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22 Replies Latest reply: Mar 13, 2012 6:41 PM by tcell_all RSS

Chromosomal Abnormalities in ALL

tburkhardt Registered Users
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Hi All,

I'm new to this forum---and am hoping that someone can help me with this stuff!

We are 4 months into our fight with our 10 year old boy diagnosed with Pre-B ALL.  I just found out about this chromosomal abnormality that is evidently associated with a poor prognosis (amplification of the AML1 locus), but there is conflicting information and our doctor is unsure also.

Here is the bone marrow chromosome analysis done at time of diagnosis:

46, XY, del(9) (p13),add(21)(q22)<3>/46,XY<12>

We would love any information that you all may have regarding abnormal karyotypes in childhood ALL with regard to prognosis, etc.

Thank you!

Tonya

  • Re: Chromosomal Abnormalities in ALL
    StillSarah'sMom Registered Users
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    Hi Tonya,

     

    Sorry that you haven't gotten a response to your question yet.  I don't know the answer either  

     

    However, it does seem that there are abnormalities that show up that are 'iffy', and some that matter more at different ages.  My daughter, for instance, had the 11q23 deletion (or maybe translocation?) when dx'd at age 12.  Our doc was very concerned but in researching further it turned out that although this was an adverse risk factor for babies it had not been shown to impact the treatment/survival stats of older children.

     

     

    Perhaps your onc will be willing to reach out to other docs to find out more about your son's specific chromosomal issue.  The oncs at CHOP (Children's Hosp of Philadelphia) were very helpful, as was Dr. Pui.  He, I believe, was in Seattle when we contacted him in 2004.  Your onc should be able to get email addresses, etc to reach out and formation for you. 

    With the info that our onc rec'd we were able to tweak my daughter's protocol-she was off study anyway due to allergy to Asparaginase-to one that was a bit lower risk than the one we were going with originally. 

    She will be OT 3 years this August and is doing fine

     

    Hope your son is doing well with treatment so far, and that you can get some answers quickly!

     

    Patty

    • "On Study" "Off Study" -- does it make a difference?
      tburkhardt Registered Users
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      Hi Patty,

       

      Thank you so much for your reply.  I was starting to get a little freaked out by the non-response, like maybe this is something that is so rare that no one knows anything about it.  But then I thought, maybe it could be that not all parents know about their child's karyotype?  I wouldn't have known anything about it if I hadn't asked about chromosome counting.  My onc is reaching out to his mentor for more information, as there is conflicting information in the studies we have read.

       

      I am curious about the on study/off study scenarios though.  We happen to be "on study" but on the standard arm (not the experimental arm).  I don't want the fact that we're on study to prohibit any necessary changes in treatment.  However, I think the fact that we are "on study" will help us to get additional testing that we want done--such as "interphase chromosomal analysis"---as the docs make it sound like being on study is helpful in this regard.

       

      What do you all think?

       

      Thanks so much...

       

      Tonya

  • Re: Chromosomal Abnormalities in ALL
    Alex'sMom Registered Users
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    I can't help you much here. When Alex was diagnosed I was in such a fog - All I heard was cancer - if they told me about chromosomal analysis or anything like that - I'm guessing I would have not processed it. I have also read a lot things on this board where parents said what the child's WBC or % of blasts were at diagnosis - again if it was mentioned I didn't hear it or it was not a part of any conversations. At this point for me it is more of a curiosity that I keep thinking that I am going to ask about but once we are at the clinic it seems that more pressing things are on the top of my list (like rashes, liver issues, avn issues ect). I am guessing if you haven't gotten much response that many of us just don't know.

    Gina

    • Re: Chromosomal Abnormalities in ALL
      ClaireC Registered Users
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      Um....yep that would include me. I have read your post a few times now and I'm completely stumped by your question. I don't recall in any conversation with Domenic's oncologist about chromosomal abnormalities. I recall they completed genetic testing in which we received the results two weeks after diagnosis as to which arm Domenic was to be placed within the treatment for pre-B ALL. I recall them telling me the three chromosomes that were problematic in the gene pattern and that was it, but I have a feeling taht what you are talking about is different. The only other genetic or chromosome discussion is actually being done through the hereditary cancer program here in Canada as my nephew was diagnosed with Lynch Syndrome and they offered genetic testing to our family as this is now two cancer diagnosises (sp?) in cousins in their youth. I'm sorry I can't be of any more help or any at all, really. I hope you are able to find some answers though as the waiting game can be a frustrating and scary one. Good luck. Claire

  • Re: Chromosomal Abnormalities in ALL
    fireking'smama Registered Users
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    Hi,

         I don't know if any of my info will help or not since my son Aidani s an AML kid.  Here's what I know (at least as it pertains to AML).  When his original bone marrow biopsy and spinal tap were done, not only did they determine things like blast percentages and type of leukemia, but they also did the flow cytometry (often called "fish) to classify what chromosomal factors were involved.  From what I understand, this is done in all cases.  Our oncologist never came right out and told us what Aidan's tests had revealed, but I do remember her telling me very early on that "based on his chromosomal mutation, he has a type that responds better to chemo".  I must have given her a blank stare, because she followed that statement with "this is GOOD news".  In my experience, it seems that most docs hand out little tiny pieces of information at a time, I guess based on what they  think the parents are capable of understanding and digesting.  Unless you already know enough to ask the questions, things like sub-type, cytogenic results and such aren't really brought up, and let's face it, when our children are initially diagnosed who has any idea what most of the information even means, let alone what are the important questions to ask.  I found out Aidan's sub-type (M2) only by reading it in the "road map" handout that the onc had prepared for us.  You know, the one that lists every immediate, short-term and long-term side effect of every chemo that is scheduled to be given?  The one that scares you to death!  Anyway, it wasn't until we went to Duke to meet with the bone marrow transplant team (as a precautionary measure) that we learned which mutation Aidan had.  His is the t 8;21, which means that some of chromosome of 8 is on chromosome 21 and vice-versa.  I believe that every spinal tap and bone marrow biopsy done subsequently, was checked for this mutation and any other ones that might have developed.

         Since all of Aidan's treatment was done in-patient, I never had cause to ask for copies of any lab-work.  It wasn't until a few months ago ( about 8 months following the end of his treatment) that I asked his oncologist for copies of his initial diagnosis lab-work.  I was really trying to get a copy of what his CBC upon admission was and find out what his % of blasts were at diagnosis.  The doc was kind enough to give me a very thorough print-out of Aidan's lab-work and how he was diagnosed.  I noticed in one section, the "chromosomal" marker percentages--it listed several and the only one that he had was the t 8:21 with about 45% of cells showing this.  I really only paid attention to this part because I have now been following various AML kids for about a year now, and would often see these letter and number combos listed as part of their diagnosis.  I have noticed some trends with some mutations seeming to do better than others.  I would imagine that this information would be readily discussed with you if you wished to bring it up with your doc, but again this is the sort of thing that you "learn" to ask about as you progress in these journies.

     

    Hope this helps,

    Klista

  • Re: Chromosomal Abnormalities in ALL
    TomsMom Registered Users
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    Hi Tonya.  This is Connie.  I have some information about different chromosome abnormalities.  I will try to find it and email it to you.  I got alot of good info from people here on this site when I was reading the fish report and couldn't make heads or tails of it.

    • Re: Chromosomal Abnormalities in ALL
      TomsMom Registered Users
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      Hey, I found some of the paperwork I had filed away that talked about the Chromosome/DNA.  I'm just copying what I had printed from the internet site I found...

       

      Cytogenetics:  The study of the structure of chromosome material.  It includes the FISH and CGH (To be explained later)

      FISH:  (Fluorescent in Situ hybridization) is a cytogenetic technique which can be used to detect and localize DNA sequences on chromosomes.  It uses fluorescent probes which bind only to those parts of teh chromosome with which they show a high degree of sequence similarity.

       

      CGH: (Comparative Genomic Hybridization) is a molicular-cytogenetic method for the analysis of copy number changes (Gains/losses) in the DNA content of tumor cells.  It will detect only unbalanced chromosomes changes.  Structural chromosome aberrations such as balanced reciprocal translocations, inversions can't be detected.

      Karyotype:  the complete set of all chromosomes of a cell of any living organism.  The chromosomes are arranged and displayed in a standard format: in pairs, ordered by size.  Karyotypes are examined in searches for chromosomal aberrations.

       

      Chromosome Translocation:  Is the interchange of parts between nonhomologous chromosomes...for example the philadephia chromosome is the translocation of specific genetic material between chromosome 9 and 22.  Translocations can be balanced (in an even exchange of material with no genetic information extra or missing) or unbalanced (where the exchange of chromosome material is unequal resulting in extra or missing genes)

       

      The shorthand t(A;B)(p#;q#) is used to denote a translocation between chromosome A and chromosome B.  The information in the second set of parentheses, when given, gives the precise location within the chromosome for Chromosomes A & B respectively -- with p indicating the short arm of the chromosome and q indicating the long arm of the chromosome, and the numbers after p or q refering to regions, bands and subbands visible in microscope.

       

      Hyperdiploidy:  the presence of additional copies of whole chromosomes and occurs in 20% to 25% of B-precursor ALL but very rarely in cases of T-cell ALL

       

      Trisomies:  the presence of 3, instead of the normal 2 chromosomes of a particular numbered type.  Thus the presence of an extra chromosome 21 is called trisomy 21.   Extra copies of certain chromosomes appear to be specifically associated with favorable prognosis among hyperdiploid ALL cases.

       

      Hypodiploidy:  Approximately 1% of children with ALL have leukemia cells showing hypodiploidy with less than 45 chromosomes.

       

       

      I hope this information can help.

      Connie

  • Re: Chromosomal Abnormalities in ALL
    nana Registered Users
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    I'm not sure really what I'm talking about because like most of us this was at the beginning of Dx and I am a little foggy.  My son has  B-cell ALL 11q23 translocation.  I know this because at the beginning my Onc sent his marrow to Boston to "grow".  We live in Canada and our hospital doesn't have the right lab machines to do this.  He told me every child gets their marrow sent at the beginning of treatment but very few grow because it is damaged by the leukemia.  He told us they really like to have the exact chromosone that went haywire because it can change protocols.  I know for my son he went from being standard risk to extremely high risk.  It ended up adding cranial radiation and about 5 wks to treatment plan. They said it did lower his relapse risk but knowing the translocation helped.

     

    I never asked for the whole analysis, I had enough numbers and info going through my head I guess I figured if I needed to know they would tell me.  I have found that different Drs tell me different things.  It just seems like they each have their own way of giving information and when I put it all together I seem to get the best picture.  When I am confused about something or just overlauded I find asking the nurses really helps.  I know for me they seem to be able to break it down into "normal" talk and make it really easy to understand.

     

    Sorry I know it wasn't very helpful, but just thought I would share my experience.

     

    Nana

    • Re: Chromosomal Abnormalities in ALL
      tburkhardt Registered Users
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      Thank you so much to everyone for your help!  It is extremely helpful just to know that I'm not the only one confused by all of this and I was feeling guilty/angry for not knowing about it sooner.  Thursday I am supposed to be getting more detailed reports from the time of this testing that were never given to me, and I'm going to request that more FISH testing be done to see if there are any changes.  This is where I'm not sure if it would be beneficial for me to be "on/off study".  I am also going to ask about that.

       

      So far, this is all I know from the interpretation of the results:

       

      Only fifteen mitotic cells were available for analysis.  Three of the fifteen were characterized by the addition of unidentified chromatin to one chromosome 21 and by a deletion of the chromone 9 short arm.  No abnormalities were evident in the remaining twelve cells. 

       

      In most pediatric ALL cases where unidentified chromatin has been added to chromosome 21 the additional chromatin is derived from repeated copies of all, or part, of chromosome 21.  The morphology of the abnormal chromosomes is extremely heterogeneous but all appear to contain multiple copies of the AML1 (RUNX1) gene locus.

       

      Chromosomal aberrations leading to amplification of the AML1 locus have been associated with a poor prognosis.

       

      Thanks again to everyone for your help and experience!

       

      Tonya

      • Re: Chromosomal Abnormalities in ALL
        StillSarah'sMom Registered Users
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        Me again! 

        As far as the off study/on study we went with our onc's advice.  She took Sarah off partly because she was allergic to the Peg Aspaginase (severe seizures, back to back, after the 2nd dose) and we wanted to find the most effective treatment protocol available that did NOT use it.  If I'd been on this board then I would have known to ask for an alternative (erwinase?) but I wasn't so that's that.

        She ended up using a protocol that's actually for lymphoma but contained all the same chemos, just at a bit higher dosage.

         

        Anyway, I wanted to mention that when they did Sarah's 2nd FISH test the abnormality was gone and my understanding was that as long as it stayed gone we were golden.  We were one of the 'lucky' few in clinic that got a bma every 6 months so we could make sure that everything looked good.  Needless to say, every 6 months I was a mess for a few weeks waiting for results but everything always came back fine.

        I have no idea if the way our clinic handled our issue was 'normal', but I liked that we were staying on top of things.

         

        I don't know if this helps at all or just causes more confusion but as you mentioned getting further FISH studies done I wanted to mention it.

         

        Patty

         

         

        • Re: Chromosomal Abnormalities in ALL
          tburkhardt Registered Users
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          I know this is an old thread, but had to go back and look because Justin's last FISH study on 2-5-10 showed a normal cytogenetic result with 46,XY(20)!  I sure hope what you say is true Patty, as I haven't had a chance to discuss this latest result yet with our onc team--they just faxed it to me with no discussion---I'll take that as a good sign!

           

          Anyway, thanks Patty for this post.

           

          Tonya

          • Re: Chromosomal Abnormalities in ALL
            StillSarah'sMom Registered Users
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            Hi Tonya,

             

            Funny, I just popped in for a minute and saw this most recent post.  I'm very happy that Justin's last FISH showed normal results, it sounds like very good news, indeed

             

            Sarah had a bma w/FISH every 6 months during LTM so that they could make sure that the cytogenics stayed normal.  They always were, including her last OT bma.  She's 3.5 years OT now and doing just fine!

             

            Yay for Justin and his normal chromosomes, and thanks for posting to let us know! 

             

            Patty

  • Re: Chromosomal Abnormalities in ALL
    mom4boys Registered Users
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    I'm sorry I didn't respond earlier.  Like many others, these chromosome tests are difficult for me to understand (we left an oncologist for giving me FISh results in the cafeteria).  We've had 3 FISH test done.  One at dx, one to confirm relapse, and one to unconfirm the relapse.  Eli had nothing that looked like yours and that's why I didn't respond earlier. This is what I found interesting about FISH testing.  At dx, Eli had trisomy 4 and 17 (my understanding is that most ALL patients have trisomy 4, 10 and 17) this kept Eli out of the "low risk" protocol.  When the FISh was done a year later suspecting relapse, it was totally clean.  2 weeks later, it showed 4% trisomy 4.  It seems to me that these BMAs and FISH results fluxuate as much as the ANC, the housing market and the DOW Jones IA.

     

    I hope you find the answers you need. Sorry I couldn't have been more help.

    • Re: Chromosomal Abnormalities in ALL
      Evan'sMommy Registered Users
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      Evan is also B-cell ALL.  During Induction the ONC told us he had hyperdiploidy which was good, later I asked about the chromosome and she just said he had 4 and 17.  And that he was standard-standard risk and not low-risk because he didn't have all 3 (4,10,&17)

  • Re: Chromosomal Abnormalities in ALL
    tburkhardt Registered Users
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    Bump for Karen

  • Re: Chromosomal Abnormalities in ALL
    Fontenrose Registered Users
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    I was wondering if I should post this article under the cause/causes of leukemia, but this topic seems to fit. I tried to post a section of the article but got the posting error, so here is just the link:

     

    http://www.nytimes.com/2011/01/11/health/11cancer.html?_r=1&ref=health

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