Questions List

Posted onMarch 20, 2022 6:57 pm

Thank you for this excellent meeting! Pascal Nieper, GermanyPosted onMarch 20, 2022 4:17 pm

thank you so much Posted onMarch 20, 2022 4:15 pm

thank you so much Posted onMarch 20, 2022 4:15 pm

Great meeting! Thank you Profs Hallek, Brown and Ghia! Posted onMarch 20, 2022 4:14 pm

If treatment does not work it could be also because of different epigenetic paterns for MAPK or other kinases involved in signal transduction. Thak you very much for interesting conferency. Posted onMarch 20, 2022 4:00 pm

To Dr Siddiqui. Do you believe that CAR T cells we be one day part of clinical routine in CLL? Lukas FrenzelPosted onMarch 20, 2022 3:58 pm

If TAK-981 induces cell death and T cells cytotoxicity this might not be a safe to usage in human body. Did you checked it?Posted onMarch 20, 2022 3:38 pm

To Dr Tonino. Very interesting talk. One question regarding the mode of cell death. In which experimental settings did you observe necroptosis after venetoclax failure? Lukas Frenzel, ColognePosted onMarch 20, 2022 3:34 pm

Are very important also NF cells for CLL development and response to therapy?Posted onMarch 20, 2022 3:34 pm

Hello and congratulation on your presentation. My question is on gamma-delta T cells, on the Vdelta 1 subset: any results similar to your published Vg9Vd2 cells? We see the Vd2 cells in CLL patients highly dysfunctional in contrast to Vd1? Thank you, Dr Andrea Knight, Masaryk University, Czech RepublicPosted onMarch 20, 2022 3:30 pm

the future will be: treatment with triplets winning over doublets, especially in high risk? and another question the movement of the dynamics of MRD will determine the finite treatments on the continuous ones? Thanks a lot July Buenos Aires Posted onMarch 20, 2022 3:27 pm

After several analysis of molecular activity of anticancer agents/biological compounds we must remeber that some drugs used in cancer cells curing, the others are used for cancer tratment, but work on immunological system modifications, and as a coexistance reduce for example the level of B cells? Do you know about it? Do humans use the easist and the most effective drug(s) to treat disease, or drug decribed previously for this disease treatment? Posted onMarch 20, 2022 3:26 pm

To Dr Brwon. Great talk and very important data. 1. Do CLL patients with mutations in MAPK (e.g. BRAF) pathway respond to Ven or are they primary resistant? 2. Does high pERK signaling in either PI3Ki or Ven resistant cells translate into high MCL1 level? 3. Any idea why IgM expression is elevated in Ven resistant CLL cells? Lukas Frenzel, ColognePosted onMarch 20, 2022 3:16 pm

I think that in 21 of resistant to treatment patients the level of epigenetic modifications could lead signal using other dictection? Could it be possible? Do we know sometimes about it?Posted onMarch 20, 2022 3:03 pm

Could resistance to treatment be a learn of cells to survive?Posted onMarch 20, 2022 2:59 pm

Posted onMarch 20, 2022 2:56 pm

Did you checked why 21 patients did not responce? Maybe because as we can have a personal differences there could be a unspecific pathway possibilities that even when inhibitor is used, this signal could goes using other way?Posted onMarch 20, 2022 2:56 pm

***** Session 9 *********Posted onMarch 20, 2022 2:36 pm

excellent answer, John.Posted onMarch 20, 2022 2:33 pm

Do you think that the good idea is to incubate simultaneously CLL cells with a therapies able for administation to find out what will be the best profitable and active for pateint. Sometimes more active will be cladribine, sometimes idelalisib or sometimes will need CART therapy? This is tailoring therapy for each patient. Do you think that this should be prepared for patients?Posted onMarch 20, 2022 2:33 pm

To John and all: when do you still use PI3K inhibitors in your personal treatment algorithm ( or sequence)? Michael HallekPosted onMarch 20, 2022 2:29 pm

Because of most monoclonal antibodies could interact only will receptors on cells, if does not induce caspases induction, so which kind of cell death could induce? Posted onMarch 20, 2022 2:16 pm

Why sometimes CART therapy are not succesful? From theory should work,. Do we need some more data to acheeve a success?Posted onMarch 20, 2022 2:10 pm

Did you know that for example vitamin D is display several function? I ask because this inhibitors could also work not on one target?Posted onMarch 20, 2022 1:48 pm

Posted onMarch 20, 2022 1:44 pm

Could we see some common tendency of time of response to therapy, MDR and immunological pateint strenght?Posted onMarch 20, 2022 1:42 pm

Posted onMarch 20, 2022 1:33 pm

Do you know that lenalidomid modulate immunological system cells and doeas not work stright on caner cells>Posted onMarch 20, 2022 1:27 pm

When is better to cure CLL using PI3K inhibitors or Bcl-2 inhibitors?Posted onMarch 20, 2022 1:24 pm

**** Day 4 ***********Posted onMarch 20, 2022 1:03 pm

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Posted onMarch 19, 2022 6:54 pm

To Dr. Frenzel: Have you been able to look at transcriptomic data of patients resistant to Ven? If so, could you observe any changes in the other BH3-family proteins? (Pascal Nieper, Germany)Posted onMarch 19, 2022 5:18 pm

To Dr. Frenzel: Did you try adding a BTKi to the cells of the BAX-mutated patient? Did that change anything about their sensitivity to Venetoclax? (Pascal Nieper, Germany)Posted onMarch 19, 2022 5:17 pm

For dr Mato: do you see pirtobrutinib in future moving towards first line of BTKi or it is going to stay as reserve option when other BTKi resestence is observed?Posted onMarch 19, 2022 5:11 pm

Does the PROTAC degrade all BTK? in myeloid cells etc. Dyer UKPosted onMarch 19, 2022 5:11 pm

Excellent presentations. Dr. Wiestner, could you give more of your thoughts on the difference in frequency of resistance mutations in BTK in patients progressing with lymphadenopathy (compared to lymphocytosis) on BTKi? True differences in mechanisms of resistance or more of an artifact of what is being tested (peripheral blood disease versus node biopsy) or timing (would equilibrate with more time)? – Paul Hampel (Mayo, USA)Posted onMarch 19, 2022 5:10 pm

Question to Dr Mato - thank you for your presentation - what depth of responses do you see with pirtobrutinib please? do you think these are quantitatively deeper from the covalent inhibitors? ie do you think the level of BTK inhibition is better with this molecule? Dyer UK Posted onMarch 19, 2022 5:04 pm

To Dr. Mato Did you observe a correlation between the development of resistance to Pirtobrutinib and a specific pretreatment therapy? (Pascal Nieper, Germany)Posted onMarch 19, 2022 5:03 pm

To Dr Zavacka: very good presentation. When you observe these clonal evolution patterns, e.g. KRAS mutations or others, do you use this to make treatment decisions? Or would you implement a targeted sequencing approach? Michael Hallek Posted onMarch 19, 2022 5:03 pm

Excelent talks! Did you check Bax mutation in venetoclax resistant cells induced by the tumor microenvironmet? Romina Gamberale from ARGENTINA Posted onMarch 19, 2022 5:02 pm

very interesting talks; To Lucas: is TRAIL mediated killing caspase 8 and or 9 dependent? Thanks, Arnon Kater Posted onMarch 19, 2022 5:01 pm

Do we need to monitor CLL patients treated with BTKi or BCL2i by NGS to detect resistance mutations?Posted onMarch 19, 2022 4:58 pm

To Dr Frenzel - lovely, fascinating and intriguing presentation - many (Many) questions!!! Here is one (or two) - BAX mutations - were these biallelic? If BAX is absent, why doesnt BAK take over? What happens to BAK? (BAX mutations otherwise are interestingly really quite rare for some reason!) Dyer UKPosted onMarch 19, 2022 4:50 pm

To Anthony: regardingthe additional BTK mutations that were now observed in pirtobrutinib resistant patients: do they result from a different binding mechanism? Do you know how these mutations affect the binding mechanism of noncovalent BTK inhibitors? Michael HallekPosted onMarch 19, 2022 4:44 pm

Patient on Gazyvaro-Venetoclax, achieved CR after 6 cycles of Ga, due to neutropenia I had to reduce and than stop Venetoclax, I continue Gazyvaro. Would you reccomend to restart Venetoclax? Thank you. Cmunt, Czech RepublicPosted onMarch 19, 2022 4:43 pm

***** Session 7 *******Posted onMarch 19, 2022 4:33 pm

Posted onMarch 19, 2022 3:59 pm

If somebody do not respond to inhibitor, it is probably a reason of diversities in this patient in cell signalingPosted onMarch 19, 2022 3:56 pm

************ Session 7 ******Posted onMarch 19, 2022 3:55 pm

Could MRD(-) be a factor to consider for stop treatment av BTKi, if patient has TP53(-) M-CLL? Angeliki Vourtsi SwedenPosted onMarch 19, 2022 3:46 pm

I think we as physicians we also have social and economic responsibilities and even political responsibilities. Michael HallekPosted onMarch 19, 2022 3:46 pm

Could MRD(-) be a marker to use for the decision to stop BTKi therapy if patient o TP53(-)?Posted onMarch 19, 2022 3:43 pm

to the entire panel: what is your strategy for patients refractory to triplets (BTKi, BCL2i + anti-CD20)? Michael HallekPosted onMarch 19, 2022 3:26 pm

Question to Sebastian: very interesting data; 2 questions: 1. what happened with PD-1 expression on CD4 and CD8 cells over-time? 2. a hallmark of TCL-1 is a reverted CD4:CD8 ratio, was this also different in the PDL-1 deficient mice? Posted onMarch 19, 2022 3:23 pm

To Sebastian Have you checked the effect of PD-L1 deficiency on different T cell populations? by Binu Sasi Posted onMarch 19, 2022 3:21 pm

Posted onMarch 19, 2022 3:20 pm

To all: thanks for an excellent session. In patients with TP53 dysfunction, do you continue therapy in patients after achieving a CR (MRD+ or MRD-)? And with which drug(s)? Michael HallekPosted onMarch 19, 2022 3:19 pm

To all speakers: comparing the available data, do you see any difference (toxicity or efficacy) regarding different triplets (AVO, GIVE, BOVE)? Michael Hallek, ColognePosted onMarch 19, 2022 3:16 pm

...Posted onMarch 19, 2022 3:08 pm

********** Session 6 ******Posted onMarch 19, 2022 2:41 pm

In aspect of lecture related with covid virus I would like to ask a question: do you think that currently is a good time for world program to increase immunal system body strength? Patients heavily pretreated have reduced immune strength and therefore are weak and therefore more often die after viral infectionPosted onMarch 19, 2022 2:26 pm

To dr. Al-Sawaf: if uMRD at end of treatment is one of the strongest prognostic markers that we have. Should we implement it in clinical practice? And if so how?Posted onMarch 19, 2022 2:18 pm

I did ask about doses, because when I did incubated CLL cells with anticancer drugs, it happen that control CLL cells incubated with anticancer reduced viability because pateints cells were more sensitive to in vitro conditions. Such patients caould be more sensitive to drugs, while might react more effectively or even for this patient drugs dosage should be reduced, if is to high will induce side effectsPosted onMarch 19, 2022 2:16 pm

Would you expect MRD status to be prognostically important in the setting of BTKi-BCL2i-based combinations? There seems to be no difference in PFS in MRD+ vs. MRD- patients within the I+V arm of the GLOW study. Inhye Ahn, USAPosted onMarch 19, 2022 2:13 pm

To Dr. Mavilia: Did you see any difference in response between the two mRNA Vaccines (Spikevax / Comirnaty)? Have you also looked at administering additional doses? (Pascal Nieper, Germany)Posted onMarch 19, 2022 2:12 pm

Do you know if exist studies comparing MDR efficacy related with different drug doses? Are drug doses related with MDR occurance?Posted onMarch 19, 2022 2:10 pm

For Dr. Mavilia: did neutralizing antibody levels have a statistically significant relationship with disease stage (Binet or RAI)? Thank youPosted onMarch 19, 2022 2:08 pm

Do you have any information on T-cell responses? For Dr. MaviliaPosted onMarch 19, 2022 2:05 pm

to all speakers: what is your preferred 1st line strategy of therapy (combo or mono therapy) in the omicron phase of the pandemic?Posted onMarch 19, 2022 2:02 pm

Question to all speakers of an excellent session: regarding the monitoring of MRD in future MRD (or response) driven treatment strategies: what is your preferred method of assessement? PB versus marrow? NGS versus flow versus ctDNA versus PCR? Michael Hallek, Cologne Posted onMarch 19, 2022 1:59 pm

Sometimes if you combine drugs, to avoid side effects is is necessary to reduce doses, better to check before drug administrationPosted onMarch 19, 2022 1:46 pm

Did you check before studies if single agent ibrutynib or venatoclax is better for single patient, than both together? I ask because some patients could be more sensitive to drugs and sometimes could be more profitable to check before administration? I ask because previously I studied activity of cladribine + cyclophosphamide + mitoxantrone and mitoxantrone was excluded, because the result of study was similar as a final effect, end mitoxantrone induced toxicity of 3 drugs. Sometimes we can see that only cladribine works, so this is not neccesary to give more drugs. Posted onMarch 19, 2022 1:42 pm

Did you check that the level of leucocytosis is important in immunological body strength? Posted onMarch 19, 2022 1:30 pm

How often CLL pateints become to be resistant? Posted onMarch 19, 2022 1:25 pm

****** Session5 *********Posted onMarch 19, 2022 1:01 pm

Are you able to find out what is the reason of resistance to therapy for all patients? I ask because a lecturer just told that, but if some data was published previously, it does not means that everybody have this mutation. It means that samples included in manuscript had. Do we have a methods to find out in each resistant to treatment cells why this patient is resistant? Posted onMarch 19, 2022 12:56 pm

What is the mechanism by which mutations appear in btk?Posted onMarch 19, 2022 12:46 pm

Did you see the personal diversity in respond to drug, instead of better drug function? Do randomization be a random way to treat, and is it possible that in randomized studies in general we can choose worst type of treatment for patient? It was happen previously that a combination of fludarabine + cyclophosphamide were given to patient and after 6 month the results showed that patient administation showed resistance to therapy? It is always better to check before treatment cells sensitivity to drug, to avoid resistance to treatment, a specially in randomized way of therapy? Posted onMarch 19, 2022 12:46 pm

Could you elaborate a little bit more about the differences in BBB penetration of the different BTKis Ibr, Acala and zanu and if this may lead to differences in clinical activity?Posted onMarch 19, 2022 12:45 pm

I understand that ibrutynib and other directed therapy could be effective in majority of patients. Are cases that are resistant to ibrutynib, and do we know why? And the other question is combined to first one: do cells become resistant after a few cycles of therapy?Posted onMarch 19, 2022 12:26 pm

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********** Day 3 **********Posted onMarch 18, 2022 5:55 pm

I can not see leucocytosis, this lady is 71 ears old and problems with HB and problems with fibrilation. Definitely wait and because of problems with aortal problems. In Poland because this women is old, usually before if treated it will be chlorambucil. Maybe something is changed know, but older patients previously had chlorambucil. Posted onMarch 18, 2022 5:46 pm

In which patients would you indicate an allogeneic bone marrow transplant? Gonzalo Ferini from ArgentinaPosted onMarch 18, 2022 5:38 pm

It looks like leukocytosis increased, but we do not know how fast, if he feals well I will check leukocytosis, and send patient to come in one month, or in case of bad problems with health earlier. I am not a person who give a therapy without more analysis. If patient feels well I will not start therapy because it could induce worst patient condition. I will wait and after one month if needed start therapyPosted onMarch 18, 2022 5:37 pm

Are zanubrutinib more effective vs ibrutynib, or this is also a personal dependence? I think that because of cells could become resistant to drugs, it is important to check before drugs administration which drugs are the most effective for patient, to avoid potential resistance. I understand that usually this is a high response to therapy, but after some time because drugs induce a stress, cells could find the way to inhibit this drug, and in this moment the other drug should be find to treat effectively patient. How long patients are sensitive to therapy?Posted onMarch 18, 2022 5:26 pm

Hi, this is Zarif Hakim from USA. What do you expect the optimal sequencing will be in terms of ibrutinib vs acala vs zanu? Will we start with ibrutinib then switch therapy for intolerance or refractory patients only?Posted onMarch 18, 2022 5:22 pm

******* Sympo ***** Posted onMarch 18, 2022 4:34 pm

It's not matrigel.. Eric EPosted onMarch 18, 2022 4:34 pm

Similarly to the group: How can we in the future study more complex microenvironmental interactions, involving more than 2 cell types?Posted onMarch 18, 2022 4:30 pm

For Emma Kennedy (nice talk!); can you elaborate a bit on the U-CLKL nonresponders (to what?) and effect of CpG on migration? How do you measure migration - what kind of assay? Thx! Eric Eldering Amsterdam. Posted onMarch 18, 2022 4:17 pm

To Dr. Nguyen: Have you looked at expression levels of LYN in tumor restraining CAFs / myCAFs? Do you think iCAFs could be reprogrammed into myCAFs? (Pascal Nieper, Germany)Posted onMarch 18, 2022 4:13 pm

@ Arnon Kater: Can you study T cell effector functions on CLL cells? Is a reprogramming needed for T cells to support CLL? Do you observe a reduced cytotoxicity of reprogrammed CD8 cells? Will this reprogramming also hold true in CAR-T cells? Posted onMarch 18, 2022 4:05 pm

Dr. Kater, the modulation of T cells by CLL cells you showed is seen both CD4 and CD8 T cells? CD4 T cell activation has also been suggested to help CLL survival. How would you see that? Baskar, NHLBI, NIHPosted onMarch 18, 2022 4:01 pm

Posted onMarch 18, 2022 3:59 pm

the mutation in myd88 changes the binding to irak-4 and the inhibition of myd88 and irak-4 would not predispose to greater bacterial infection?Posted onMarch 18, 2022 3:38 pm

Can CD49 d be done by IHC.Dr Jyoti Sawhney ,IndiaPosted onMarch 18, 2022 3:34 pm

@ Chris Pepper: 1. Does CD49 Outside-In signaling itself contributes to chemoresistance/progression of leukemic cells? Or might it rather facilitate the redistribution into the homing sites, where other signals promote leukemia resistance/adverse outcome? 2. Is CD49 signaling/expression associated with transformation of CLL into Richters? Posted onMarch 18, 2022 3:22 pm

Dr. Pepper, do you see that CD49d and CD38 are generally co-expressed? Baskar, NHLBI, NIHPosted onMarch 18, 2022 3:08 pm

******* Session 4 ********Posted onMarch 18, 2022 2:30 pm

Could we have some new data concerning mobitity of miRNA production in CLL patients?Posted onMarch 18, 2022 2:18 pm

Do you use any of these rare mutations in clinical routine for taking any management decsions? If you would have to implement ine or a few of these genes in clinical routine/practice, which would it be?Posted onMarch 18, 2022 2:11 pm

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Did you compare the cases with mutation and without mutation to find out what is a reason of cancer , a specially without muatation, and what other factors are needed for mutation formation?Posted onMarch 18, 2022 1:52 pm

Maffei (Italy) to Dr.Rossi: Do rare mutations (RAS, XPO1, BIRDC3) have a prognostic value inside M-CLL and U-CLL subsets?Posted onMarch 18, 2022 1:50 pm

A question to Richard Rosenquist: I noticed that TTFT curves comparing U-CLL and M-CLL were limited to Binet A patients, am I right? As some patients with high-risk mutations may be diagnosed in Binet B or C stage - were there any difference if you considered all patients? Thank you. Sarka Pavlova, Czech RepublicPosted onMarch 18, 2022 1:48 pm

Could Richter Syndrome be a reason of to high doses of anticancer therapy that could change genes expression? Posted onMarch 18, 2022 1:46 pm

For Richard Rosenquist: What could be the possible explanation for the negative prognostic impact of individual genetic defects in only one and not the other IGHV subset? (Dimitar Efremov, Italy)Posted onMarch 18, 2022 1:38 pm

Is it true that the presence of trisomy 12 and an unmutated IGHV status together could be associated with a high risk of RS? Thank you!Posted onMarch 18, 2022 1:37 pm

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Question for R. Rosenquist; Did you see mutations that are connected with not good prognosis in all patients who had later a shorter life? (Malgorzata Rogalinska from Poland)Posted onMarch 18, 2022 1:24 pm

Is there a chronological emergence of these mutations & do these timelines differ in U vs M-CLL?Posted onMarch 18, 2022 1:20 pm

******* Session 3 ******Posted onMarch 18, 2022 1:00 pm

Orcun (Turkey) My question is to Kostas: According to recent data, overall life expectancy is about to 80 years. What is your favourite therapy option for 17p(-) uIgHV patients who are about 60 years old. (If we choose V+G, PFS rate may decrease. If we choose continuous BTKi, you can see resistance in 5 years, if we choose I+V there’s not longer follow-up)Posted onMarch 18, 2022 12:59 pm

What is the best treatment option for short fixed duration of time, in young fit CLL patients who has treatment indication without del17 . thanksPosted onMarch 18, 2022 12:54 pm

What you think about mutations using continuous treatment vs fix treatment? Posted onMarch 18, 2022 12:52 pm

Maffei (Italy) Do we need to check BTK, PLCG2 or BCL2 mutational status during targeted therapies?Posted onMarch 18, 2022 12:50 pm

One of the arguments often raised is that there is (still) no clear OS advantage of 1st-line targeted versus CIT in the majority of patients. How does this impacts the discussion. Need to wait for such data? Arnon KaterPosted onMarch 18, 2022 12:31 pm

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********* Day 2 *************Posted onMarch 17, 2022 6:25 pm

my name is Najeem from UK londonPosted onMarch 17, 2022 6:08 pm

Have you correlated UGT2B expression with IgVH expression?Posted onMarch 17, 2022 6:07 pm

A follow up question - how early you see the sIgM increase? Baskar NIHPosted onMarch 17, 2022 5:50 pm

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Was high/low sIgM expression related with the IGHV mutation status? Thank youPosted onMarch 17, 2022 5:46 pm

Would you please clarify if the sIgM expression increase is seen IgM+ clonal CLL B cells or sIgG+ CLL B cells following IB treatment?Posted onMarch 17, 2022 5:44 pm

What do we know about the recycling of CD180 in CLL, i.e. rapid turn over from surface to cytoplasm? Baskar NHLBI, NIHPosted onMarch 17, 2022 5:41 pm

Thank you for chairing the session so well, Sigrid and Carsten. Michael Hallek Posted onMarch 17, 2022 5:35 pm

Interesting study. Any insight on the mechanisms how CD86 or CD27 are influenced by inhibition of BTK?Posted onMarch 17, 2022 5:31 pm

********** poster walk ********Posted onMarch 17, 2022 5:23 pm

What s the rule of cell free DNA in CLL specially in the Era of targeted therapy Posted onMarch 17, 2022 5:12 pm

To Dr. Al-Sawaf: In your figure displaying the MRD-status of patients halfway through therapy I noticed there was also a part of patients who went from being at the lowest MRD level (10^-6) to higher levels of MRD at the end of therapy. Have you looked at the outcome of those patients? Did they continue to increase their MRD-level? Was there any clinical correlate? (Pascal Nieper, Germany)Posted onMarch 17, 2022 5:10 pm

Could pathways that usually help as to fight with stressful conditions be used inside cells to become resistant, because usually drugs could introduce stress for cells and it could work this way? Posted onMarch 17, 2022 5:10 pm

To both: How could one incorporate dynamic assessment strategies (MRD under treatment) in routine therapy using combinations of targeted agents? How can we prove that such a strategy is superior to non-supervised therapy (fixed duration or continuous )? Michael Hallek Posted onMarch 17, 2022 5:09 pm

I think that we need to search for some characteristic for resistant to treatments cells, for example in level of oxygen drops i cancer, it increase expression for genes important for metastasis. I think that because cells do not think that must be some factor, or group of factors important to allow cell to become resistant to drug, a specially, when during treatment patient becomes resistant, and in this moment we need to search for other effective drug? What do you think about my idea that must be some factors that is important for cell to become resistant?Posted onMarch 17, 2022 5:05 pm

What role do you see at the moment for MRD detection in clinical practice outside clinical trials?Posted onMarch 17, 2022 5:04 pm

Is MRD a good marker for all resistant cells? I ask because I think that this is more complexed and cancer cell which wants to live will arrange and change gene expression to increase the efficacy for drug molecules exflux from cells. When I see this lectures this looks like easy and organized: I must ask if was some patients which react not standardly and this test was not fully informative. I ask because, majority of patients, who react in standard way will react as others, but for this who display unstandard way, tha might have some problems Posted onMarch 17, 2022 4:52 pm

************** Sympo *********** Posted onMarch 17, 2022 4:15 pm

Serajul Islam, UK-do you recommend checking for low VAF TP53 in young CLL patients going for CIT, to prevent VAF expansion which intern will improve outcomePosted onMarch 17, 2022 3:55 pm

Were you able to isolate CLL clones (families other than V1-69) as well with the phage peptide pull down method? Can you identify the potential antigen from the peptide used? (from Baskar, NHLBI, NIH, USA). Posted onMarch 17, 2022 3:38 pm

To Dr. Baliakas: 1. Do patients with High CK have mutual abnormalities with low- and intermediate CK? Or is it a completely different pattern? 2. Do you think using computer vision could improve the capabilities of chromosome banding analysis? (Pascal Nieper, Germany)Posted onMarch 17, 2022 3:37 pm

What's the correlation of MRD between Flow and AS-qPCR? Would any of you consider to prolong time-limited venetoclax-based therapy in MRD+ (MRD1-3) patients at planned EoT? Upcoming recommendations? Thanks, Christian BrieghelPosted onMarch 17, 2022 3:36 pm

For Andy Rawstron: Will NGS become standard method for MRD assessment and when? Michael Hallek Posted onMarch 17, 2022 3:36 pm

To Dr. Pospisilova: 1. Have you looked at clonal evolution of the P53-mutated fraction during Watch & Wait? Is it expanding or stable? 2. Would you suggest there is a survival benefit in completely avoiding CIT for all patients with low-burden P53 mutations? Or is the expansion of the P53-subclone after chemo irrelevant for the response to targeted therapy? (Pascal Nieper, Germany)Posted onMarch 17, 2022 3:34 pm

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Hana Svozilova, Czech Republic - question for Panagiotis Baliakas: How does complex karyotype evolve within individual patients in time? If it changes a lot, does the spectrum of aberrations change as well? Posted onMarch 17, 2022 3:32 pm

Question to Panagiotis Baliakas: Is it a chance that in patients with lower immunological strength and low expression of antistess factors, chemical agents from drugs or diet in patients will disturb homeostasis and for example high ROS production will be able introduce mutations or even brakes in chromosomes?Posted onMarch 17, 2022 3:26 pm

Katrina Rack Belgium for Panagiotis. Can you comment on how the number abnormalities should be counted based on microarray analysis when defining complex karyotype? Posted onMarch 17, 2022 3:18 pm

To Dr Baliakas: There is an increasing body of evidence that CKT is also relevant as a predictive marker for target agents (BTKi, Ven combinations). Where do you see its place in practice? Would it be relevant for early recognition of dismal outcome, even Richter transformation? Do you see a correlation of CKT and later RT? Michael Hallek Posted onMarch 17, 2022 3:14 pm

Some studies suggest that patients with both del(17p) and a TP53 mutation have an even worse outcome than those with a single TP53 aberration. Do we know whether multiple TP53 aberrations are biallelic or biclonal? And was multiple del(17p) observed in the CK ERIC study? Thanks, Christian Brieghel, Rigshospitalet, CopenhagenPosted onMarch 17, 2022 3:11 pm

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Question to Sarka Pospisilova: did you compare your results with potential epigenetic modification and therefore different TP53 function in gene expressions,; when P53 is mutated will loss its function?Posted onMarch 17, 2022 3:03 pm

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What about 'subclones' TP53 deleted by FISH (no TP53 mutation). Do you advice also a comment in the report if at cut-off to 10%? Sabine Franke, BelgiumPosted onMarch 17, 2022 2:51 pm

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******* session 2 *****Posted onMarch 17, 2022 2:32 pm

To Julia Maier: Have you looked at why Card9 is expressed in some Richters patients? Did you find mutations? Or epigenetic changes? (Pascal Nieper, Germany)Posted onMarch 17, 2022 2:12 pm

to Silvia Deaglio. Do you think it could be a possible strategy in RS to test IDO inhibitors? Also in combination with NAMPT inhibitors? thank youPosted onMarch 17, 2022 2:11 pm

Has it been studied if there is an association between clonal hematopoiesis and MBL? (Laura Palomo, Spain)Posted onMarch 17, 2022 2:07 pm

TO DR. MIER - excellent study. Have you looked at Bcl-2/other anti-apoptotic molecules expressed in U-RT1 cells?Posted onMarch 17, 2022 2:06 pm

Paulo Miranda - USA: Will AKT inhibitors, currently being developed for solid tumors, be a potential agent to try in combination with NAMTi and BCRi in RS PDX models?Posted onMarch 17, 2022 2:06 pm

Is there any association between MBL and clonal hematopoiesis? (Dimitar Efremov, Italy)Posted onMarch 17, 2022 2:05 pm

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Could CLL transform into Richter Syndrome in patients heavily pre-treated or more sensitive to drugs (treated with to high doses of drugs) Posted onMarch 17, 2022 2:03 pm

Posted onMarch 17, 2022 1:59 pm

Question to Silvia Daeglio: In model studies using animals models related with drugs activity, did you see some diversities in drug activity between animals? Because there are diversities between human reaction, I am interested if you can see diversities in animal models?Posted onMarch 17, 2022 1:52 pm

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Why inhibition by mutation of TP53 is important in cancers? Because of their several function leads to problems in cells proper function. but it is usually a passenger mutation and the good question is which conditions force to changes in TP53 in advanced cancer to dis-regulate cells function? Do stress linked from environment could cause a diversities that in long lasting condition could cause several diseases, including in some condition also cancers? The type of stress and immunological strength of patient and other personal condition of factors work usually as anti-stress factors could be important.Posted onMarch 17, 2022 1:46 pm

Could MBL occure as a consequence of unhealthy diet rich in chemical agents, that in some patients lead to decrease in immunology strength? Posted onMarch 17, 2022 1:24 pm

Posted onMarch 17, 2022 12:07 pm

Posted onMarch 17, 2022 12:07 pm

Day 1Posted onMarch 16, 2022 9:43 pm