Greetings every one.... recently my mom is diagnosed with CML but which is of rear type. It began all in 26 jan 2018 with a routine annual check up as she is having thyroid problem since 25 years so we have regular annual checkup & as in routine check up on 26-jan-2018 we got a totally abnormal CBP which is showing WBC of 84,000 & they suggested to rule out for any myloproliferative neoplasms. So we went to medical oncologist and he suspected CML & suggested for P-210 BCR-ABL qualitative test with blood & he started hydraxurea 500MG X 3times a day to correct the abnormal numbers of blood cells. And the result of BCR-ABL came negative so he again suggested for bone marrow biopsy & P-210 BCR-ABL test from bone marrow &the test was negative too. & he took other test if any JAK2 mutation & it was negative too. & now the things started to get complicated & he was shocked and was assuming if it is atypical CML, but before jumping into conclusion he suggested to search whole MPN panel for any abnormalities before ruling out as atypical, so we went for other test and then a micro transcript BCR-ABL was detected in P230( E19A2) , which he was also shocked as it is a very rear disorder. Now back to numbers of CBP in 26 jan 2018 WBC 84,000 RBC 3.2 millions/cumm, hemoglobin 10.2, platlets 4.09 millions/Cumm, lymphocytes 07%, promyelocytes 06%, myelocytes 09%, meta myelocytes 06%, band forms 10%, blast cells 01%, & bone marrow biopsy on 02-Feb-2018 was showing 09% of basophillia which they said may be in accelerated phase. We started using Hydraxurea 500 MG X 3 times from 05-feb-2018 & yesterday ie 12-March-2018 we had one more blood test and all numbers returned to normal with WBC 5500,RBC 4.9, hemoglobin 13.2, lymphocytes 38%, platlets 3.35, and no visible blast cells, band forms. So can we consider this as complete hematologic response ? If yes what will be the next phase of treatment ? Or should we continue Hydraxurea from now ? And for the second suggestion we went to other doctor and he straight away suggested for Nilotinib a second generation TKI 600 MG/ day as it is P230 CML, but as per my research it has lots of adverse side effects, so I’m just little bit in a cone of confusion. So please if any one has faced this P230 pls help me out with suggestions and a correct approach for the treatment.
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P230 (E19A2) CML
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Hello there,
Welcome to the forum and thank you for your detailed post.
Importantly, I'm sorry to hear about your mother's rare diagnosis and to that i sincerely hope that you will find the answers you're searching for soon.
On my part, before i trek any further on the subject, i'd like to disclose fully that i'm neither a medical professional nor have i ever worked in the healthcare sector to truly place merits in my statement/ speculations on the subject matter. In fact, I'm a classical CMLer and am a corporate accountant by profession! Thus, please ensue to seek firm medical advice/ assistance from your qualified professional MD relative to diagnosis and treatment of your mother's respective disease.
Reading from the various blood studies and BM biopsy results you've outlined on your post, it doesn't appear that your mother is suffering from either classical CML or atypical CML given the absences of each disease's prominent markers; Ph+ translocation (fusion oncogene BCR-ABL) or CSF3R mutations, respectively. What she may be having is what's called neutrophillic CML (CML-N), also referred to as chronic neutrophillic leukemia (Kim-Hien et al., American Society of Hematolog, 2016). This is assumed the case with your particular mention of one mRNA transcript detection of the micro bcr protein 230kd, p230/ e19a2. And indeed, this disease is as rare as atypical CML in itself with limited corresponding treatment options to consider. But I may be completely wrong in my entire speculations of your mother's disease, so please note down with extreme prejudice!
Of the topic of interest; on the below link, you can read more about CML-N & atypical CML with respects to their clinical management and new directions in their treatment practices.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266507/
Best Regards,
Ellie.
Hi Dinesh,
Your mother is going to be fine, but she does need to start treatment with Nilotinib (Tasigna).
https://www.hindawi.com/journals/crihem/2013/871476/
P230 transcript is a variant of the bcr abl translocation (9;22 chromosomes). Nilotinib is very effective and can lead to a complete molecular response in patients with P230.
Treatment with hyrdraxurea was correct to get her counts down quickly in preparation for tTKI treatment, but that is not a hematological response. The disease is still growing and needs to be attacked directly.
Nilotinibi is well tolerated. Although there are key side effects that have to be monitored (Qt elongation), these side effects are rare and with dose modifications can be managed. The key is to follow the drug taking protocol of twice a day between meals.
Your mother needs to get treatment started. The people on this forum will gladly help with shared experiences throughout all phases of treatment.
Your mother is at the beginning. We have all been there. The good news is her CML variation is very treatable and she will likely respond. In a relatively short time she will be back to normal.
Hope this helps.
Hi Scuba,
As we all know, TKIs are only effective in the treatment of Ph+ leukemias with confirmed detection of BCR-ABL% positivity in the BM myeloid blood cells. But the case presented above stated overall negativity of the oncogene BCR-ABL presence on both the cytogenetic tests from blood and BM biopsy which then rule out classical CML? Subsequently, I can sort of understand why the first treating physician was reluctant to commence treatment with a TKI.
Additionally, given the JAK2 mutations also presented negative for MPN, i assume atypical CML is also out of the running in this case scenario?
Anyhow, i might be entirely presumptuous in my overall deductions of this unique case given the fact that I'm no subject matter expert to assert any findings/ facts.
Nonetheless, it would good to know what is the exact disease responsible for those blood abnormalities posted.
Best Regards,
Ellie.
Hi Ellie,
From Dinesh's post:
"...a micro transcript BCR-ABL was detected in P230( E19A2)"
That is the key phrase. BCR-ABL WAS detected. They didn't know to look for it which is why it didn't show up for the more common P210 or P190 fusion transcripts.
It is rare, but can be treated effectively with Nilotinib and probably with Dasatinib as well.
Hello maaam ellie thanks for the reply ..... ya it’s kind of rear so was bit worried and thought to ask the expert openion over here .... & really thanks for the reply .... tomorrow is the consultation with the doctor again so have to wait what would be his course of action .... as of now she responded well with hydraxurea and total hemotologic profile became normal ... hope it’s the good sign of the treatment .... just hope and prayers as of now as it is a rear kind of CML
Hello scuba ....
First of all lemme thank u for the reply, I was also doing some research on internet and found that Nilotinib is the medicine which got good response in P230 CML patients .... tomorrow we r visiting the first doctor again to see his response with the present CBP, as last time he was also talking about Nilotinib... so will be starting I guess soon, and ya scuba hope she will be fine ,, & how is ur CML now? Hope everything is fine ... as per my research I came to know that diet can make lots of difference, we started the food diet consists of wheat grass juice in the morning & carrot & bestroot juice after one hour break Breakfast after 1 hour break, & pomegranate juice after an hour break, & a quarter of soursop fruit before lunch and lunch after an hour break and rest ... & evening orange juice & a moderate dinner,, just correct me if anything’s r not well in the diet thanks in advance .... wishing u a speedy recovery and good prognosis .... god bless all
Just one word of warning ... pomegranate juice may interact with an enzyme (CYP3A4) that is important in breaking down nilotinib. Whilst a few pomegranate seeds in a salad isn't going to cause any issues, drinking lots of the juice is probably not a great idea. It's not as bad as grapefruit in this regard, but it can stop the TKI being broken down, increasing exposure to it more than is expected / planned.
David.