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Questions about blast crisis in CML

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Hi,

My mother(52y) was diagnosed with CML in March 17 and was started on imatinib immediately. After 8 months on imatinib she started experiencing evening fevers and chill and body aches. Bone Marrow tests revealed 40% blast cells in November and WBC 2x10^5. Doctors suggested the presence of Blast crisis.

She was immediately started on a round of chemotherapy hoping to reduce the percentage of blasts, but after 2 months of therapy it only reduced to 22%. 

Thereafter for two months the doctors gave her 2 rounds of Azacitidine to try and control the disease. However there was little or no response to Azacitidine and her counts were off charts again. 

Finally she was put on 100mg Dasatinib OD, but within a week she experienced thrombocytopenia while neutropenia was induced.  the medication was stopped for 10 days to allow for platelets to increase but WBCs also increased in the meantime. This cycle repeated after she was restarted on Dasatinib. The blast counts were up to 50% in the meantime.  

Since then she has been on-off Dasatinib for 4 months now. the dosage has been reduced to 50mg OD so that she can tolerate the medication. Each time, she seems to be on Dasatinib for a little longer than before but ends up with low platelet counts (~15k) and WBC(~2k) and we discontinue Dasatinib for 10 days and start back again. she has been needing blood and platelet transfusions almost every 10 days.

Is this a normal thing to do? To go on and off Dasatinib ? I wanted to know if other patients have experienced something similar.  

How can we better manage Thrombocytopenia (low platelet counts)? Any tips would be greatly appreciated!

On again - off again pulsing of Dasatinib is a standard protocol for dealing with myelosuppression (neutropenia, etc.). Her doctors don't want to give her neupogen ("stimulation" shots) in order to keep her on Dasatinib because research is suggesting that 'stim' shots stimulates the cancer as well. Given she is in blast crisis, managing blasts is their top priority. There is also evidence that lower dose Dasatinib is actually more effective than the higher dose when myelosuppression occurs. Her doctors are doing the right thing. However ...

There is evidence that high normal vitamin D levels induces blast cells to differentiate. And through differentiation blast cells decrease in number and go through more normal apoptosis and die. Vitamin D activates our immune system. It is used by the bone marrow to signal blood cell differentiation. Blast cells are an itermediate cell that under normal hematopoiesis very quickly differentiate into the rest of the blood cell types. Normal blood will have very few if any blast cells detected because they differentiate quickly once created (and need vitamin D to do so). In unchecked CML blast cells will accumulate by not differentiating. Blast crisis occurs quickly when this occurs. Blast crisis is dangerous. It is what kills in CML (chronic phase doesn't kill - you just feel bad). Vitamin D is a vital component in blood cell differentiation and immune function overall.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725501/

"3. Utilizing Vitamin D in Antineoplastic Therapy
3.1. Vitamin D as Differentiation Therapy for Myeloid Malignancies

In vitro studies show that vitamin D promotes differentiation of normal hematopoietic precursors and malignant myeloblasts, which has led to significant interest in studying vitamin D analogues as treatment for myeloid malignancies"

Perhaps your mother has very low vitamin D blood levels? Many people are deficient in vitamin D and don't know it. I maintain my vitamin D level around 70 ng/ml having started at 17ng/ml!. Once I achieved 70ng/ml, my residual blast cells disappeared from my blood counts. Your mom should have an immediate vitamin D blood level test. Assuming she is very low on vitamin D (which I suspect), she should consider taking vitamin D3 supplements (which converts to vitamin D active form in the body) to raise her vitamin D level to around 70 ng/ml. I take 10,000 IU's one day followed by 5,000 IU's the next (during fall/winter months). If she is very low to start, she should take much more to get her level up (50,000 IU's per week at 10,000 per day for 3 weeks). Vitamin D3 supplements need to be taken with fat to absorb.

Oncologists don't know to suggest vitamin D by and large. They are focused on drugs not nutrition. Adding a vitamin D3 supplement to her program won't hurt (and won't interfere in any way with Dasatinib) and could very well help. There never is a guarantee, but worth a try.

Time is not her friend, your mom needs to act now and should be monitored very closely. Blast crisis is what kills in CML. She needs to convert from blast crisis back to chronic phase. It's possible and vitamin D therapy may help.

Keep us posted and God speed to your mom.

 

Thank you for your response. I'll follow up on the VitD levels and check with the Doctor.

She has also started experiencing low platelet counts and they dont seem to increase. We are taking 2 platelet transfusions per 10 days almost.
For reference, on Monday, her WBC counts were 3000 and platelet were 12000, the Doctor stopped the 50mg Dasatinib that she was taking alternate day and prescribed 1-Single Donor Platelet infusion. On Friday, the WBC counts were 11000 and platelets were 14000 and we took another Platelet infusion.

Each time the platelets go down, she starts experiencing lots of pains. So I'm wondering how others deal with thrombocytopenia.
We have been including the following foods in diet - pomegranate, spinach, asparagus, pumpkin seeds, pumpkin, beetroot, carrots, etc.

I’ve sufflerad from low thrombocytes, but in chronical phase. Paus and start again was the  protocol then. Beeing able to keep on medication longer and longer sounds like good news. I hope it is a turning point for you!

I think pomegranate is one of those things to avoid:

http://www.nationalcmlsociety.org/living-cml/drug-food-interactions