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Questions submitted by readers and answered by the CLL Society Medical Advisory Board
I have been diagnosed with CLL but my numbers are great to date and I have no symptoms. I have had no FISH or specialized tests yet. In my readings, they indicate that CD20 is dim in flow cytometry for CLL but mine is bright and they say my CD 23 is weak. My father had large B cell NHL and I wondered if the CD20 bright would put me more at risk for transformation.
The classic immunophenotype of CLL is dim CD20 and CD23 positive, which can be dim or bright. The CLL cells themselves never read the textbook and there is always variability in a biological system, so nothing is precise. There are a group of CLL patients who do have bright CD20, most notably those with trisomy 12. There are no prognostic indications based upon the brightness of the CD20 expression.
What is the relationship between 17p and TP53? Can one have TP53 and not 17p, or vice versa? If a person can have TP53 without 17p, how serious is it?
17p represents the short arm of chromosome 17. It is found missing in cases of CLL. The gene believe to be responsible for the behavior of cases with deletion 17p is the gene for p53, also called TP53. p53 is a protein that plays an important role in cell death. When it is missing (deletion 17p) or mutated (TP53 mutation), it does not work to induce cell death as it should, making the cells more resistant. Since there are two copies of every gene (alleles) present, someone could have:
1. one allele mutated and the other normal, which equals normal function
2. one allele mutated and the other deleted, which equals no function
3. one allele missing and the other allele normal, which equals normal function
4. one allele missing and the other mutated, which equals no function
5. both alleles mutated, which equals no function
6. both alleles missing, which equals no function
You need to have one gene functioning in order to have normal p53 function in the cells. When patients have refractory disease, it is often because both alleles are not working or not present.
Since CLL is a chronic disease, are you ever really in remission? The two words, chronic and remission, seem to contradict each other in this instance. Can you clarify?
We use the term remission to mean there is no evidence of CLL by routine assessments. Patients can be in remission, even MRD negative (no minimal residual disease), but still relapse. Remissions can therefore occur with chronic diseases.
Does postherpetic neuralgia have an adverse effect on the lymphatic disease, causing it to recur more quickly?
No, postherpetic neuralgia does not impact upon the CLL itself.
What treatment is possible for respiratory issues for someone who has been on Ibrutinib for 2 years?
The treatment for respiratory issues depends upon what they are and what the current immune system function is.
Does Rituximab treatment lower T-lymphocytes? Many drugs can cause Warm Autoimmune Hemolytic Anemia (WAIHA), especially antibiotics. Are there any antibiotics that are relatively safe to take if you get any kind of infection and you have CLL and have been treated for WAIHA?
Rituximab does not impact upon T cell numbers. While many drugs do cause autoimmune hemolytic anemia, their occurrences are rare. There are no data to suggest that CLL patients, who are more likely to develop AIHAs, are more likely to develop drug induced AIHA. Therefore, no need to avoid any antibiotics in particular.
Are you aware have anyone on Ibrutinib having symptoms of narcolepsy?
I am not aware of any cases of narcolepsy associated with ibrutinib use.
I am 17P deleted and Trisomy 12 and have been in a clinical trial with both ibrutinib and venetoclax for the last 9 months and am doing well so far. My numbers are back to normal. I started treatment in Jan 2017. The labs cannot tell if I am mutated or unmutated.
I have a few questions:
1. If the drugs knock out all the bad CLL Cells or I get to MRD negative shouldn’t it take a long time for the bad CLL cells to come back? The goal of the trial is to get to MRD negative and get off the drugs for a while.
2. I am told that the problem in CLL is in one’s STEM cells as well. How does this play into the disease treatment? Can STEM cells be fixed without a BMT?
The goal of the trial is to deplete enough of the CLL cells that it might not come back at all. The lower the number of CLL cells, the longer it would take to return. If you get to zero, then theoretically, the CLL won’t come back.
The term stem cells is applied in a lot of various ways, with each use meaning something different. We really do not know whether there is a CLL stem cell. We always refer to one cell that is the originator, but any of the cells might give rise to more CLL cells. With bone marrow stem cells, the difference is that there is one cell that can give rise to all of the different blood cells.
Is there anything I can do to avoid CLL progression or Richter’s transformation? I am exercising regularly, getting good sleep, keeping my stress down and eating a healthy mostly Vegan Diet.
There really is nothing that can be done from the patient’s perspective to avoid progression of disease. It really is something biological about the cell itself.
I have relapsed after ibrutinib and am now in a deep partial remission with venetoclax. My Canadian doctors have recommended an allogeneic transplant, but they don’t know when to stop the venetoclax prior to transplant. As my CLL took off very quickly when I stopped ibrutinib, I am not keen on stopping too soon. Thank you for your advice.
We don’t know the impact of the venetoclax on stem cell grafting, so the venetoclax should definitely be stopped prior to re-infusion of stem cells. Beyond that, there is not downside to just continue it until you start the preparative regimen.
I’m 36, diagnosed with CLL in January, three months after giving birth to my first baby. I’m early stage CLL, with no symptoms and my bloods have been stable the past 6 months. My consultant has advised that if we would like to add to our family it’s better to do that sooner rather than later. I’m aware data is limited but wondered whether you could provide any advice regarding CLL and pregnancy, primarily that there is no risk to the baby and also whether there is any evidence that pregnancy can result in CLL progression? Many thanks
There are no data that pregnancy will impact upon the clinical course of CLL. One important aspect regarding this decision would be how quickly the CLL is progressing. Observing for a short period now, and perhaps looking at the prognostic markers, would help guide how much time there might be before treatment is required. All that is necessary that there be sufficient opportunity to avoid treatment and that there will be no lymphadenopathy that might impact upon carrying the pregnancy. If treatment is required during the pregnancy, we do have experience with rituximab and other therapies such that they could be used to enable a full-term delivery.
Richard Furman, MD is Director of the CLL Research Center at Weill Cornell Medical College and a member of the Lymphoma/Myeloma Service in the Division of Hematology/Oncology. He is a member of the Medical Advisory Board for the CLL Society.
Originally published in The CLL Tribune Q3 2017.