Some Life Lessons Take a Lifetime

Patience and Pacing

If you let go a little, you will have a little peace.

If you let go a lot, you will have a lot of peace.

If you let go completely, you will know complete peace and freedom.

Your struggles with the world will come to an end.

~ Ajahn Chah, A Still Forest Pool

I believe that challenges (including people) show up in life because there is something I need to work on, learn, or accept. Sometimes I'm an exceptionally slow learner.

Patience and self-pacing have never been my strong suit. I like to live fully and make the most of every heartbeat: no regrets.. don't take life for granted.. live out loud.. expand my comfort zone.. learn something everyday.. help others.. push through fears.. you get the picture. Living with urgency has served me well. I've always had more interests than time. I lived a full, active life; I was highly productive and able to achieve many things. Sure, I'd crash periodically. But I could always recover and carry on.  

Pacing for Dummies

Then along came blood clots and Polycythemia Vera... my body said "No more!" to my career in community development at a particularly difficult time in the real estate and lending markets (circa 2007).  I went from fast-forward to the ICU. No one saw it coming. 

It took my body more than 3 months to recover from the surgery and my normal energy never returned. When I went back to work, I was hard-pressed to work 8 hours; I would collapse on the sofa as soon as I got home. Less than a year after the surgery I had to resign from my job. I was crushed!

I then kept my brain active with some part-time consulting and a lot of volunteer work that had flexible timelines. I also got more involved with my kids' activities. 

I believe the illness occurred to make me slow down and to re-direct me to be more present for my children during the teen years. I became the mom that could cart smelly kids to/from sports practice and help at school functions that took place during business hours. It became a gift for my soul. 

Pacing for Big Dummies

When I pushed through the extreme fatigue, headaches, and other symptoms of the Polycythemia Vera, the Universe devised a new challenge: Behcet's Disease (a rare auto-immune disorder). 

The physical manifestations were excruciatingly painful. Both the disease and the treatments caused severe physical issues that limited my mobility. For a time I needed a cane to walk, couldn't climb stairs, and certainly didn't leave the house unless absolutely necessary. I gained 60 pounds (and had the steroid "moon face"). I was so miserable, self-conscious and depressed. I became resigned that old age wasn't in my future. 
That slowed me down big time. I tried to make the most of "good days" even though a productive day would cost me a couple of days in bed afterwards. 
Apparently, that wasn't enough.

Patience and Pacing for Obtuse Big Dummies

This February came the curveball we didn't anticipate: aggressive secondary myelofibrosis. My bone marrow is no longer able to produce enough blood. Without a blood stem cell transplant, I could look forward to maybe two years of a transfusion-dependent life. 

Since none of my siblings "matched" me, we put our hopes and faith in the US and International Marrow Donor registries. 

The waiting was a real test of patience. I felt like the crocodile in Peter Pan who swallowed the clock: tick tock, tick tock, tick tock pounded in my head.

Then my chance for a miracle: a 22 year old young man from Germany is my perfect match! Talk about a 2nd chance!

45 Days Post-Transplant

The "typical" allogeneic transplant (donor cells) shows engraftment between days 10 - 25 after the transplant. 

What is time anyway?

My new stem cells are still not fully-engrafted. The whites are all donor cells. But they aren't producing platelets nor red cells yet. I'm still transfusion dependent; I need platelets every week and red blood cells every couple of weeks. 

The doctors and clinic staff remind me that it will take a lot longer because my bone marrow is hard (full of fibers), making it difficult for the stem cells to find a place to settle in. Over time, the bone marrow should return to its original spongy form (at least enough for a successful transplant). 

Here is where my patience is thin. Objectively I know that my body is starting over ~ in producing blood to support the organs. 

The feeling of helplessness and lack of control can be overwhelming some days. I try visualizing spongy marrow, talk to my precious donor cells, and count my numerous blessings. I'd eat broccoli and brussel sprouts if it would help (they would need to show me studies first). 

I do know it will all be worth it in the end. And I try my best each day (some day's "best" is better than others). One thing that helps A LOT is reinforcement from family, friends, and the medical staff that this is just part of the deal; I haven't done anything wrong; and resting is the best thing to give those fighting stem cells the chance to dig in and do their jobs.

I'm hoping to become a calm, cool, collected person through this experience. One who feels and exudes patience. One who enjoys life reasonably without creating physical burnout the next day. Patience and Pacing. These are my lessons.

The Outs and Ins of MPNs

My last phlebotomy was on June 29, 2012. It took about 15 minutes to withdraw 500 ml of that RBC-rich blood from my body. Now, almost eight months later, I'm receiving my first transfusion of packed red blood cells.  What a ride this is!

When my hemoglobin (hgb) and hematocrit (hct) was not stabilized with Hydrea last summer, I needed a couple of phlebotomies to get me back in the zone. Since last fall, these counts have slowly but steadily fallen. 

Now, with Hgb at 8.2 and Hct at 27.4, I can't walk up the stairs without my heart pounding. I get light-headed and dizzy when I walk or stand for much time around the house. (You know something is not right when you find yourself looking for things to lean against as you move around. Similar to when I was pregnant and had to scope out the nearest restrooms)

One of the great take-aways from the Joyce Niblack MPN Patient Conference held in Arizona this month was encouragement from experts like Susan LeClair, PhD and Ruben Mesa, MD that blood counts and ranges are not absolutes for every patient. We are encouraged to pay attention to our individual symptoms and let our doctors know.

This gave me the confidence to let my local hematologist know that I need a blood transfusion now (with at Hgb of 8.2)  -- I don't want to wait for it to reach 8.0 (the standard accepted level to begin transfusions). I've been very fatigued with it in the 9's for the last few weeks; when it fell lower this week, I had to cry "uncle."


Additionally, I plan to start taking Jakafi when it's approved by my insurance. Since blood counts often drop during the first few weeks, I want to start from a position of strength.


So yesterday I went to the hospital's outpatient infusion center to get my blood typed and cross-matched. Here is a good explanation of the blood transfusion process.

My "energy pack"

Today I'm getting 2 units of B negative packed red blood cells from a donor in Riverdale, Georgia. A nurse came in with a cooler that contained what I'm now calling my "energy pack." After verifying the info on the blood bag with the info on my wristband, the transfusion commenced.

As I sit here and write this while someone's generous gift is flowing into my veins, I feel quite humble. Someone took time (and energy) from his/her daily routine to help a stranger. It is an unconditional gift. No questions or judgments about my race, religion, age, gender, political views, sexual orientation, family situation, employment status, or the reason I need the blood. A pure gift of care and concern for others. 

One of the nurses explained that this donor helped me with the red cells, and another with the white cells, and a third person with the platelets. How is that for leveraging a donation? 

My mom was an ICU nurse while I was growing up and we learned how important blood donation is to saving lives. I started donating blood when I was 18 and in college. Because "B negative" is not a common blood type, the blood bank would sometimes call me in. I continued donating until my early 30's and quit due to chronic anemia. Later, in my 40's, I became symptomatic and diagnosed with Polycythemia Vera. I've been assured that my blood was good and safe for donation in my early years; the JAK2 mutation that triggered the PV occurred later. 

I have no idea how much blood I donated in my healthy years. But I'm sure it not enough to cover the blood I will be receiving over the coming months. Some have told me that they would like to donate to someone they know. I remind them that should they ever need blood (due to illness or accident), the donor who saves them will likely be someone unknown to them. 

Blood donation is the ultimate random act of kindness. I receive this gift of kindness and life with love and gratitude. It is yet another reminder of the interdependent web of life. 

These Tired Bones Need a Makeover

After several days of tests and consultations with experts at Mayo Clinic Scottsdale, I returned home with a worse-than-expected diagnosis. Here's the quickie Bad News/Good News version:

My bone marrow has gone from over-achievement to under-achievement. Instead of producing too many red blood cells, it is now in the "spent phase" and is not producing enough blood. This transition called my spleen and liver into action to produce blood. They are working hard, but will not be able to sustain their efforts forever. I'll soon need blood transfusions to keep my hemoglobin at a livable level. What irony! From phlebotomy to transfusion in less than one year.

A blood stem cell transplant is in my near future;  a successful transplant will cure me of the myelofibrosis AND the auto-immune conditions that rage inside.
Without a transplant, I'm at great risk for acute leukemia (no cures) and could expect less than three years on the sunny side of the ground.

Now that the test results and reports from Mayo are in my local doctors' hands, I'm preparing for the insurance approval / denial / appeal process. Quite frankly, I'm more anxious about getting the transplant approved (with the best transplant center for my particular leukemia) than the transplant process itself.

The kids and Robert are taking the news like champs. So are my mom, dad, and siblings. We're going to get through this together as we do all challenges ~ with love, laughter, the occasional cuss word, and toasts to the present and a bright future. 

Some have asked what they can do to help.  If you are so inclined, please consider:

1. Become a blood donor. You can be sure that me, or someone like me, is grateful for your gift of life.
2. Join the National Bone Marrow Donor Program. With a simple swab of your cheek, you will be "typed" (not blood type, by the way) and entered into the database. When a patient needs a donor, our info is compared. Donors are contacted and must agree to be considered for donation before the patient is contacted. Donors can say no at any time. Also, I won't need your bone marrow ~ just your blood stem cells (it's like donating platelets).
3. Keep us in your happy thoughts, prayers, meditations. My mom alerted her international, multi-faith 'God Squad' and I am here to tell you that I do feel the love. It manifests in hope, energy, and strength.  

NOTE:  I especially encourage my friends of Asian, African, Jewish, and Native American descent to sign up. Matches for are very limited for children and adults of color compared to white European descendants. 

Here are some specialty donor programs (they tie into the large database):  

Asians for Miracle Marrow Matches

BlackBoneMarrow

Gift of Life Bone Marrow Foundation

#  #  #

If you like more technical terms, read on:


I. My Polycythemia Vera (PV) has transformed to post-polycythemic Myelofibrosis (MF) in recent months.

• I have completed the “spent phase” of Polycythemia Vera and my bone marrow now has lots of reticulin, which crowds out the blood-making stem cells. 
• Extra-medullary hematopoiesis is now at work – the spleen and liver are beginning to produce blood due to the bone marrow fibrosis.  Over time, this puts extreme stress on both organs.
• The overall goal is to prevent the MF from progressing to an acute leukemia from MPN;  it is very difficult to treat and very high mortality.
• The auto-immune conditions and portal vein blockage add complexities to my circumstances. My “youth” is an advantage.

II. I will start a newly-approved medicine called Jakafi to help improve the symptoms of the disease.  
While it won’t slow the progression of the disease, it should reduce the spleen size, night sweats, itching.  May cause more anemia.  I’ll likely need blood transfusions (when hemoglobin falls below 8.0

III. Need to plan for a blood stem cell transplant in the next year or so.
Because of the rapid rate of disease progression, I'm not a candidate for a clinical trial.
We need to prepare for a transplant:

• “Type” me
• Look for a match – my siblings, then www.bethematch.org
• Get insurance & local docs on board with this plan
• Stay as healthy as possible

I was hoping that a transplant could occur after Alexander graduates high school and heads out to college (mid-2014).  The doctors said that is highly unlikely.  There is a window of opportunity for successful transplants and weekly monitoring of my blood counts will inform us of the timing. That bums me out because I want to be fully present for his last year at home. He said, "Don't worry about me, mom. The sooner you get the transplant, the sooner you feel good enough to do all the things you want to do." 

As long as I make sure he has gas money... (wink, wink)

Let's Kick It Up a Notch (or more) -- to Mayo Clinic

I had a Bone Marrow Biopsy done at Northside Hospital on January 24th. The bone marrow biopsy and aspiration report came back with some news:  lots more reticulan fibers and fibrosis "consistent with post-polycythemic myelofibrosis."  The report didn't look good from this patient's perspective but I was pleased that I wouldn't have to wait too long for Dr. Mesa's review.


We decided over the holidays to try to get a consultation with Dr. Ruben Mesa, hematologist/oncologist at Mayo Clinic Scottsdale. I really must thank my mother for making this happen.  She prepared a concise yet thorough letter to Dr. Mesa explaining the changes in my symptoms and asked questions regarding my suitability for a clinical trial that we've been pursuing.  All this before we had the BMB.
  
Dr. Mesa is one of the top experts in the world on Myeloproliferative Neoplasms (MPN), which includes Polycythemia Vera and Myelofibrosis.
Since Mayo Clinic Phoenix is hosting the Joyce Niblack Memorial Conference on Myeloproliferative Neoplasms this coming weekend, we wanted to schedule the consultation for the same trip.  This conference is organized by the MPN Education Foundation and is rich in sharing the latest research in language patients and their loved ones can understand.  This will be the 3rd such conference mom and I will have attended.  I'll be reporting on the conference as it occurs.

So yesterday (Tuesday) I had the initial consult with Dr Mesa. 
Unfortunately, the chronic leukemia has progressed from Polycythemia Vera (PV) to post-PV Myelofibrosis (MF). This means that my bone marrow has gone from producing too many red blood cells to producing not enough of any blood cells (eventually makes one transfusion-dependent).

He explained that all the MPNs are on a spectrum -- my PV appears to be on the aggressive end of the PV spectrum.  [Blood clots in 2007;  uncontrolled hemoglobin and hematocrit in 2009 (when it was diagnosed) to now:  low blood production, unexplained weight loss, increased anemia, bone pain, excessive fatigue, etc.]

Myelofibrosis (both primary and secondary), like the Polycythemia Vera, is a chronic leukemia -- meaning one can live for quite some time with appropriate medications and monitoring.  (Acute leukemias are much more aggressive). 

He needs more info to determine where my MF is in the DIPSS 4 stage range.  It's likely somewhere in the middle -- not early and not severe.  This is good news.

The 20+ pounds I've lost in the last 2 months is likely from increased calories that the cancer is burning.  I'm still not to my Weight Watcher's goal weight, so no concern about it yet.  I finally found an advantage to being chubby ~ it gives cancer more to chew on while the doctors prescribe more toxins to help you get better.

We were hoping that my treatment would change from hydroxyurea to pegylated interferon.  Despite the potential side effects, the peg-interferon has reversed fibrosis in many PV cases.  Unfortunately, the interferon is likely not an option for me now (too late in the disease process AND it may exacerbate the inflammation problems).  We were considering this in 2012 and it never came to fruition. The hydroxyurea (pill chemo) has run its course, too.  No need to continue suppressing the bone marrow.

One of the new JAK-2 inhibitors will likely be a good fit, along with other meds to address the anemia.  He mentioned Jakafi (it's a pill, not an exotic tropical island where cancer patients sun and heal).

There are no medicines to cure secondary MF at this time;  what is available can slow the progression of the disease and reduce the likelihood that it transforms to acute myeloid leukemia.

Before Dr. Mesa develops his recommendations, he needs more information.  So off for more tests:
*  I had lots of blood drawn that is on its way to Mayo Rochester for evaluation.
*  I had a chest X-ray in part because he noticed my fingernails are "clubbing" which is a sign of pulmonary problems.  It could also be a result of all the inflammation.
*  I had an ultrasound on my big spleen and gut.

Dr. Mesa also wants to consult with a rheumatologist for the Behcet's and the other mystery inflammation (see my earlier posts). The inflammation is not related to the blood problems.  While it may not be due to Behcet's, he wants the rheumatologist's opinions. The rheumatologist can't see me until next Tuesday morning, so I have to extend my trip.

Also, he believes that at some point a bone marrow/stem cell transplant may be a good option for me.  This is the only known cure for MF.  He says you don't want to do it too early nor too late in the disease process.  He wants me to consult with their SCT doctor.  That appointment is this Thursday morning.  I'll know a lot more about SCTs as a result.

Dr. Mesa also says that my "youth" is a big advantage (most are diagnosed around age 65). 

The kids know I haven't been feeling well and are glad that I'm seeing a world-renowned expert. Their love and teenage chaos pulls me out of self-centered funks and remind me of all things good. Laughter is truly the best medicine!

I will know a lot more on Friday and will also learn a whole bunch about the state of MPNs and other patients' experiences at the symposium this weekend.

Stay tuned!  Never a dull moment!

The Traffic Jam Within: A Primer on Blood Clots and Thrombosis

The 6th Annual International MPN Patient Symposium began with Dr. Babette Weksler giving us a fascinating overview on the invisible threat to people living with Polycythemia Vera (PV) and Essential Thrombocythemia (ET):  thrombosis.

Dr. Weksler is with the Weill Cornell Medical College and Center.  She has studied and treated patients with thrombosis for over 35 years.  Dr. Weksler focuses on diseases of platelets, bleeding and thrombotic disorders, sickle cell anemia, and immunologically mediated blood disorders.  She is a teacher, researcher, and clinician.

This article includes some blood basics along with the specialized information provided by Dr. Weksler.

We all have arteries, which flow blood from the heart to the rest of the body and veins, which return blood from various organs and parts of the body back to the heart.

There are “major” (large) and “minor” (smaller) veins and arteries throughout the body system.  There are also capillaries (very small passageways) for blood to move through the system.

Remember, the blood clotting function is necessary for us to heal wounds and prevent excessive bleeding.  Thrombosis is when the blood clotting function works against the body’s interest (also called “dis-regulated clotting”).   A thrombosis can fill a vein or artery and prevent blood from flowing to its intended destination.  This causes blood to back up, organs to suffer, and often end life as we know it.  This happened to me;  the cascade of problems from three blocked veins is now legendary in my family.

Sometimes a clot gets pushed from where it formed to an organ; this is called an “embolism.”  An “embolism” is an obstruction of a blood vessel (typically a blood clot) that travels through the bloodstream and lodges, resulting in loss of blood flow.  The embolus could be a blood clot, fat mass, air bubble, or other mass.  The most common is a blood clot in the leg gets pushed up into a lung and causes trauma or
death.

So... clots are good;  thromboses are bad.

An “aneurism” is when the wall of a blood vessel (vein or artery) bulges out and weakens.

Anatomy of a Blood Clot:
The clotting function produces fibrin strands, creating a mesh;  then platelets contribute to clot initiation and firmness of the mesh.  Red blood cells get trapped in the mesh and give the clot bulk.

Dr. Weksler explained that the clots in MPN patients are different from blood-healthy patients.  People with MPNs experience thrombosis due to their blood composition and abnormal functioning of the blood, endothelium, and platelets.

Hemostasis is limited clotting that preserves the integrity of blood vessels and maintains normal blood circulation.  It is important to maintain the vascular integrity (healthy blood vessels) and normal blood flow despite continual minor injuries.

High hemoglobin (Hb) in Polycythemia Vera leads to high blood viscosity (thickness), which slows blood flow and leads to thrombosis.  Think about a milkshake going through a straw compared to water).  If the milkshake contains small bits of fruit, it can get clogged in the straw.

The abnormal vessel wall favors thrombosis and blocks clot dissolution.  If the vascular integrity is compromised (blood vessels are weak or damaged) the risk for clots and thrombosis is increased.

Blood clots and thrombosis are frequent in Polycythemia Vera (PV) and Essential Thrombocythemia (ET).
They occur in both veins and arteries, and in large and small vessels.  Clots and thrombosis are major contributors to morbidity (death) for MPN patients.

Interesting note:   Both clots and excessive bleeding may occur in the same person at the same time or different times.

The Why:  Pathophysiology of Thrombosis in MPNs
It is generally understood that when blood stops moving, it clots.  For example, in Polycythemia Vera, a high red blood cell count (seen in high hematocrit) can block small vessels and slow blood flow.  Did you know there are other causes?  I didn’t.

Dr. Weksler offered the clearest explanation I’ve heard of the many ways MPNers experience clots.
There are four different causes of Blood Clots:

1. Endothelial Activation
The endothelial cells line the veins and arteries.  They issue commands to the blood elements and certain organs.  With MPNers, the endothelial cells may shift from non-reactive/anti-thrombotic to pro-thrombotic surface properties.

2. Platelet Activation
Sometimes platelets are activated for enhanced adhesion, aggregation, secretion.  The platelets then gather together and form a clot mesh that catches RBCs that try to flow through the vessel.

3. Blood Coagulation
The blood can initiate the clot when its viscosity (thickness) is increased and thereby slows the flow.  The thick blood can also cause increased thrombin generation and fibrin formation, causing clot formation.
Blood coagulation can also cause decreased fibrinolysis (the body's natural way to break down clots).

4. Red Blood Cells
The RBCs also sometimes push platelets to sides of blood vessels where platelets can interact with vascular endothelial cells.  The RBCs trigger the response by the platelets and endothelial cells.   This can cause microscopic clotting of the platelets.

Dr. Weksler also discussed several differences between Arterial and Venous thrombosis:

Arterial (arteries – taking clean blood from the heart to the body) thrombosis:
Arteries are the fast flow system.
Endothelial injury key
Platelets initiate when activated
“White clots”
Primary preventive treatment:  Antiplatelet therapy (e.g., aspirin)

When the platelet count is over 1 million or 1.5 million, it promotes bleeding:
Acquired von Willebrand (vWD)
These platelets absorb von Willebrand factor, an important clotting factor, resulting in mucosal bleeds.

Venous (veins – taking “used” blood from the body to the heart) thrombosis:
Veins are a slow flow system
Venous stasis key
Fibrin formation mainly;  platelets less involved
“Red clots”
Primary preventive treatment:  Anticoagulant therapy mainstay  (e.g., warfarin)

What are the chances I’ll experience thrombosis?
If you meet any of the following criteria, you are at higher risk for a thrombosis than the general population:
• Advanced age (>65 years of age)
• Control of MPN anti thrombosis with medication
• Prior Thrombosis
• JAK2 mutation burden *
• Acquired risk factors:  hypertension, high cholesterol, smoking, diabetes, CV disease
• Inherited thrombophilia

Persons with Polycythemia Vera have a 33% risk of a major thrombotic event.
Persons with Essential Thrombocythemia have a 17% risk of a major thrombotic event.

*  The JAK2 mutation burden affects thrombosis in MPN patients due to:
1. More immature and activated platelets
2. Higher numbers of activated WBC
3. More RBC precursors capable of epo-independent growth

Interesting Note: In Essential Thrombocythemia (ET), the presence of JAK2 mutation increases the risk of arterial thrombosis.

Platelet-Leukocyte aggregates and micro-particles promote thrombosis.  The different kinds of cells can act together to promote thrombosis.

To reduce the risk of a thrombotic event, MPN patients should lower the hematocrit (HCT) to normal (men <45%, women 42%).  This decreases blood viscosity.
Note:  If one only lowers platelet count, thrombosis may still be a risk.  

Role of Various Drugs with Thrombosis (clots):
• Hydrea inhibits Tissue Factor expression, decreases platelet-leukocyte aggregates, and decreases the immature platelets
• Aspirin relieves erythromelalgia (excessive dilation of blood vessels of feet or hands)
• Interferon preferentially decreases JAK2+clones
To date, JAK2 inhibitors have not decreased thrombosis

For those of us taking warfarin (Coumadin), Dr. Weksler said that the newer anti-coagulants are “not there yet”.  Some patients have tried Pradaxa and gone back to warfarin.  Pradaxa must be taken twice a day consistently and this is problematic for many patients.  She believes that we’ll have a better alternative in a few years.

Here are my take-aways:

1. There are several different ways our blood may clot and then thrombose (sounds grandiose, doesn't it?!).
2. Aspirin reduces one kind of risk (arterial clots). 
3. Warfarin/Coumadin reduces another kind of risk (venous clots).
4. Hydrea reduces yet another kind of risk (platelet-leukocyte aggregates).
5. All the preventive treatments must be closely monitored by your physician.  If the blood levels get out of whack (CBC and for those on warfarin, the INR), thrombosis can occur.  
6. It is possible to suffer from a thrombosis AND internal bleeding at the same time.
7. PVers and ETers have different blood thrombosis challenges.
8. Women's hematocrit should be at or below 42%.
9. Men's hematocrit should be at or below 45%.
10. Endothelial cells can influence the blood that flows through the blood vessels.  This is a leading edge in study.

I am grateful for those with healthy blood who donate regularly.  Our MPN blood, when taken out by phlebotomy/venesection, can not be shared with others;  thanks to Dr. Weksler, I understand why.

A Few Quick Thoughts from the MPN Patient Symposium

I just got back home from the whirlwind trip to New York City for the 6th International Patient MPN Symposium sponsored by the MPN Research Foundation and the Cancer Research & Treatment Fund.  The day was filled with fascinating speakers (several of whom were new to me) and each of them taught me something new.

I'll organize the 25 pages of notes later, but I thought I'd tempt you with these nuggets. :)

Cool Terms I Picked up at the MPN Patient Symposium

Somatic mutation:  a change in a gene that occurs after birth (you aren’t born that way)

Molecular mimicry:  some genes mimic others

Epigenome:  the new area for research

We are all entitled to our own opinions, but not our own facts.

JAK2 and Exon 12 and TET2 – a few of many mutations under exploration

Genomic Instability:  affects the micro environment and what happens with MPNs

Specialized Niche Cell:  cells that are highly specialized (example:  Endothelial cells)

Endothelial cells:   lining of blood vessels;  they also instruct other cells and broadcast directions throughout the body.  They also instruct organ regeneration (eg, liver and lungs). 

Inductive angiogenesis:   uh, i forgot already!

Proliferative angiogenesis:   forgot this one, too!

Role of vascular niche cells in self-renewal of stem and tumor cells:

The micro environment that are created by the mutations have huge impact on what happens. 

Angiocrine Factors                

Niche cell:  activate endothelial cells

Leukemic initiating cells – they expand the vasculature in the bone marrow.

Factoids and A-Ha’s! 

• Platelet-Leukocyte aggregates and micro-particles promote thrombosis.  The different kinds of cells can act together to promote thrombosis. 

• We need drugs that target the endothelial cells.   Endothelial cells expand hematopoietic stem and progenitor cells by angiocrine expression of Notch ligands.

• The first hematopoiesis occurs with the endothelium. 

• The leukemia from MPNs is completely different from the normal leukemias.  We need different treatments because the biology is different.

• The Chronic Myeloid Leukemia is triggered by the Philadelphia chromosome, so it is regarded as a different disease process from MPNs.

• JAK2 is not a “switch” that can be flipped on or off; it has at least 10 different mutations, which cause different disease results in patients.

JAK2:  The One Mutation, Three Diseases problem.

Why do patients develop ET, PV, or PMF?

Level of JAK2 allele burden determine ET, PV or PMF – more so in men than women

How much is the disease versus the host predisposition to develop an MPN?

Are there other cooperating somatic mutations?

• Despite all the advances, we still have a long way to go – do not be misled by where we are.

• For those of us taking warfarin (Coumadin), Dr. Weksler said that the newer anti-coagulants are “not there yet”.  Some patients have tried Pradaxa and gone back to warfarin.  Pradaxa must be taken twice a day consistently and this is problematic for many patients.  She believes that we’ll have a better alternative in a few years.

• Much of the knowledge gained and progress made has occurred because patients before us and among us have shared their tissue samples, DNA, and whole selves for testing and clinical trials.

There was so much more covered.  I hope this tempts you to watch the video when it is available online at the MPN Research Foundation

Stay tuned!

peace,

Marina

4th Anniversary of my Second Chance

October 14, 2007 -- a day as important as my birthday!
Four years ago today, Dr. Darryl Tookes quite literally saved my life with his expert emergency surgery.
October 14th or 15th could very well have been the date after the dash on my tombstone (if I had one).

Dr. Tookes discovered clots in the portal, mesentary, and splenic veins in my gut.  These clots caused part of my intestine to rot and triggered peritonitis which put vital organs in distress.  During my two week stay at the hospital, the doctors searched for the cause of these clots.  I detailed the experience in posts in the Winter of 2007 and early 2009, so I won't digress today.

It wasn't until October 2009 that we learned that I have Polycythemia Vera.  The hematocrit rose to over 69 and I had symptoms that put me at high risk of a stroke.  A bone marrow biopsy confirmed that I am JAK-2 positive;  the protein/gene malfunctioned.

I have not regained the energy, stamina, and mental acuity to return to a 40+ hour career.  I want the old "me" back!  I still dream of making significant contributions to our world.  I want to be back in the compensated career track.  I am continually frustrated by the unreliable and inconsistent "good days" that chronic illness offers.

Shifting focus from frustration to gratitude is part of my daily spiritual practice.  I am aware that my life is much easier than millions of people in this country and the world.  I have a loving and supportive family, excellent affordable health care (which is expensive for chronic illnesses), great friends and community -- both local and on-line, clean water & electricity on demand, plenty of food, a safe and comfortable home...
I don't take my gifts lightly.

With great gifts come great responsibility.  That belief is ingrained in my soul.  Perhaps that is where the frustration is fueled.  There is so much I want to do to act on my gratitude and help others.  I derive intense joy from helping others, easing another's burden.  When I cannot DO, I must focus on BEING... and today I am grateful.

So today, I exclaim a heartfelt THANK YOU to Dr. Tookes and all the great Kaiser Permanente docs and staff who saved my life and keep me going.

May you share gratitude and love to someone who has been there for you.  Trust me, it feels great!

Tired of the Rat Poison? Alternatives to Warfarin (Coumadin) are "Available"

Friday afternoon I received a phone call from Andrea, my Anti-coagulation Pharmacist at Kaiser.  She wanted to know how I'm feeling and what's been going on with me.  It wasn't a personal call;  I had my blood drawn earlier in the day and the results came back:  my Prothrombin Time PT/INR was 5.7.  This is WAY higher than where it's supposed to be (in the 2.0 - 3.0 range).

The INR (International Normalized Ratio) measures how "thin" the blood is.  In truth, the blood doesn't get thinner;  the platelets get slipperier and don't form clots as easily.   People take anti-coagulants (aka "blood thinners") to avoid blood clots and strokes.

Warfarin (brand name: Coumadin) is the old standby drug.  It is affectionately called "rat poison" because it is, indeed, the poison in rat bait.  The rats eat the bait and go back home and die of internal bleeding.  Those of us who have a history of blood clots (I had the clot trifecta in 2007 that almost killed me) must stay on anti-coagulants forever.  There is no amount of exercise or dietary change that will alter the deficiencies in my blood that cause it's propensity to clot.

Back to Andrea's call and questions:
Any bruises, she asked.  I did a quick scan and noticed 2 bruises on one calf and a bruise on 1 arm and a big toe.  And I have no idea from whence they came (sorry -- no wild activities lately!)
Any changes in your medicines?   No.  
Any changes in your alcohol in-take?  Hmmm... (be honest!)  Yes -- I haven't had any all week.  
Any changes in your diet?   Well, I've got 2 Behcet's ulcers in my mouth so I haven't been able to chew all week.  Soup or broth each day.
BINGO!  When you take the same dosage of warfarin but your diet changes significantly, it can throw the blood level off.
She told me to stop taking the warfarin for the weekend and come back on Monday for another PT/INR test.  She will call me with the results and advise me on the next dosage.
Until then, she said, be careful!  If you have any accidents or falls, go straight to the hospital and tell them you're on warfarin and your INR is high.  (I know that I am highly susceptible to internal bleeding when the INR is this high).

I've become accustomed to this in the last 3.5 years, but I tell you that I do not enjoy getting "stuck" every 3-6 weeks.  Since I have been trying different medications for other chronic illnesses (sounds much more dignified than "experimenting with drugs" doesn't it?!), my body is constantly re-calibrating.

There were rumors for years about more stable alternatives to warfarin.  Anti-coagulants that are more patient-friendly would not be sensitive to how much spinach salad we eat this week (vitamin K), would not require frequent blood testing, and could be administered in a consistent dosage.

Guess what!  Such a drug exists.  It's used in Europe and Canada.  It's been approved by the FDA, but is expected to be cost-prohibitive for most of us "regular" users.  And if the insurance companies and medicare won't cover it, we won't get it.   Here's a few links to information about Dabigatran (brand name:  Pradaxa).
NOTE:  I am not recommending or endorsing Dabigatran.  


I really like MedScape website.  It has lots of helpful information:
Dabigatran -- A Good New Replacement for Warfarin

Here's the pharmaceutical company's website for Pradaxa:  Pradaxa website

If you hear more info or get to try the new med, let me know.
Peace,
Marina

Myeloproliferative Neoplasms Conference - Day 2 Highlights

All the powerpoint presentations from the conference will be available through the MPD Net listserv sometime in the next week or so (let's give Ian, Antje, and Bob time to get home and back to their computers).

The morning began with Dr. Richard Silver, Director of Leukemia & MPD Center at Weill Cornell Medical College.  He talked about Primary Myelofibrosis and a study with low-risk PMF patients on interferon.  The study showed clinical benefits in 60% of patients and disease stability in 24% of patients.

Dr. Silver is a long-time proponent of the benefits of interferon alpha as treatment for PV and MF.

More info to come in full notes.

Dr. Ruben Mesa shared these thoughts after hearing feedback on the uncertainty and unanswered questions about our diseases:

• We know much more about the cause of the MPN illness than we have ever known.
• We have many more therapies than ever before.
• As you look at the range of cancers, some 300-500 of them, there is probably only 1 that goes away with a single drug.  It is unrealistic to expect that 1 drug will cure any of the MPNs.
• MPN Patients can expect to have many therapies over time.
• All the therapies are in evolution.
• Science is a journey.  It is a muddy road, but we are making progress.  It is a hopeful road.

Stem Cell Transplant Panel

This was really cool!

Four gentlemen who have had Stem Cell Transplants (Rick Posner, Larry Gersh, Ron Anderson, and Julius Dix) and Dr. Joachim Deeg from Fred Hutchinson Cancer Research Center, Seattle answered questions about the experience.   They range from 2 to 11 years post-transplant.

Here are some highlights:

Greatest Challenges:

• Physical:  the chemo can give you sores from your mouth all the way down to the other end -- very painful.
• Huge mental adjustment.
• Maintaining sense of self through overwhelming illness.

Advice:

• Work with your insurance company before hand and get everything figured out and approved.  It is stressful enough without those worries. 
• Try to keep some sort of normal routine.
• Stay ahead with meds for nausea.
• Develop communication mechanism and use a web-based tool like Caringbridge so you don't have to take all the calls.

Graft vs. Host Disease (GVHD):

• Would expect more GVHD with female donor to male recipient, particularly if female had been pregnant; yet relapse rate would be lower (per the Doc).
• Sibling donor makes it milder.
• Patients who acquire GVHD require prednisone for about 2 years; some may need it longer.
• Patients often report they need to take more notes, get tired, have shorter attention span.
• Common issues are dry eyes, dry skin.
• UV light helps with some skin GVHD issues, but prednisone is still the mainline medicine at this time.

Any Big Surprises?

• The day-to-day living after getting out of the hospital;  the amount of time and energy it takes for cleaning the house, prepping food, cleaning the lines, hydration, going out...
• Naive about GVHD.
• Takes a year to feel better.

Research Trends in Stem Cell Transplants:

• Donor Matches -- looking at partial matches to improve the regimens.
• Refine cellular therapy as a vehicle to implant modified T-cells to combat viruses.

= = = 

there's more, but i'm tired... stay tuned!

Making It Through With an MPN

Dr. John Camoriano, Mayo Clinic

Dr. Camoriano had us laughing throughout the conference as the master of ceremonies.  On Sunday morning, he shared eight (8) key principals of being a successful patient and caregiver.  He called them TENACITY principals.

T = Training and Teaching:   learn as much as you can about your disease & share with your doctors

E = Exercise  (single most beneficial thing most can do to improve health) 

N = Nutrition:  eat whole foods, lean meats, olive oil, reserveratrol-laden foods, less milk products...

A = Activism,   Anti-aging:   get involved with the MPN community as you can

C = Calming & Connecting:  keep the limbic system strong, keep laughing, keep connected with others.

I =  Individualization:  personalized medicine is the way of the future

T = Team Building:  be the glue to connect your primary doctor with your haematologist;  connect with MPNers

Y = Yes You Can   “Act As If…”

Know Thyself & Thine Disease.

Become as much of an expert on your illness(es) as you can be.

Bring your physician along with you as your learn:

·       With peer-reviewed literature when possible.

·       With updates at office visits from experts

·       With respect & deference

Exercise Recommendations:

·       Aerobics:  Increase heart rate for 1 hr/day, 6 days a week.

·       Stretching.  Yoga and slow stretches.  15 minutes/day, 2 days per week

·       Resistance.  Weights and bands and calisthenics 2 days per week.

·       Make it fun.

·       Make it a joint exercise.

"You gain strength, courage, and confidence by every experience by which you really stop to look fear in the face.  You are able to say to yourself, ‘I lived through this horror.  I can take the next thing that comes along.”  ~ Eleanor Roosevelt.

Living an Intimate Life with Blood Disease

Teri Britt Pipe, PhD, RN

We got to talk about sex on Sunday!
Dr. Mesa introduced the session by reminding the group that intimacy is more than sex; and intimacy begins in infancy.  In the international survey of MPN patients, Sexuality Problems was ranked #4.

Dr. Pipe

Assumptions:

·       There’s more right with you than wrong with you.

·       You are a unique individual.

·       You are dynamic;  you change.

·       You are on the journey together and alone. 

·       Sexuality and Intimacy “belong” in the clinical encounter, even if it is uncomfortable for the provider.

Where does sexuality reside?

·       Mind/brain – the most important sex organ.

·       Senses – experience what you see, hear, taste, feel.

·       Body – the skin is the largest organ and touch is important.

·       Communication

·       Being – a sense of being in this world.

Possible Impact of Chronic Illness on Sexuality

Performance                                                           

Relational

Sexual Response model by Masters & Johnson

We’ve learned that it’s not as linear as M&J described.

Sometimes the arousal curve gets disrupted by a negative thought…

It’s much more useful and comforting if the orgasm is not the goal.

Mind/Brain

Signals:

Gender Differences
Personal differences – change over time

Mind-Body Approach

Preparation for Conversation with Your Partner

·       Reflect on your own preferences and needs:  what is it like when I feel loved and cared for?

·       Reflect on what your partner may be experiencing.

·       Breathe, cultivate an attitude of appreciation.

·       Listen with appreciation and compassion.

Conversation(s)

·       I feel close to you when ___

·       I like it when ___

·       I want to show you how much I care for you.  Please share with me some ways you  might like me to show you.

·       I would like to try ___  Would that be okay with you?

Limitless Expressions

·       Cuddling

·       Holding hands

·       Eye contact

·       Humor

·       Art, poetry, music, food

·       Phone calls, cards, tokens

Location, Location, Location

·       Keep the bedroom as a place for intimacy and sleep

·       Talking about difficult/awkward things elsewhere

·       Having shared signals for intimacy 

·       Comfort, serenity, peace, belonging

Mindfulness

Paying attention, intentionally

Enjoyment with awareness

Bringing attention to the senses

Asking for Additional Resources

Health care team

“Cuddle Sutra” book by Rob Grader

“Relationships” cd by Bellaruth Naparsek

“Baggage Claim”  -- this illness time is a good time to

To love a person is to learn the song in their heart and sing it to them when they have forgotten.

Supplements and MPNs

Larry Bergstrom, MD

Dr. Bergstrom provides integrative medical consultations for patients.  Integrative medicine is a holistic medical program that addresses the physical aspect of health but also treats the emotional, mental and spiritual aspects within the framework of exercise, nutrition, and stress reduction.

While there is no consensus or recommendations for incorporating supplements into the treatment of myelodysplastic or myeloproliferative disorders, supplements are helpful when people do not eat a balanced diet.

Utilizing food as a source of health and energy.

Emphasis is on food first.

Supplements are used to fill in where food is not there.

He promotes:

Mediterranean/Anti-Inflammatory Diet

Mediterranean Diet Pyramid

Apoptosis =  cancer cells die

Anti-cancer foods:

tomato, garlic, carrots, tea, ginger, soy, basil, rosemary, turmeric/cumin, broccoli, watercress,

Cruciferous vegetables:  broccoli, brussel sprouts, cabbage, …

Any mushrooms must be cooked to get any benefit from them.

Alzheimer protector:  cumin/turmeric

These are the Recommended Supplements Summary  

·       Resveratrol:  500-1000 mg/d  (inhibitor of CYP2D6 and CYP2D9)

·       Indole-3-Carbinol 300-400 mg/d   (replaces broccoli)

·       Turmeric (black pepper (300-100 mg/d

·       EGCG 500-750 mg/d                                   ~3 cups of green tea per day

·       DIM 300 mg/d

·       Vit D  1000 IU/d

·       PEITC    watercress

·       Fish Oil (sum of DHA+EPA) 1000 mg/d   <-  pay attention to the DHA and EPA Omega 3’s

Cancer cells makes lots of reactive oxygen species (ROS) – stimulates cell production.  Watercress suppresses ROS.

A Medical Doctor asks:  What’s making you sick?

A Naturopath asks:  What’s keeping you from being well?

Closing Session:  Mindfulness Meditation

Teri Pope

Mindfulness Meditation

An awareness of moment-by-moment experiences that arises from intentional

Mindfulness Based Stress Reduction (MBSR) by Jon Kabat-Zinn at U-Mass Medical Center

Attitudinal Foundations:

·       Non-judging

·       Patience

·       Beginner’s mind

·       Trust

·       Non-striving

·       Acceptance

·       Letting go

This is an effective tool in leadership. 

Resonant Leadership (Boyatzis & McKee, 2005)

Healthy Mindfulness Practices

·       Breath awareness

·       Positive emotion/relive a positive emotion

·       Mindful eating:  look at your food, notice the texture, taste it, chew it, enjoy it before you swallow; what would it be like if I did every meal like this?  Think about all the hands that brought this to you.

·       Kindness tracking:  those that have come to you and that you’ve extended to others.

·       Gratitude practice:  even with your to do list

·       Gentle movement: 

Please Note:   These are ROUGH notes.  A more complete report will be written when the powerpoints are made available and my mom's notes are combined.  I'll make them available in a PDF document.