13 replies to this topic

[momruns]

Greetings everyone,

We 6 weeks ago my ANC (absolute neutrophil count) went down to 0.8.  My ONC stopped my Gleevec for 2 weeks and restarted me on 200mg (I was taking 300).  At the end of the 2 weeks I was scheduled to have my BCR-ABL drawn.  Well it showed "partial response".  I had my CBC done today and my ANC is 2.0 and my WBC is finally up to 4.0     I am hoping to stay on the 200 and maybe even alternate will 100mg/QD.  I take Curcumin every day and feel it has made it necessary to cut my dose and that is just my thought and I will remain faithful taking it.   I am to see my ONC next monday to chitchat about what is next.  Being on 200 has made a big difference in my world.    The nurse in his office also said he does have a patient that has been on 100mg per day with success.

Loreta

[Trey]

The thing that will make the biggest difference in your world is to get to CCyR response.  Most people do not get there very well on 200mg, although a very few do.  Personally, I think a person should endure the harsh side effects early on and take the dosage that works best against the leukemia, or maybe switch drugs.  Then look forward to reducing side effects in the future.  This disease requires sacrifices in the battle.  Curcumin is likely not very useful.  Sorry that I am not on that bandwagon. 

[pamsouth]

Do you get the curcumin at the health food store?  Is it in the form of a pill?  How much and how often do you take it?

Trey I understand why you made the statement about withstanding the harsh side effects...  I did that for two years, but I can tell you now at the age of 64 I could not physically or mentally go thru that ago. I have enough aches and pains, and a low stress level with my heart.  It would be to much on my plate.

I think I would just soon give up the fight, then go thru that, seriously!

PamSouth

[scuba]

Loreta - I started at 400mg. Gleevec and had a hematological response. But shortly after, I also continued to have myelosuppression like you experienced with ANC dropping to 0.8 or so. My Gleevec dose was reduced to 300mg. - and my ANC stabilized, but my FISH started to go back up. I agree with Trey on this point - 200mg. is likely not going to work for you. You have too much Leukemic burden. It would be better for you to stay on 400mg. or even go higher (600) and then manage the ANC/WBC numbers by periodic drug interruptions if necessary until your body adjusts. Or switch drugs to Sprycel or Tasigna and perhaps get a deeper response. When it was clear that 300mg. Gleevec was not lowering my FISH number (used to determine CCyR), I switched to Sprycel.

I disagree with Trey on Curcumin. Trey wrote, "Curcumin is likely not very useful". There is too much research on Curcumin available now that reports its apoptosis affect on CML cells. But one has to take a lot of it to get enough into the blood for its effects to be felt (8 grams). I think of Curcumin as a CML population control agent. It makes life difficult for CML cells. It enables the TKI (in my case, Sprcel) to work more effectively. And it is good for you for other reasons (anti-oxidant, anti-inflammatory). I would take Curcumin even if I did not have CML, although it was CML that led me to learn about Curcumin.

I only take 20mg. of Sprycel - 1/5th the recommended dose and I am in MMR. I may be the only patient at M.D. Anderson that is on this low dose and in MMR at the same time (they're checking on this right now). And the best benefit - no side affects.

Curcumin alone is not likely going to control CML for long - it may slow it down, it may even keep CML in a steady state for a time; but only a TKI that is matched to your clonal population of CML cells can CML be wiped out almost to the stem cell and prevent progression of the disease. To me, Curcumin helps the TKI do its job.

[momruns]

Thank you for all your responses.  I see there is no straight forward answer.  I see my ONC on Monday, We will see what he says about "response, dosage, levels".  I love this sight because as Trey put it, "Not everyone gets on all the bandwagons" and for that I am grateful.  I get put on a certain path and it is nice for someone who "is not me" to see other options or concerns.  Again thank you.

Loreta

[Happycat]

Speaking of curcumin, I am now seeing curcumin derivatives cross my desk at work. My company sells research compounds to life science community, usually used in drug discovery.

Anyway, we have at least one compound called FLLL31, which is a JAK2 inhibitor, and was originally tested against CML.  Can't remember the details, but I think it was developed for mutations using alternate pathways, like JAK2 and SRC.

So, in answer to Trey, while curcumin itself might not have great activity, the analogs developed from it might have some promise. That's often the way it shakes out. Test a naturally derived material, see some activity, then tweak the structure to improve it.

Traci

[momruns]

Hey everyone,

Just got back from the ONC.  My dx was Feb 2011, started on 400, cut to 300 in June, cut to 200 last month.  Here are my labs:

WBC 3.4

ANC 1.3

BCR-ABL   0.002  Log reduction 3.386

FISH (interphase cells 300  Metaphase cells 0)  positive for BCR-ABL1 Fusion.  "positive cells has decreased from 13% to 4/7% a finding consistent with a partial response to therapy"

So I stay on the 200 and get labs every 2 weeks for a while to see if this stays.

Thank you all again for your comments, I am tunneled visioned at times when it comes to this so again thanks.

Loreta

[hannibellemo]

Loreta,

Your results confuse me. I'm not used to seeing PCR results that show you at MMR, but FISH results that don't show you at CCyR. That doesn't jive. Can someone clarify, please?

Pat

[pamsouth]

Hannibellemo,

That is way my labs were for about 6 years.  FISH sometimes at negative, but sometimes would show 1% to 3 % +  while PCRU. 

I know my new oncologist was confused, too, so he ran a test to see if I had other mutations, because the BCR/ABL lab, only checks for #9 & # 22, I think that would be the P210. I did not have any other mutations only the P210 BRC/ABL, same as when diagnosed. 

The FISH (3/19/12) came back at 1.5 % positive, which was 3 nuclei out of 200, but the PCR was 7 %.  I have only had 1 lab there.  The onc said he would do two more labs before final conclusions. At consultation back in Nov 2011,my new oncologist did say, he did not go by the national guidelines, as treatment is a very individual thing.  He said as long as I stayed in a range, even if it was not PCRU, that was Ok, as long as numbers did not steadily go up. He is a CML Specialist at the #1 cancer center of indiana.  Although when the nurse called me about the FISH & PCR, for some reason she seemed only concerned about the FISH.  She did mention Tasigna,  She was not present when I talked to doctor, so I don't know what is up with that.  I did mention to her I wouldn't want to think about changing anything, at least not until I turned 65 next January as I would be Medicare age. My Blue Cross give me grief about paying anything, it is an uphill battle.  I usually get them to pay but only after several exhausting phone calls and a push of saying OK I am calling the UAW Benifit rep, that seems to make a difference and to think it has been 6 1/2 years and still the same hassle.  Anyhow the nurse said no worry you are not in any imminent danger.  So I'm cool with that. I know chronic is slow, so as long as I do the labs and we watch the numbers are not steadily going up, I'm good with that.  I read where you can still be under radar and have a million or so PH+.  In fact I don't think the disease has changed at all for me, I think it is just the lab was reporting and changing over to IS.

My old labs were sent from my home state Indiana to N.J. My new labs are draw in the oncologist office and interpreted at the lab/hospital that is connected to his office.  I think part of the confusion has something to do with where/how the labs do their calculations.  I don't know.

It does seem odd, but it has been an ongoing thing for 6 1/2 years for me of sometimes the FISH showing a slight positive an PCRU and I don't not have any other mutations.

Seem like circumstance and situations vary from person to person and doctors and labs and TKI's.

PamSouth

[momruns]

Pam,

This also confused my ONC.  He said the FISH is not as important as the BCR-ABL and BMB but they draw this at MD Anderson.

Loreta

[pamsouth]

momruns,

I don't know, everyone seems confused, especially me!!  That is the way my labs have been for over 6 years, until the lab in New Jersey, changed over to IS last year. My previous onc drew the blood in her office and sent them to N.J.  However I found out that Indiana University draws their own blood and interpret them and they are only 15 miles from my home, so why go to a onc that send them to New Jersey.  My FISH would sometime be positive, only a few 3 or 4 nuclie found.  while PCR was Undetected.  The labs ran that was for over 6 years until the lab changed over to IS, then there was a big jump up, then 1 week later, it dropped significantly. I would have to pull the labs I don't remember the numbers.   My new oncologist look at the old labs and was confused why the FISH were not always negative when the PCR was negative, at least that is what he said.

However my new onc was a bit confused.  At least he made me think he was confused, he kept mentioning he wanted to run the cytogenetics to see if I had other mutations as he (looking at my previous labs for the last two years that were ran in the lab in New Jersey) thought the FISH should be zero. He said normally when you run the test it only looks for BCR/ABL and he thought maybe I might have had other mutations. My blood draw was on march 19th 2012, and it turned out I didn't have any other mutation ("P190 Not Detected), negative for e1a2 bcr-abl.  I only had the P210 BCR-ABL BID QN PCR, report on 3/19/12. which was 7.6 IS and Fish 1.5 %..  Of course that was the first labs that were taken at Ind univ. Then when the nurse called to read my labs to me, she mainly seemed to be concerned about the FISH, i guess she thought it should be 0 and it was 1.5. and I thought that was odd, I am not sure where they are going with it.  I have an appointment on May 10, 2

I think I will call the nurse and see if I can get my labs done about 3 weeks earlier then appointment so when I go to appointment on May 10th, we will know what the lab report is, instead of having to call me and all.  I mean you really don't have anything to talk about, without the labs, except for a short exam and a few questions.  It is the lab we want!!

Hopefully after the next lab I will know where they are going with this. Last fall I called LLS and asked if they could refer me to another onc, they said that Indiana University was rated as the #1 cancer center of Indiana.  It was only 15 miles from me and when I found out they do their on labs, well there was no contest.

I hope I said that correctly.

Confused PamSouth

[valiantchong]

1.5% FISH results could be within FISH detection error. I do not think Fish is sensitive when CCR is achieved. The error may caused by overlapping of 2 different 9 and 22 chromosomes randomly located so close together that it looks deceiving to the eye as if it is a 9-22 crossed chromosome... Anyone else in this board has any input ?

[pamsouth]

Valiantchong,

My previous labs (of 6 years ) went to New Jersey.  On their lab report it distinguishes the counts on the Beae and the b3a2, sometimes there will be positive on one and sometimes a positive on both.  On the new lab for Mar 19th 2012, It groups them together beae/b3a2 under the percent.  I said something to the nurse at Indian University and she said they just look at the total and other then that it would be more detail then a onc would care to know.  I guess I am just use to look at the New Jersey labs reporting.

I hear what you are say the overlapping, of 9 and 22, is that the same as the b2a2 and b2a2, or are you talking about something different.

Thanks for your input.

PamSouth

[valiantchong]

pls refer to this site on FISH test explaination: A pictorial information on how to identified BCR-ABL gene

http://www.ncbi.nlm....les/PMC2500019/

Figure 2

BCR/ABL1 fusion at 22q11.2: "small" and "large" insertions with recurrent distal breakpoints. (a) Diagram showing the small size ins(22;9)(q11;q34.1q34.1) seen in 3 patients (no 1-3). The BAC clones covering the distal breakpoint region are presented with green lines. The ABL1 breakpoint marks the proximal boundary of the insertion (< 1 Mb) while the distal breakpoint (shown by red arrows) falls within a 280 Kb breakpoint cluster housing the UCK1, POMT1 and RAPGEF1 genes. (a₁) A representative metaphase cell in patient no 3 with co-hybridization of FISH probes RP11-323H21 and RP11-413M3, showing a split signal from RP11-323H21 (green signals at both chromosome 9 homologues and masked Ph) and duplication of the masked Ph (green signals on 2 masked Ph). (a₂) BCR/ABL1 D-FISH (Vysis) in patient no 2, showing the absence of green signal at der(9). ( Diagram showing the large size ins(22;9)(q11.2;q34.1q34.2) seen in patient no 4 and CML-T1. The ABL1 breakpoint marks the proximal boundary of the 3.9 Mb insertion, while the distal breakpoint lies within the clone RP11-92B21 (red arrow). (b₁) A representative metaphase cell in patient no 4 with co-hybridization of FISH probes RP11-92B21 and RP11-413M3, showing a split signal from RP11-92B21 (green signal at both chromosome 9 homologues and masked Ph). (b₂) BCR/ABL1 D-FISH (Vysis) in CML-T1, showing absence of green signal at der(9) and duplication of the masked Ph (two fusion signals).

Gains and deletions in the Ph negative BCR/ABL1 positive cell line CML-T1. (a) Array CGH reveals gains of sequences downstream of the ABL1 breakpoint. The genome profile of the 9q34.1-qter region is shown at the top and the 22q11.2-2 region is presented at the bottom, aligned at the ABL1 and BCR breakpoints (vertical dashed line). Results of the SGI2600 BAC chip are shown in red and 44 K Agilent oligonucleotide in blue. Both BAC and oligo array detect a gain of the 9q34 sequences proximally flanked by the ABL1 breakpoint and distally by the RXRA gene. ( A representative tetraploid metaphase cell with co-hybridization of FISH probes RP11-138E2 and RP11-17O4, showing the proximal breakpoint of the 9q34 deletion arisen in this sub-clone (the arrows show the two missing green signals from RP11-138E2). © A representative tetraploid metaphase cell with co-hybridization of RP11-323H21 and a 9q sub-telomeric probe (Stretton), showing the duplication of the masked Ph and that the genomic loss affects not the der(9) but the "normal" homologue (the 2 green and 2 red signals from the two normal 9 are missing). The top box on the right shows 4 green, 2 red signals as seen in interphase tetraploid cells with deletion, while the bottom box on the right shows 6 green, 4 red signals as seen in the interphase tetraploid cells without deletion.