You are here

Tasigna - very low pallet count, low white cells count and granulocytes count

Categories:

Hi,
My mum was diagnosed with CML in November last year. Initially she was given chemotherapy and then imatinib. Unfortunately, imatinib did not work and just under two months ago she started taking Tasigna. Initially she was feeling much better and her blood results went back to normal after 2 weeks of taking it. Unfortunately, 2 weeks later she had another follow up visit and the doctor decided to stop giving her the medicine because of a low pallet count. 2 weeks has passed since then and her blood results did not improve. They actually got worse. Her pallets are at 30k (the norm starts from 150k), white blood cells are at 2 (the norm starts at 4) and she also has a lower level of granulocytes. Upon review of the blood test results the doctor said that they should start considering a bone marrow transplant.
Has anyone had similar response to Tasigna? If yes, how was it handled?
I would be very grateful for any response. My father had a bone marrow transplant (he was lucky to find a donor) and it was not an easy path. Unfortunately, he is not with us anymore…

E

Sorry to hear about your Mom. Low blood counts are a very common side effect of TKI's.  Mine were suppressed for a while when I was on full dose Tasigna (600 mg/day), but not nearly as much as you Mom's. Her doc was right to stop the medication for a while to let her counts improve.  

What dose is she on right now per day.  Many who have had your Mom's reaction have reduced their dose and found it to be just as effective in controlling the CML while not totally tanking their blood counts.  I am currently on 150 mg/day and my PCR is undetectable.

SCT is a last resort.  Prior to that, lower dose TKI should be explored with your Mom's doc.  If that doesnt work with Tasigna, she could next try Sprycell 50 or 20 mg/day.  Best of luck with this.

Eda,

What your mom is experiencing is very common during the initial phases of CML treatment - especially in the first year. Stem cell transplant is a very last resort and only if there is evidence of CML transition to accelerated phase and everything else fails. She is no where close to exhausting her options.

It is important to know if she has blast cells present and in what amount (usually expressed as a percentage of cells). As long as her blast percentage is low (i.e. < 5%), she has time to acclimate to the drugs.

She should stay off drug until her blood counts get close to normal and then restart a TKI on a much lower dose and build from there. She may very well not need a higher dose and still have very good results. I would suggest 20 mg sprycel for her to re-start once her blood counts rebound. The key blood counts are neutrophils (should be around 1.0 before re-starting drug and not allowed to fall below 0.4) and platelets.

I went through what your mom is going through. My counts became dangerously low and my doctor was experienced enough to suggest I "pulse" my treatment (on and off) in order for my body's blood system to adjust. It took nine months to a year. I was then placed on 20 mg sprycel (1/5th normal dose) and my CML disappeared. I am currently "undetected" and still take 20 mg. I am soon to stop treatment altogether next year. Your mom could very well follow this path. I take vitamin D3 supplements (5,000 IU/day) which has been shown to keep leukemic blast cells in check (i.e. causes them to differentiate into daughter cells).

Understand what is happening. At diagnosis, your mom's blood system was largely leukemic. After starting a TKI, her leukemic system was getting wiped out, but her normal system was too depressed to make up the difference. This is the low counts she is experiencing. When she stops treatment both leukemic and normal systems rebound, but then the leukemic system gets hit again and again and again. Over time, this leads to her normal system replacing the leukemic system. This transition process can take months to years. Vigilance is key to tracking progress. Her doctor should know this and help her through this transition.

I have a feeling your mom will be fine without the need for a transplant.

Edna....What scuba said...he had one of the top Onc in the world at MD anderson.  DO NOT lock down on a doctor.  Find out how many CML patients this doctor has treated.  Research research research  Ask questions

Hi Eda,

I switched from Imatinib to a high dose of Tasigna and my counts dropped very suddenly  after only a few weeks on the new drug. My platelets were 34 and even after stopping treatment they continued to fall to 21 and Neutrophils (important type of white cell) to 0.4. It took 9 weeks for the counts to go back up which is a long time but they did go back up eventually, so please try to give the break from treatment time. 

I then started on a low dose of Tasigna, first 150mg and now 200mg, and it is proving effective at bringing my PCR down. My blood counts remain low but in a safe zone with platelets stable around 60 and Neutrophils around 1.3. I’m 13 months on from diagnosis.

One thing that could be worth exploring is having a bone marrow biopsy if your mum hasn’t already had one? They can show mutations that can help suggest which TKI is going to be the best treatment. For me it has shown a slightly unexpected separate issue to CML which could help explain why I have struggled with blood counts. 

Regards

Hi David,

Thank you very much for your response.

My mum’s Neutrophils were at 0.53 2.5 weeks after the treatment with Tasigna was stopped, the pallets went back to being norm and the leukocytes were very close to being within the lower norm. She is supposed to repeat the test at the end of this week and has an appointment with her consultant on the 14th Aug.

She did have a bone marrow biopsy to determine which TKI should work best for her (at least this is what the consultant said) and I believe on that basis Tasigna was selected. May I ask what issue was discovered when you did the biopsy? Maybe I could ask the consultant if she checked for that….

I discussed the suggestion of the bone marrow transplant with another consultant (which happens to by my mum’s consultant boss and I do not think it is a good thing) and he told me that it was very likely that my mum would need a transplant. I am really shattered by this news and I do not fully understand why they believe so (I did ask the question but I have not received a clear response). When she was admitted to the hospital back in November she had 8% blasts and he BCR/ABL was 97%. I cannot find any information about the blast count in her further documentation but the BCR/ABL was 43% back in March. They also mention 100% Ph (+) in the cytogenic test. I understand the meaning of blasts but not really of the BCR/ABL and PH (+)…

Thank you,

Edyta

Hi Scuba,

Thank you for all the information.

My mum started taking a 4k dose of vitamin D3 and K2 last week following your suggestion. She is also going to check the level of vitamin D3 in her blood.

In relation to the blast count, it was quite high at 8% when she was diagnosed back in November. I cannot find any update on the blast count in her further tests. Her BCR/ABL was 97% and then 43% back in March. They also mention 100% Ph (+) in the cytogenic test. I am not sure what this means.

I discussed the suggestion of the bone marrow transplant with another consultant (which happens to by my mum’s consultant boss and I do not think it is a good thing) and he told me that it was very likely that my mum would need a transplant. I am really shattered by this news and I do not fully understand why they believe so (I did ask the question but I have not received a clear response apart from poor morphological response to Tasigna). My mum’s Neutrophils were at 0.53 2.5 weeks after the treatment with Tasigna was stopped, the pallets went back to being norm and the leukocytes were very close to being within the lower norm. Can it be because her blasts were quite high when she was admitted?

Thank you,

Edyta

Her dose was 800mg/day... 

In relation to the blast count, it was quite high at 8% when she was diagnosed back in November. I cannot find any update on the blast count in her further tests. Her BCR/ABL was 97% and then 43% back in March. They also mention 100% Ph (+) in the cytogenic test. I am not sure what this means.

Dear Edyta,

During diagnosis of CML doctors verify number of cells with BCR/ABL gene. This gene is created by translocation of parts of the chromosome 9 and 22. Chromosome 9 is now longer and 22 is short. We have two main techniques to check them.

One is called FISH where we "colour" chromosomes and we can see those who are "short" and "long" This kind of "long" chromosome is called Philadelphia (first time it was seen in lab in Philadelphia, USA). It is done by technician who visually count those changed chromosomes. So he/she take usually 100 or 200 of cells nucleus and count how many of them are with changed chromosomes. So it appear that at your mom's diagnosis all of nucleus taken into account where with Ph+.

Other technique is more precise and it is made by qPCR where at lab they take a sample and multiply/replicate them many times and check expression of that gene. They measure expression of the reference gene (called housekeeping gene). This gene is expressed at constant rate (not only when needed). Usually in CML they use one of ABL, BCR, B2M, GUS. Because techniques, equipment, environment may differ between lab hospitals they make reference to known lab. After that they introduce conversion factor so we can provide result in local lab "units" and standardized "units" they are called IS (International Standard). So in my wife's example at diagnosis she had: 85k BCR/ABL and 119k GUS, BCR/ABL divided by GUS gives 71% and conversion factor is Cf=1.6. 71%*1.6 gives 115% IS. Because it is measured against other gene expression and because of Cf result can be more then 100%. 

CML is defined with 3 phases: chronic, accelerated, blast. Besides number of white blood cells, platelets we measure no. of blasts. During normal blood cell life cycle blast differentiate into different types. Because of CML they are not. Instead of normal blood cells patient get only blasts. Chronic phase is below 10%, accelerated 10-20%, blast more then 20%.

At which hospital your mom is treated? 

Best regards / Chris

Edit: 

IS is of course International Scale not Standard.

David posted link to a document with better explanation here: https://cmlsupport.org.uk/thread/13195/quick-question-bcr-abl-numbers#po...

“She did have a bone marrow biopsy to determine which TKI should work best for her (at least this is what the consultant said) and I believe on that basis Tasigna was selected. May I ask what issue was discovered when you did the biopsy? Maybe I could ask the consultant if she checked for that….”

Hi Edyta,

Through the biopsy it was discovered that I had a second chromosome abnormality in addition to the 9:22 issue that is seen with CML. It is called Monosomy 7, but I’ve been told it’s rare so it’s unlikely your Mum would also have this. My point is that the biopsies are a much better than blood tests in finding any further issues or complications so the results may help drive your Mum’s future treatment, which seems to be the case. If she has already had a biopsy then chromosome abnormalities would be detected when cells are cultivated in the lab.

Neutrophils of 0.53 are low but they should rise with time off treatment. I have my fingers crossed for you. 

Hi Chris,

Thank you very much for your response & for the links. It is really really helpful.

I was waiting for my mum to obtain a copy of her latest molecular test results (QPCR). It was done at the end of June and it states that B-A1/ABL1 is 61.5% iS. Progression from 43% in February.

I am still not completely clear on why the 2nd consultant (the boss of my mum's main consultant) said that it is very likely that my mum would need a stem cells transplant... And I also do not understand why she was given such a high dose of Tasinga (800mg) as the European LeukemiaNet Recommendations seem to suggest 600 mg per day. There might be something in her results I am not aware of.

My mum has another appointment with her main consultant next week so we will see what she says in terms of the recommended treatment but I feel it might be worth trying to see someone else. Someone who is not working at the same hospital (My mum is being treated in Poland...).

I hope your wife responded well to the treatment and that you and your family can live a normal life without thinking too much about CML.

I just wanted to say something that is probably fairly obvious but people's contributions to this forum (and the forum itself) is incredibly helpful on all possible levels.

Thank you again

Edyta

Hi David,

Thank you for sharing that with me. She has had two biopsies so far so one would hope that any additional abnormalities would have been discovered... However, during my dad's very long fight with various very serious health issues we met both absolutely amazing doctors and really bad ones so I do not fully trust her consultant as yet...

My mum has another appointment on Thursday and we will see what the next steps are.

Thank you & all the best

Edyta

Dear Edyta,

you can find more deep explanation of the CML in Polish in this Ph.D. thesis: http://www.wbc.poznan.pl/dlibra/plain-content?id=157731

We cannot say bad word for my wife's doctors in Poland, they are really good at what they are doing. The system itself is quite a different story, but you know that. 

Are you taking with the hematologist or oncologist? CML is really rare and we found that oncologist may not be aware how to proceed with it.

Ask questions why they thinking of SCT. Is it lack of the response? Mutation found? Did you saw this pocketbook https://www.leukemia-net.org/content/leukemias/cml/recommendations/e8078...

There was progression from 43% to 61.5% in 4 months while on treatment with Tasigna?

Hope your mum will be better soon, 

BR / Chris

Hi Chris,

I did not realise that your wife was also treated in Poland and I am glad to hear that the treatment she received was good.

My mum is being treated by a haematologist who apparently did her PhD in CML and I know that they are treating over 100 patients with CML in that hospital.

The consultant has not been very approachable so far but we will try to ask why SCT is being considered.

Yes, I have seen the pocketbook. It seems that whenever there is resistance to a Imatinib, HLA type + sibs should be checked. That might be one of the reasons. There were no mutations found but she was on Tasigna between the 22nd May and the 11th July and the progression was registered between the beginning of February and the end of May (apologies it wasn't the end of June as per my previous post)… Thanks for bringing this to my attention. Let’s see what happens on Thursday (this is when the appointment is).

Best Regards,

Edyta