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When to start treatment

My wife was diagnosed in August 2018. It was diagnosed very early. She had no symptoms other than a white count that keeps climbing. Her doctor said she will eventually start to feel “crummy”. We are wondering how long this has taken for others who were diagnosed very early. And how can you tell it’s the disease progression and not just a virus, cold, etc. she has been sick a lot more often in last few months???


"When to start treatment"

NOW !!

The sooner she starts treatment the better her long term outcome will be. By the time white count starts to climb she has already had the disease several years. It takes that long before the body begins to lose control over it ... white cell count increasing occurs when CML has taken most control over the blood system.

Without additional information from you we don't know where she is on progression (blast cell count, etc.). We would need to know her FISH level and PCR if available (FISH more important at diagnosis). I assume she has, in fact, been diagnosed with CML.


I was diagnosed very early when my normally low WBC started climbing. I was at WBC 80 at diagnosis, some folk on here have been near 100,000. I started imatinib right away, and had little of the issues many others had who were diagnosed at a later stage. If her FISH result (and PCR if she has it) confirms CML then she should be on treatment now, as Scuba says.

I am now 2 months in to having stopped treatment (11 years post diagnosis). I am sure that starting treatment early helped minimise the impact of the condition, and put me on the track to where I am now.

Absolutely positively NOW - please have her start treatment.  What Scuba and Alistair said is 100% correct.

I'm of course thing to agree with everyone who says start NOW. 

CLL, a different form of leukaemia can often have a "watch and wait" policy, but not CML. Treatment needs to start as soon as possible after diagnosis. 

I will add one more thing. Get a new doctor - if your one saw CML and thought the best course of action was to do nothing, you want nothing to do with them ever again. 


If her doctor waits until she feels symptoms, it could possibly be too late for successful treatment and she may die from CML.  Has she been positively diagnosed as having the Philadelphia chromosome in her blood or bone marrow?  If so, what level was it at?

Scuba says "By the time white count starts to climb she has already had the disease several years."

Hello Scuba. Is this an authoritative statement or your opinion? I would be interested in reading any papers that support this view. Regards Stephen 

Stephen when one "gets" CML is an interesting question, but I'm not sure about the extent to which it matters for treatment or progonsis. My CML was diagnosed in 2007; it most likely happened as a result of radiotherapy I had in 1987. When did I get CML? Sometime between those two dates I guess, but no idea when.  I do know I was diagnosed by good fortune  at a very early stage. I think the important thing is that it is identified as early as possible, and appropriate treatment is started promptly to maximise the chance that the patient will ultimately die with CML, after a normal lifespan unaffected by the condition.

Hi Stephen,

Not my opinion. See below:

From the article,

"What are the symptoms of CML?

Because CML is, by name, a chronic leukemia, it may take quite a while before symptoms start to show—people often live many years without knowing they have CML."

I was told by M.D. Anderson that CML is a slow cancer in chronic phase and takes years to develop. Once blast phase transition occurs (again years after chronic phase has initiated), then CML can progress quickly. Over 85% of patients are diagnosed in chronic phase. Many who are diagnosed, their CML is discovered through a routine blood test and can be caught early, but still years after CML started. There were no physical symptoms at the time.

The chronology of CML starts with blood stem cells mutating into bcr-abl (9;22 translocation). There is debate on how many cells are needed to mutate at the start to sustain the disease. Radiation is a known trigger of CML. During CML expansion and growth, the body (spleen), manages the disease without the patient knowing. This is what takes years. There comes a point when physical symptoms appear - enlarged spleen, night time sweats,low grade fever. By this time, WBC's have become largely leukemic and in great numbers. It is at this point when treatment starts and the disease is often brought under control.

A key point to keep in mind - a thought experiment if you will. Recall your own treatment chronology.

How soon after you started treatment did you feel well again? In my case, in less than a couple of weeks I felt great again. WBC's dropped quickly to normal and all symptoms disappeared. This is the so-called hematological remission. However, my FISH level was 85% and PCR over 100%. In other words, I was loaded with CML, but felt fine. Many months later my FISH went to zero, so-called cytogenetic remission and an important milestone, but PCR still showed 'residual' disease. During my odyssey I had to stop treatment for a time due to severe myelosuppression. It took months before blood counts rose sufficiently to near normal. Eventually I became "undetected" and I stopped treatment to test durability. It took nine months before my PCR moved up 1/2 log - FISH still zero. I know several patients who went through pregnancy - had to stop treatment and their CML rose one or two logs, but no symptoms whatsoever and their blood counts remained normal. It is because CML is slow (only in chronic phase) that doctors who are skilled know they have time to work out an individuals personalized treatment plan involving which drug and at what dose. And while CML is "growing", a simple blood test won't show that there is anything wrong. Only when the body loses control do the WBC's start to explode in number. It's the high white blood cell count that first alerts a doctor that something is wrong.

In summary, when a person sees a doctor complaining about symptoms for the first time, their CML was "started" years earlier. Not until disease burden is so high (FISH often 100%), and the body loses ability to manage that they feel sick. Are there exceptions? No doubt. But for most, this is the chronology.

I had a series of cat scans in 2001 around my hips (large blood forming bones). Nine years later, I was diagnosed with CML. I will never have a cat scan again.

Another reference and nice summary overall on CML:

See section on Phases:

"Chronic phase. The blood and bone marrow contain less than 10% blasts. Blasts are immature white blood cells. This phase can last for several years. However, without effective treatment, the disease can progress to the accelerated or blast phases (see below). About 90% of people have chronic phase CML when they are diagnosed. Some people with chronic phase CML have symptoms when they are diagnosed and some do not. Most symptoms go away once treatment begins."

"Thus, radiobiologic analyses show that CML incidence peaks within 10 years after radiation, but several decades, and perhaps a half-century, can separate CML initiation and diagnosis.
Updated radiobiologic data and modeling strongly indicate that the CML latency time distribution has an extended large-time tail. All current cell population dynamics CML models that deal with clinical (rather than epidemiologic) issues substantially underestimate the length of the tail. For CML treatment, one conclusion is that voluntary discontinuance, voluntary interruption, or poor patient adherence to protocol of TKI treatments should be regarded with caution, especially for females, at least pending the final outcome of the STIM and similar trials. Long and highly variable latency times suggest that unpredictable relapses could occur, even after decades."

Sandrea - Good to see you here@!

I have a lot of experience in quantitative models (your reference). Math models are notorious for "tails".

I don't believe them. It's just math. Not biology.

But your point echoes mine. CMl takes a long time to get established and a long time to get extinguished. In the end, it's the capability of our immune system. Improve your immune system health and you will go a long way to "guarding" against cancer.

Thank you, Alistair.

At the outset of my career, I worked in a microwave radio laboratory which is probably of no great interest. However,1998 to 2001 I worked in an office that was 3 metres away from one of the feet of an enormous microwave radio mast in Coventry. I have read that radio frequency is thought not to cause leukaemia, but with high power levels and proximity, it makes me wonder whether this has a bearing on my eventual diagnosis.

Hi Sandra!

i read the link you posted. So does it mean that if someone successful stops their TKI with no recurrence of cml that they can still relapse sometime years later?

Thank you, Scuba, for providing the various references to the proposition that CML could be in place for 5 to 10 years before the white blood still count starts to rise.

I have been carrying out some web searches. The expressions "clinical manifestation" and "clinically manifest" appear to be the terms used to establish the point at which the first signs of CML become apparent. Hence CML may be clinically manifest before diagnosis. I cannot find any strict authority for the proposition that CML may be present for many years (5 to 10) before clinical manifestation.

I presume that there has been no large-scale study where FISH tests and similar have been conducted across a wide population of normal people over ten years.

Interesting thread and discussion. I can only offer my own anecdotal experience.  I was diagnosed in May 2009, with absolutely no symptoms, following a blood test (which was done for the purposes of a different investigation) with high platelets but a WBC only just above normal, if that.  It was however rising.  My spleen was not enlarged at all. 

The relevant bit is that I had also had a similar blodd test (also for the different investigation) two years before and when the haematologist at the first hospital I attended in 2009 reviewed that earlier test, he said there were indications there that all was not quite right even then (although all was normal). I recall him saying my blood looked "a bit thick" from the previous test, in hindsight.

So, this would support a view that CML can be around for some considerable time before diagnosis or, especially, symptoms. It fits with its generally slow progression in early chronic phase.

I was put on imatinib within a day of diagnosis and I distinctly recall the consultant insisting on this. 

Agree with all that starting treatment at diagnosis is absolutely right. And with David that if your doctor is suggesting otherwise they do not know what they are talking about regarding CML and you need to find someone who does.