The Ups and Downs of Gene Therapy

I saw Dr. Kipps on June 19, 2008. I had an excellent week the week of June 7th. I had lots of energy and got a lot done. Not quite as good this past week, but not bad.

My WBC has unexpectedly taken a turn down, which of course is good. I don't have the exact numbers, but they were up around 60,000, and have now dropped down to the 30,000 range. This is a pretty good drop. Dr. Kipps says that isn't unexpected after the gene therapy, and even after the counts have gone up the past three weeks.

To re-cap, I had the ISF35, inter-nodal injection on May 5th. I was very sick, but recovered fairly well after a couple of days, though I waited until May 12 to go back to work to be on the safe side. My counts dropped very nicely the next two weeks, but started heading upwards the third week, so I was off the trial (though there were no other treatments scheduled anyway, since this was a one-shot deal). The next appointment in early June saw my counts go up even higher. So, we started talking about FCR or FCR+lumiliximab (CD23 antibody). However, by June 19th, the counts dropped. So, there may have been a somewhat delayed action of my immune system? No one knows.

I found out that there is a FCR+L trial in Sacramento at UC Davis, through Dr. Tuscano. It would certainly be much nicer not to have to travel to San Diego and spend the money on flights and hotel rooms, instead staying here in SacTown. I did have an appointment with UC Davis on Monday, June 23 to check into the trial. I'm not sure exactly what to do right now.

I'm thinking of having another CBC (complete blood count) to see where my WBC are now. I must say that my nodes in my abdomen aren't shrinking, and this is an area of proliferation. I suppose a bone marrow biopsy would be a good idea to see what is going on as well. The danger is waiting too long for treatment; the danger is also treating if another treatment is still working, and doing something that isn't necessary right now.

However, Drs. Kipps, Castro and Weirda all think FCR or FCR+L are probably a good idea right now.

And then there is the problem with the huge radiation dose from multiple CT scans; of the neck, thorax, and abdomen. It is about 500 times the background radiation. Of course, with my probably limited lifespan, it may be that I just won't have time for a new cancer to begin. However, it still is of concern to me, if for no other reason than an MRI would be just as good.

So, we are in limbo now.

On a personal note, I noticed one of our dogs had a cyst-like lump on his side that was bleeding. This was on Thursday. We arranged for surgery yesterday, Friday. Sparky is out of surgery and doing well this Saturday. If he holds, we will bring him home tonight. Poor guy is an older gentleman of about 15. He is a funny dog who loves to be with the family.

A hot day in Sacramento, and I'm cranky

I get cranky and out-of-sorts when it gets above 100. The A/C is out at work (they swear it is working (sigh) but I've attached a thin piece of paper to the vent, and this paper moves like crazy when air is coming out. The paper is dead, not moving. There is no A/C) so I've been hot all day. I got a lot of work done today, but once I got to the shop this evening, working out in the garage, it's been terrible.

I go to San Diego to see Kipps tomorrow. He's been out of town doing the presentation and hob-knobbing bit again, so he is doubling up on clinic days. I'm sure he is tired from his trip and seeing so many patients. His patient load is growing more and more, I think.

For the first time, I'm worried about my treatment. I've failed two treatments so far, and the FCR plus lumiliximab just seems dangerous to me. This is real chemo with nasty drugs that cause mutations in normal and CLL cells.

I don't have anything to base this on, but I'm usually accurate in my prognostic dreams and feelings. I'm not happy about feeling worried. But I suppose I have to do something for my growing CLL problem, and they don't have anything good to offer me. We are down to the second and third tier drugs that have major side effects.

And, Dr. Castro two weeks ago said I should be thinking of moving to a transplant. Dr. Weirda just about promised me three years of remission with FCR, but obviously UCSD doesn't think I'll last that long.

Worrisome. But we all die sometime. I'm having that lesson drummed into me like there is no tomorrow (bad choice of words?).

What Will Be My Next Step?

We are weighing the merits of my next treatment. I've failed two so far, meaning my CLL cells are quite resistant to treatment.

My plan at the beginning was to use less toxic treatments with the idea that this would preserve my immune system as long as possible, and save the more powerful treatments for when I needed them. The downside to this approach is that mild treatments won't give a long remission, and meanwhile the clone is more and more unstable, leading to a complex karyotype, meaning a mixture of more and more chromosomal abnormalities, i.e. 6q del, 11q del and perhaps a mixture of even more abnormalitites.

This can make treatment more difficult.

The positive news is that I have not had any more real problems, I continue to work, I've not come down with any additional infections, and I've gotten permission at work to move to a more isolated part of the building, where I will come into contact with fewer sick people. This is one strategy I am attempting to prolong a healthy life.

I have an appointment June 6th to consider my next move. Dr. Kipps says he does not want me to get into an emergency situation with my growing abdominal nodes, perhaps requiring intervention here in Sacramento.

An update

I've been getting slightly worse as time goes on :(

I finally succeeded in getting into the Ad-ISF35 gene therapy trial offered through UC San Diego. Dr. Castro is the principal investigator.

I had a rough time of it during the aftermath of the injection process. I had significant chills and vomited three times during the night and the next morning. I would recommend not eating lunch and dinner the day of the injection. According to staff, you will be sick.

My results were good for about a week! Two weeks after the trial, I noticed all of my nodes were down about 1/2, and my terrible abdominal nodes seemed to be smaller, to the point I was actually thinking of going back down a couple of waist sizes.

Unfortunately, that was not to last. At this point, three weeks after my trials and tribulations, my nodes have returned to pre-treatment levels, and I've grown a new, large node at the mid-line of my abdomen. This is proving to be very painful and troublesome. I am worried at this point about abdominal obstruction. I've been taking medication to make sure I don't get constipated.

At this point, I'm not sure what I will be doing. I am a bit worried about Richter's transformation. It is more common in patients with 11q del (me), large abdominal nodes (me) and increases with length of time with CLL (me).

I am trying a heating pad morning and evening to try to 'soften' the lymph nodes. Maybe it is helping as I don't feel quite as bad today.

What is the Incidence of Richter's?

Traditional estimates of Richter's transformation range from 1% to 8%. The CLL clone can transform into an acute lymphoma, similar to a diffuse B cell lymphoma. Hodgkin's disease can also arise in CLL patients. Transformation occurs almost exclusively in the unmutated patient.

The DBCL or Hodgkin's can also arise 'de novo', which means it just pops up, and it's unrelated to the CLL cell. In other words, it doesn't transform from the CLL cells, but is a new cancer (secondary malignancy) altogether.

The latest I've read suggest that the incidence can be viewed as an increasing probability as the disease progresses over time. The rate estimated is about one percent per year in unmutated patients. That means if one lives for 10 years with CLL, there is a 10 % change the clone will transform into Richter's.

All of the amazing news coming in CLL is wonderful, but there is little progress in treating Richter's. I'm going to concentrate my charitable giving on Richter's, as the options are poor, and I'm at risk.

'Here Be Dragons'

The 2007 ASH (American Society of Hematology) meeting is currently underway in Atlanta, Georgia. I am all to well aware of this since my researcher-doctor-CLL expert is in the Peach State, I suppose delivering what few items he has learned this year to the rank-and-file hematologist.

CLL remains a terrible mystery and so little is known about the disease.

If there were a map of the CLL terrain, much would be labeled, 'Here Be dragons'.

My RDC (see above) has told me, as I get sicker and sicker, that 'We have to do a better job'. Well, yeah. Since I am most likely doomed by CLL, ya think?

I told him not to be too hard on himself, since there is much blame to spread around, and, well, you know, lifting the curtain on God's mysteries is not easy work.

Test!

Just sending a test post out to see if I can get it published OK.

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Yes, it posted OK! So, now I am a blogger, for good or for ill. I will be posting on my 'journey' battling CLL, chronic lymphocytic leukemia.