Living with CLL

Yesterday, after having had my upteenth follow up at MD Anderson, I was talking with my son about our respective days and what the doctors shared with me. During our conversation, he asked me, sort of timidly, “I understand that your ‘numbers’ have been going the wrong direction, but what do you actually DIE from when you have CLL?” That was a very good question…that I’m sure many folks who don’t have cancer might wonder. 

Cancer starts when cells start to grow out of control. Cells in nearly any part of the body can become cancer and can spread to other parts of the body. Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. It's a type of cancer that starts in cells that become certain white blood cells (called lymphocytes) in the bone marrow. The cancer (leukemia) cells start in the bone marrow but then go into the blood. In CLL, the leukemia cells often build up slowly. Many people don't have any symptoms for at least a few years. But over time, the cells grow and spread to other parts of the body, including the lymph nodes, liver, and spleen. Leukemia is cancer that starts in the blood-forming cells of the bone marrow. When one of these cells changes and becomes a leukemia cell, it no longer matures the way it should and grows out of control. Often, it divides to make new cells faster than normal. Leukemia cells also don't die when they should. This allows them to build up in the bone marrow, crowding out normal cells. At some point, leukemia cells leave the bone marrow and spill into the bloodstream. This increases the number of white blood cells in the blood. Once in the blood, leukemia cells can spread to other organs, where they can prevent other cells in the body from functioning normally. This is just a scratch on the CLL surface as there are so many additional variables such as negative markers…which I have…but I won’t get into that. Suffice it to say, it makes it harder to treat.

So…the answer to my son’s question is this. An infection (usually pneumonia) is the most likely cause of death of a CLL patient. CLL impairs our immune system, so that we are not as able to resist infection as someone with a normal immune system. Either that or a shutting down of the vital organs due to the limited “good” blood flow…or lastly, negative reactions to treatments…like Richter’s Syndrome when CLL transforms into a more aggressive form of large cell lymphoma. (Though I have a dear friend where it happened the opposite way…lymphoma to leukemia.)

So what does all of this have to do with LIVING with CLL?! I guess the first thing that I wanted you to know is that unless the Lord puts His Hand on my head and says “Be Healed,” there is no cure for CLL. And we’re ok with this. We weren’t at first, obviously…but we are now. We’re all going to die of something. I just have a higher percentage of knowing what mine’s going to be from…unless I get hit by a bus or we fall off a cliff when hiking! The Lord has appointed our days. That’s why I don’t worry. He’s got this. I just need to be faithful in pursuing my best options of staying around as long as possible. 

Which brings us to yesterday. Dr. W reviewed my treatment history…Campath to reduce leukemia prior to transplant, stem cell transplant, two donor lymphoctye infustions, and two CAR T-Cell trials. Only the transplant got me into remission for a couple years. Everything else were attempts to get me back there. They all failed…BUT they bought me TIME! They worked just enough to slow things down a bit. And give my body a chance to recuperate before ramping up for the next treatment. Dr. W has given us three paths to review and research. We actually have already started the research the last time we talked about this, but yesterday’s info was more intense. So as to not completely lose the majority of you, I will not go into too much detail about each of these protocols. Just enough that it makes sense for those who have asked…. 

Aberrant signaling of the B-cell receptor pathway has been linked to the development and maintenance of B-cell malignancies. Targeted inhibition of Bruton's tyrosine kinase, or BTK, has improved clinical outcome in patients with relapsed (and treatment-naïve) CLL. Acalabrutinib is one such BTK inhibitor with somewhat fewer side effects than its predecessor, Ibrutinib. 

Apoptosis is an orderly, programmed intracellular signaling cascade that leads to cell death. BCL-2 encodes an anti-apoptotic protein and was the first oncogene identified that primarily exerted its oncogenic effects by inhibiting cell death, rather than by promoting uncontrolled cellular proliferation. Venetoclax is one of a new class of cancer treatments that operates by directly promoting the cellular process of apoptosis, or programmed cell death. It is even been shown to work well with 17p deletion (which I have). 

Lastly, Obinutuzumab is a monoclonal antibody (antineoplastic cytotoxic chemo drug) that affects the actions of the body's immune system. Obinutuzumab strengthens your immune system to help your body fight against tumor cells. Combined with other drugs, it has shown to be effective in treating CLL. I say all this because ONE of the three choices included all three of these drugs…where the first two were either just BTK inhibitors or just BCL-2 inhibitors. The new trial, which just began a couple weeks ago at MDA, offers in our opinion the best of all options, plus it’s a 2-year trial with the goal of getting back to remission and buying me some more time. My name is on the list. 

So why not start now? Well, that’s a good question, too! I have several numbers that we follow…white blood count, hemoglobin, platelets, plus my absolute neutrophils and lymphocytes (part of the WBC). While most of my numbers continue to move in the wrong direction, my hemoglobin and platelets have been on the low but steady side. So because of the toxicity of treatment, they don’t get in a big hurry to rush into things until ALL my numbers are going south. Plus, they look at physical symptoms as well such as swollen lymph nodes (check), fatigue (check), night sweats, weight loss and enlarged spleen…ok on those currently. So as is so common with CLL…we wait. Another three months. And check again. Unless my physical symptoms worsen before then. 

I know this was a LOT of information, but so many of you have asked specific questions and asked how to pray. While I appreciate prayers for “healing,” outside of a massive miracle, CLL doesn’t just go away. But it can get squashed down for a while. So that’s my prayer. Always has been. That God will give us time. Time together. Time to do the things we love. Time with our family. Time with friends. Time to travel. Time to help others. Time to build our house and retire in the country. Time to enjoy this life He has given us. 

At the end of our lives, people often reflect and ask themselves…Did I live? Did I love? Did I connect? Did I matter? Did I contribute? Life has given me a second chance…a “golden ticket.” I intend to make sure I have used it well. 

What will you do to live today? To make difference? To be intentional? Will you have any unanswered questions when your day comes? Life is about choices. Choose well. 

 

 

It’s all in the details….

Many of you have asked for more information as to what exactly the “17p deletion” is and what it means.  Others have asked for details about the bone marrow transplant.  I am going to include both here.  Please forgive the lengthiness and the sterile dialogue.

17p Deletion

To put it as simply as possible, and to quote my oncologist, 17p deletion involves a molecular change in chromosome p53 which creates resistance to chemo.  “Preliminary data indicate that the presence of chromosome 17p deletion (17p-) by fluorescent in-situ hybridization (FISH) in chronic lymphocytic leukemia (CLL) may be uniquely associated with resistance to standard therapy and dismal survival.”   

Bucket A CLL patients can “watch and wait.”  Bucket B patients can be “managed.” But…

“For the last third of patients with the most aggressive form of CLL and all the bad prognostic indicators, accurate diagnosis and risk classification are even more important. These folks are in high risk “Bucket C”. They don't have the luxury of a lot of time to waste.  Dithering is not an option for them.  For this unfortunate subset of CLL patients, making the right first therapy choices is essential.  Under-treating an aggressive form of CLL, waiting too long or wasting time with ineffective and tentative therapies spells trouble of the worst sort.

If you are a younger patient with high risk profile, the game plan becomes a lot more critical. Unlike more elderly patients with a middle of the road prognosis, you are not going to be able to “run out the clock”.  A five to ten year survival prognosis is not good enough, you face too much of a penalty in reduced life span.  Even our best chemotherapy regimens are not going to hold the line for what would otherwise be your normal life span.  I am extremely happy to report that modern advances in stem cell transplants now give us options we did not have just a few years ago. Emerging consensus is that young patients with high risk CLL should be looking at stem cell transplants sooner rather than later.

Think of stem cell transplants as getting rid of your cancerous, no-good-bum of an immune system and replacing it with a healthy immune system from a compatible and willing donor. It helps if you have a well-matched sibling donor, since it saves the hassle of finding a matched unrelated donor, a task that becomes next to impossible for ethnic minorities.  Stem cell transplants are coming up the curve awfully fast.  Survival statistics are improving each year.  But making the decision to go the transplant route is still a tough call and you really need to get your ducks in a row before you can make it.”

There are basically two schools of thought in treatment.  One, wait until I’m more symptomatic before treating.  Or, two, treat now while I’m still young and healthy (yes, my doctor said that 50 is young!) and have a better shot of handling the treatment and transplant.  This is the decision that the MD Anderson specialists and my oncologist will be discussing over the next week or two after they get the results back from all my upcoming tests.

Allogeneic Stem Cell Transplant (via MDA Patient Education)

This section is for patients who may be receiving stem cells from a donor’s peripheral blood or bone marrow. 

General Information

Stem cells are found in a person’s:

· blood,

· bone marrow (spongy tissue found inside the large bones of the body) and a

· newborn baby’s umbilical cord.

During an allogeneic transplant, physicians collect stem cells from a donor and infuse them into a patient.  A special blood test called HLA (human leukocyte antigen) typing checks if a patient and a donor are a match. The donor may be: 

· an identical twin (a syngeneic transplant), 

· a relative, 

· someone who is not a relative (matched unrelated donor, or MUD transplant), or

· a newborn baby (umbilical cord blood transplant)

Before the transplant, the patient receives high doses of chemotherapy and/or radiation to destroy the disease; however, this also damages other parts of the body, including the bone marrow and immune system.  (The immune system is the body’s defense against disease and infection.) Also, the body is not able to make healthy blood cells.  The transplant repairs these effects and creates an environment to accept the donor’s stem cells. 

Graft-Versus-Leukemia Effect

Graft-versus-leukemia or graft-versus-disease effect (GVL/GVD) is a major benefit of an allogeneic transplant. It occurs when the donor’s cells destroy the patient’s cancer cells because it “sees” them as “foreign” and different.

HLA Typing

If you are being considered for an allogeneic transplant, you will need HLA typing.  Antigens are proteins found in white blood cells that make each person’s tissue type unique. HLA typing is a special blood test that finds these antigens and then compares them to the donor’s. Both the patient and all eligible family members should be HLA typed to find a suitable donor.

Finding an HLA-Matched Donor

It is important to find the most highly matched donor available. If the donor and patient are HLA-matched, there is less risk of complications.   The best donor for an allogeneic transplant is an HLA-matched sibling. This is because parents pass on one-half of their HLA typing to their children. Therefore, each brother or sister has a 25 percent chance of being a match with the patient. There is about a 1 percent chance of being matched with a parent, child or distant relative.

Collection of Peripheral Blood Stem Cells or Bone Marrow

Stem cell collection is a procedure that involves separating and collecting stem cells from the blood or bone marrow, then the stem cells are stored for transplant use. 

There are two main ways of collecting stem cells: 

· Apheresis is the process of collecting peripheral blood stem cells (PBSC) from the

bloodstream. 

· Bone marrow collection (harvest) is the process of collecting the cells directly from the bone marrow.

Admission for Stem Cell Transplant

Pre-admission Testing

Before you are admitted for your stem cell transplant, you will need a series of tests. All of the tests evaluate your disease or personal health. Unfortunately, some of the tests are repeats of tests you have already had, but they need to be done within 30 to 45 days of your transplant.  (NOTE:  My tests begin October 10.)

Conditioning Phase

During the conditioning phase, patients receive high doses of chemotherapy and/or total body irradiation before the transplant. This:

· Eliminates the existing bone marrow cells to make room for the donor’s new, healthy cells

· Destroys any existing tumor cells if there is cancer or a tumor

(NOTE:  my doctor has already decided on the FCR regimen.)

Stem Cell Infusion

The collected cells are infused after the completion of the high dose chemotherapy and/or radiation. Using your CVC, the cells are infused into the bloodstream, similar to a blood transfusion. The infusion lasts from 30 minutes to several hours.

Initial Recovery Period

After the stem cells are infused: 

· You will stay in the hospital for about three to four weeks while your counts recover. 

· Your treatment team will monitor your blood counts daily and help manage any side effects. 

· You may take many IV medicines and fluids. 

· Once you have “engrafted,” meaning that your white blood cells have recovered, and you are eating and drinking well, you will be discharged from the hospital.

· Each patient will be evaluated on an individual basis and circumstances will vary. For example, you may need to stay in the hospital if you have a fever or other condition requiring care.

Follow-up/Post-Discharge Recovery

After being discharged from the hospital:

· During this time, you must have a caregiver with you 24 hours a day.  

· You will be monitored in the Ambulatory Treatment Center (ATC) for up to 100 days after the transplant.  Some patients may need to stay longer in the ATC. Follow-up is generally every day and will adjust to every other day or twice a week depending on your health and needs.  

· Each patient will be evaluated on an individual basis and circumstances will vary

· Our goal is that you will be able to return home after the first 100 days, but this may vary depending on individual needs. Once you are told that you may leave the Houston area, you will continue to have follow-up appointments with your cancer or primary care physician in your home community. Some patients may require continued monitoring and symptom management. If this is the case, you will need to stay within 30 minutes of MD Anderson until your physician tells you it is okay to stay further away.  

· Before you are discharged from the Houston area, you will attend a survivorship class.

Once you are discharged home, you will be asked to have regular lab tests done and the results will be sent to MD Anderson for review. You will need to return for tests and exams every three to six months for at least the first year and then every six to twelve months thereafter. This will vary for each patient, depending on your condition. Your physician will make the follow-up plan for you.

Potential Complications of an Allogeneic Transplant

Complications could occur when having an allogeneic transplant. These are: 

Graft Failure

The immune system may reject the transplant. This is uncommon because the chemotherapy and/or radiation given before the transplant suppresses (damages) the patient’s immune system.

Graft-Versus-Host Disease 

Graft-versus-host disease develops in patients who receive any type of allogeneic transplant.   GVHD occurs when the new bone marrow (the graft) reacts against the tissues of the body (the host). There are two forms of GVHD: acute GVHD (short-term) and chronic GVHD (long-term).

Acute GVHD

Acute GVHD happens in the first 100 days after a transplant. You will receive medicines before, during and after the transplant to help prevent and/or treat acute GVHD. The seriousness of GVHD varies from mild and temporary to serious and chronic. It can be life-threatening.

Chronic GVHD

Chronic GVHD develops from three months to several years after the transplant, and it affects multiple tissues in the body.

Weakened Immune System

The immune system is very weak for several months after an allogeneic transplant. It takes over a year for the immune system to recover completely. The first three months after a transplant are critical. Physicians normally prescribe antibiotics during this period, and they monitor patients closely for infections.

Just as an FYI, this is just a nibble of all the information that we have been ingesting over the last couple months.  Please pray for my doctors (and us) as we decide which course of action to take and when.  I hope these excerpts provided some answers to the many questions that have been asked. 

Walking with Him…

Psalms 119:105 “Your word is a lamp to my feet and a light for my path.”

And so it began...

The weekend of June 11, 2011, Paul and I hosted my family reunion at our place in the country. Oletha. Thirty miles west of Centerville, TX, between Marquez and Groesbeck. A little slice of heaven! It's been several years since our last family reunion. Uncle James passed, kids have grown up and have had children of their own, many have moved from Houston to various other cities in Texas, lives have changed. But once together, it was like no time had passed at all. That's the way it is with family.


"Does anyone know what this rash might be?" I asked my cousins.  Impetigo...poison ivy...no one was quite sure.  By Monday, June 13, it was driving me crazy so I called and made an appointment at a convenient medical clinic down the street.  It was easier than going to my regular doctor and waiting two hours just to confirm that I indeed had a rash!  When the doctor came in, she just smiled at me and said that it was not either of those; I had the Shingles.  Pooh!  This was going to get worse before it got better.  Shingles is from the same family as the chicken pox virus...as well as the Bells Palsy I had a few years back.  Supposedly it is aggravated by stress.  They took some blood as part of the routine procedure and told me to come back in three weeks.  


July 6.  I went back for my follow up appointment.  The Shingles had begun to improve, but I had gotten a spider bite over the Fourth of July weekend at the country.  They noted that my blood test showed an elevated white blood count but that it was probably from the Shingles.  They wanted to do another test just to check.  So they sent me to the lab and then started me on a steroid for the spider bite.  Come back in three weeks.


Before the three weeks were up, I got a call saying that my tests had come back and my white blood count was still elevated and even though it was probably first attributed to the Shingles, then to the spider bite, they wanted to refer me to a hematologist...just as a precaution.  Thorough is always good.  So I made my appointment and then googled the doctor they referred me to and learned that he was a hematologist/oncologist.  "Why are they sending me to an oncologist?!"  After worrying about it for the next 24 hours, I decided that it was not a big deal.  He was probably their hematologist of choice who just happened to also be an oncologist.  No worries.


July 18.  Wow!  I wonder if all oncology office staff are so incredibly nice?  From the receptionist to the phlebotomist to the good doctor himself, everyone was attentive, kind, and caring.  Here the finger prick would deliver results in just minutes.  When I saw the doctor, he already had the results.  Still high.  Not horribly high.  But definitely above normal.  Just as a precaution, he decided to do a CBC, complete blood count.  By this time, I had already googled "elevated white blood count" and read about leukemia and the various types.  But I don't have leukemia.  I don't even feel bad.  He is just being thorough.  It has simply been a series of things that have slightly elevated it during this crazy hot/dry summer.  Shingles, spider bite, steroid....  It'll be fine.


August 8.  Heading back for the results.  I have assured my mom that everything is fine.  You know how moms worry....  Another finger prick and in I go.  The good doctor comes in and goes over all the details of my CBC.  My white blood count and lymphocytes went down a tiny bit but were still elevated.  My neutrophil % was low.  In all other areas, I look like the picture of health.  There must have been something there, however, that raised suspicion because he had a pathologist friend of his review my tests as well.  He recommended a flow cytometry test just to rule out leukemia.  More blood.  Come back in three weeks.  He's very thorough.  Yes, mama, he's just taking precautions.


August 29.  All the other times I have been to the office, my wait was short and there was rarely another person there.  Today, the waiting room was full of folks with cute little hats, somewhat obvious wigs, all talking and hugging and sharing with one another how good they each looked, what side effects they were experiencing, how others were doing who weren't there right then, and how back in the old days people would die and never know why...now we die but at least we know why!  They all seemed quite comfortable with this conversation.  I was not.  I hadn't needed to be.  I was there today to find out if I might need to be.  Tears stung my eyes and those of a husband across the room who obviously wasn't ready for this yet either.  "Did I say how good you're looking today?"


After what seemed to be an endless wait, I was called back for my now regular finger prick and weigh in.  I've lost a couple pounds....  In the examination room, I waited for the good doctor, still thinking about the lovely, honest people I just met.  He came in carrying a stack of print outs.  Each week I had been given the one blue sheet with that week's stats and a second blue sheet with my next appointment.  This was different.  This was a dozen or more pages filled with information that I wasn't sure I wanted.  "You have what is called Chronic Lymphocytic Leukemia.  It is the slow growing type.  If there's a good cancer, this is it.  People usually die of old age rather than the disease.  You are only at Stage 0!  We'll schedule a bone marrow biopsy in four weeks or so, but the recommended treatment at this stage is to 'Watch & Wait.'  Try not to research the entire internet as it is not regulated.  Stick to the national cancer and lymphoma and leukemia society sites."  After further explanations of test results, the good doctor rose, took my hand, and said, "I'm so sorry."  I'm so sorry?  Why is he saying that?  


I wandered out to my car.  I called my mom first because she worries so and I knew that my conversation with Paul would be much more lengthy.  "Mama, I have leukemia...but he said that it's going to be ok......"  I called Paul, told him the same, and asked where we could meet for lunch.  We sat at China Bear, me eating my sushi, edamame, and spring rolls...Paul eating all his fried Chinese favorites...while he poured over all the papers I had brought home.  When we finished, he held me tight and then I went home to get back to work.  Less than thirty minutes later, Paul walked in the door.  "What are you doing home so early?" I asked.  He simply said, "This is where I need to be."  That's when I realized that I had cancer.


The next two days, Paul poured over the information sent by the doctor, the additional recommended sites, and probably a lot of material that would have been better left alone.  He made endless notes.  He took all the data he was learning and tried to analyze my test results...trying to understand what it all meant.  And we just spent time together.  He finally realized that he had information overload, but he desperately needed to understand.  He wanted to fix it.  He asked me to schedule a consultation with the good doctor.


September 1.  Another finger prick, just for good measure.  My white blood count had jumped a little higher.  :/  We met with the doctor who patiently answered all of Paul's very good questions.  In fact, the doctor said that he had a couple of them on his board exams!  I had questions about nutrition, etc.  Once Paul's questions were satisfied, he asked why we needed to wait four weeks for the bone marrow biopsy.  The doctor said that we didn't and he could do it right now.  OK....  Shift scene to prepping for the test.  Nurse and doctor each doing their role.  I had heard that this test could really hurt, so he injected a hefty dose of Lidocaine into my hip.  I definitely felt the first two, but the medicine took effect quickly and I didn't feel the last two or any aspect of the test itself.  Paul watched while he screwed that T-bar into my pelvic bone.  Glad it was numb!  Once he was done and I was bandaged up, I turned over to prepare to leave.  My speech began to slur and my body began to tingle.  They quickly got me back on the table.  Within minutes, my breathing was labored, my blood pressure elevating, and I couldn't move or talk.  The nurses freaked!  They wanted to get me to the ER immediately.  But the doctor came in and checked me.  I could still wiggle my toes and stick out my tongue.  They started an IV of saline to begin diluting the Lidocaine.  At first they thought it was an allergic reaction, but I've had it dozens of times.  I think the hefty dose was just a bit much for my non-hefty back side.  It took over two hours to regain my feeling and ability to move.  They poured me into a wheelchair and then into Paul's truck.  He drove me home and then poured me into bed.  That was enough excitement for one week!  Paul called my mom and the kids....


September 15.  Paul and I head back to the good doctor's office for the bone marrow biopsy results.  Another finger prick.  These are beginning to not bother me as much....  He joined us in the examination room with most of the results.  They were not as positive as he had expected.  Two out of three markers were considered "unfavorable."  But he was still confident that treatment would be later than sooner.  As soon as the FISH results are printed, we will have all the information we need.  What we do not want to see is the "17p deletion."  It is fairly rare, but missing that portion of the chromosome can render treatment ineffective and usually results in a bone marrow transplant.  But we have no reason to expect....  The nurse popped in handing him the results.  For the briefest moment, the good doctor lost his composed, calm, positive demeanor.  Paul and I both saw it.  Immediately, he regained his confident doctor face and showed us the results.  17p deletion.  "This does not have to mean doomsday.  It simply means that treatment will now be sooner than later."  


With orders for an abdominal ultrasound and a bone marrow evaluation at MD Anderson, Paul and I realize that this journey has just taken a different turn.


I am thankful that God allowed me to get the Shingles.