Cycle 2, Day 14

PERSONAL MESSAGE

It has taken me three years to finally cry. Believe me, I don’t cry easily. I was afraid to cry before, because I was worried that I would never be able to stop. Now finally something is being done to help me and I am so relieved. I am not good at doing nothing and sitting idly by. These tears are tears of hope.

My friend George asked me what it means when I wrote that I am a person of faith. I told him that I try every day to live my life so that my actions are loving and they speak louder than my words. It doesn’t always work out that way, but I keep trying. Perhaps this quote sums it up better than I can:

“Love the Lord your God with all your heart and with all your soul and with all your mind. This is the first and greatest commandment. And the second is like it: Love your neighbor as yourself.” (Matthew 22:37-39).

And what does this have to do with leukemia? Everything. My faith is my foundation. It is what keeps me grounded in this crazy world with this stupid cancer diagnosis. My faith also makes me accountable. I am reminded of the words of Mahatma Gandhi:

“I like your Christ, I do not like your Christians. Your Christians are so unlike your Christ.”

There is truth to that. So this is something I need to work on every day.

08-22-2012 BLOODWORK (Cycle 2, Day 14)

My bloodwork from August 24^th – two weeks after the 135,000 white blood cell count – shows a decrease to 114,300. This is about two weeks earlier than the average time in the study. Usually it isn’t until Cycle 3 that this occurs. This means that if all goes well, I am on the downhill slide of getting rid of the malignant B-cells that have been targeted by the Ibrutinib. In two weeks my body has gotten rid of about 20,000 B-cells. When you consider that a normal person only has 3,000 to 10,000 B-cells total in their blood, that is pretty amazing.

My lymphocyte count is still high. Lymphocytes, as you recall, are a type of white blood cell in the immune system.

My I-Bili (Indirect Bilirubin) is slightly elevated at 0.7, when it should be 0-0.6 mg/dL. This has to do with liver function.

My monocyte count is 1% and it should be between 2-8%. The low monocyte count is a side effect of illnesses of the bone marrow. This often also indicates deficiencies in vitamins such as folates and B-12. I am still getting my B-12 shot every month and taking those pink vitamins every day. Maybe that is why I at least have 1%.

My segmented Neuts are low. They are 5% when they should be 45-75%. Neutrophils are produced in bone marrow and are the body's primary defense against bacterial infection and physiologic stress.

My red blood count is normal.

My blood glucose level is normal. That is the amount of sugar present in my blood.

My platelet count is 156 (normal range 130-400). When the number of platelets is too low, that means that you will bleed easily. If it is too high, blood clots resulting in a stroke can occur.

The only side effect I have been having is a little dizziness when I wake up in the morning, look up, or move my head suddenly. I close my eyes, hang on to something, and breathe slowly. It goes away quickly, unlike my vertigo episodes. It is very minor in comparison.

ON A GOOD NOTE

Dr. Farooqui and Dr. Wiestner are having me work on an infographic illustrating how this magical drug works. This was my suggestion, mainly because I want to understand this process better, and many participants and their families also want to be better informed. It is a work in progress, because the experts are just now finding out the details of how Ibrutinib works.

Finishing Cycle 1 and on to Cycle 2

I just completed Cycle 1 of my experimental treatment at NIH and “donating” 12 tubes of blood. My white blood count has increased from 69K on Day 1 to 135K on Day 28. One more cycle of climbing – dumping those bad boys from my lymph nodes into my blood – and then I will brace myself for the decent to a normal range, which is 4,500-10,000 white blood cells per microliter (mcL).

Hemoglobin has remained steady at 13. The average for adult women is 12 to 16 gm/dL. Low hemoglobin level means a low red blood count or anemia.

Unlike normal cells, platelets do not have nucleuses. Their lifespan is only twelve days at most. The main purpose of these cells is to form blood clots. Platelets have gone from 150K on Day 1 and continued to rise to 191K. The normal range is 150K to 400K platelets per microliter (mcL), so I am headed in the right direction.

The NIH computer had issues, so I will get my full blood work numbers mailed to me by Susan Soto, the NIH nurse.

I had my first real symptom on Day 27 – a massive leg cramp in my left Tibialis anterior. I had never had a leg cramp there. I was suddenly woken in the middle of the night and did not know which way to pull or push my foot. I finally figured out I needed to push it like I was pointing my toes in ballet. I did my Lamaze breathing and massaged the muscle until the cramp went away. It seemed like it took forever. The doctor did not know if it was caused by the drug or my overdoing it at the gym on the cycle. One teaspoon of mustard is supposed to help, along with eating my bananas for potassium and replenishing my electrolytes. Mercy!

One of my Ibrutinib colleagues suggested a book for me to read called The Emperor of All Maladies: A Biography of Cancer, (2010). It was written by a physician named Siddhartha Mukherjee. I believe I will put it on my wish list. Still reading the bio of Steve Jobs, along with a couple more books on my night stand.

Just started Cycle 2…

How a BTK inhibitor works

In the average healthy adult between 50 and 70 billion cells die each day due to apoptosis (cell death). B-cells, which are lymphocytes, are part of the immune system. When a person gets a cold, these white blood cells increase, attack the germs, and when they have done their job, they die. All it takes is a mistake in one cell that leads to the cloning of white blood cells that do not die. It is just bad luck.

There has been a decade of scientific research supporting the importance of the B-cell receptor signaling pathway in rapidly out-of-control growing B-cells (leukemia). Dr. Michael Keating from Houston’s M.D. Anderson was the first physician to tell Carl and I about the new drug PCI-32765, which was later named “Ibrutinib.” I remember the excitement in his voice when he showed us photos of before and after lymph nodes, and exclaimed, “This is what you need!”

The proteins in my leukemic white blood cells prevent cell death, so they continue to proliferate in my blood, my lymph nodes, and my organs. Because, quite frankly, blood runs through every organ of your body. The white blood cells crowd out healthy red blood cells and platelets and enlarge lymph nodes, which often affect blood circulation. With a weakened immune system, there is constant worry about getting infections.

BTK is an essential kinase (a type of enzyme) in the signaling pathway downstream of the B-cell receptor. The pathway in which BTK is involved turns several protein enzymes that prevent cell death either on or off.

Scientists are hoping that Ibrutinib, which is a BTK inhibitor, will target the pathway and not affect other organs or tissues of the body. When Ibrutinib molecules target and irreversibly bind to the kinase, it will do so for as long as 24 hours, which means I have to take the drug every day until it stops working.

When Ibrutinib is ingested in the body, the leukemic white blood cells in the lymph nodes dump into the blood stream. This causes a temporary increase in white blood count (WBC) for about two months. When the drug blocks BTK, it induces cell death in white blood cells that refuse to die and the cells leave the body.

That, my friend, is how it is theoretically supposed to work.

Since I am experiencing the mutation in which the short arm of chromosome 17, where the gene for p53 resides, is deleted, my B-cells are free of the tumor suppressor. This is not good, and is a poor prognosis. This is what some of my doctors have termed “a true death sentence.”

However, I beg to differ… I do not believe I have been given a death sentence. I believe Ibrutinib has just given me a life sentence.

Update and future clinical studies

Day 10, Saturday, July 21 I woke up with a runny nose. It only lasted one day and turned into a sore throat, which lasted for a few days. The physician at NIH said it looked like I had a cold. For the past week I have had no runny nose, no sore throat, but lots of coughing. Thursday, August 2^nd I coughed up a small amount of what appeared to be dark red blood. Considering the fact that internal bleeding is one of the side effects of Ibrutinib, I got a little concerned.

Well the good news is that I am not bleeding internally and I do not have pneumonia. But I do have bronchitis – a cold that seems to have worked it’s way to my lungs. So an antibiotic is in order. It’s funny how one gets overly cautious about the toxic combination of drugs, so I would not take the antibiotic until I got the okay from Dr. Farooqui. I can’t take aspirin or Ibiprofin anymore because of it’s blood thinning abilities. No more red wine for La Verne either (BOO! HOO!), until the researchers figure out the issues of alcohol and the experimental drug.

I also wanted to mention that it was announced August 1^st that three additional Ibrutinib Phase 3 clinical trials at undisclosed locations will soon be posted -- two are for CLL/SLL and one is for mantle cell lymphoma (MCL). Pharmacyclics and Janssen (two drug companies) will begin to invite participants into the clinical trials any day. The California-based Pharmacyclics is a biopharmaceutical company developing and commercializing innovative small-molecule drugs for treating cancer and diseases related to the immune system. The New Jersey-based Janssen is a pharmaceutical company of Johnson & Johnson that provides medicines ranging from ADHD to mental health to neurologics to pain management. Jenssen immediately saw the potential of Ibrutinib and paid Pharmacyclics $150 million upfront for a worldwide collaboration. In total Pharmacyclics will potentially receive $975 million for collaborating with Jenssen on the experimental drug I am taking. Hmmm… Who says it’s not all about the money?

The three studies will include the following:

1. A random study of the combination of Bendamustine/Rituximab plus Ibrutinib in comparison to Bendamustine/Rituximab plus a placebo in relapsed or refractory CLL/SLL patients. What this means is that participants sign up for the clinical study and have a 50:50 chance of getting Ibrutinib or the placebo. Bendamustine (tradename Treanda) is a nitrogen mustard used in treating CLL and lymphomas. Rituximab is a chimeric monoclonal antibody, which was FDA-approved in 1997. A placebo is a simulated treatment for a disease intended to deceive the recipient.

2. A frontline study of Ibrutinib alone compared to a comparator (Waiting to find out what this will be) in elderly CLL/SLL patients. Again, as a participant, it is the luck of the draw whether you get Ibrutinib or not. Also, please note that “elderly” means you are 65 or older. Most of the participants in my study are fuming at the use of the term “elderly,” so my doctor calls them the “other” cohort. LOL.

3. A study outside of the United States for patients with relapsed or refractory mantle cell lymphoma (MCL), who have received at least one prior chemotherapy regimen. The participants will be randomized and will receive either Ibrutinib or Temsirolimus. Temsirolimus is an intravenous drug for the treatment of renal cell carcinoma (kidney cancer).

Click for the full article:

http://files.shareholder.com/downloads/PCYC/1987224025x0x587541/287a7482-75f0-4e60-881d-a8b7ede67e58/PCYC_News_2012_8_1_General.pdf

I thank God every day that I was able to get into a clinical trial in which every participant received the drug Ibrutinib. I celebrate each day. I will be forever grateful for this opportunity regardless of the outcome.

“(S)He is a wise (wo)man who does not grieve for the things which (s)he has not, but rejoices for those which (s)he has.” — Epictetus

2-week update on Ibrutinib (PCI-32765)

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GOOD NEWS!

Just flew back from NIH. The drug is working!!!

This time only six vials of blood were taken. I always make sure I am hydrated 24 hours before getting my blood drawn, and I make sure to keep my arms warm. This helps, since I have crooked veins and am a hard stick. I am getting used to having my blood drawn, and now I can look at the process of the technician filling the vials. Still have to close my eyes and meditate when I get the needle; however.

My white blood count (WBC) has escalated to 101,000, but that shows that the cancer cells are leaving my lymph nodes and are dumping into my blood. Hopefully, after two months of escalating, the WBC will begin to decrease to a normal range (3,000 to 10,000).

My hemoglobin has slightly decreased to 13 and may decrease more on this drug before it increases. Normal levels for an adult is between 12 to 18 grams per 100 milliliters of blood. Dehydration and lung cancer can cause levels to be above normal. Anemia, kidney, and liver disease can cause levels to drop below 12. If it decreases to 8 then I will need a transfusion. If I was in my 70s, had heart disease, and shortness of breath, then I would get a transfusion right away. But I am not, so no worries.

LDH (lactate dyhydrogenase, which is an enzyme in red blood cells) increased slightly, but no worries at this point. It is a marker for hemolysis (rupturing of hemoglobin in surrounding tissues) and myocardial infarction (heart attack), so the medical team will need to watch this. 

I am having a Beta 2 microglobulin value decrease already, which is good. It is still high at 2.1 (previously was 2.2) and the normal range is 0.9-1.7 mg/L. These are markers for the activation of the cellular immune system, as well as a tumor marker in certain hematologic malignancies.

My platelets are increasing and aggregating in the normal range, which means my platelet function is normal. This is good.

My neutrophils are low at 5.1 (normal range: 34.0-71.1%). A neutrophil is a type of mature (developed) white blood cell that is present in the blood. White blood cells help protect the body against diseases and fight infections.

My eosinophils are low at 0.0 (normal range: 0.7-5.8%). They are also a type of white blood cell that helps protect the body against diseases and fight infections.

My basophils are low at 0.0 (normal range: 0.1-1.2%). are a type of white blood cell that are involved in inflammatory reactions in your body, especially those related to allergies and asthma.

My monocytes are low at 0.7 (normal range: 4.7-12.5%). These are white blood cells made in the blood marrow. They attack any foreign material, such as a bacteria or virus, and consume it so that it cannot hurt the body. They preserve an antigen, so that the body will be able to recognize the foreign material in the future.

SIDE EFFECTS and BENEFITS

No major side effects after two weeks. Physical symptoms are improving. Dr. Farooqui said that other patients have experienced canker sores, rashes, severe leg cramps, bleeding, heart palpitations, and shortness of breath. So far, so good for me, but I am only two weeks out from the initial treatment, so it remains to be seen.

I mentioned to Dr. Farooqui that occasionally I would experience painful joints and muscles when I got up from sitting for a while. Since I have been on Ibrutinib, I have not had any pain. Dr. Farooqui said that the drug was has potential effects for patients with autoimmune arthritis, so I get an extra benefit.

My fatigue has been improving. I can’t believe I don’t need a 3- to 4-hour afternoon nap every day in order to function. I hope this continues. I am still sleeping longer at night than my normal pre-cancer life, but I figure my body needs it to heal itself.

I have been fighting a respiratory infection (the common cold) and I can’t believe what a baby I am about it. I really don’t like the feeling of not being able to breathe fully. My ribs are sore from sneezing and coughing. I cannot take an aspirin or any type of blood thinner while on Ibrutinib, so I have resorted to gargling with salt water for fear of taking something that will cause internal bleeding. I have also had to be careful about laughing too much when I have a cold, because it makes me cough. Carl (my little worry wart) is worried that I am going to bleed internally from one of my MaMa La Verne sneezes and he has been hovering around me like a protective eagle. I believe it must be harder on the caregiver than the patient at times. I believe I will be just fine.

FUTURE TRIPS TO NIH

I will be taking a number of trips to NIH this summer and fall. I will be flying in the night before the blood work and meeting with the medical team, and flying out that evening, unless I need a transfusion. The plane ride home is uncomfortable and long (since I have been up since 3:00 am AZ time for blood work), and I am exhausted when I get home. I will have to consider whether to spend another $200 on another night at the hotel. The good thing is that my cousin Sammy has dinner with me when I arrive, and that is a wonderful bonus.

The January trip is a longer one with a number of medical procedures. Carl and I will be staying by the metro so we can get around DC. Since we are spending all our vacation money and savings on these medical trips, DC will have to be our vacation destination for the next couple of years. I am okay with that.

IMPORTANT NOTE

When my WBC drops to the normal range, this will not mean that I am cured of cancer, because if I stop taking the Ibrutinib (PCI-32765), within a week my WBC will begin to escalate, according to what has happened to prior patients. What I am hoping for is that my cancer will be manageable and it will buy me some time. Researchers do not know if eventually the cancer cells will be intelligent enough to figure out another pathway, just as Gleevac has done after 10 years. If so, there are at least two other kinase inhibitors in the works. I will deal with that when the time comes. What a lovely word… “time.”

To get all there is out of living, we must employ our time wisely, never being in too much of a hurry to stop and sip life, but never losing our sense of the enormous value of a minute. -- Robert Updegraff

Cycle 1 of NIH Ibrutinib (PCI-32765) clinical trial

07-17-2012 Leukemia Update

La Verne Abe Harris, Ph.D.

If any of you have read the novel by Mary Shelley (1818) or watched the horror film Frankenstein (1931) with Boris Karloff, you are well acquainted with the most famous line of the story, “It’s alive! It’s alive! It’s alive!” (http://www.youtube.com/watch?v=xos2MnVxe-c). That is how I felt after returning from the National Institutes of Health (NIH) in Bethesda, Maryland this week. LOL.

The day after Carl and I arrived, I had my blood work done (12 tubes of blood) and a meeting with Dr. Mohamed Farooqui, Dr. Saba (a research fellow), and a medical student. The only meds I am on prior to the clinical study are herbal supplements, which have been approved by Dr. Farooqui.

Cycle 1, Day 1: July 12, 2012

I had a rough night on Wednesday, July 11. I am not sure if it was nerves or that I was being tested again. I went to bed with the start of vertigo, which entails dizziness and nausea. It lasted off and on all night long. I did get a little sleep. Luckily it was not the full-blown vertigo I have had before from Meniere’s Disease, which feels like seasickness lasting eight hours. Carl was concerned that my lymph node biopsy would be cancelled. It was not, since I was able to hold myself together for the procedure. That is, until the nurse asked me to sit up from the surgical bed and I was visibly dizzy. They wheeled me into the hospital on a bed and I felt pretty pampered. I got through the lymph node biopsy in my right under arm with local anesthesia and a discussion of politics with Dr. Chang’s team. He said I would probably be in pain afterwards, but I was not and did not even need a Tylenol. I did not have pain during the procedure, which he found unusual.

Carl was my drug dealer for the day and picked up the following prescriptions:

Acyclovir (800 mg, 2X/day) to prevent Zoster infections (shingles) in the middle of the study.

Allopurinol (300 mg, 1X/day) for 14 days to prevent tumor lysis syndrome (TLS).

When a person with leukemia is treated with chemotherapy, the content of CLL cells is destroyed and the toxic content of the cells go into your blood and can hurt your liver and kidney. Alloprurinol is a drug that is used to prevent this from happening. Ibrutinib (PCI-32765) is not known to give leukemia patients TLS; however, allopurinol is given as a precautionary measure.

Ibrutinib (PCI-32765): Take three tablets a day (420 mg total) alone (so that it can be properly absorbed) for as long as it works. This drug has been tested in clinical trials for only 11 months. Ibrutinib, a kinase inhibitor, disrupts the signaling pathways of B-cells and pushes them out of swollen lymph nodes, and hiding places in the spleen, etc. Scientists do not know the adverse effects of long-term usage.

I need to return to NIH every two weeks this summer, then every month, and then every three months after the first of the year. No naprocin or aspirin. No alcohol intake the first month because it may raise the concentration of the drug in my liver.

I took the first treatment Thursday with no side effects. I did manage to sleep three hours in the afternoon, but I think that was warranted after all my body had been through.

Cycle 1, Day 2: July 13, 2012

Eight tubes of blood were taken from me. After one day, my white blood count (WBC) increased 1,000, which is less than expected. My platelets were decreased 27K, which was expected. Every patient is different.

My second lymph node biopsy was done by Dr. Brad Wood. Six samples were taken from the same node under my right arm. One sample will be sent off in formalin and the other five will be taken in saline. They will be studying the tissue samples separately.

Side effects:

1. Five people in the study have had bleeding of the brain resulting in one death. These participants were on a blood thinner called Coumadin. My patient advocate Dr. Chaya Venkat advises eliminating blood thinners, such as fish oil from my herbal supplements.

2. Because of the potential side effect of internal bleeding, I need to watch out for excessive bruising and rashes. Bruising may mean my platelet count is too low.

3. Rashes may indicate I am allergic to the experimental drug. Benedril should help with the rash temporarily.

4. Participants have also complained of muscle and joint pain and diarrhea.

5. Dr. Farooqui warned me that several patients have had a strong reaction to mosquito bites. That is not new to me, since my mother always said I had “sweet blood” when the mosquitoes attacked me. Glad I am not in Houston. I will heed the warning.

6. Leg cramps are another side effect. Dr. Farooqui said to take electrolytes, water, massage the legs, and take one teaspoon of mustard. I asked him if Dijon mustard counted. He chuckled.

Emergency situations:

1. If I begin to suffer extreme fatigue or have lots of bruising, it is an indication that my platelets may be low (<100K) and my hemoglobin levels may be too low (<11.0). It may also indicate internal bleeding. I may need a transfusion at this point and I am supposed to go to the hospital immediately.

2. If my neutrophils are less than 500 (0.5), then I am at risk. This usually comes with a fever and is a medical emergency.

3. Evidence of a rash may indicate that I am allergic to Ibrutinib.

In Conclusion

I am B22 (the second cohort of 17p deleted patients), and No. 41 overall (out of 64). Two of the Ibrutinib clinical studies in the U.S. have closed, and the NIH study will close this fall. I consider myself lucky.

All we have in this thing called life is what happens in the here-and-now. Being stuck living in the past or living in the future is a waste of your beautiful life.

We have to determine what risks in life we are willing to take, and weigh the benefits to the losses. This also applies to the people in our lives. Dump the toxic people and surround yourself with people who make you happy.

Dr. Brian Koffman, who is a medical doctor with leukemia, says, “ There is a cost to doing anything. There is also a cost to doing nothing.”