33 replies to this topic

[cwad20]

This cbc differential was just uploaded from last Friday if this says much.

% Neutrophils 43.8 % Final
Neutrophils-Auto Diff 2860 2188-7800 /MM3 Final
% Lymphocytes 40.7 % Final
Lymphocytes-Auto Diff 2660 875-3300 /MM3 Final
% Monocytes 9.6 % Final
Monocytes-Auto Diff 630 130-860 /MM3 Final
% Eosinophils 5.2 % Final
Eosinophils-Auto Diff 340 40-390 /MM3 Final
% Basophils 0.5 % Final
Basos-Auto Diff 30 10-136 /MM3 Final
% Immature Granulocytes 0.2 % Final
Immature Granulocytes 10 /MM3 Final

[Trey]

The older CBCs are only partial.  Partial list shows progressively lower WBC, which is good.  But it would be more useful to see Basophils (BAS), Eosinophils (EOS), and blast counts from diagnosis to see if they were high then.

 

Current BAS, EOS, and blast counts are all good.  That is another reasonably good sign. 

 

The BMB is only 10 days away, which is OK.

 

How about monthly FISH and PCRs?  Have any been done since diagnosis?  If not, that does not reflect well on the Onc.  FISH and PCR are the most important tests to show progress or lack thereof.  They will tell the real story, so they need to be done monthly because of your unusual diagnosis.

Edited by Trey, 03 February 2015 - 02:16 PM.

[cwad20]

Trey, here are the results of past cbc I was able to find.  Including the first cbc that was taken when I was first admitted into hospital.  For some reason the first cbc that was done does not list the BAS, EOS etc... it seems the first time they did that analysis was on 12/4.

 

Very first blood test was done in E.R. on 11/24/14 and came up with following:

 

WBC                                                            72.4

RBC                                                             3.62

Hemoglobin                                                 10.6

Hematocrit                                                   32

RBC distribution width, standard deviation  54.4

RBC distribution Width                                 17.2

 

That is all the info this first cbc listed on E.R. report.

 

First complete cbc report they have shown again was 12/4, which is as follows:

 

%Manual Neutrophils         50.5               %

Segs-Manual Diff                19792 (H)      2188-7800/MM3

%Manual Lymphocytes      19.0               %

Lymphocytes-Man Diff        7469 (H)       875-3300/mm3

%Manual Monocytes          1.9                 %

Monocytes-Man Diff            747               130-860/mm3

%Manual Eosinophils          2.9                 %

Eosinophils-Man Diff           1120 (H)        40-390/mm3

%Manual Basophils             1.0                %

Basos-Manual Diff               373 (H)         10-136/mm3

%Manual Bands                   9.5                %

Bands-Man Diff                    3734 (H)       0-406/mm3

%Manual Metamyelocytes   4.8                %

Metamyelocyte-Man Diff      1867 (H)       <=0.0/mm3

%Manual Myelocytes           8.6                %

Myelocyte-Man Diff              3361 (H)       <=0/mm3

%Manual Promyelocytes     1.0                %

Promyelocytes-Man Diff       373 (H)        <=0/mm3

%Manual Blasts                   1.0               %

Blast-Man Diff                      373 (H)        <=0/mm3

ANC (Absolute Neutrophil Count)       23526              /mm3

 

 

I also found the following reports that were completed since the 12/4 one.

 

Name                                                               12/18/14       12/26/14       1/9/15    1/15/15       1/30/15

%BASOS-AUTO DIFF                                           0.7                1.3                0.9         0.2              0.5

%EOS-AUTO DIFF                                                13.0              3.7                0.9         0.8              5.2

%LYMPHS-AUTO DIFF                                         24.8              34.5              49.8       47.8            40.7

%MONOS-AUTO DIFF                                          4.5                8.9                9.1         8.5              9.6

%NEUTROPHILS-AUTO DIFF                              56.7              51.3              39.1       42.5            43.8

%IMMATURE GRANULOCYTES                          0.3                0.3               0.2          0.2              0.2

BASOS-AUTO DIFF (10-136 / mm3)                     50                 50                40           10               30

EOSINOPHILS-AUTO DIFF (40-390/mm3            950               140              40           40               340

LYMPHOCYTES-AUTO DIFF (875-3300/mm3)    1810             1320            2300       2370           2660

MONOCYTES-AUTO DIFF (130-860/mm3)          330               340              420         420             630

NEUTROPHILS-AUTO DIFF (2188-7800/mm3)    4150             1970           1810       2110           2860

IMMATURE GRANULOCYTES                             20                  10               10          10               10

 

 

I don't pretend to understand what all this means, but if you could provide some insight on which numbers are critical and if things appear to be heading in the right direction.  Waiting for reply from onc to setup another meeting before biopsy and ask why haven't done any additional FISH / PCR. 

 

One other question I've been wondering, I was given impression by onc that the sprycell I have been on will only help with wbc and blast cells, but will not really help with the other chromosome abnormalities, which is why they are working toward a likely transplant.  Is that because it's not targeted for that function?

 

Thanks again

[Trey]

I have not seen any platelet (PLT) numbers.  I know -- never satisfied.  But the Inversion 3 has an impact on PLT count, so it would be useful to see the PLT counts over time.  Such things can give a hint about whether/how your mutations are affecting the blood. 

 

The one item which stands out is the individual white blood cell counts.  The percentages of the various blood cells are not very instructive because normal levels can appear high or low by percentage when other cell counts are out of whack.  But the absolute numbers are more useful.  Look at your absolute EOS during Dec - Jan which were 950 in Dec, then dipped nicely, but came back up in Jan, although not technically high at this point.  This bears watching.  Otherwise your WBC has reduced nicely, your blast counts have always been relatively low which is a good sign, and your BAS was never far off, also a good sign.  With your complex mutations these specific items can be significant indicators.

 

So your CBC shows you are responding to Sprycel.  The most recent CBC has some upticks in the various white blood cells such as EOS which is at "high normal" at this point.  It will be important to watch where they go from here.  The PLT history would also be useful. 

 

The reason these things are important is they give some clues into what the mutations are doing to your blood.  Generally, CML causes major disruptions in blood counts, sending most of them either high or low.  But some issues are more significant than others.  To make an informed decision about continuation of TKI drug therapy vs BMT you will likely only have clues, not firm data points (unless you suddenly lose drug response).

 

As previously mentioned, the best indicators of drug response are BMB. FISH, and PCR.  You really need to have very regular testing -- more than the rest of us with "regular CML".

 

You asked:

"I was given impression by onc that the sprycel I have been on will only help with wbc and blast cells, but will not really help with the other chromosome abnormalities, which is why they are working toward a likely transplant.  Is that because it's not targeted for that function?"

 

The purpose of the TKI drugs is generally to interfere with the Philadelphia Chromosome (Ph+) and its signaling processes.  By shutting down the Ph+ signals it slows down leukemic cell reproduction.  As your BMB showed, nearly all of your white blood cells were leukemic at diagnosis (all 20 inspected had the Philadelphia Chromosome).  Your overall WBC has decreased, showing the TKI drugs are actually interfering with the leukemic cells production, but again FISH/PCR are overall better indicators of progress.  The blasts are also Ph+ leukemic cells (immature ones).  So Sprycel should interfere with all Ph+ cells and bring down your WBC, which has happened so far.  So yes, Sprycel works to bring down WBC and blast count (your overall blast count was never high). 

 

As for the other abnormalities, your Onc may be technically correct that they are not directly targeted by Sprycel, but that is not the whole story.  Beside the Ph+ you have a second translocation, an Inversion, an isochromosome, etc.  However, these are all embedded in cells which are also Ph+.  Since Sprycel is targeting all Ph+ cells, it is by default targeting all your mutated white blood cells as far as we know.  I add that last part because the BMB only inspects 20 white blood cells in a specific state of division, and there could potentially (although less likely) be cells which only have non-Ph+ mutations.  So if some cells only have Inversion 3, that would mean those cells would not be targeted by Sprycel.  But as far as we know, they are all Ph+ (a likely assumption) so are all being targeted.  So the BMB could -- over time -- show reduction and disappearance of all the mutations as a result of Sprycel therapy.  But the probability of this happening is not yet known.

 

So far, based on the limited information I have seen, the expected negative effects of your additional mutations have not been demonstrated in your blood counts.  The absolute best case scenario would be that the TKI drugs wipe out the Ph+ leukemic cells, and by default the other mutations also disappear as collateral damage.  I do not know if this will happen, and you are definitely higher risk than most CML patients, but no one can tell you it is impossible. 

 

You alone must decide if it is in your best interests to stay on TKI drug therapy (either short term or long term), or go to transplant in the relatively near future.  I do not know the right answer for you.  But gathering "clues" from all your tests will give you data which will enable a more informed decision.  So far the clues are relatively encouraging, but these things can turn around, especially in unusual cases.  In the end you will not have all the information you would like to have.

[cwad20]

There are platelet counts listed on previous page from each cbc lab.  Are those different than the platelet counts you were asking about?  They've pretty much stayed in range of 150-200 with the exception of dropping to 107 at one point.

[Trey]

Good eye, Pat.

 

So your platelet (PLT) counts have been fairly stable from diagnosis until now.  The Inversion 3 [written as inv(3)(q21q26), and also called both MECOM and "3q21q26 syndrome"] would normally produce thrombocytosis (overproduction of platelets).  So far, at least, your blood does not show thrombocytosis.  This is a good sign.  Again I repeat "so far" because these things can change.  But the relative stability of your PLT counts demonstrates that you have not shown the downside effects from Inversion 3 to this point. 

 

http://atlasgenetics...alies/inv3.html

 

The historical data on Inversion 3 / MECOM / 3q21q26 syndrome (all the same thing) associated with CML is sparse, and much of it was before TKI drugs were available.  The transplant Onc explained that Inversion 3 is very bad.  But not every case is exactly the same.  It is possible that the Inversion 3 embedded with the Philadelphia Chromosome (Ph+) can be eliminated, but the probability of this is not known.  If Inversion 3 was not embedded with Ph+, it could not be targeted without chemotherapy and transplant.  But due to the sparse historical data, there is not one single answer on the probability or outcome. 

 

I will try to describe a concept which is difficult to explain, but here goes: The chromosome mutations you have are not harmful by themselves.  It is the downstream effects of the signals caused by these mutations which can be harmful through blood cell overproduction or underproduction.  Leukemia is harmful, and even deadly, when it causes out of control production of certain blood cells, and underproduction of other blood cells.  "Normal" CML causes overproduction of neutrophil white blood cells (WBCs) which crowds out other blood cells (red blood cells and platelets) which in turn causes destruction of body tissue due to lack of oxygen.  Also, the overproduced neutrophils are leukemic, and are increasingly less effective at doing the job, so the patient eventually cannot resist or fight off even minor infections.  So lack of oxygen in the organs and infections become the issue as the disease develops over time.  What I am explaining is that since the downstream effects of the disease are the issue, you can draw clues about your unique version of it from those downstream effects. 

 

So if you had very high platelets, or high blast count, or very high basophils, there would probably be no reason to continue with TKI therapy.  Might these develop over time?  Maybe.  Might the TKI drugs work for you over the long term?  Maybe.  Might the TKI drugs stop working after a while?  Maybe.  For better or worse, your case is very unique, so the outcome is less certain.  That may work in your favor, or maybe it won't.  But your blood will give you clues along the way.  That is why you must be very closely monitored by all types of testing -- CBCs weekly, FISH and PCR monthly, BMBs regularly, and others such as Flow Cytometry, etc.  If your Onc isn't doing this, get a new one.  If it were me, I would require the top Hem/Onc at UIMC to be present at your next appointment.  Your current Onc is not well qualified to handle your case.  The fact that she has so poorly explained your case to you is not encouraging.  The lack of monthly FISH and PCR given your complex diagnosis is concerning.  And a "CML geek" is explaining what your Onc should have.  That does not inspire confidence.

[Gail's]

Kind of a bottom line question, Trey. Is the BMB the only way to see the other translocation a or can it be done with venous blood?

[Trey]

Only a BMB on marrow, which is why a BMB is absolutely necessary for a complete and proper diagnosis.  The poster here (CWAD20) would not know anything about these issues if a BMB had not been done.  The cells which can show these chromosomal translocations generally stay in the marrow, and are even hard to find in there.  The cells must have "stem cell" status (simplifying the issue) and must also be in a very specific state of cell division whereby the chromosomes can be seen under a microscope.  That is why a BMB generally only reviews 20 cells, since they are hard to find even in the marrow where they live. 

 

Some mutations can be seen in peripheral blood by specific tests, but the lab must first know what they are looking for so they can test specifically for them.  That is because each test generally only looks for one specific mutation, and there are many thousands of possibilities so there would need to be thousands of tests done on the blood looking for a needle in a haystack.  But an Onc can often "guess" that a person has CML when the WBC is very high, and a peripheral blood BCR-ABL PCR or BCR-ABL FISH can confirm the suspicion.  But these guesses do not extend to other possible mutations.

 

So if someone wants to argue that a BMB is not required to diagnose CML, they just need to read this entire post and see why it is so important.

[cwad20]

Just thought I'd post an update. 

 

They just got results of second BMB back and results were somewhat promising.  Most levels are back to normal, blast is down to 1%, and surprisingly it looks like most of the other chromosome abnormalities have disappeared for now (although their not sure about inversion 3 yet, still waiting for final report on that).  But the iso 17 and p53 deletion did not show up on new biopsy.  The pH+ has decreased and gone down to like 1.3%. 

 

Even with this response and these results though, I have been informed by both my Onc and stem cell doctor they still want to move forward with a BMT.  They are planning on starting it in 2-3 weeks.  Their reasoning for still doing the transplant despite these results is that they feel I would only have probably a 20% chance of long term disease control staying on sprycel, but could potentially gain long term control if transplant is successful.  It was the fact that when I was diagnosed I was in accelerated phase, with leukemic lumps on chest and high blast percentage, as well as other chromosome abnormalities that they feel moving to transplant still is best choice.  As they fear the chromosome abnormalities and TKI could potentially stop working at some point and then I would not be in as good of health as I am now to perform the transplant.

 

My onc spoke with dr. talpaz at U of Michigan about my case, and said he agreed with this move.  I also personally consulted Dr. Druker's opinion as well, and he seemed to also agree that because of the leukemic lumps and blast percentages at diagnoses, the best chance of long term disease control is through transplant. 

 

So that's where were at now I guess.  Any advice on a BMT?

[hannibellemo]

cwad20,

 

Sorry to hear that they are still pushing for a BMT. I will let others who know more than I speak to that. I guess I would want to know if U of I is the very best place to go for a BMT. How many do they do, what is their success rate, how many have been for CML, etc. etc.?

 

There is a transplant discussion area on this board and Tex is very helpful. I believe this past year was his 10 year post-transplant anniversary. I think Tex had AML and I'm not sure how transplants vary from leukemia to leukemia, if they do at all.

 

I'm an Iowa transplant (no pun intended) up here in Mason City for the past 25 years. We lived in Davenport when we were first married and I'm still pretty familiar with the area. I chose to go to Mayo because it was closer for me.

 

I wish you the very best of luck!

[Trey]

You asked "Any advice on a BMT?"  None of us are qualified to do anything except provide some things for you to think about.  First, I would like to know if you have read the link I provided which has some basic information about BMT:
http://community.lls...t +introduction

 

The question is: Should you proceed with a BMT now?  The options are: 1) proceed now as your Onc wants, or 2) take a "wait and see" approach and make a final decision later if a BMT is unavoidable due to loss of TKI drug response.  Only you can make the decision.  Don't let anyone else make the decision for you.  Not your Onc, or anyone.  Only you.

 

I believe most Oncs would agree with your Onc regarding BMT since there are a number of unknowns.  They do this because they don't know whether you will have a long term response, so they suggest a BMT now in case you have a sudden and deep loss of response.  But they are not the ones having the BMT, and I am not so sure they would take the same approach if it were their loved one, or even themselves.  Medical professionals have the luxury of not having to live with the results of their decisions.  Some people live, others don't, that's just the way it goes.  It's not personal to them.  That is why you need to make your own decision.

 

Issues to consider regarding a BMT near term would seem to be:
1) That is what your Onc recommends.  Presumably due to the overall unknowns regarding your unique case including multiple secondary mutations
2) In case you have a sudden and deep loss of response leading to loss of overall health

 

Issues to consider regarding a "wait and see" approach would seem to be:
1) You have responded far better than the Oncs believed you could (recall they said the secondary mutations could not be controlled by TKI drugs - they were wrong).  But I will add that sometimes initial responses can be lost.  But the secondary mutations are combined with the Philadelphia Chromosome positive cells, making them targets of the TKI drug.
2) You have a ready donor (sibling) who is a match.  Many patients need to proceed with a BMT right away due to donor uncertainty.  You have one ready to go if/when needed, making a "wait and see" approach more feasible in that regard.
3) BMTs are inherently very risky.  Your BMT Onc said your chance of survival is only 50/50.  If you believe that is true (who knows?) that is not very good odds.  When I think of our friends on this site we have lost, almost all were lost during a BMT. 
4) BMT changes your life.  Some amount of Graft vs Host Disease will be with you the rest of your life.  To what degree, no one knows.  Sibling donor maybe less so.  The pre-treatment with chemo and radiation can cause secondary cancers later on.  Various tissues may be permanently damaged.  You will probably become sterile.
5) BMTs can fail: 1) failure to engraft (take hold), 2) relapse of the CML after BMT (possibly up to 30% of cases in some reports, and possibly more likely with a sibling donor)

 

The length of the lists are not so important.  This is all about making a decision you and your family can live with, no matter the outcome. 

 

I am somewhat known for posing the "If it were me..." to simply state what I myself would be considering.  I am older, with no youngsters around.  But "if it were me", and my Onc said I had only a 50/50 chance of surviving a BMT, that might be enough information already.  But with a very good response so far on TKI drugs (and I might add that so far you have responded faster than many patients who don't have any secondary mutation issues), that is encouraging.  And with a ready and willing donor waiting, the risks of the "wait and see" are less than in many cases where a donor must be found when needed (most Oncs don't think very hard about these things, oddly enough).  And with the significant downside effects of the BMT itself, the process is not to be entered into unless absolutely necessary.  Regarding drug response uncertainty, that just doesn't play against you, but often for you.  And would any potential "sudden and deep loss of response" preclude the BMT option, or just increase the risk somewhat (how much beyond 50/50 anyway, I wonder)?  But I am not trying to tell you what to do, just some thoughts I would have.

 

In the final analysis it is a decision based on imperfect information.  Make sure you are the only one who makes the decision.

[mamawarrior]

I know nothing about cml but have found this whole post fascinating. I am a nurse and my son was 18 when diagnosed with aml, 20 when relapsed and sent to transplant. He had a transplant because chemo did not work for him and it was his only chance for survival. I took my son out of state for transplant and lived in the hospital with my son during all his treatment before, during and after transplant which was well over a year. I learned alot.

I cant even guess nor am i qualified to say what is the best decision for you but having been through transplant with my son, be careful in comparing the type of transplant with others. There is so many factors when it comes to a transplant being successful and being successful in curing your disease.

Your disease is unique as is every transplant. The conditioning part of transplant is so different for every individual. When my son went to transplant i tried to compare but was very hard pressed to find anyone that had aml, was in his age range, had a double cord, and had the same conditioning (conditioning is huge).

Because of your age and your specific disease, considering the mutations etc, those may dictate a pretransplant conditioning much more ablative than most transplant folks. My son had total body irradiation and while he struggled with many complications related to the TBI and full ablation, it may have been a large part of what saved his life, but it is also very difficult and statistics continue that transplant is a very risky procedure, not just because of transplant but because of many things including the conditioning used.

I am not trying to sway you either way, because you have a very difficult decision but i am just saying be careful when comparing. Yes statistically, in general,sibling matches do better in surviving the transplant itself,but there is so much more to it than that. And young folks are often treated more aggressively because they are younger and stronger with less risk factors.

And also one thing you might want to ask, will you be on TKI's post transplant? Again i know nothing aboutcml but i have seen a few post about theories on that. Whats your docs thoughts on that??

If you feel transplant is best for you, the transplant forum while much smaller than cml, could be a huge resource for you.

Wishing you the best.

[Gail's]

Mama warrior, how long ago was your sons BMT and how's he doing now?

[mamawarrior]

Sons transplant was in October 2006. We were at duke childrens transplant center in North Carolina even though son was 20 at time. We stayed at the hospital and in the area a total of 5 mos When we left duke my son was a bubble boy for nearly a year. He had no immune system. He was also on 7 ivs a day and 30 pills and while driving home from NC to florida i had to pull over at rest stops to start and stop IV's.

Son had to be hospitalized about 12 times post transplant, numerous infections, had to be re-immunized from birth, had to run back and forth from florida to Duke in NC every 3 mos for a year then yearly for several years, we are now at every 3 years. And countless physician appointments.

Amazingly son returned to college, he actually took 2 course while in NC recovering from transplant, i dont know how the heck he did that, he was puking several times a day, we had garbage cans strategically positioned in every room and in the car. He lost 52 pounds and every bit of muscle. But slowly he recovered , he took online classes till he was freed to return to campus, got his BS degree, than his masters and is now taking his CPA exam. I find it amazing that he can do accounting after TBI.

He is engaged, bought his first house and really enjoys life. Shortly after he was freed to get out of the bubble and do things, he called me from the beach, told me he was surfing. Not what i wanted to hear. Yikes. He really does love life, he has gone on cruises and traveled and done alot more in his 28 years than most including myself.

And even to this day, when the phone rings and i see his name or number come up, there is still that slight panic, that uh oh whats wrong.

And there are those who have much quieter transplant journeys and those that have much more difficult ones and sadly those that dont make it. But for my son, he survived because of it, transplant saved his life.

But transplant was an easy decision for us, there were no other options.