Thanksgiving

My Thanksgiving was stellar. My son, his girlfriend, another woman friend and her boyfriend arrived while my Honey prepared most of the meal. He spoils me so much! We played a word game for two hours afterwards. The "kids" cleaned up completely. They are all in their mid thirties. One of my cats made himself useful by being the welcome committee making friends with everyone, while the other three cautiously remained in the perimeter as they checked everybody out. I really enjoyed myself. These next two days, though, I am exhausted.

I will see the Heme/Onc on Tuesday and see what is next for me. I just wish there was something to treat the rash! It is like sandpaper skin, mostly upper body and of course, as I mentioned, worse on my face. I hate it! I was actually hoping for nausea as my side effect so I could lose some weight!  ;D

'Til Death Do Them Part

This stuff is complicated and I am trying to learn what it means!

The eye of my cat, Timmy

What is the Philadelphia Chromosome and what does it have to do with me?

The chromosome abnormality that causes chronic myeloid leukemia (CML). Abbreviated as the Ph chromosome. I have this in my bone marrow. It is not normal to have it.

The Ph chromosome is an abnormally short chromosome 22 that is one of the two chromosomes involved in a translocation (an exchange of material) with chromosome 9.

To the best of my understanding chromosome 22 has divorced it's partner and is now marrying chromosome 9. They cannot get divorced. They will reside in my body until I die.

This translocation takes place in a single bone marrow cell and, through the process of the production of many cells from this one mutant cell, it gives rise to the leukemia.

The discovery in Philadelphia in 1960 of the Ph chromosome was a landmark. It was the first consistent chromosome abnormality found in any kind of malignancy. Now other cancers are being identified genetically.

The discovery led to the identification in CML cells of the BCR-ABL fusion gene and its corresponding protein. ABL and BCR are normal genes on chromosomes 9 and 22, respectively. 

The ABL gene encodes a tyrosine kinase enzyme whose activity is tightly regulated (controlled). In the formation of the Ph translocation, two fusion genes are generated: BCR-ABL on the Ph chromosome and ABL-BCR on the chromosome 9 participating in the translocation. 

The BCR-ABL gene encodes a protein with deregulated (uncontrolled) tyrosine kinase activity. The presence of this protein in the CML cells is strong evidence of its pathogenetic (disease-causing) role. 

The efficacy in CML of a drug that inhibits the BCR-ABL tyrosine kinase has provided the final proof that the BCR-ABL oncoprotein is the unique cause of CML.

The Ph chromosome is also found in a form of acute lymphoblastic leukemia (ALL). It seems highly probable that this form of ALL is due to the same chromosomal and molecular mechanisms as CML.

Where to Next?

I have a very dear friend who is dealing with very challenging issues.

I'm posting this picture I found on the web, because I didn't have a bear around here to pose for me.

My cat refused to put on the costume!

Like the bear in the picture, we all find ourselves in the oddest places sometimes and just have to hang on a minute and assess the situation, get our "bearings" and follow our instincts to find the path to the next level of our lives.

May the furs be with you, dear Karen!

If it's Normal, Why Continue With Chemo?

Each time I visit my oncologist, I will be asked to have my blood tested. All people with CML have to do this regularly. What caused me to be referred to the oncologist in the first place was my high white cell count.

These blood tests are to monitor the disease and ensure that treatment is working effectively.

Art Glass from Monterey Bay Aquarium
photo taken by Elizabeth Munroz

My blood tests have returned to normal already as I mentioned in yesterday's post. I had a blood test in June which was normal.  It was not indicating the possibility of leukemia. August 24th the same test was done, a CBC, which made the doctor suspicious of Leukemia. In September the test was run again, and still it indicated the same.
That is when I was told I have leukemia. After that, the bone marrow biopsy was done and it verified that I have CML for sure.

Before I started the chemo pill, my blood test was run again. This time the white cells had quickly raised up to 51,000. Alarming to say the least.

I've been taking the chemo pill daily for a few weeks. Now I have what is called hematological response which shows how well the treatment is normalizing my white blood cell count. Complete hematologic response is normal white blood cell and platelet counts, no blasts in the peripheral blood, and less than 5% myelocytes and metamyelocytes in the blood.

It is now my understanding that a cytogenetic response is the next thing to be looked for to verify there is a response inside the bone marrow. But, I wont have that information until  I get my next bone marrow biopsy. I was told that would happen in about six months. Just because the blood looks normal doesn't mean it's normal deeper within.

CBC Blood Test Results

Went to the oncologist on Tuesday. These are my blood results. Everything is back to normal except Lymphocytes. They've been low for a very long time even way before the diagnosis of CML.

I called his office today to ask if I should be continuing to take the Chemo pill. I am concerned that it might push my blood values to below normal. I had to leave a message with the person who answered the phone. She said she would pass the message on to his nurse. I asked if I could speak to the nurse. I was told she was busy. I asked if I could have the nurse call me back so I could talk to her about this. I was told no, the doctor has to make the decision.

Then, why the heck is the message to be passed on to the nurse?

I told the woman who answered the phone that I didn't want to have the same thing happen as last time when I called just before a weekend. And then no one called me back on that day, and then no one called me back until late on the following Monday leaving me a message on my phone to call back the next day. I didn't want to go through the weekend without having an answer.

So, today, I did get a phone call... from the nurse. Dr. Wong is too busy to talk to me. He says must continue to take the medicine. When I asked her if the medicine was going to continue to push my blood results below normal, she didn't know the answer.

I know there are other patients who are in much worse condition than I am. I have the "easy" cancer, the chronic cancer, which is now much more controllable than in the past. So naturally, the doctor is going to be more involved with the others. But, I wish I could get my questions answered even if they are stupid questions. I am not finding the answers myself.

Forgot to mention that my eyes are infected. When I saw Dr. Wong on Tuesday, I went to Urgent Care and was seen by a doctor there, who ordered antibiotic eye drops for me. They sting! but at least my eyes are not so gunky and red!

Wednesday I went to the dermatologist because the rash has gotten much worse, especially on my face. Dr. South ordered two prescriptions for me. I hope they work. He told me to put ice packs on my face to treat the burning of my cheeks.

I need to accept that I have a doctor who needs to apply himself to the patients who have more serious problems. I really shouldn't be complaining. I am very fortunate that things are not worse than they are.

Below is my almost perfect blood test results.

Component	Your Value	Standard Range	Units	Flag
White Blood Cell Count	8.3	4.0 - 11.0	K/uL
Red Blood Cell Count	4.00	3.90 - 5.40	M/uL
Hemoglobin	12.7	12.0 - 15.5	g/dL
Hematocrit	39.7	35.0 - 47.0	%
MCV	99	80 - 100	fL
MCH	31.8	27.0 - 33.0	pg
MCHC	32.0	31.0 - 36.0	g/dL
RDW	13.6	<16.4 -	%
Platelet Count	317	150 - 400	K/uL
Differential Type	Automated
Neutrophil %	73	49.0 - 74.0	%
Lymphocyte %	16	26.0 - 46.0	%	L
Monocyte %	6	2.0 - 12.0	%
Eosinophil %	3	0.0 - 5.0	%
Basophil %	2	0.0 - 2.0	%
Abs. Neutrophil	6.1	2.0 - 8.0	K/uL
Abs. Lymphocyte	1.4	1.0 - 5.1	K/uL
Abs. Monocyte	0.5	0.0 - 0.8	K/uL
Abs. Eosinophil	0.2	0.0 - 0.5	K/uL
Abs. Basophil	0.2	0.0 - 0.2	K/uL

CML Treatment

HOW IS CHRONIC MYELOID LEUKEMIA TREATED?

The treatment of CML depends on the phase of the disease and the patient’s overall health.

The goal of treatment is a complete cytogenetic response, meaning that there are no cells with the Philadelphia chromosome.

The initial treatment for chronic phase CML is targeted therapy with the drugs imatinib (Gleevec), dasatinib (Sprycel), or nilotinib (Tasigna).

If there is no evidence of the Philadelphia chromosome and the blood cell counts are normal during the initial treatment, patients should continue the medication throughout their lifetime with regular monitoring to see how well the treatment is working.

Bone marrow/stem cell transplantation may be an option if targeted therapy is not effective.

Above information came from here

I Have So Much to Learn!

Low BCR-ABL expression levels in hematopoietic precursor cells enable persistence of chronic myeloid leukemia under imatinib

1. Ashu Kumari1, 
2. Cornelia Brendel1, 
3. Andreas Hochhaus2,
4. Andreas Neubauer1, and 
5. Andreas Burchert1,*

+Author Affiliations

1. ¹ Philipps Universitaet Marburg, Universitaetsklinikum Giessen und Marburg, Klinik fuer Haematologie, Onkologie und Immunologie, Marburg, Germany;
2. ² Universitaetsklinikum Jena, Klinik fuer Innere Medizin II, Abt. Haematologie/Onkologie, Jena, Germany

1. ↵* Corresponding author; email: burchert@staff.uni-marburg.de

Abstract

BCR-ABL overexpression and stem cell quiescence supposedly contribute to the failure of imatinib mesylate (IM) to eradicate chronic myeloid leukemia (CML). 

However, BCR-ABL expression levels of persisting precursors and the impact of long-term IM therapy on the clearance of CML from primitive and mature bone marrow compartments are unclear. 

Here, we have shown, that the number of BCR-ABL positive precursors decreases significantly in all bone marrow compartments during major molecular remission (MMR). 

More importantly, we were able to demonstrate substantially lower BCR-ABL expression levels in persisting MMR colony forming units (CFU) compared to CML CFU from diagnosis. 

Critically, lower BCR-ABL levels may indeed cause IM insensitivity, since primary murine bone marrow cells engineered to express low amounts of BCR-ABL were substantially less sensitive to IM than BCR-ABL overexpressing cells. 

BCR-ABL overexpression in turn catalyzed the de novo development of point mutations to a greater extend than chemical mutagenesis. 

Thus, MMR is characterized by the persistence of CML clones with low BCR-ABL expression, which may explain their insensitivity to IM and their low propensity to develop IM resistance through kinase point mutations. 

These findings may have implications for future treatment strategies of residual disease in CML.

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