Platelet Numbers Increasing

I've had CLL since October, 1998. I 'celebrated' my anniversary this last October by doing nothing, since being diagnosed with a terrible, incurable disease which will likely take my life is nothing to celebrate. Curse, maybe, but not celebrate.

As my rare reader probably knows, I started on a phase II clinical trial of Alvocidib (flavopiridol) in late July. I'm a bit more than half-way through the trial, which, if I make it that far, will last nine months and end in the latter part of March, 2010. (An aside: I wonder if this change in the year will FINALLY cause people to stop saying the year in the most ridiculous manner possible, i.e. two thousand and nine instead of the proper, twenty-oh-nine. Correct me if I'm wrong, but did we say, for example, 1998 as one thousand, nine hundred and ninety eight? I don't think so...)

I get a weekly blood draw; when I'm in San Diego, it's through my port, when on my infrequent trial holidays, it's through the veins in my arm here in Sacramento. I noted a trend about a month ago that my platelets were up a bit. I've been running below normal in my platelets since about 2003. Nothing major, but they've oscillated up and down between 55 and 95, usually hanging out around 70-80. My count on October 9, 2009, for example, was 82. This is not a dangerous place to be, but I don't go skydiving or race cars as I don't what a subdural bleed. No siree!

The last three blood tests in November, the last two done here in Sacramento, show the improvement continues. My 11-12 test shows my platelets were at 95. On 11-18, they topped 100 for the first time in many years at 101. My November 25 blood draw had the platelet numbers at 134, the first time it has been in the normal range, as I've said, in many years.

I can only guess this is the doing of the flavopiridol. None of the other treatments that I can recall worked so well on platelets.

Obviously, I'm pleased.

And while this happy situation won't last forever, and my number will likely slink back to the less happy situation of low platelets and increasing tumor burden, today, I will make the most of it. I was thinking that I don't have to have any real worries about shaving, getting cut, having nosebleeds, bleeding profusely at the slightest nick, and so on. I might even take a fish oil tablet for the heck of it, since heart disease runs in the family, and I now have enough platelets to clog an artery or two.

The other numbers are still in the abnormal range, though the hemoglobin has been above 10.0 for over quite a while, at least out of the danger range for well over a year (I've had to have blood transfusions on a number of occasions - thank you blood donors!!!).

So the platelet counts are fab, and I'm thankful for that. I still have CLL cells everywhere, but they have been beaten back for the time being. And in spite of those bureaucrats, especially in socialized medicine England, who say six months of extra life if just no big deal, I will tell you that my decent health since I've started flavopiridol is priceless to me.

Cholesterol and CLL-How's it Going?

My one reader will remember that I've decided to postpone killing CLL cells by dying. One thing to do this is to deny the cells the means with which to grow. Cholesterol levels are dysregulated by CLL, possibly because the rapid growth of the clone (that is, the CLL cells) require cholesterol to form the cells themselves. That is one theory, at least.

Believing that reducing cholesterol in my diet and reducing it further by adding a bit of fiber to my diet probably won't hurt me, I embarked about a month ago on a fiber-added diet. I must report that the results of my little experiment is inconclusive at best.

One of the 'problems' is that, at the present time, my WBC is quite low, below even the normal range due to my recent bad experience with FCR (fludarabine, cyclophosphamide, and rituximab) for my CLL. So I can't report a huge drop in the WBC numbers. I can look at the ratio of neutrophils to lymphocytes (the two largest components of the white blood count). It has bounced around, but still shows too many lymphocytes. The ratio has not changed for the better.

So, I am not bouyed by these results. I will continue to add a teaspoon a day to my diet, because I probably don't get enough fiber as it is, and adding a bit won't hurt. Didn't seem to help, don't think will hurt.

I'm thinking on embarking on a different CLL journey in the near future; alternating EGCG with curcumin. A recent paper shows that the combination seems to work better than either does alone.

More later.

Vitamin Might Help Boost Neutrophil Counts

Anybody seen this one? This is an interesting idea. I tried reading the abstract of the paper itself and I must say I would not have drawn this conclusion, but I didn't read the full paper, so...

Niacinamide is a form of vitamin B3, and is generally found to be safe even in relatively high doses. Caution is called for, though. It's a good idea to check with the doc regarding the use of this or any other supplement. Also, the increase in counts is temporary (darn!). It may help us be safer from infections, though.

I hope there are more studies in this area. Neutropenia is a serious problem that (obviously) can kill.

The doses cited in the paper work out to between 750-1500 mg for a 165 pound man. The RDA is only 16 mg, so this qualifies as more medicine than supplementation. Also, niacin, the other common form of vitamin B3, has been linked to the growth of new blood vessels in the tumor. Tumors can't grow past a certain point without vascular support. This is true even in CLL, since lymph nodes need new blood vessels to grow, and increase microvascularization in the marrow has been linke to CLL progression.

Any comments?

**************
Vitamin B3 Fuels Neutrophil Production 2/23/2009

As the first line of defense against invading microbes, neutrophils
are the “foot soldiers” of the innate immune system. Upon release
from the bone marrow, neutrophils circulate in the blood for only a
few hours before homing to peripheral tissues where they survive at
most for 2 or 3 days. To keep up with the heavy demand for these
short-lived cells, a normal healthy adult produces approximately 10 to the 11th power
neutrophils each day and up to 10 times that number in the setting of
acute infection.

Cancer patients undergoing chemotherapy often experience disruptions
in neutrophil homeostasis, which places them at increased risk for
infection. The ability to boost neutrophil production with
recombinant granulocyte colony stimulating factor (G-CSF) has
revolutionized care for patients with chemotherapy-induced febrile (fever)
neutropenia. However, the molecular mechanism by which G-CSF induces
myeloid differentiation remains poorly understood.

A team of researchers at Hannover Medical School in Germany recently
reported a major breakthrough in neutrophil development that may have
important clinical implications. Upon binding to its receptor on the
surface of myeloid progenitor cells, G-CSF turns on an enzyme that
converts intracellular vitamin B3 (nicotinamide) into an activate
metabolite (nicotinamide monocleotide). The researchers found that
this is the rate-limiting step in a signal transduction pathway that
triggers granulopoiesis.

Addition of vitamin B3 or its precursor induced granulocyte
differentiation of cultured hematopoietic stem cells. Administration
of high doses (10-20mg/kg/day) of vitamin B3 to six healthy
individuals resulted in significant increases in neutrophil count over
a 7 day period and a return to physiological cell counts when vitamin
B3 was withdrawn.

These findings identify a new role for vitamin B3 in granulopoiesis
and beg for clinical trials to evaluate the use of vitamin B3 either
alone or in combination with G-CSF for the treatment of neutropenia.

Source

Skokowa J, Lan D, Thakur BK, et al. NAMPT is essential for the
G-CSF-induced myeloid differentiation via a NAD+-sirtuin-1-dependent
pathway. Nat Med. 2009;15(2):151-158.

Still Waiting

I'm waiting for approval of my MRI imaging studies before I can enter the FCR+lumiliximab trial at UC Davis. The trial coordinator is Dr. Tuscano, who was nice enough to speak before the Sacramento CLL patient's group in 2006. He has been working on his own antibody, but I've not heard whether anything will come of it. It looks to be a less than rousing success, but the delays may be due to funding or other administrative problem.

So I'm in a holding pattern, in more ways than one.

One development is that I'm going down to UCSD to see either Dr. Kipps or Dr. Castro. We will see what is happening with my run-away CLL. I am less than happy with the skyrocketing counts that are not, so far, really apparent except in my large abdominal nodes. I don't feel any changes, still working full time and in the evenings seven days a week. Haven't been back in the mountains since I'm now anemic and I don't want to give myself a heart attack by hiking. Energy level has been dropping, but I'm sleeping fairly normally.

Lumiliximab is a CD23 antibody. CD23 is not expected to be a slam-bang MoAB like rituximab for the simple reason it doesn't seem to has as much killing power.

The most recent study and the reason I think Dr. Kipps has recommended this study to me is that the complete remission rate is almost 50% in previously treated patients, which is a very good result. Overall response rate is 95%.

There are two arms to the study, and you don't know what you are getting into before you sign up. You do know once the treatment is underway, so I will get at least one FCR course if I am accepted into the trial. I have more negatives (low platelets, etc.) than I did before trial number one and two. The more things wrong you have with you, the less likely they will choose you to be in their sample. They do want a success, and some folks have been accused of 'cherry-picking' patients that they think will do well for a particular trial.

It's such a game; a game with deadly consequences for the patient, at least.

I saw an oncologist at UC Davis regarding the FCR+Lumiliximab trial (a word she cannot pronounce accurately). This is the same trial which was offered (recommended?) to me by Dr. Kipps. However, Dr. Hamblin calls this trial just a 'marketing scheme,' a phrase that I don't understand. I'll have to write him and ask him to explain.

I don't want to use fludarabine, of course, since it is linked to significant T cell suppression, secondary malignancies, premature death and a whole host of other problems. Once you are refractory to fludarabine (and you will become refractory), then they are no real options left for you; make sure your affairs are in order!

I was more interested in the lumiliximab trial (which is a randomized phase II trial, somewhat rare) as offered by UCD over that of UCSD, since the trial at UCD offers the option of MRIs instead of CT scans. Funny that the same company would have different protocols for different institutions. I did e-mail the company complaining that MRIs would be just as effective as CT scans at tracking the disease. The company MD who replied to me said it would be up to the trial administrator. However, the written protocol is different for the two institutions.

I'll keep this blog posted as to what happens.

Vacation from CLL

I last saw Dr. Kipps on June 19, 2008. I cancelled the July 3 appointment with Dr. Castro because it relates to the ISG-35 internode injection trial which I failed in late May. (I went from 30k to 60k in three weeks. Bummer.)

I've had several major issues with my wife. She has asthma and the hot and smoky weather in Sacramento (we always have very hot Julys, but not smoky ones) has affected her in a major way. I've shifted my focus from my CLL to her asthma.

So, the last week, I've been feeling so good I decided to cancel the July 24 appointment with Dr. Castro (also on the failed clinical trial. I thought blood work here in Sacramento would give them a picture of what is going on with me, without having to fly down to San Diego, and spending the full day down there. I hate that!

I decided I would take a slight vacation from my CLL, in a way. I thought I would take the last week and one-half, and just not think about my CLL or any other medical problems.

I got a blood draw on Monday. I'm hoping the WBC is still low, and all of the other numbers continue to be stable.

I went for a hike on Sunday and did extremely well, felt fine, and thought about doing a long hike in September or so, if I can get in appropriate condition. I was worried about anemia as I had a night of blood pounding in my ear (see Dave's blog; he found it was associated with autoimmune hemolytic anemia), but I did fine and felt wonderful. I don't think I have significant anemia, if I have any at all.

It is nice to not have to think about CLL for a week and a half.