Guest guest Posted November 21, 2008 Report Share Posted November 21, 2008 Hi Kathy, It would appear that you've had three tests here, a PCR (2 of them in fact), a FISH and a cytogenetic test. The PCR from the marrow is the strangest and the most controversial. PCR's from patients who are not in CCR, often are not considered very reliable which is why they recommend these patients to continue having regular BMB's. Certainly, your two PCR's aren't even in the same ball park. You have one that shows virtually a 5+ log reduction (the one taken with peripheral blood the day before) and another one that shows virtually no log reduction at all. Very strange and again reinforces the perils and implications of getting a negative or undetectable test. Although it's not perfectly clear from what you type, I have to assume that they analyzed 200 cells for the FISH and 20 for the cytogetetic test (these are the standard number of cells analyzed for the two tests). The FISH, as you know, has a rate of false positivity and your result of 1% definitely falls into that category. This means that your FISH shows a very low positive which may or may not be a true positivity. The gold standard for CML testing, especially when not in CCR is the cytogenetic testing. This appears to have turned up one Ph+ cell as you wrote: " The Philadelphia chromosome was seen in one of the twenty cells analyzed " . One cell out of 20 represents 5% which isn't bad but isn't CCR either. The karyotyping isn't really that important. That's done with any standard cytogenetic test where they look at the sex cells as well as the regular chromosomes. The result should be 46 XX. The 46 refers to the number of chromosomes and the XX refers to your sex chromosomes that show you're a female (a male will show 46 XY because they have a Y chromosome). It appears from this BMB that you're not in CCR and since you were diagnosed some time ago (back in 2005 if I remember correctly?), I would have to agree that the 400mg of Gleevec isn't really working well enough for you. I can't say that you're " relapsing " as I don't have any information from your previous BMB's but it does appear that the Gleevec isn't working well enough so a change in treatment would be reasonable. Do you have your past BMB results? Have you ever been in CCR? Most of the top doctors will continue to do BMB's every 6 months until you are confirmed to be in CCR, then you can rely more on the PCR's and either spread out your BMB's farther or perhaps even eliminate them all together. I hope that helps a bit, Tracey > > Hi everyone. I received my test results, and I need some help sorting > it out. As I posted before, a PCR in August was .006. Then Oct 20 it > was .015. As Zavie and Tracey recommended, I had another PCR on > peripheral blood on Nov.6--that PCR was negative. I was stunned--I > never expected that. The lab report from Quest says " no evidence of > expression of the BCR-ABL fusion transcript. " Great news, it seems. > > The next day, Nov 7, I had a BMB. Here is where I become VERY > confused. A PCR on the marrow was also done at Quest labs (their > baseline for peripheral blood PCR is 4.1325 and PCR on marrow is 5.09). > The BCR-ABL:ABL ratio on the marrow was 2.616. Does that mean only a > 1/2 log reduction, and how could that be if a peripheral blood PCR the > day before at the same lab was negative? > > Also done on the marrow sample was FISH karyotype, and I will type this > directly from the report: " The Philadelphia chromosome was seen in one > of the twenty cells analyzed. Concurrent FISH analysis verified this > as a low level clonal abnormality. " 20/200 cells were analyzed, 20 > cells were counted and 4 were karyotyped. This yielded 1% positive by > FISH. I've had a false positive FISH before, I know the margin of > error can be as high as 10%. Is karyotyping a separate test, or part > of the FISH analysis? > > Sorry to put in so much info, but then I'm not sure I have included all > the information you might need to help me understand where I'm at. My > Dr conferred with a colleague who agrees with her that I am relapsing > on gleevec and wants me to go to dasatinib. How could they be so sure, > as the PCR on the blood was negative? So please tell me what you think- > -do I celebrate being PCRU for the first time, or do I change treatment > because marrow trumps blood? > > Thank you for reading this long post and for sharing so much wisdom and > experience. Have a great day! > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 21, 2008 Report Share Posted November 21, 2008 Thank you, Tracey Your response was very helpful, and I hope I'm not wearing you out with all my questions. I have great confidence in your knowledge, but not so much in my ability to give you the relevant information and ask the right questions. You do remember correctly--dx'd in May 05 and a BMB in Nov 05 showed no Ph. I also had two BMB at MD (May 06 and April 07) that were also CCR. In Jan 08, my local Dr did a FISH on peripheral blood (b/c my white count by CBC was up slightly) tha showed 4% positive. That's when I learned about false positivity. b/c the BMB done for followup was clean. So the FISH of 1% doesn't trouble me, but if the cytogenetics was done in addition to FISH, and the translocation was actually SEEN, then that was concerning. It didn't seem to lend itself to a false read if it was seen in the cytogenetics. Am I wrong about that? And I will tell you more about the PCR on marrow--I may have given you the wrong ratio. From the report: BCR/ABL gene rearrangement BCR-ABL T(9:22) fusion 0.010 H ratio 0.000 BCR-ABL: ABL ratio 2.616 log reduct In the body of the report: " the median of BCR-ABL:ABL ratio in previosly untreated CML patients is 4.1325 in peripheral blood samples and 5.09 in bone marrow samples " Perhaps I assumed incorrectly, but I have compared their ratio of 5.09 to my ratio of 2.616. If I should really compare their 5.09 to my ratio of 0.010, the results are much better. But I tried to compare apples to apples. Thank you for your help with this. Have a great day " The Philadelphia chromosome was seen in one of the twenty cells analyzed " . One cell out of 20 represents 5% which isn't bad but isn't CCR either. The karyotyping isn't really that important. That's done with any standard cytogenetic test where they look at the sex cells as well as the regular chromosomes. The result should be 46 XX. The 46 refers to the number of chromosomes and the XX refers to your sex chromosomes that show you're a female (a male will show 46 XY because they have a Y chromosome). It appears from this BMB that you're not in CCR and since you were diagnosed some time ago (back in 2005 if I remember correctly?), I would have to agree that the 400mg of Gleevec isn't really working well enough for you. I can't say that you're " relapsing " as I don't have any information from your previous BMB's but it does appear that the Gleevec isn't working well enough so a change in treatment would be reasonable. Do you have your past BMB results? Have you ever been in CCR? Most of the top doctors will continue to do BMB's every 6 months until you are confirmed to be in CCR, then you can rely more on the PCR's and either spread out your BMB's farther or perhaps even eliminate them all together. I hope that helps a bit, Tracey > > Hi everyone. I received my test results, and I need some help sorting > it out. As I posted before, a PCR in August was .006. Then Oct 20 it > was .015. As Zavie and Tracey recommended, I had another PCR on > peripheral blood on Nov.6--that PCR was negative. I was stunned--I > never expected that. The lab report from Quest says " no evidence of > expression of the BCR-ABL fusion transcript. " Great news, it seems. > > The next day, Nov 7, I had a BMB. Here is where I become VERY > confused. A PCR on the marrow was also done at Quest labs (their > baseline for peripheral blood PCR is 4.1325 and PCR on marrow is 5.09). > The BCR-ABL:ABL ratio on the marrow was 2.616. Does that mean only a > 1/2 log reduction, and how could that be if a peripheral blood PCR the > day before at the same lab was negative? > > Also done on the marrow sample was FISH karyotype, and I will type this > directly from the report: " The Philadelphia chromosome was seen in one > of the twenty cells analyzed. Concurrent FISH analysis verified this > as a low level clonal abnormality. " 20/200 cells were analyzed, 20 > cells were counted and 4 were karyotyped. This yielded 1% positive by > FISH. I've had a false positive FISH before, I know the margin of > error can be as high as 10%. Is karyotyping a separate test, or part > of the FISH analysis? > > Sorry to put in so much info, but then I'm not sure I have included all > the information you might need to help me understand where I'm at. My > Dr conferred with a colleague who agrees with her that I am relapsing > on gleevec and wants me to go to dasatinib. How could they be so sure, > as the PCR on the blood was negative? So please tell me what you think- > -do I celebrate being PCRU for the first time, or do I change treatment > because marrow trumps blood? > > Thank you for reading this long post and for sharing so much wisdom and > experience. Have a great day! > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 21, 2008 Report Share Posted November 21, 2008 Hi Kathy, Don't worry about " wearing me out " . If I can help, even just a little bit, then I'm more than pleased to do so. You're right about your interpretations of the slightly positive FISH considering the one cell they found in the cytogenetics test (there are no false positives with cytogenetics). Keep in mind that these are still very low numbers, right at the threshold of CCR so it's not like you need to go into panic mode but you do need to take action since you're not getting as good of a response as you should. I can't say for sure without seeing the actual report but it would appear to me that your PCR result is actually 0.010 and the 2.616 is the log reduction that your result represents. A very rough estimate of how PCR results correlate with CCR is that CCR " usually " occurs in the neighbourhood of a 2 log reduction in PCR. Now since you're flirting with CCR (having just one bad cell), it would stand to reason that your PCR would be very close to 2 logs and in fact it is. I hope that helps, Tracey " The Philadelphia chromosome was seen in one > of the twenty cells analyzed " . One cell out of 20 represents 5% > which isn't bad but isn't CCR either. > > The karyotyping isn't really that important. That's done with any > standard cytogenetic test where they look at the sex cells as well as > the regular chromosomes. The result should be 46 XX. The 46 refers > to the number of chromosomes and the XX refers to your sex > chromosomes that show you're a female (a male will show 46 XY because > they have a Y chromosome). > > It appears from this BMB that you're not in CCR and since you were > diagnosed some time ago (back in 2005 if I remember correctly?), I > would have to agree that the 400mg of Gleevec isn't really working > well enough for you. I can't say that you're " relapsing " as I don't > have any information from your previous BMB's but it does appear that > the Gleevec isn't working well enough so a change in treatment would > be reasonable. > > Do you have your past BMB results? Have you ever been in CCR? Most > of the top doctors will continue to do BMB's every 6 months until you > are confirmed to be in CCR, then you can rely more on the PCR's and > either spread out your BMB's farther or perhaps even eliminate them > all together. > > I hope that helps a bit, > Tracey > > --- In groups (DOT) com, " kathymhyland " <kathymhyland@ ...> wrote: > > > > Hi everyone. I received my test results, and I need some help > sorting > > it out. As I posted before, a PCR in August was .006. Then Oct 20 > it > > was .015. As Zavie and Tracey recommended, I had another PCR on > > peripheral blood on Nov.6--that PCR was negative. I was stunned-- I > > never expected that. The lab report from Quest says " no evidence > of > > expression of the BCR-ABL fusion transcript. " Great news, it seems. > > > > The next day, Nov 7, I had a BMB. Here is where I become VERY > > confused. A PCR on the marrow was also done at Quest labs (their > > baseline for peripheral blood PCR is 4.1325 and PCR on marrow is > 5.09). > > The BCR-ABL:ABL ratio on the marrow was 2.616. Does that mean only > a > > 1/2 log reduction, and how could that be if a peripheral blood PCR > the > > day before at the same lab was negative? > > > > Also done on the marrow sample was FISH karyotype, and I will type > this > > directly from the report: " The Philadelphia chromosome was seen in > one > > of the twenty cells analyzed. Concurrent FISH analysis verified > this > > as a low level clonal abnormality. " 20/200 cells were analyzed, 20 > > cells were counted and 4 were karyotyped. This yielded 1% positive > by > > FISH. I've had a false positive FISH before, I know the margin of > > error can be as high as 10%. Is karyotyping a separate test, or > part > > of the FISH analysis? > > > > Sorry to put in so much info, but then I'm not sure I have included > all > > the information you might need to help me understand where I'm at. > My > > Dr conferred with a colleague who agrees with her that I am > relapsing > > on gleevec and wants me to go to dasatinib. How could they be so > sure, > > as the PCR on the blood was negative? So please tell me what you > think- > > -do I celebrate being PCRU for the first time, or do I change > treatment > > because marrow trumps blood? > > > > Thank you for reading this long post and for sharing so much wisdom > and > > experience. Have a great day! > > > > > > > > > > > > > > > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 21, 2008 Report Share Posted November 21, 2008 Thanks again, Tracey! You are more helpful than you could realize. When you have the time, I'd love to know more about how you aquired your tremendous understanding of this illness--I wonder if your background is in science? It is so good of you to share all that you have learned. Based on our discussion, would an increase in gleevec address my issues, or be a waste of time? We're driving to Dallas for Thanksgiving, so I can't face the fatigue of 800mg until we return. But that is MY current plan--800mg and test again in 3 mos. As I said, my Dr wants to go to dasatinib. What do you think? Thanks again for all your time. Your kindness is really appreciated. Love, Kathy From: Tracey <traceyincanada@...> Subject: [ ] Re: Test results Date: Friday, November 21, 2008, 1:22 PM Hi Kathy, Don't worry about " wearing me out " . If I can help, even just a little bit, then I'm more than pleased to do so. You're right about your interpretations of the slightly positive FISH considering the one cell they found in the cytogenetics test (there are no false positives with cytogenetics) . Keep in mind that these are still very low numbers, right at the threshold of CCR so it's not like you need to go into panic mode but you do need to take action since you're not getting as good of a response as you should. I can't say for sure without seeing the actual report but it would appear to me that your PCR result is actually 0.010 and the 2.616 is the log reduction that your result represents. A very rough estimate of how PCR results correlate with CCR is that CCR " usually " occurs in the neighbourhood of a 2 log reduction in PCR. Now since you're flirting with CCR (having just one bad cell), it would stand to reason that your PCR would be very close to 2 logs and in fact it is. I hope that helps, Tracey " The Philadelphia chromosome was seen in one > of the twenty cells analyzed " . One cell out of 20 represents 5% > which isn't bad but isn't CCR either. > > The karyotyping isn't really that important. That's done with any > standard cytogenetic test where they look at the sex cells as well as > the regular chromosomes. The result should be 46 XX. The 46 refers > to the number of chromosomes and the XX refers to your sex > chromosomes that show you're a female (a male will show 46 XY because > they have a Y chromosome). > > It appears from this BMB that you're not in CCR and since you were > diagnosed some time ago (back in 2005 if I remember correctly?), I > would have to agree that the 400mg of Gleevec isn't really working > well enough for you. I can't say that you're " relapsing " as I don't > have any information from your previous BMB's but it does appear that > the Gleevec isn't working well enough so a change in treatment would > be reasonable. > > Do you have your past BMB results? Have you ever been in CCR? Most > of the top doctors will continue to do BMB's every 6 months until you > are confirmed to be in CCR, then you can rely more on the PCR's and > either spread out your BMB's farther or perhaps even eliminate them > all together. > > I hope that helps a bit, > Tracey > > --- In groups (DOT) com, " kathymhyland " <kathymhyland@ ...> wrote: > > > > Hi everyone. I received my test results, and I need some help > sorting > > it out. As I posted before, a PCR in August was .006. Then Oct 20 > it > > was .015. As Zavie and Tracey recommended, I had another PCR on > > peripheral blood on Nov.6--that PCR was negative. I was stunned-- I > > never expected that. The lab report from Quest says " no evidence > of > > expression of the BCR-ABL fusion transcript. " Great news, it seems. > > > > The next day, Nov 7, I had a BMB. Here is where I become VERY > > confused. A PCR on the marrow was also done at Quest labs (their > > baseline for peripheral blood PCR is 4.1325 and PCR on marrow is > 5.09). > > The BCR-ABL:ABL ratio on the marrow was 2.616. Does that mean only > a > > 1/2 log reduction, and how could that be if a peripheral blood PCR > the > > day before at the same lab was negative? > > > > Also done on the marrow sample was FISH karyotype, and I will type > this > > directly from the report: " The Philadelphia chromosome was seen in > one > > of the twenty cells analyzed. Concurrent FISH analysis verified > this > > as a low level clonal abnormality. " 20/200 cells were analyzed, 20 > > cells were counted and 4 were karyotyped. This yielded 1% positive > by > > FISH. I've had a false positive FISH before, I know the margin of > > error can be as high as 10%. Is karyotyping a separate test, or > part > > of the FISH analysis? > > > > Sorry to put in so much info, but then I'm not sure I have included > all > > the information you might need to help me understand where I'm at. > My > > Dr conferred with a colleague who agrees with her that I am > relapsing > > on gleevec and wants me to go to dasatinib. How could they be so > sure, > > as the PCR on the blood was negative? So please tell me what you > think- > > -do I celebrate being PCRU for the first time, or do I change > treatment > > because marrow trumps blood? > > > > Thank you for reading this long post and for sharing so much wisdom > and > > experience. Have a great day! > > > > > > > > > > > > > > > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted November 21, 2008 Report Share Posted November 21, 2008 Hi Kathy, When I was diagnosed back in January 2002, I was close to finishing my BA in Psychology. I had taken all of my core courses and had only electives left to complete my degree. Having just been diagnosed, I suddenly became interested in science and as a result, I decided to take all of my electives in science including Genetics, Neurobiology, Chemistry, Natural biology and a few others that I can't think of off the top of my head. I also spent weeks and months on the internet reading all the medical journals I could that had anything to do with CML. I still try to keep up with the latest but I have to say that treatment options are moving at such a fast rate now that I have a hard time keeping up with all the new trials that are being done. What a difference a few years makes! Back when I was diagnosed Gleevec had just barely been approved and there was nothing else on the horizon, now we have dozens of drugs to choose from! In your case, you could try a higher dose of Gleevec to see if you could get a better response, this has worked for some people. The problem though is that your side effects will no doubt increase substantially. Many doctors would prefer that a patient switches drugs to a standard dose of a new drug than to double the dose of Gleevec and possibly create a problem of intolerance due to side effects. In the end it's your choice but I think if I were in your shoes, I would go with the new drug which is known to be much more potent than Gleevec. The only other thing that I would add is that I would ask for a mutation test just to see if there are any mutations which could explain why Gleevec isn't working so fantastically. If it turns out that you do have a mutation, this information will help you choose between Sprycel and Tasigna since some mutations work better for one drug and others work better on the other drug. I hope you have a wonderful Thanksgiving in Dallas! Tracey > > > > > > Hi everyone. I received my test results, and I need some help > > sorting > > > it out. As I posted before, a PCR in August was .006. Then Oct 20 > > it > > > was .015. As Zavie and Tracey recommended, I had another PCR on > > > peripheral blood on Nov.6--that PCR was negative. I was stunned- - > I > > > never expected that. The lab report from Quest says " no evidence > > of > > > expression of the BCR-ABL fusion transcript. " Great news, it > seems. > > > > > > The next day, Nov 7, I had a BMB. Here is where I become VERY > > > confused. A PCR on the marrow was also done at Quest labs (their > > > baseline for peripheral blood PCR is 4.1325 and PCR on marrow is > > 5.09). > > > The BCR-ABL:ABL ratio on the marrow was 2.616. Does that mean > only > > a > > > 1/2 log reduction, and how could that be if a peripheral blood > PCR > > the > > > day before at the same lab was negative? > > > > > > Also done on the marrow sample was FISH karyotype, and I will > type > > this > > > directly from the report: " The Philadelphia chromosome was seen > in > > one > > > of the twenty cells analyzed. Concurrent FISH analysis verified > > this > > > as a low level clonal abnormality. " 20/200 cells were analyzed, > 20 > > > cells were counted and 4 were karyotyped. This yielded 1% > positive > > by > > > FISH. I've had a false positive FISH before, I know the margin of > > > error can be as high as 10%. Is karyotyping a separate test, or > > part > > > of the FISH analysis? > > > > > > Sorry to put in so much info, but then I'm not sure I have > included > > all > > > the information you might need to help me understand where I'm > at. > > My > > > Dr conferred with a colleague who agrees with her that I am > > relapsing > > > on gleevec and wants me to go to dasatinib. How could they be so > > sure, > > > as the PCR on the blood was negative? So please tell me what you > > think- > > > -do I celebrate being PCRU for the first time, or do I change > > treatment > > > because marrow trumps blood? > > > > > > Thank you for reading this long post and for sharing so much > wisdom > > and > > > experience. Have a great day! > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > > Quote Link to comment Share on other sites More sharing options...
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