Hi Dr. Aussie Neil! I am pleased to write to you once again about my test result. As i previously indicated, a year ago i was diagnosed with CLL Rai Stage II B and put on R-CVP chemoimmunoterapy and now 4 months since i took the last 6th infusion of 6 cycles recommended for my treatment. But still i have swollen sub-mandibular lymph nodes and recently increased size of my neck on both sides. I do have drenching night sweats as if my shirt is socked in water and still i have mild spleenomegally. previously my treatment regimen was initiated prior to conducting cytogenetic tests to identify genomic aberrations related to my CLL cases. I recently got my blood sample tested abroad and the result showed that the cells analyzeby FISH Panel test were negative for deletions of 13q14.3, TP53( 17p13) and ATM(11q22.3). But the result showed positive results for trisomy 12 with negative result of the IGH/CCND1 translocation. would you kindly give me your expert suggestion on what my treatment option would be for this faulty trisomy 12 chromosome with negative IGH/CCND1 translocation. I would be very grateful as usual for your help.
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I'm not a doctor, just a well read person of medical papers concerning CLL. We also have over 16,000 members, including those with actual medical training, along with members with Trisomy 12, who could personally share the success of their treatment experiences with you. We really can't give people medical advice in this forum, even if we were a CLL specialist. That's because the best medical advice for you depends on your medical history, your circumstances, your access to appropriate medical care and other considerations that we just can't appreciate. Most importantly, you don't know what in your medical history is relevant to share in order for you to get the best medical advice specific to just you.
It seems to me that the results of the IGH/CCND1 translocation test just confirm that you do indeed have CLL, not MCL, a close cousin to CLL.
The test which would most help with your treatment decision is your IGHV mutation status. I suspect that given you have Trisomy 12, this along with your limited response to your R-CVP chemoimmunotherapy treatment indicates that you are most likely unmutated IGHV. See
So I suspect that it is unlikely that you will do any better on other chemoimmunotherapy options, plus it is desirable if possible, to have non-chemo treatments for subsequent treatments. This is where your choice will be determined by reasonably achievable 'local' medical oversight and what you are able to afford. We are only just beginning to gather data on how different limited time non-chemo treatment options perform with the different prognostic marker classes, which would be a lower cost option to monotherapy with a BTKi inhibitor like Acalabrutinib or Ibrutinib, or a BCL-2 inhibitor like Venetoclax. Venetoclax treatment may also require in hospital monitoring if you still have a reasonable tumour burden, which seems to be the case. Given your poor response to R-CVP, I suspect you would not do well on time limited Obinutuzumab treatment, (Obinutuzumab is a second generation and slightly better performing version of Rituximab, the R in R-CVP.
While I'd appreciate further comments from Jm954, you really do need to try and find a specialist somewhere near you with a better understanding of what treatment fits best with your local medical support circumstances.
Thank you Neil for your detailed information to my question. The problem here in Ethiopia is that the only one referral hospital in the country is il-equipped in terms of material or trained man power. The hospital does not have laboratory machinery to diagnose genomic markers of patients like conducting FISH test nor immunophenotype flow cytometry to make definitive diagnosis of CLL. The most important tests for blood cancer patients are not done locally but sent abroad with high cost. At hospital, only 3 or 4 hematologists and in rare cases general onchologists are available to help assistant physicians with complicated cases. They cannot even attend to individual patients but rather go around the wards to advise attending subordinate doctors on how to handle the cases or to tell what drug regimen to prescribe. Even if you get your sample checked abroad, there is still big problem with physicians in correlating your test results with your clinical context to initiate the right choice of treatment for you. This is mainly due to lack of exposure of doctors to new drugs like ibrutinib or acalabrutinib which are being suggested for those patients with del 17p, 11q, trisomy 12 and unmutated IGHV cases. These new drugs and recently developed diagnostic technologies are not available at the hospital. one justification for this complaint is that physicians put most of newly diagnosed patients on chemo therapy before checking their genomic aberrations which is not helpful anyway as suggested by many in this post particularly for those with 11q and 17p deletions and trisomy 12 with unmutated IGHV. So there are no local CLL specialists to consult let alone going for second opinion for further consideration. one doctor i consulted about my lab test said to me he can't do anything for me because these good drugs such as ibrutinib and other targeted drugs are not available in Ethiopia but promised me to help if i could find CLL specialists online to guide them on treatment options. So my only option is to get expert advice from our CLL Suppot community or contact cllsociety.org/.. to advise me or to guide my local doctors on how to proceed with my treatment options. I appreciate your suggestion on my plan.Thank you.
Many with CLL share your difficulties in having appropriate testing and then gaining access to drugs more suitable to their markers. Even in the USA, where such testing is readily available, many patients are not tested before being started on treatment which is not appropriate for them, despite the availability of drugs more suitable for them. See: cllsociety.org/cll-101/test...
It is worth asking CLL Society if they can recommend a suitable doctor in a country near you if your doctors can't find one. If you can't get IGHV mutation testing done, it would still be worth trying to arrange treatment with a new, non-chemo drug, as they work fairly well whether you are unmutated or mutated IGHV.
Thank you again for your wonderful advice on my future treatment options. you have put clear direction for me to contact cllsociety.org/cll-101/test... and i will do it right away and will let you all know about my progress with them. May the almighty God relieve all of us from distress of CLL disease.
I also have Trisomy 12. Have you also been tested for Notch 1? Some with Tri 12 have Notch - another negative indicator. I also have it.
During a recent visit with my oncologist, though we were discussing different issues, I took away some information that might help you.
The main determinant for treatment type is unmutated IGHV. Chemotherapy is not very useful. I have been on Ibrutinib for 4 years and doing very well. There are other targeted therapies available too.
The other negative indicators raise your risk level. The higher risk you are the less likely you are to have an extended remission after stopping treatment. There are all kinds of variations of treatments being developed now that may change that.
I was not tested for NOTCH1. My sample was sent abroad only to check the major genomic aberrations such as del 17p, 11q, 13q and trisomy 12 and IGHV mutation status. I myself have not heard of this additional related factor. I am afraid i could not do it again because of high cost to get it done abroad. These high level genomic tests cannot be done locally. i am very grateful to you for your interest in my situation.
Testing for NOTCH1 is next generation genomic sequencing and not routinely done. I’m also Trisomy 12 (IGHV unknown) and am on a clinical trial in the U.K. I haven’t had these tests carried out either and to be honest am not pursuing them at the moment. I’m taking the view that I cannot change outcomes apart from seeking out the best treatments available to me. I’m on I&V and it’s proving to be an exceptionally successful CLL treatment. I’m not sure if you have access to this treatment but Tri 12 seems to react very favourably to it as in fact do most chromosomal deletions and additions.
The hyper mutational status in Tri 12 can be very significant in terms of time to first treatment and remission times. I was 7 yrs to first treatment. When I learned of my chromosomal addition (it’s not a deletion), I scoured hundreds of cases of CLL patients with similar prognostic factors to assess trends. Tri 12 does offer an intermediate outcome but I detected very good results across the treatment spectrum. One of my observations (and it’s only that), is that Tri 12 patients seem to relapse more quickly when treatments are ceased so it’s important to keep monitoring. Outcomes were generally very good.
One of our volunteers on here lankisterguy is very knowledgeable on Trisomy 12 having this biomarker himself and may see this post and offer additional information.
This is very technical but you may wish to work through it;
Hi Newman! Thank you very much for your timely response to my desperate need to find someone to help get out of this turbulent time. Your detailed technical advice has added more optimism to what many others have said about me. Your explanation is very informative expert advice and it will have great impact on me to have more awareness about CLL treatment options. The problem here in Ethiopia is that, the quality of healthcare system is not yet up to the standard of developed countries like yours. There is no any lab facility that can perform high level diagnostic tests such as FISH test, karyotyping or flow cytometry or recently developed techniques. Apart from this, new drugs such as ibrutinib, acalabrutinib and venetoclax are not yet available at Ethiopian hospitals. Treatment options such as CAR-T cell therapy, stem cell therapy, bone marrow transplant and application of gene editing therapies such as CRISPR/cas9 are even unheard of in the country among CLL patients. So we are at the mercy of CLL support community and cllsociety. org/... and other professional expertise in the field of CLL specialization to guide our local treating physicians in finding solutions to our problems by getting their hands on newer drugs possibly by importing through public hospitals. Local doctors are willing to work with CLL specialists where ever they may be to tackle this supply barrier and knowledge gag. In this regard i am planning to consult cllsociety.org/cll-101/test... to advise me on how to get access to these drugs like inrutinib and venetoclax. No other option is available. I sincerely appreciate your suggestion on this view.
I think consulting a specialist through the CLLSociety is a very sensible idea if they will consent to this amaagabg. I think you’ve done very well so far pursuing your genetic profile elsewhere and I learned a little bit about Ethiopia when my brother was working there in Addis Ababa. He met some wonderful people but I appreciate the medical options are more limited. You may be surprised to hear that even in a developed country like the U.K., my only first line treatment option would have been FCR chemo (unless I had a TP53 deletion) which is why I elected for a trial. Sadly my IGHV test proved inconclusive but if I have mutated status, chemo could still have offered me a decent chance of remission. I can see however that immunotherapy drugs are a preferred option and I wish you much luck in accessing them.
Thank you again for your close attention to post and please do continue with your expert advice in my subsequent posts on CLL subjects. I also wish you the best of lucks and good health.
I am 80 and have trisomy 12 unmutated. Diagnosed 2010. Chlorambucil for 1 year with short remission. On ibrutinib since early 2015. So far so good. I did, however, get afib. I decided on an ablation, and the afib is gone now for 1 year, so I am off of Eliquis. Doc. and I agree to continue with ibrutinib.
Thank you for your experience sharing. i have known before couple of days after cytogenetic test that i am trisomy 12 mutated. this is a new journey for me and my family. As new drugs such as ibrutinib and acalabrutinib and genomic diagnostic tests are not available in Ethiopia, i don't know what to do right now. any way i hope you guys members of CLL Support community are at the service of any patient with CLL like me and i look forward to hearing from all of you on this post. thank you all for advice.
If you are mutated, that is better than unmutated. You may be able to use one of the older drugs successfully, from what I have learned. Unmutated people like me really do need one of the newer drugs. The problem in many countries is cost. Ibrutinib in the USA is now about $200,000 US a year. Those with good insurance can afford it. There is also help available for those with lower incomes. In Europe it is usually covered by the national health plans, but there are sometimes restrictions.
I have heard there are cheaper versions of ibrutinib made in India. I do NOT know if these are real or fake. There are internet sites that claim to sell it to you. Again I have no idea of the quality. Your doctor might know from experience.
In any case, if you are MUTATED, drugs like chlorambucil, which is cheap, might help if that is all that is available. Again, your doctor might know.
I wish you the best. Life is not fair and health care is not equal from country to country. We in USA and Europe are lucky and often forget how lucky we are.
my lab result showed i am positive for trisomy 12 (40%) with negative IGHV status. nothing more was explained except that i am negative for 11q, 13q and 17p deletions. Actually i don't know what does it mean by mutation and unmutation of trisomy 12. For this matter, the impact of IGHV mutation status on prognosis is clear with mutated IGHV having good prognosis contrary to poor prognosis associated to unmutated IGHV. But trisomy 12 mutation is not clear to me. please would you elaborate on this confusion? I sincerely appreciate your effort.
From what I have learned, trisomy 12 is an "in-between" genetic abnormality, not good, not terrible. If you are mutated, that is good and MAY mean you can use older chemo drugs if the newer expensive ones are not available. But your doctor would know far better than I.
Sorry, now I see a problem. When they talk about mutated and unmutated they do not mean mutated trisomy 12. If you have trisomy 12, as I do, THAT gene is indeed changed, or "mutated". But that is not what any of us mean when they say mutated-unmutated. That refers to another variable. I admit I have never bothered to learn what exactly it refers to. So when I have said that if you are "mutated" the older drugs may work, I was NOT referring to trisomy 12. I apologize for the confusion. It may be a language issue.
You should read again the suggestions from others here who know more about mutated-unmutated than I do. In any case you may have trisomy 12 and be mutated OR unmutated.
I am still keeping contact with lab people who conducted my blood test and hope they will let me know more about my test results. A lot of thanks for you attention.
I am also a Trisomy 12 & 18, bright cd20 & cd38. I was told at the time that trisomy 12 is the driver to my Cll and because I had bright cd20, drugs targeted to cd 20 would do very well. This was prior to approval of Ibrutinib.
Fairly recently I found out I am also mutated, it wasn't available to me prior to treatment as the Notch isn't either.
I was on Ibrutinib for 14 months and switched to Alacabrutinib due to side effects. I am doing very well on the Alacabrutinib.
In my lab test i was told i am positive for trisomy 12 (40%) with unmutated IGHV and negative for 11q, 13q and 17p deletions. nothing else explained. But yours is clear with all things described in the results. I am still approaching lab experts to elaborate on what is remaining of my test results and hope will have full result sooner.
Given you are "unmutated IGHV", you will not do well on any chemotherapy treatments. This is why your last treatment gave you a poor outcome. ( IGHV mutation status doesn't change with treatment, nor does Trisomy 12 status). Having been previously treated with R-CVP, the R (Rituximab) being an immunotherapy, (hence R-CVP would be termed chemoimmunotherapy), repeating this or another type of chemoimmunotherapy will most likely be even less effective than the R-CVP was for you. As I mentioned before, R-CVP is not generally used for CLL. It is used for low grade Non-Hodgkin's Lymphoma. cancerresearchuk.org/about-... While CLL is strictly a low grade Non-Hodgkin's Lymphoma, there are more specific chemotherapy or chemoimmunotherapy treatments used for CLL which you should also now avoid, such as Chlorambucil, Bendamustine+Rituximab (BR) and Fludarabine+Cylophosphamide+Rituximab (FCR). Hence your next treatment ideally should be Acalabrutinib, Ibrutinib, or Venetoclax or perhaps a short term combination treatment of Venetoclax with Acalabrutinib or Ibrutinib. Unfortunately, these drugs are not readily available for CLL treatment in most countries. In some countries, it is possible to be treated with these new drugs AFTER first being treated with chemotherapy or chemoimmunotherapy, when the first treatment fails to work, or remission ends. Even so, these new treatments were only approved in the last few years. Ethiopians with CLL share the same difficulty of gaining access to the newer drugs faced by CLL patients in most other countries.
Sorry i have not seen your latest post in which you described much more details of treatment options for CLL patients like me. for sure this explanation will remove much of the confusion surrounding CLL treatment. My junior doctor who analyzed my lab test before a week wants to keep me off any treatment for 3 months to see disease progression and then to plan another option which is not clear to me right now. It seems to me that symptoms like drenching night sweats, fatigue, increased size of lymph nodes and mild spleenomegally which i have now, are suggested by many as clinical indications for initiation of treatment for CLL patients if i am not mistaken. As a result, i am scheduled on the next Friday to see another senior hematologist for further consideration. let's wail and see what the doctor would have to say. in the meantime your comment is important to lead the course of direction.
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