, I'll start with a few silly photos....


Me on third day in hospital and whopping steroid dose in anticipation of gettng Arzerra (later canceled though) - corticosteroid euphoria:

 

A little help with the small bit of work I did while in hospital (note the Phanatuc was gift from one of the teams I work with...and the laptop was "kindly" brought to me by my fellow editors, so I could finish a project

 

 

 

 

 

AND NOW MY VERY DISGUSTING LOOKING LEG:

 

A curveball just out of reach...or delayed treatment due to bizarre leg infection

So now I am here in hospital, day 8 to  be exact.  A few days before Arzerra infusion #3 I had noted a a non-tender area of redness and thickened skin with a dark scab in center about dime sized on my left ankle. Walking about my property or in the woods, in shorts and sometimes with no socks, I figured it was a bug bite or a scratch from a thorn from the brambles that abound. I did not show my onco because it did not hurt or itch and I figured it was slow to heal...a day after Arzerra #3 the area got bigger, redder and began to hurt. I waited until 2 days later to show to onco since was there for follow-up CBC. Since I had no fever it was decided to try to treat this presumed cellulitis with amoxicillin-clav (Augmentin). I did not realize at the time that I was neutropenic (but my oncol did, thankfully) but in retrospect I guess a trial of oral meds still would have made sense Note that since I live in deer tick area and have had acute Lyme twice, this was one of the reasons for using amox-clav which would cover Lyme. My doc was worried about whether I should get my next Arzerra and scheduled an infectious disease consult for 2 days later. The sore area increased with more pain, particularly while walking and when I saw the ID doc he recommended admission for IV antibiotics.

Over the last week I have received antibiotics to cover MRSA, Pseudomonas and even Lyme (titers pending). The area of redness spread and the central dark area (necrotic tissue) enlarged. A skin biopsy was done and fungal cultures, nothing found yet. I have had packed RBC twuce and platelets 3 times. Needless to say the Arzerra was held.

Today for the first time the redness seems less and I can walk flat footed as opposed to on my toes. Still with pain but less, I think. Some studies still pending including Lyme titer and specail stains of fhe skin biopsy for weird bacteria like atypical mycobacteria. Going to get an MRI of the area to rule out bone involveent and or abcess underlying, hopefully today (maybe should hav done sooner but I am second guessing my docs here...)

So the best scenario for me is if continutes to improve and can get my Arzerra in a few days. My spleen is much smaller as are nodes in underarm area and total WBC is less than 5K.... so may have started to respond.

"Well now life throws us curve balls we never can reach" -- Jimmy Buffett

Third Arzerra infusion went OK, sort of..and other concerns

I was admitted to hospital last Friday so could get the whole 2,000 mg of ofatumumab if rate had to be slowed due to reaction.  My onco had me take the equivalent of 20 mg of dexamethasone (~130 mg of prednisone) the night before, which along with another loading dose of same and Benadryl we had hoped to avoid another infusion reaction. Unfortunately I did have a cough and wheeze reaction at 100 cc/hr (half the max rate) so we dialed the rate back and slowly worked up again to 100 cc/hr, but no higher as I was resigned to staying overnight. So, at 3:30 AM the infusion was complete. I got a unit of platelets as my count was 5K again, but my hemoglobin on admission was 9.5 (3 days past transfusion). My total WBC was in the 80K range which was disappointing but I was reassured that may have been due to the steroid load....

So far no lymph node decrease that I can tell but am trying to tell myself my spleen seems less palpable. Three days after the hospital stay my counts were as follows total WBC 20K, Hgb 7.5 and plts 7K. Only got platelets yesterday.

Two new issues, of concern:

• What I thought was an insect bite on my ankle slow to heal has gotten necrotic looking with some surrounding redness and increasing pain. My onco was alarmed, started me on amoxicillin-clavulinate and am to see an infectioius disease specailist tomorrow as it could be something more exotic - atypical Lyme perhaps? Have had before with a necrotic looking skin lesion rather than the typical halo appearance. Many deer ticks in the woods where and I walked the dogs in the woods almost daily this past week. Having had Lyme X 2-3 and anaplasmosis, I am very careful to check for ticks. Since one sees far fewer in the heat and humidity of July and August, I may have let my guard down. ..so far 24 hours on the antibiotic there has been no spread but it sure is painful. If something exotic or worrisome, my onco may hold my Arzerra this week, again to be given in hosptial...
• Yesterday in the onco office my weight was only 159 lb, which is the lowest its been.. I weighed myself clothed only in birthday suit  this AM and was only 153, which is about right - shoes and clothes usually weigh about 6 lb....I guess I really do have signiificant muscle wasting - cancer cachexia, as it were - and don't know if increasing calories may help. I may try the Ensure Muscle Health shakes and if I can get feeling just a bit better, ie less need for RBC transfusion may do some light weight lifitng (dumb-bells no more than 20 ob apiece)

Oh well the games go on...I am not going to feel too sorry for myself especially since I just heard a friend with lung cancer has brain mets.....

A glimmer of progress, and more on U Penn-Novartis partnership

So today I came in for a scheduled RBC transufusion, as my Hgb was 7.7 last Friday when got my second ofatumumab dose. I expected to also need platelets again especially since have had an ongoing bloody nose...got both and was delighted to hear my total WBC was down to 18.7, presumably due to the partial dose of Arzerra I recieved last week.

There was an expanded story on the U Penn partnership with Novartis in the Daily Pennsylvanian, the college newspaper.

Some excerpts thereof:

The first steps in the Penn-Novartis collaboration involve a focus on developing cell production facilities, bringing to Penn the first Center for Advanced Cellular Therapies. This new building will allow researchers to develop and manufacture chimeric antigen receptor technology for the treatment of cancer, according to Novartis’ press release. Research collaborations will also begin during the first year

The construction of new cancer research facilities at Penn will allow for the expansion of the number of patients who can be treated. “Because the clinical results were so striking, Penn had more than 5,000 patients or families contacting us wanting to enroll on clinical trials,” said Bruce Levine, a professor of pathology and laboratory medicine at the medical school

Not hard to believe since CLL is most common  adult leukemia, and justifies my prior skepticism about getting into that trial, even though the patient profiled in New England Journal article sounds a lot like me (except for the 17p deletion part, so far not applicable to me)

The patient received a diagnosis of stage I CLL in 1996. He first required treatment after 6 years of observation for progressive leukocytosis and adenopathy. In 2002, he was treated with two cycles of rituximab plus fludarabine; this treatment resulted in normalization of blood counts and partial resolution of adenopathy. In 2006, he received four cycles of rituximab and fludarabine for disease progression, again with normalization of blood counts and partial regression of adenopathy. This response was followed by a 20-month progression-free interval and a 2-year treatment-free interval. In February 2009, he had rapidly progressive leukocytosis and recurrent adenopathy. His bone marrow was extensively infiltrated with CLL. Cytogenetic analysis showed that 3 of 15 cells contained a deletion of chromosome 17p, and fluorescence in situ hybridization (FISH) testing showed that 170 of 200 cells had a deletion involving TP53 on chromosome 17p. He received rituximab with bendamustine for one cycle and three additional cycles of bendamustine without rituximab (because of a severe allergic reaction). This treatment resulted in only transient improvement in lymphocytosis. Progressive adenopathy was documented by means of computed tomography (CT) after therapy.

 Now however with this new push, many more patients could be studied, hopefully to include moi!

 

Second ofatumumab treatment

So this past Friday I had my second infusion of ofatumumab (Arzerra), this time a total dose of 2000 mg was to be given by the same slowly increasing rates, this time in the onco office. I had gotten through the 300 mg dose last week without reaction but was not so lucky this time,  about 3-4 hours into the protocol I got feeling weird with some shivering, after I had sweated profusely. The infusion was stopped, I was given more Decadron. My doc elected to send me downstairs to get platelets as once again the count was only 7K. (no RBC since did not have much time and Hgb 7.7) The only good news on my counts was that the WBC fell to 40K from 80K the week prior, presumably in response to the first albeit low dose of ofatumumab.  After getting the platelets I went back upstaris for an attemtpt to get more of the infusion, but had a sweating reaction again and they had to stop again. I probably did not get even a third of the total dose so the plans for next week are do the infusion in the hospital so can get even if takes all night...and if I need blood cells can also get. As much as I hate the idea of staying in hospital I need to get the full dose of Arzerra to get any benefit.....

Novartis to partner with Penn in development of chimeric antibody T-cell program

Exciting news yesterday:
Novartis and Penn enter into multi-year collaboration to study chimeric antigen receptor (CAR) technology for the treatment of cancer!

Here is one of the news stories from NJ newspaper.And another from a pharma news site.

See my prior post on my own visit to Penn to see if I may benefit from this therapy.

What is exciting here, as Dr Sharman points out in his new CLL and Lymphoma Blog, is that this partnership may increase access to this potentially curative therapy, not only in terms of clinical trials, as the 10 patients or so who have undergone this therapy were in a privately funded pilot study, but also to mainstream if the technique continues to be useful and is licensed by the FDA.

We can only hope this approach pans out. Some potential drawbacks are noted by Sharman and also in a post on CLLTopics, highly recommended because this therapy is not without its downside...

Started Arzerra!

To update my situation up to yesterday:

• Bone marrow: packed with small lymphocytes, no sign of Richter's
• PET scan many lymph nodes, no sign of activity suggestive of Richter's
• quite enlarged spleen, easily palpable by even myself, as well as increasing axillary nodes
• whew!
• ongoing need for platelet transfusion once weekly, at least made it 2 weeks between RBC

So from the 2 or 3 options  for treatment my onco team picked Arzerra (ofatumumab) in part because I have already had rituximab 3 times and Campath not so good for nodal disease and has significant immune suppression...

Got the first dose, in slowly increasing amounts by infusion, to total 300 mg, in hospital yesterday. Because of a high rate of infusion reactions, my oncos wanted to do as inpatient. It went well, no reaction, since they load you with steroids, antihistamines and acetaminophen. The problem was the inherent inefficiency in hospital, I arrived at direct admission office at 9, got to the floor, IV in place at 10 AM but did not get premeds until about 1:30 and Arzerra started about 2:30, and finally done at 10PM. Felt good though and elected to go home by my usual train/bus combo, enjoying the exuberance of youth, first the disgruntled Phils fans on the train (another story there, they are having a sucky year), and about 40 teenagers coming from a concert in Camden jammed on the bus. I knew where to stand so got the first seat up front, so could get off easily, home by 12:30, slept like a baby.

Next week dose of Arzerra is 2000mg and I will bend over backward to arrange as outpatient, which since I had no reaction, should be able to convince my oncologists.

Although I had blood work on admission, I forgot to ask for results -- I had profuse bleeding from IV site on removal last night requiring a pressure dressing but no problems today. Since have been requiring platelets once weekly, I will go on Monday and get another count.

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.....