PCI-32765 monotherapy Clinical Trial cycle 3, a rock and a HEART place - part 2

[Guest guest]

During Cycle 3 I had to be in a cardiac telemetry ward of a hospital in NY for 8

days to assess and co-ordinate oncologist/cardiologist info prior to catheter

ablation for right atrial flutter. I checked in on Sat. 9/10/11 and made call to

the to get instructions as to whether to continue with PCI given my

situation. Dr. Byrd called from a Buckeye's game to tell me it was OK to suspend

PCI and proceed with Cardiologist game plan. My main concern was over risk of

internal bleeding from advised blood thinning drug verses danger from clot

formation as my heart was clocked at 240bpm in the ER. My platelet count at the

time was 89. This balance of polar risks was to become more acute in the

following days from an unanticipated drop in my RBCs, Hct, Hgb and platelets.

I drove to OSU one day following hospital discharge but Dr. Byrd was away so I

was unable to get his take on what happened. Professional assessment will have

to wait but I will give you my uncredentialed observations and comments as to

what I think I know.

PCI capsules are taken every day and its purpose is to block a key point (BTK)

in a signaling pathway that stimulates the growth and anti-apoptotic properties

of the CLL cells. This blocking has been 100% effective in my case and must be

daily maintained or the cancer resumes its aggressive course. The expectation

was that I was nearing the peak of an observed phenomenon whereby the cancer

cells leave the lymphnodes and bone marrow and actually increases in the

Peripheral Blood (PB). Before taking PCI my WBC was 25k (6/28/11) on 8/23/11 WBC

appeared to peak at 95k with no visible lymphadenopathy and only some barely

palpable nodes in groin and axilla. On 9/10/11 I stopped PCI but was still

" blocked " at time of bloodwork which showed WBC at 78.3k indicating I had

reached the PB peak and the cancer was now diminishing in the PB. Dr. Byrd had

predicted at the beginning of Trial that I might peak at or just over 100k.

Below is a pre-hospitalization CBC lab for reference and the bloodwork during 8

days of hospitalization for atrial flutter and followup CBC from recent OSU

monitoring.

WBC RBC Hgb Hct Platelet Creatinine

OSU Reference 8/23/11 - 95k 3.74 12.0 36.4 105 1.74

1st day NY Hosp. 9/10/11 - 78.3k 3.87 12.4 38.6 89 1.5

9/12/11 - 72.4k 4.27 13.9 42.7 104 1.5

9/13/11 - 38.1k 3.73 12.3 36.6 85 1.5

I resumed taking PCI on the 14th

9/15/11 - 26.9k 2.90 9.4 28.3 63 2.0

At this point I was getting concerned because I was on a heparin (anticoagulant)

drip at the time and had chronic micro hematuria since '09. This looked like a

trend of a rapid drop where I could speculatively attribute the WBC to the

unblocking of the BTK (Bruton's Tyrosine Kinase) but I was puzzled by the red

cell drop that included the platelets. In my mind was the trend of the rising

Creatinine numbers that I tried unsuccessfully to draw the attention of my

doctors in '09 that led to my renal failure event with permanent kidney damage.

On the 15th I had the catheter ablation. Drugs for conscious sedation were

Versed & Fentanyl.

WBC RBC Hgb Hct Platelet Creatinine

9/16/11 - 20k 2.75 9.1 26.6 59 1.6

When I awoke on the 16th I was shaky and demanded to see a doctor to ask for

some reassurance that I was not undergoing Hemolysis. The hospital had no

irradiated blood on hand, had I needed a transfusion (I had been treated in '09

with Fludarabine which requires that irradiated blood be used for such

patients)The doc ordered additional blood labs, at my request, to reflect

bilirubin, haptoglobin and LDH which did not point to a crisis of hemolysis

unfolding. Hgb came up to 10.0 hopefully reflecting a bottoming out of the

trend.

WBC RBC Hgb Hct Platelet Creatinine

9/17/11 - 24.7k 2.87 9.5 27.6 59

OSU monitoring 9/20/11 - 43.7k 3.42 11.3 33.3 89 1.6

Note the fairly rapid increase in WBC as I regained blockage of BTK by

resumption of PCI reflected on 9/17-20/11.

This experience raises some interesting questions regarding the proper

interpretation of what happened. Questions I am asking myself include the

following:

Does the rapid drop of lymphocytes from 9/12/11 to 9/16/11 represent the

consequence of lymphocyte migration back to the lymphnodes and marrow due to

unblocked BTK by not taking PCI for four days?

If that is true, why should that migration reflect a severe drop in RBCs and

platelets?

Does the jump in Creatinine from my baseline of 1.5 to 2.0 coupled with uric

acid levels at high normal reference range indicate lysis of cancer cells

reflected in the drop?

Is the drop in cell counts due in part to my being put on a heparin IV drip and

having frequent blood draws prior to ablation procedure on the 15th?

Although a platelet count of 59 is in itself not critically low, is the drop

predictable for what I went through and if it was, would patients with a plt

baseline of 60 be at high risk for bleeding under a similar scenario?

I was discharged on Sat. and although a bit out of shape I mowed our lawn for

3hrs on Sun and drove to Columbus OH on Mon.

For lessons learned from my hospitalization and what my heart issues may mean

for anyone contemplating PCI treatment, see " Cycle 3 Part 3 "

WWW - Dancing with the Bear is not always a waltz.

[Guest guest]

Wayne, What a journey !! And thanks for your meticulous

documentation.

One factor you haven't mentioned is Mr Spleen. This lay

person wonders, when you see HgB and Platelets going

somewhere if they are not heading to his party, which

without the BTK, may be more accommodating? Wishing you all

the best in your continuing with the PCI trail.

Lynn

Wayne Wells wrote:

> If that is true, why should that migration reflect

> a severe drop in RBCs and platelets?

[Guest guest]

Lynn65,

Good point about the specialized node " Mr. Spleen " . I have

no way to assess what happened and was hoping to see Dr.

Byrd but that must wait. Maybe we will be lucky and get feed

back from generous Docs who help us on the forums.

WWW