21 replies to this topic

[Tedsey]

So, in what test exactly do they determine a person's blasts at dx and otherwise (for CML)?  BMB, CBC?  Karyotyping?  I am leaving out FISH since I never had one.  I find I am still in the dark about this.  And what blasts are they looking for?  All WBC?  Lymphocytes?  Monocytes?  etc.  From what I can tell, mine have always been looked at via BMB.  I had some report that mentioned RBC blasts (I think I understood it correctly--and they were nucleated--whatever that means).  I found that very confusing.  

Thanks,

Teds

[GerryL]

Hi Teds,

Let me have a go at this -

Blast Cells

In CML the bone marrow produces too many white cells, called granulocytes. These cells, sometimes called blasts or leukaemic blasts gradually crowd the bone marrow, interfering with normal blood cell production. They also spill out of the bone marrow and circulate around the body in the bloodstream. Because they are not fully mature, they are unable to work properly to fight infections.

The doctor uses a BMB to find what phase your are in by counting the number of blasts in the blood and bone marrow and the severity of symptoms -

• Chronic phase. In this phase there are few blasts (fewer than 5%) in the blood and bone marrow. There may be no symptoms of CML or symptoms may be mild. Most cases of CML are diagnosed at this phase.
  
• Accelerated phase. The number of blast cells increases to about 15%.
  
• Blastic phase, or blast crisis. More than 30% of cells are blasts. Sometimes blast cells will form tumors outside of the bone marrow in the bone or lymph nodes. At this point chronic leukemia has become an aggressive acute leukemia.
  

The number of blasts appear on my two BMB reports, not sure if yours will be exactly the same as mine, but see if you can compare.

My report is called

BBone Marrow Report

Bone marrow aspirate and trephine submitted for reporting. Material was taken for chromosomal analysis and surface marker studies.

The report then runs through BBlood Counts.

The next bit is the BReport on Marrow Aspirate

BMB preformed 13/07/2010                                                                 BMB performed 29/11/2010

Blasts 1.8%                                                                                       Blasts 1.0%

I've now moved to PCR blood tests and they are looking at the level of BCR-ABL rather than things like the number of blasts. If the BCR-ABL level starts to climb, then they'd start doing BMBs again to see what is happening.

Okay now for the brain exploding bit regarding your RBC blasts

Pathophysiology

Most cases of CML appear to be induced by a translocation known as the Philadelphia (Ph) chromosome, which is demonstrable in 95% of patients. It is a reciprocal translocation t(9;22) in which a piece of chromosome 9 containing the oncogene c-abl is translocated to chromosome 22 and fused to the gene BCR. The fusion gene ABL-BCR is important in the pathogenesis and expression of CML and results in the production of a specific tyrosine kinase. CML ensues when an abnormal pluripotent hematopoietic progenitor cell initiates excessive production of granulocytes, primarily in the bone marrow but also in extramedullary sites (eg, spleen, liver). Although granulocyte production predominates, the neoplastic clone includes RBC, megakaryocyte, monocyte, and even some T and B cells. Normal stem cells are retained and can emerge after drug suppression of the CML clone.

Trey can happily correct me - but I think it means that though white blood cells make up most of the blast cell, it can include RBC, megakayocyte, monocyte and even some T and B cells.

On another note - did I read somewhere you're off overseas or over the border for a holiday?                                                                          

[GerryL]

Hi Teds,

A little bit more on nucleated RBC - I read an abstract from 2006 which showed that that Ph chromosome, concentration of LDH, percentage of Hct, peripheral blood basophils, marrow blasts, promyelocytes, presence of nucleated RBCs and treatment were the most important prognostic factors for CML.

This was before Sprycel and Tasigna - where achieving the milestones is a major factor.

[cometbro]

Hey Tedsey, I will hijack your post.  I have very dumb questions about blasts.

If you hit complete Cytogenic Response, does that mean you don't have any more blasts?

If you hit CCyR, but you were diagnosed with a high blast count, does that mean that your CML can develop faster if you stop TKIs?

Talk about being lost.

[PhilB]

That depends where you are looking for the blasts.  A blast is simply an immature cell and is part of the cell's lifecycle.  Even a normal healthy person would expect to have some blasts in the marrow as that's where the cells are born and grow up.  Only when production is out of control do you start to see high levels of blasts in the marrow and blasts escaping to the peripheral blood as they are created faster than they can mature in the marrow.

As to what happens if you stop treatment from CCR, I doubt there's much data for obvious reasons!  My guess is that on average yes you would get a faster progression as you'd be likely to have more higher level Ph+ stem cells if you were dx at a more advanced stage.

[Tedsey]

I just read something that said that blasts are not found in the peripheral unless there is a problem.  I also read that people with healthy marrows can have up to 3% blasts (in the marrow) and that is normal.  Does this seem right? Man, I am going to have to get another degree in cellular/molecular biology and hire a nanny.  (I am usually reading with two whining toddlers who are hanging all over all over me, so I am not sure how much correct info I am digesting).  Ugggggh!

I am just confused because I just looked up my dx reports and it appears there are all kinds of blasts reported that seem pretty high (.  As for the ones that determine that I have CML.  Which I fear that I was misdiagnosed and actually have some acute form of leukemia.  I have been on Sprycel almost a year (and 18 mos since dx) and I have yet to get close to a MMR.  I know the success rate is only about 50%, but it appears most who write on this board are very quick healers.  I am still waiting for my PCR number to come back for my 18 month.  I have been very nervous and very irritable.

[Tedsey]

I just found a differential WBC count for the day I was admitted.  It says absolute blast 12.6 when it should be 0.  And a few days later, my blasts went down to 2.4 without TKI treatment (I wasn't put on TKIs until about 3-4 weeks later--onc wanted my WBC to go lower first (dx at 180,000), in my opinon, I should have been put on Gleevec right away).  So confused now after thinking I understood this.

Gerry,

Is there any published chart that defines what pathologists look for when determining white kind of leukemia a patient has?  Thanks for all your info.

Teds

[Tedsey]

OK, sorry.  I am in a mini freak-out mode and need to reach out.  I assume that I should only go by the path report.  It was amended a few times, which I am not really sure why.  But I was lucky to be dx on a major U.S. holiday.  Seems everyone's mind was on something else except an awesome fellow (medical fellow), who was kind and seemed a bit excited to see a CML case--but I could never fault him for this although it was totally not exciting for me).

Anyway, the bone marrow aspirate flow cytometric and immunophnotypic studies came out that my blood was CD34 positive and dim CD45 positive blast population comprising about 1% of the total cells with myeloid lineage markers (CD13 and CD33).  They reported an aberrant partial CD7 positivity (overall 20% of the blasts), but from what I still understand about CD7, the presence of this is still inconclusive.

OK, the next part says the predominent cell type is myeloid and there is a shift to immaturity with a small proportion of blasts (2.6%), which determines a "chronic myeloid" issue, I think.

What is the difference between the 1% and the 2.6%?  These numbers are both reported as blasts.  This is where I get confused.  And are CD34, CD45, CD13 and CD33 all myeloid lineage markers?

Again, I feel that I understand and then I get all anxious and feel like I don't get anything.  I guess I am writing this just to reassure myself.

Man, it sucks waiting for the PCR to come back!

Wishing everyone good health!

Teds

[CallMeLucky]

Sorry you are having a mini freak out.  Waiting on test results can mess with your head really bad.  If I were you I would try not to rehash your diagnosis too much.  It is unlikely that you have an acute form of leukemia and were misdiagnosed.  By 18 months if you had an acute form it would have likely showed itself by now.  I know you have had many challenges, but most seem like isses related to treatment more than issues related to disease.

I know you want to get to MMR and I really hope you do.  Try to take comfort in the fact that there are people who are still alive and well today who have not made it to MMR and keep plugging along.  You are CCyR and the studies I have read show that is the milestone associated with long term survival.  If you can hold your CCyR, you will likely be fine.

Try to hang in there, you'll have the results soon and I really hope you get that MMR.....

[Tedsey]

Luck,

Thanks for the support.  I guess with all I have been hearing about how Sprycel is such a "miracle drug" and so many reaching MMR so fast, it makes me feel sad.  I find I am worrying a lot about my kids.  I just wonder why I am such a slug.  I cannot help but think the worst.  I have a rare blood type, I have no siblings and I get anaphylactic shock when given donor's blood.  This has me all freaked out that there is no way in the world I would ever survive a SCT.  I am almost feeling sick waiting for my results.  Glad to hear you are considered MMR.  There is some justice in the world.

[Trey]

Good attempts, but....

Blasts are often called "immature white blood cells", and I have used that phrase myself.  But that is an overly simplistic definition that does not tell the real story.  Blast cells are the precursor white blood cells (mid-tier progenitor cells) that have been formed starting with the high level blood stem cells, which have now divided many times to form these precursor cells.  These blast cells are white blood cells which can now only make a certain type of white blood cell(s) in either the myeloid or lymphoid lines (one or the other, but not both).  They have differentiated beyond being able to make red blood cells and platetets.  This is because blast cells have become significantly differentiated along the way after the many cell divisions that went from the blood stem cell to this mid-tier level of cells.  These blast cells will further divide a number of times and make the final stage "worker bee" WBCs (granulocyte blasts make neutrophils, basophils, eosinophils, etc, and lymphocyte blasts make T-cells, B-cells, NK cells, etc).  The lowest level worker bee WBCs cannot divide any longer.

So the blast cells are called "immature" white blood cells because they are not the final stage cells that will do the work of providing immunity for the body.  The worker bee WBCs do that work.  The job of the blasts is to make more worker bee cells.  So it is more accurate to say that blasts are white blood cells which are not the final product of the blood forming system, but rather a step along the way (namely, a precursor cell).  Blast cells normally reside in the marrow, not the circulating blood, but some venture out occasionally; and when the marrow blast count is high, a lot more get pushed out into the circulating blood, but usually blood blast percentage is lower than marrow.

So why is a high blast count bad?  It is becuase the blood forming system has become out of control.  The mid-tier WBCs should be a rather low percentage of the total cell count, and the end stage worker bee WBCs should be a very high percentage of the WBCs.  Leukemia allows the mid tier WBCs to run amok and throw the whole system into chaos.  The blast cells do not do a quality job, but just divide endlessly and make inferior quality worker bee cells which do not function well.  As a result, the body becomes less and less protected as immunity to disease, infection, etc is eventually degraded and lost.

In CML we are mostly concerned with the myeloid line of WBCs (the "M" in CML).  As such, we are more concerned with the myeloblasts than lymphoid cells and lymphoblasts (the "L"in ALL).  Read here for extra credit:

http://en.wikipedia....wiki/Myeloblast

Blast count is determined by a Flow Cytometry Test.

As a side issue, WBC stimulators such as Neupogen stimulate blast production and cause the blast count to rise for a short time.  That is because Neupogen, Neulasta, etc work at the progenitor (precursor) white blood cell level.

[Trey]

Regarding the CD7 issue, we discussed this before.  Your blast ratio was 80% myeloid and 20% lymphoid as you described it.  That is CML, otherwise the percentages would be reversed.

http://community.lls...age/51733#51733

[CallMeLucky]

Sprycel is a good drug, but your system is your system and it doesn't really matter what the other kids are doing, because for the most part you are doing well.  You have acheived the major milestone that matters most, your disease is under control and it is not progressing.  The last few posts I read from you seemed to indicate that your energy level is a bit better and you are able to get out a little with the kids and live a life.  I know you are struggling a bit with the mouth sores, which has to suck, but I believe you are not getting sick frequently or anything to indicate the immune system is compromised.

You got a double dose of crap in the hand with your diagnosis, you got the cancer with a good treatment option and yet its been a challenge for you acheiving milestones and struggling with low counts.  But slowly but surely you seem to be plugging along and holding your own.  I don't want to seem like I am simplifying in anyway, I'm just trying to put out there what I see from my side that you have been writing, kind of a pros and cons list.  Overall it seems women have a harder time with CML, I'm sorry that is the case.  I think measuring yourself against others is only going to serve to disappoint you and take away from the fact that your disease is not progressing, you are alive, and there is no immediate indication that is going to change anytime soon.

As I put in another post, everyday you survive with CML inceases your odds for overall survival.  I know that sounds backwards, but when Dr. Mauro explained it at a seminar I went to, it really made sense.  These first few years should be the toughest.  I don't expect it to become so easy down the road, but the studies show the longer you have the disease under control, the less likely you are to relapse.  I know it is hard right now and your mind is going all kinds of places, we are on a very similar schedule, you are usually a week or so ahead of me getting back PCR results.  I know how you feel right now.  I know I am MMR at this point, but don't think for a second I am not freaked out that my status could change.  It could have easily been a low read on the last PCR that was not accurate.  I also had a PCR stay flat (actually slightly uptick) a short while back, which makes you suspicious and unsettled.  It is crazy how we pin our hopes and dreams on a test that is notoriously known for being inaccurate, or at least inconsistent.  Your anxiety is higher than mine right now I know.  You will have your answer soon and I am betting in typical slug fashion you will inch a little further down the log reduction trail.  It may not be ideal but hopefully it will conitnue on this way and each time you will see yourself getting further away from the demise you are speculating about.

I think you read the other post I had and if you didn't let me repeat it for you.  Imagine yourself 30 years from now looking back over the last 30 years, how do you want to remember it?

I hope you can relax a little and get your results soon.....

[Tedsey]

Dear Gerry,

We were due to go to Japan to visit one of my dearest and best friends and visit the grave of another dear friend who died recently.  My husband thought it would be best not to put off this trip because of my dx.  But I don't think I need to tell you why we had to cancel (also at the urging of our U.S. State Dept.).  We will try again this Sept./Oct.  Since we don't really have a choice but to fly into Tokyo, we want to see how the radiation levels are because of the kids.

[GerryL]

Hi Teds,

Hopefully Tokyo will be okay for you to visit later in the year, and if Tokyo is still out of the question, perhaps you and your family could travel somewhere else, somewhere you could sit out in the sunshine with your children running around having fun and someone else waiting on you. Fiji maybe?

I'll keep my fingers crossed until we get your results and even if you've only inched along, you're still going forward - turtles do eventually catch up with the hares.

Gerry

[acb]

Can I chime in with an ignorant question as well. Is the Flow Cytometry Test always done with peripheral blood? (I had one at diagnosis, done with peripheral blood, but wasn't sure if that was always the case since I have never had a BMB.)

Thanks!

[Trey]

Flow Cytometry should normally be done on marrow samples.  Peripheral blood samples are less useful for items that a Flow Cytometry would be looking for.

[Marnie]

Hey, Teds. . .if it makes you feel any better. . I'm one of the turtles, too.  Doing better on Sprycel, but still just plugging along.  It's about time for my second PCR post-Sprycel and I'm starting to worry, too.  And it doesn't help that my employer has switched insurance plans, which means I'll be paying $4000 out of pocket when I have to order my Sprycel in August.  

Wish I had some good advice for you and could help you out with your questions.  Hang in there and try not to let the stress become overwhelming.  Easier said than done, I know. . .but stress can do terrible things to a person.

Marnie

[Happycat]

Teds,

Maybe the difference between the 1% and 2.6% is:

2.6% of the total cells are blasts

1% of the total cells are CD45-positive blast cells (meaning the other 1.6% blast cells are CD45 negative)

I have no clue what CD45-positive means, though.

Traci

[Happycat]

Trey,

Re:  "Blast count is determined by a Flow Cytometry Test."

Would the flow cytometry say "blast" cell, or would it state some sort of CDXX-positive marker?  My report say "CD34/CD33-positive immature myeloid precursors are not increased and comprise 0.2% of the total".  Does that mean blast cells??  I've never been able to figure that one out.

The other part of the report says "maturing myeloid cells comprise 88% of the total", which I take to mean "not blast, but not neutrophils either".

Thanks,

Traci