Hello,
I have just been diagnosed. My WBC count is close to 50k. The differential count indicated basophils well above normal. Is that typical/high/low for this stage? I am advised start on a daily dose of imatinib (800). Just wanted to check if that is how it start typically, or if I would be well advised to go for a second opinion? ALso, is it at all possible to continue working while starting with this, or is complete rest important?
Thank you.
Mihir
Hello Mihir and welcome,
I am not sure why you have been advised to start on such a high dose of imatinib - 800mg? The standard dose for chronic phase CML is 400mg a day, and for those who may not respond quickly enough to that dose, 600mg is then recommended. I am not sure about your basophils being high... how high? Has your doctor given you a Sokal score? This takes several factors at diagnosis and scores your risk - high low etc. It may be helpful if you get a second opinion from an expert CML clinician if possible. But sooner rather than later as you need to start therapy with a TKI as soon as you can now your have a diagnosis.
Sandy
Was just wondering about being diagnosed in the accelerated phase. Anyone who can point to any information anyone that? I understand it is rare, so.struggling with obtaining information. Thank you.
Generally your doctor will be able to assess the stage of disease you are in. Accelerated stage disease is usually identified by at least one of the following:
A rapidly increasing number of white cells in the blood
An increase or decrease in platelets (blood clotting cells)
A high percentage of blast cells (immature lymphocytes) of more than 10 - 19% in both blood and bone marrow
A basophil count in the peripheral blood of more than 20%.
There can sometimes be further cytogenetic changes in the CML cells in addition to the Philadelphia chromosome pointing to clonal evolution.
There is usually some evidence of enlargement of the spleen.
Overviews of the different phases of CML can be seen here and a more detailed one here.
In accelerated phase (AP) imatinib (or a 2nd generation TKI) at higher doses are given, typically 600 - 800mg, which have shown significant efficacy in a proportion of patients diagnosed in later phase disease..... although in Blast phase (BP) responses are usually not durable and other treatments should be considered.
Sandy
Thank you Sandy.
Sorry I was not clear. Yes, my diagnosis is in accelerated phase and perhaps that is theone reason for 800mg. I meant to ask whether - given that diagnosis in accelerated phase appears to be rarer than in chronic - I need toto consider any other options. I have consulted and taken a second opinion but I am not very confident if TKIs work in AP. I presume that it is a lengthy road ahead. And also while I have read about responses to treatment, are those guidelines something at all realistic for a diagnosis in AP?
TKis and accelerated phase.
Yes, TKIs can work very well in some patients, but it depends on how long your disease has been in AP, whether there has been any further clonal abnormalities etc. as well as your individual clinical profile. One of the 2nd generation TKis may be preferable for you - or at least you can discuss this option with your clinician. Otherwise, there are clinical trials ongoing of a new drug call ABL001 (Novartis). https://www.mskcc.org/cancer-care/clinical-trials/14-168
Sandy
Dear Sandy,
Thank you very much for your help.
This forum is a great source of information, as well as inspiration.
As I mentioned, I was diagnosed in AP and started on a higher dosage of imatinib (veenat is a generic which I began with). I thereafter took a second opinion and a second consultation with a CML specialist, as you suggested, which was very helpful. I was advised to switch to dasatinib after some further results came in (F359V).
I was also reading online that potentially, a combination treatment of dasatinib + interferon may also be useful. (One recent piece I came across is http://www.nature.com/leu/journal/v30/n9/full/leu2016121a.html) If I may bother you, or others on the forum: is such a 'combination' therapy commonly done?
I fully realise that I should not be playing my own doctor, but only wanted to see whether this is something which is at all to be raised with my doctor. Currently, it seems that I have not done as well as I should have: or maybe, that is just the AP diagnosis which makes things more bleak. I wonder if there are any other options to explore. It has been a few weeks since diagnosis, and I hope that I have not missed the bus for any treatment. (I have not become worse, but not improved much either I guess, and symptoms are also more apparent now)
Thanks again.
-M
Hi Mihir,
Yes, I know of a clinical trial in Germany - the German CML IV study- that treated patients with a combination of imatinib + peg. IFN. PegIFN seems to be better tolerated and is a form that has been manipulated so that it remains bio-available for a longer period so is given in lower doses (as opposed to the 'normal' form of IFN which has horrendous side effects for most people).
I personally know of someone who benefited from this trial.... he is now treatment free and has been for some years. However, he was in chronic phase CML when he started the trial. See this very interesting overview of CML and TFR by Prof. Tim Hughes (Adelaide) "Moving TFR to Mainstream Clinical Practice" which only briefly mentions the German CML 1V study - but it is an interesting read nevertheless.
"Areas of future investigation
Several studies of IFN in combination with TKI have been completed in recent years or are in progress. Rates of deep molecular response in 2 independent studies in France and Scandinavia were higher in the pegylated IFN-imatinib combination arm than in the standard imatinib arm,39,40 but no such difference was seen in the equivalent arms of the German CML IV study.41 TFR rates for patients achieving deep molecular response with combination therapy have not yet been reported. These data may help to clarify whether a finite period of IFN exposure does have a durable effect on the probability of TFR."
There C/trials I can find for combination therapies are for CP CML.... including the link you provided in your post.... and this one with dasatinib and pegIFN, however there is a C/trial using bosutinib (Pfizer) which includes patients in all phases of CML here. There is also ponatinb which has been sown to be effective in AP phase and the new study of ABL001 as mentioned in my previous post.
You may be interested in reading this article on a very interesting development in identifying a biomarker for immune responses to TKI therapy.... "Immune Cell Protein Expression Could Offer Predictive Biomarker in CML" "Expression levels of L-selectin (CD62L) and related immunologic markers are correlated with treatment responses and outcome in patients with chronic myelogenous leukemia (CML), according to a new analysis. The markers could have prognostic value if validated in other cohorts"
Sandy
