Questions List
Vignir Helgason (Glasgow): Feedback/Comment: Another fantastic meeting - many thanks Jorge, Tim and Daniela!!! Posted onOctober 10, 2021 4:31 pm
Mike Mauro, New York; 1 question 1 comment, question- thoughts on the effects of IGFR from imatinib on the results regarding insulin differences with NIL and IM; comment, any thoughts on pleural effusion on bosutinib being an effect still ongoing from prior exposure despite differences in the TKI at switch after DAS?
great talks great session!Posted onOctober 10, 2021 4:23 pm
Vignir Helgason (Glasgow). Q for Pavel: Following drug treatment, did you check if HTB-153 try to compensate for the reduction in carnitine input by increasing glucose consumption? Posted onOctober 10, 2021 4:21 pm
does high doses of carnitine decrease intracellular activity of imatinib in leukemic cells?Posted onOctober 10, 2021 4:15 pm
what was the real incidence rate per dose dasatinib? correcting for the number of patients using a specific dose
Posted onOctober 10, 2021 3:44 pm
Did you check if treatment induce stress? Any agent that brake homeostasis lead to stressful conditions. Did you check it? If it is true, than it is better to avoid traditional chemical drugs, but turn into how to teach our immunological system to fight cancer? One of such drug, this is interferonPosted onOctober 10, 2021 3:33 pm
Posted onOctober 10, 2021 3:29 pm
No role for transplant in young patients with good donors with reversible CV side -effects on ponatinib? Posted onOctober 10, 2021 3:29 pm
Posted onOctober 10, 2021 3:28 pm
In his experience, he has seen the complication of hemorrhagic pericardial effusion secondary to some TKI?
M. Ayala MEX.Posted onOctober 10, 2021 3:28 pm
Clearly drug toxicity impacts compliance and TFR. Many of us tend to taper doses of TKI in the real-world, to maintain MMR, but this is not included in NCCN or ELN guidelines. How do we optimize our efforts to include this in future guidelines? Tariq Mughal (Boston)Posted onOctober 10, 2021 3:27 pm
With regard to your question - when is it acceptable to have an irreversible AE- Do you think it is acceptable to continue on ponatinib if a young patient ( age 30) develops ponatinib induced hypertension? Definitely related to low dose ponatinib , bp 160/100, symptomatic ,would require anti hypertensive treatment, resolves on ponatinib interruption. Posted onOctober 10, 2021 3:22 pm
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Question to Katia Pagano: Did you know that to avoid Covid or to decrease symptoms everybody on this earth should supplement probiotics and quercetin (induce immune cells expression and lead to increase the number of leukocytes, important for defense from every pathogen, viruses and bacteria). There are scientific papers that confirm probiotic bacteria activity on immune system strength. Posted onOctober 10, 2021 1:46 pm
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QoL clearly matters and impacts compliance. In this regards it is noteable that many CML experts tend to utilize the lowest dose of TKI to maintain MMR and this is not in the ELN or NCCN guidelines. In this regard how do suggest we address this issue in the QoL studies in CML? Tariq Mughal (Boston)Posted onOctober 10, 2021 1:25 pm
Jeroen Janssen (Amsterdam NL) I can imagine that in the first year after stopping TKI QoL is suboptimal in view of the withdrawal syndrome and stress because of fear of relapse. But how is this > 1 yr after stopping?Posted onOctober 10, 2021 1:23 pm
*******************Posted onOctober 10, 2021 1:05 pm
Can you explain the term copy number?
Does copy number mutation affect BCR-ABL 1? If so, what is the implication?
From Dr Augustine N Duru (Nigeria).Posted onOctober 10, 2021 12:57 pm
Posted onOctober 10, 2021 12:57 pm
Are you able to detect in sample from resistant patient if there are some mutations that coexistance usually with resistancePosted onOctober 10, 2021 12:56 pm
In pts who have mulyiple CHIP muts, does the order in which you acquire them impacts risks for subsequent myeloid or lymphois malignacies and perhaps their phenotypes? Tariq Mughal (Boston)Posted onOctober 10, 2021 12:55 pm
it seems that the presence of CHIP is quite rare in CML... Is this your experience? What is your interpretation? (Marc Berger, France)
Posted onOctober 10, 2021 12:55 pm
Is there any any predictive hematologic parameters when there is M-CHIP for CML? High platelet count? high basophil count? Posted onOctober 10, 2021 12:54 pm
B-cell CLL has a lower in incidence in East Asia. Have you looked in these populations for lymphoid CH? Tiong Ong, Singapore.
Posted onOctober 10, 2021 12:54 pm
Peter van Galen, Boston: is there any new insight into why the effects of different blood cell mutations on cardiovascular disease phenotypes converge to some extent, despite the different epigenetic fundctions?Posted onOctober 10, 2021 12:50 pm
Question to round table: What do you think: will choosing active drug and monitoring of its activity will be more profitable for patients, then application for treatment for example interferon, a known drug directed towards IL-2, so strictly directing on immunological system modifications, not strictly on cancer cells.Posted onOctober 10, 2021 12:46 pm
********* Special lecture 7 ********Posted onOctober 10, 2021 12:45 pm
Great discussion, thank you !Posted onOctober 10, 2021 12:34 pm
question to Mahon: how did you first think about possibility to stop TKI at teh STIM?
Posted onOctober 10, 2021 12:27 pm
Maybe we need a change in terminalogy? Like 'treatment-free holiday'? Holidays can be short, long, or event permanent!Posted onOctober 10, 2021 12:26 pm
Posted onOctober 10, 2021 12:25 pm
What about Treatment-dependent remission instead of "relaspe"?
Delphine ReaPosted onOctober 10, 2021 12:24 pm
some patients present without splenomegaly and with low WBC counts. These patients get MRD negativity earlier. Are these patients candidate for cure?Posted onOctober 10, 2021 12:20 pm
Are withdrow symptoms better when you stop gradually?
Posted onOctober 10, 2021 12:10 pm
AS only about 5 % of all CML patients around the world can reach successful TFR, even if we double this number how can it become the ultinate goal? what about the 90 % ?Posted onOctober 10, 2021 12:06 pm
***************** Round***********Posted onOctober 10, 2021 11:32 am
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Maaike Luesink, Utrecht, The Netherlands
Why do the lymphocytes stay BCR-ABL positive? Posted onOctober 10, 2021 11:23 am
Posted onOctober 10, 2021 11:23 am
Thank you for great presentation. Have you studied granulocyte PCR during TKI therapy after the start of TKI therapy after the diagnosis; how fast it is decreasing and how that is correlating with various BCR-ABL IS levels? and similarly regarding other leukocyte fractions as well?
Posted onOctober 10, 2021 11:23 am
Why do you think it is the PCR-positivity in granulocytes and not in dendritic cells or lymphocytes considering CML is a stem cell disease and BCR-ABL1 should be equally distributed amongst all cell types? Thanks, Daniela Krause, Frankfurt, Germany
Posted onOctober 10, 2021 11:22 am
Mike Mauro, New York; Great talk! have you noted any difference in granulocyte PCR (+) between different Tkis as of yet?
Posted onOctober 10, 2021 11:21 am
Claudio Sorio, Verona :
granulocytes in CML are different from granulocytes in healthy donors based on surface and morphological features? Could this interfere with purification methods?Posted onOctober 10, 2021 11:20 am
@Ilaria: great talk, congratulations. From your data, it seems as if the NK cell PCR would be just as good if not better to discriminate TFR from relapse after TKI cessation. Why did you choose granulocytes for the further analysis ? Tim BrümmendorfPosted onOctober 10, 2021 11:20 am
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Question to Rebekka Schneider: What is your opinion: Could we use TLR4 as a target to block its function to stop fibrosis? Could it be some natural agent with less or non side effect?Posted onOctober 10, 2021 10:10 am
Posted onOctober 10, 2021 10:01 am
Question to Goran Karlsson: Could you do this analysis for patient bone marrow in low disease development, later in more aggression, and after treatment when is resistant to treatment to find out what has happened in their expression that might be important for patient resistance? Is it possible to analyze for each patient what is changed in gene expression, because in our body one genes are switch on and others switch off for some reason, what we currently do not know how it worksPosted onOctober 10, 2021 9:52 am
Unlike, imatinib, dasatinib and ponatinib, bosutinib does not inhibit KIT. Did you assess emergence of KIT -ve cells in bosutinib treated pts?
Manley, SwitzerlandPosted onOctober 10, 2021 9:45 am
With enhancers could you look at BM (or peripheral blood) cells from patients at the stage of losing MMR for upregulation of efflux transporters (e.g. P-gp)?
Manley, SwitzerlandPosted onOctober 10, 2021 9:41 am
Ram Thakur (Lund, Sweden)
To the speaker Ana Cevijc:
1. Do the intermediate states such as MEMPs and LMPs contain truly oligolineage cells that express genes of more than one lineage simultaneously or, are these heterogenous populations containing indidual cells with unilineage priming?
2. It is intriguing that transcriptional heterogeneity is observed at the level of chromatin accessibility but not gene expression. Why so?Posted onOctober 10, 2021 9:23 am
Question to Ana Cvejic: You told that in stem cells the low expression is genes usually related to differentiation genes, but what about cell cycle? Because of high potential for this cells to proliferation to grow a body, genes related to cell cycle should be more expressed. If is variable, it is interesting how in detail this works, because it could be some logical explanationPosted onOctober 10, 2021 9:19 am
Can we differentiate cells from stem cell into different cell line? Posted onOctober 10, 2021 9:08 am
********** Day 4 **********Posted onOctober 10, 2021 7:30 am
Posted onOctober 9, 2021 7:25 pm
Thanks a lot.
What would be your recommendations to prevent ischemic events (besides adapting ponatinib doses)
?Posted onOctober 9, 2021 4:42 pm
**************** Poster walk **************Posted onOctober 9, 2021 4:04 pm
To what extend data from Ph ALL will bring insights into the unrdtsanding of TFR in CML?????
Posted onOctober 9, 2021 3:58 pm
Richard Clark (Liverpool, UK): Question to Margarita: Most relapses happen within 6 months of stopping and even more within 12 months. What proportion of your patients have been followed for at least 12 months of stopping?Posted onOctober 9, 2021 3:42 pm
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Posted onOctober 9, 2021 3:27 pm
TFR bosutinib question
Toni Montserrat (Patient)Posted onOctober 9, 2021 2:49 pm
As patient, who relapsed after only 4 months, having before had DMR on bosutinib for more than 3 years, any recommendations to have a chance on TFR2?
Is asciminib a new way?
ThanksPosted onOctober 9, 2021 2:48 pm
Does adding another treatment like IFN really increase the chance of successful TFR? Doesn't the kinetics show the biology of the cells and achieving sufficiently low level by adding another medication may not produce TFR necessarily???Posted onOctober 9, 2021 2:48 pm
For the halving time, did you use ABL or GUS for your control? (Soledad Undurraga, Chile)Posted onOctober 9, 2021 2:47 pm
Q to D. Ross: Is there something known, whether the halving time effect (early response) is related to the described group (STIM) of patients loosing CMR after TKI stop but not experiencing a molecular relaspe in term of loosing MMR?Posted onOctober 9, 2021 2:42 pm
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Any data about using a combination of demethylating agent such as 5-Aza and TKI for patients who are resistant to TKI (Hamid AL-Jamal, Malaysia)Posted onOctober 9, 2021 2:13 pm
Prof G-P: Good and interesting Byond data. Considering the deaths noted during the study (in total 17) - did you detect any pattern? Posted onOctober 9, 2021 2:04 pm
Posted onOctober 9, 2021 2:03 pm
Question to Carlo Gambarcorti: I understand that 88 % of patients respond to treatment. My question is: What is your strategy for 12% of patients who did not respond to therapy? Posted onOctober 9, 2021 2:03 pm
Posted onOctober 9, 2021 1:56 pm
I have seen in last 3 lectures that patients in cancer react like medical doctors wants, but this is not true. When patient walk through the door you do not know how patient will react, if it is well tolerability t this moment it will change in time. Only patients with strong immunological system will react like you show. My question is: Do you know that most drugs induce in human body stress, and human body wants to revert this staus to bring homeostasis? Posted onOctober 9, 2021 1:56 pm
Were any patients P190 or all P210?
Posted onOctober 9, 2021 1:47 pm
Question to Ingo Roeder: This models and simulations will work on statisticaly reactive pateints. What's about peoples resistant to treatment and additionally react not similarly like other patients.?Posted onOctober 9, 2021 1:38 pm
When you treat patient, have you seen previously patient sensitive who have to have lower dose? Posted onOctober 9, 2021 1:29 pm
(Jeroen Janssen Amsterdam NL) In the end overall survival is most important. This is the same for all three arms. Would you recommend then to still use the 45 to 15 mg strategy instead of 15 mg continuously? Especially in view of the AOE rate, which is 3x as high in the 45 --> 15 mg arm?Posted onOctober 9, 2021 1:28 pm
Could you explain a little more about the advantage of reducing TKI dose progressively for TFR (Soledad Undurraga, Chile)
Posted onOctober 9, 2021 1:10 pm
Are prognostic markers effective for all patients? What is your opinion, is it better to choose therapy using molecular markers, or better to incubate cells with anticancer drugs and check if this therapy will be effective before therapy administration to patient?Posted onOctober 9, 2021 1:10 pm
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Did all patients who were transferred NK cells positively responded to therapy? Posted onOctober 9, 2021 12:46 pm
Could your strategy be used for MRD?Question from a non-clinicianPosted onOctober 9, 2021 12:45 pm
Paulo Rodrigues-Santos (Coimbra, Portugal): Outstanding talk, congratulations. Do you see a role for KIR alloreactivity in your studies?Posted onOctober 9, 2021 12:44 pm
Excellent talk, thank you. 1. Do you think the antigenic targets may be the same as described in CML, i.e. WT1, Proteinase 3 etc? 2nd question: Are some HLAtypes more responsive to NK cell therapy than others? Thanks,
Daniela Krause, Frankfurt, GermanyPosted onOctober 9, 2021 12:44 pm
Outstanding talk, congratulations. Do you see a role for KIR alloreactivity in your studies?
Posted onOctober 9, 2021 12:42 pm
Brilliant work. Thank you.
Posted onOctober 9, 2021 12:42 pm
@Todd Fehninger: are you certain that memory-like NK cells are being rejected after allo SCT or could they simply exhaust ? Tim BrümmendorfPosted onOctober 9, 2021 12:40 pm
Could NK cells kill also Covid virus? How we can regulate the number of NK cells in the human body?Posted onOctober 9, 2021 12:33 pm
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Comment: Thank you for a remarkable and insightful talk on the potential to target LSC in CML using a novel mechanistic approach. A challenge will be how to integrate the emerging approaches into the clinics a future JMG awardee) (Tariq Mughal, Boston)Posted onOctober 9, 2021 12:22 pm
(danilo, Baltimore MD) Beppe, great talk. I have a question. You showed apoptosis in CML-BC cell lines who have p53 mutated. This means that there are other apoptotic pathways induced by your drugs. Do you have any idea of which pathways maybe involved. Second question: did you investigate the effect of this drug on the TKI-resistant quiescent LSCs?Posted onOctober 9, 2021 12:19 pm
Jeroen Janssen Amsterdam is there any in vivo (mice) data on Meds433 already available? Is it orally available for example?Posted onOctober 9, 2021 12:10 pm
Posted onOctober 9, 2021 12:01 pm
*************** prize *********Posted onOctober 9, 2021 11:26 am
Is it possible to combine affords and foe example all person who had lecture will study ALL on different way (mutations mtDNA, mutations in general, changes in metabolism, cell cycle, alterations in methylotransferases, apoptosis and response to treatment? I can for examle incubate MCL or ALL cells with drugs, reed the viability, do lysate and send lysates for other analyses, alternatively we can also frise cells for other studies. Is it possible to organize such studies? This is important a specially for patients resistant to treatment.Posted onOctober 9, 2021 10:46 am
Q for Deborah: Could the additional genetic aberrations (del in IKZF1,...) be connected to the chemotherapyPosted onOctober 9, 2021 10:35 am
Excellent session and discussion
Thanks to all!Posted onOctober 9, 2021 10:34 am
@Dr Pagani. Great talk, thank you. What do you think is the relevance of mutations in COX1 and COX, i.e. possibly the generation of an inflammatory phenotype via cyclooxyrgenase and prostaglandins?Posted onOctober 9, 2021 10:18 am
@Dr Kamachi: How specific is OR21, i.e. does it also have an effect on DNMT3A? Also, I was surprised at the high percentage of Lin- GFP+ cells in the BM the retroviral model. Is it really 60%?? Thanks, Daniela Krause, Frankfurt, GermanyPosted onOctober 9, 2021 10:16 am
Question to Kazuharu Kamachi: Did you compared result based on MT methylation with analysis of cell cycle and metabolism? Posted onOctober 9, 2021 10:13 am
Claudio Sorio, Italy: Have you evaluated the modulation of the TSG PTPRG, whose expression is known to be increased by demethylating agents, following treatment with OR21 ?Posted onOctober 9, 2021 10:08 am
Did you combine results based on deletions in ALL with metabolism changes and epigenetic alterations? Posted onOctober 9, 2021 10:05 am
Question for Ilaria Pagani: Could you say that mutations in mtDNA are a reason of resistance to treatment?
Question for Carolyn Busch: Could apoptosis level be important in analysis of CML response to treatment? Posted onOctober 9, 2021 9:52 am
Vignir Helgason (Glasgow): Q to Ilaria: Do you think mitochondria mutations can be used as a predictive marker for Treatment Free Remission (TRF)?Posted onOctober 9, 2021 9:45 am
Did you analyze mitochondrial DNA from non leukemic cells in these same patients and if so, were there mutation?
How frequent are mitochrondrial DNA mutations in the general population?
Thanks a lot
D Rea ParisPosted onOctober 9, 2021 9:37 am
Posted onOctober 9, 2021 9:28 am
Can you say anything about brain penetration of asciminib?Posted onOctober 9, 2021 9:21 am
Vignir (Glasgow): Q to Oliver. Thanks for a great talk. How is myristate binding to the myristate pocket regulated under normal situation in wild type c-Abl? Posted onOctober 9, 2021 9:21 am
Tim Hughes, Australia: Great talk Oliver. How potently does asciminib inhibit the kinase activity of native cABL? How does this compare to ATP competitive TKIs?Posted onOctober 9, 2021 9:16 am
Good morning
I couldn't access to the record or get the livePosted onOctober 9, 2021 8:50 am
Posted onOctober 9, 2021 8:48 am
************* Day 3 **********Posted onOctober 9, 2021 8:16 am
Dr Abdullah Al-wajeehPosted onOctober 9, 2021 7:27 am
Posted onOctober 8, 2021 6:10 pm
I think I was not really clear. What I meant was to do deep WGS on the bulk, then use all somatic mutations to infer clonal attribution of single cells based on mutation calls that you pick up by RNAseq. I did not mean WGS on single cells. Or are there not enough somatic mutations in hematologic malignancies? Mike DeiningerPosted onOctober 8, 2021 5:40 pm
To Peter: have you tried to use WGS identified non-driver mutation to infer clonal attribution to single cells - Mike Deininger/MilwaukeePosted onOctober 8, 2021 5:25 pm
are there any workshops on techniques presented by Peter?Posted onOctober 8, 2021 5:25 pm
Question for Peter: Do you see clonal hematopoiesis and in general tumor evolution field as a more bioinformatic field nowadays? Posted onOctober 8, 2021 5:20 pm
Technical question: Are there any differences in performing CutTag protocol in hematopoietic stem cell progenitors and other (adherent) cell lines?Posted onOctober 8, 2021 5:10 pm
Posted onOctober 8, 2021 3:12 pm
(Danilo, Baltimore, MD) Claudio, great work. Did you try to use phosphatase inhibitors to prevent the PMN effect on BCR-ABL1?Posted onOctober 8, 2021 2:48 pm
Please comment on the cytogenetic abnormalities in these leukemiasPosted onOctober 8, 2021 2:18 pm
*****************Posted onOctober 8, 2021 1:57 pm
Excellent symposium thank you
Posted onOctober 8, 2021 1:57 pm
To Dr. Ong: For the clinical application of epigenetic/genetic information in the clinical practice, what do you think is the bottle neck?Posted onOctober 8, 2021 1:46 pm
Posted onOctober 8, 2021 1:45 pm
@Mhairi and/or Aleksandar Could you please comment on the choice and timing of post-allo TKI maintenance therapy ? Tim BrümmendorfPosted onOctober 8, 2021 1:41 pm
Not only achieving second CP, is there a role of achieving MRD prior to BMT as seen in ALL and AML? Is there any data?
Nobuko Hijiya, New YorkPosted onOctober 8, 2021 1:40 pm
Not only achieving second CP, is there a role of negative MRD (e.g. flow cytometry) prior to BMT as seen in ALL and AML? Is there any data?
Nobuko Hijiya, New YorkPosted onOctober 8, 2021 1:36 pm
Jeroen Janssen (Amsterdam) have you looked at the impact of conditioning regimens on OS/PFS/Relapse rate (RIC vs myeloablative)?Posted onOctober 8, 2021 1:35 pm
Posted onOctober 8, 2021 1:23 pm
how did you define CMR? Did I understood you do not transplant when CMR at 3 months? Posted onOctober 8, 2021 1:20 pm
@Koji: was there a difference in response, PFS and OS and outcome after SCT for patients with p190 vs. p210 in the Hyper-CVAD-Pona trial ? Tim BrümmendorfPosted onOctober 8, 2021 1:17 pm
We currently have a 47A patient with CNS extramedullary myeloid blast crisis. It culminated: induction(7+3) + 2 consolidations(HD- AraC) + new TKI(Dasatinib)+ intrathecal chemotherapy and pending Allo HSCT. What other therapeutic alternatives do you suggest in this case?
Thank you for the great opportunity. Dr. López Sacerio, Cuba.Posted onOctober 8, 2021 1:12 pm
Jeroen Janssen, Amsterdam: What conditioning regimens for alloSCT do you recommend for BC CML once patients are in CR? myeloablative/RIC? Would you try to reach MMR? Or CCyR, before alloSCT?Posted onOctober 8, 2021 1:07 pm
@Robert (again) What is the frequency of overt bone marrow fibrosis in BC-CML and is it different for Lymphoid vs. Myeloid BP ? Tim BrümmendorfPosted onOctober 8, 2021 12:57 pm
@Robert Hasserjian: In the cases discussed, have you been able to look whether BCR-ABL+ Inv(16)-negative subclones existed in the patient at diagnosis argueing for the acquisition of inv(16) as a secondary event following BCR-ABL ? Tim Brümmendorf
Posted onOctober 8, 2021 12:55 pm
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Live feed is not working.Posted onOctober 8, 2021 11:40 am
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****** Symposium ************Posted onOctober 8, 2021 11:11 am
Thank you for the nice and valuable presentations!Posted onOctober 8, 2021 10:41 am
Samuel (Addis Ababa University, Ethiopia), What is your view with regard to HLA of host and heterogeneity of mutation accumulation? do you think some potential "neogenetics" has impact? Thank youPosted onOctober 8, 2021 10:21 am
Amazing and lovely. Gianantonio Rosti
Posted onOctober 8, 2021 10:21 am
Not a question
Just wanted to thank you for this wonderful lecture and for your work and that of your team
You deserve this price
Kind regards
Delphine Rea and Franck NicoliniPosted onOctober 8, 2021 10:20 am
Does the F359V mutation confer resistance to asciminib, and if so , what is the mechanism?Posted onOctober 8, 2021 10:19 am
************* Janet Rowley *************
Posted onOctober 8, 2021 9:56 am
Thank you Valeria for your response. I think it still would be of interest to treat mice with TKIs as they might also have some direct effects on NK cells and those would be great to follow. Best regards from Satu to all great presenters and chair!Posted onOctober 8, 2021 9:48 am
Could I ask questions about MDSC, are they BCR-ABL positive and if yes Gr or M-MDSC? Thank you!
How they interract with different types of T regs?Posted onOctober 8, 2021 9:46 am
Posted onOctober 8, 2021 9:35 am
Q from Kasia Piwocka to Virginia:
Have you compared the Treg activity and level together with immunosupression in your mouse model at the stage of blastic phase not early chronic phase?Posted onOctober 8, 2021 9:30 am
Question to Valeriya: Thank you for nice presentation. In your mouse model, have you treated them with TKIs and followed what happens during therapy to NK cell phenotype and function? How does the leukemia microenvironment change during the treatment and in remission? Question by Satu Mustjoki, Finland
Posted onOctober 8, 2021 9:18 am
Question for Valeriya Kuznetsove: Could we induce production of NK cells in human body to increase the number of cell that are able to find and destroy metastatic cancer cells?Posted onOctober 8, 2021 9:12 am
Question for Julian Swalter: Is it possible that in vessicle are transported some factors important for Leukemia development?Posted onOctober 8, 2021 9:10 am
Did you observed maybe the role of T reg and also NK cells in leukemia development?Posted onOctober 8, 2021 8:59 am
Thank you Dominik for a terrific talk!Posted onOctober 8, 2021 8:52 am
Tim Hughes Australia Great talk! What is driving the inflammatory response at diagnosis seen on some patients but not others? More aggressive disease? patient specific factors?Posted onOctober 8, 2021 8:49 am
TKI's are being explored in treatment of autoimmune diseases including refractory ITP. What are the clinical results so far?Posted onOctober 8, 2021 8:48 am
Posted onOctober 8, 2021 8:47 am
Do you seen an opening for any immune-based therapeutic approaches in patients who already doing very well with TKIs, e.g. in MMR/DMR? Tiong Ong, Singapore.Posted onOctober 8, 2021 8:45 am
Mhairi Copland, UK. Do you think there may be a inflammatory protein signature within the bone marrow microenvironment that will be predictive for successful TFR?
Posted onOctober 8, 2021 8:44 am
Thank you Dominik for great presentation. What do you think of antigen specific immune responses in CML; how important are for example LAA specific T cells in comparison to NK cells or other cell types? (Satu Mustjoki, Finland)Posted onOctober 8, 2021 8:43 am
What about immun-senescence - how is that inked to TKI and inflammation? NK cell anergy or senescence in particular?
Posted onOctober 8, 2021 8:43 am
can you elude to the various potential roles IFN alpha may have in this context given its past and present applications in treatment?
Christoph Klade, AustriaPosted onOctober 8, 2021 8:41 am
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********* Day 2 **********Posted onOctober 8, 2021 7:05 am
Update treatment options for a child with CML living in developing country, the patient is now in chronic phase, being treated with imatinib.
Dr.ferdousi begum, NICRH, Bangladesh.Posted onOctober 8, 2021 5:45 am
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Posted onOctober 7, 2021 5:08 pm
Question is already answered - Mike Deininger
Posted onOctober 7, 2021 4:57 pm
For Catherine Smith,
How are you planning to add the patient specific primers into the single cell seq system? Do you need to order special barcoding reagents from the supplier company?Posted onOctober 7, 2021 4:56 pm
Did you check simultaneously cell signaling, metabolism, presence of CD, and genetic alterations i the same cells? I think that what we see in cells that is a sume of several pathways, and even one difference could lead to unspecific changesPosted onOctober 7, 2021 4:56 pm
Great work Catherine: How do you estimate the false negative rate for BCR-ABL1 expression? Adam Mead struggled with this a lot. Have you tried to include junction-specific fusion (DNA) primers? Mike Deininger, Milwaukee, USPosted onOctober 7, 2021 4:52 pm
**************
Posted onOctober 7, 2021 4:39 pm
Posted onOctober 7, 2021 4:39 pm
Ahmed from Glasgow, UK
Do you think the effect of TNT is specific to HS5 cells? Posted onOctober 7, 2021 4:36 pm
For Wei Liu: do you see differences in expression of cytokine receptors? Is the reduction in cycling cells LSCs after TKI exposure related to an intrinsic signal or to non-response to an extrinsic signal? Mike DPosted onOctober 7, 2021 4:34 pm
Posted onOctober 7, 2021 4:32 pm
Question to Prof. Naka: How we can explain FL function and involvement with cellular metabolism?Posted onOctober 7, 2021 4:29 pm
(Perrotti, Baltimore MD) question for W. Liu: if your data indicate that MYC and its signature are highly expressed in quiescent LSCs, how do you fit your data with the knowledge that MYC is an inducer of G1/S cell cycle progression as it induces cyclin Ds, CDK6 and E2F1/3, and with the fact that work from different groups indicate that Cyclin D and CDK6 are down regulated and essential for normal and CML LSC quiescence?Posted onOctober 7, 2021 4:28 pm
Ahmed from Dr Helgason, Glasgow, UK
For Prof Ravi
For complete free remission of CML through targeting stromal cells, Do you think CML will be affected in terms of homing to bone marrow and may infiltrate into CNS? Posted onOctober 7, 2021 4:22 pm
How would modifying the Gdpd3 expression affect pathways unrelated to CML? Posted onOctober 7, 2021 4:21 pm
Vignir (Glasgow): Q for Piotr:
Q1:Does mitochondrial respiration (oxygen consumption rate) chance in the stromal cells when co-cultured with CML cells?
Q2: Can you inhibit oxygen consumption rate in CML cells in the co-culture by inhibiting tunneling nanotubes? Posted onOctober 7, 2021 4:08 pm
Posted onOctober 7, 2021 3:55 pm
Great work. Just confirm that p53 is relatively low in quiescent LSCs, and further downregulated by TKIs - Mike Deininger/Milwaukee/USPosted onOctober 7, 2021 3:55 pm
What was the reason, why some LSC cells was cycling, and some other Go. Is it possible to make upcycling cells to become cycling? Posted onOctober 7, 2021 3:50 pm
************Posted onOctober 7, 2021 3:45 pm
Vignir (Glasgow)
Are c-Kit low less metabolically active? Do they have lower ROS?Posted onOctober 7, 2021 3:39 pm
Could we add all necessary factors to stem cells cultures to study development of these cells. do we know currently which factors are important? If factors are known, how we can say that these results are similar to present in the human body? Posted onOctober 7, 2021 3:38 pm
The importance of the vasculature in CML has been suggested. In your studies, have you evaluated if there are alteration in the CML endothelium?Posted onOctober 7, 2021 3:34 pm
Great talk. What's the relative proportion of KITlow LSCs and is there a large variation across different newly dx pts? Mike Deininger, Milwaukee, USPosted onOctober 7, 2021 3:33 pm
Samuel (Addis Ababa, Ethiopia), Your view on host hormonal effect on microenvironment of LSC? Thank you for your comprehenive presentation. Posted onOctober 7, 2021 3:32 pm
outside of discovery research - is there a routine role for DNA based PCR in the monitoring of patients in TFR. Sean Young - vancouverPosted onOctober 7, 2021 3:32 pm
************** session 2 *********Posted onOctober 7, 2021 3:19 pm
To what extent would metabolite from Leukemia cell affect itself (auto-modification)? Posted onOctober 7, 2021 3:09 pm
Do you think altered metabolism is the cause or consequence of LSC? Therefore, can the strategy of inhibiting metabolism be a method to just stop leukemia development or eradicate LSC? Thanks. Shaowei. BirminghamPosted onOctober 7, 2021 3:07 pm
... and by the way: Tessa would have loved Craig Jordan's talk !!! Tim BrümmendorfPosted onOctober 7, 2021 3:01 pm
******Posted onOctober 7, 2021 3:00 pm
How important is 5-aza in the triple etoxomir/venetoclax/5-aza regimen? Especially in pts who have failed a 5-aza containing regimen? Mike Deininger/Milwaukee/USPosted onOctober 7, 2021 2:58 pm
@Craig Jordan: Super talk ! Have you had a chance to check whether Azazytidine potentially inhibits FA oxidation and thereby sensitizes relapse AML cells to Venetoclax ? Tim BrümmendorfPosted onOctober 7, 2021 2:58 pm
Have you got maybe some data confirming that all drugs could interact with many different targets leading to cell signaling, changes in metabolism, or as you show also changes in energy (if caused changes on mitochondria)?Posted onOctober 7, 2021 2:56 pm
Peter van Galen, Boston, USA (repeating question): when treating with azacytidine + venetoclax, do the drugs target different cancer cell populations or synergize to target LSCs?Posted onOctober 7, 2021 2:55 pm
Vignir (Glasgow).
Q1: Is the effect of Venetoclax on Oxphos independent on it's effect on Bax/Bak activation on mitochondria and cytochrome C release?
Q2: Do you think CML stem cells are different from AML stem cells in terms of their ability to cope with ROS?Posted onOctober 7, 2021 2:55 pm
When treating with venetoclax and azacytidine, do the drugs target different tumor cell populations or synergize in LSCs?Posted onOctober 7, 2021 2:54 pm
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Ahmed (Glasgow, UK)
Do you think inhibiting CaSR in AML may lead to infeltiration into CNS due to loss of homing to BM?Posted onOctober 7, 2021 2:35 pm
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Danilo Perrotti (Baltimore, MD USA) question for Martha: Is modulation of SHIN1 and AMPK altering BCR-ABL1 expression and activity in CD34+ CML and/or K562 cells? Posted onOctober 7, 2021 2:28 pm
Some reported data have shown that combining TKI with asciminib is effective against mutant forms of BCR-ABL1 in CML and Ph+ALL, my question is that if there is any interest in combinational therapy with TKI and asciminib for TKI-resistant CML in clinics and even in clinical trials for developing such novel therapeutic strategies?Posted onOctober 7, 2021 2:26 pm
For Dr. Copland: Our practice has been to treat lymphoid BP with an ALL regimen. Based on you data, would you advocate for Flag-Ida irrespective of immunophenotype? Mike Deininger/Milwaukee/USPosted onOctober 7, 2021 2:23 pm
Question for Martha M. Zarou,
From- Rahul Kumar, Frankfurt Germany
Thank you for the talk, very interesting data.
Stroma is a contributor to leukemia chemoresistance. Did you try your double inhibition experiment, with Imatinib, in a co-culture system with stroma cells?
and can you comment if 1 carbon inhibition could also affect the stromal population?
Posted onOctober 7, 2021 2:23 pm
Could you see some differences in disease development in CML patients affected with covid virus?
Posted onOctober 7, 2021 2:17 pm
Vignir (Glasgow). Question for Raquel: Do you know if intracellular concentration (i.e. in endoplasmic reticulum) of Ca2 is different in CML and AML cells? Posted onOctober 7, 2021 2:15 pm
For Dr. Pereira: please speculate on the differential function of CaSR in CML vs. AML. Also I missed which AML model(s) you used for the in vivo experiments. - Mike Deininger/MilwaukeePosted onOctober 7, 2021 2:13 pm
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@Katia Pagnano: were the access death in AP/BC patients really due to COVID19 or CML ? Tim BrümmendorfPosted onOctober 7, 2021 2:09 pm
For Ms Copeland. What were the TI/TIi variants identified in your cohort? Would any predict response to open or compassionate access to alternative treatment (eg IDH1/2). Sean Young - Vancouver, canadaPosted onOctober 7, 2021 2:06 pm
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is there experience in AP/BC with T315I mutation treatment with combining asciminib and ponatinib?Posted onOctober 7, 2021 1:48 pm
Jeroen Janssen Amsterdam: was ponatinib continued during chemo and conditioning regimen?
Posted onOctober 7, 2021 1:46 pm
Tim Hughes Australia. Question for Mhairi: Great study. I wasn't clear about what determined whether patients received a second cycle of ponatinib plus chemotherapy.Posted onOctober 7, 2021 1:46 pm
The clinical behavior of a de novo or progressive blast crisis, in our experience is different and it may not be necessary in the first place, to perform a transplant if there is an adequate response to chemotherapy + TKI in the de novo BC.
M. Ayala MexPosted onOctober 7, 2021 1:46 pm
@Mhairi Copland: great presentation ! Would you recommed only one cycle of PON-FLAG_IDA now before allo based on your results ? Thanks Tim BrümmendorfPosted onOctober 7, 2021 1:45 pm
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Tim Hughes Australia: For Johan Richter: it's really surprising that duration of MR4 has lost its pre-eminence as a predictor of TFR success. TKI duration is now the only variable that matters with longer follow up. Do you have an explanation?Posted onOctober 7, 2021 1:30 pm
Out of the total death on the study how many were CML related?
Posted onOctober 7, 2021 1:19 pm
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what happens to the 5-10 % of patients who went on TFR and needed to restart treatment and did not regain the molecular response level they had before stoping?Posted onOctober 7, 2021 1:13 pm
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Superb talk, Catriona, congratuklations !!! Have you been able to check telomere length in the astronaut longitudinally ? Are telomeres elongated as a result of telomerase activation or vice versa, is telomerase activation a result of accelerated telomere shortening happening in space ? Tim BrümmendorfPosted onOctober 7, 2021 12:49 pm
Do you have any idea on how ADAR1 activates Beta catenin?Posted onOctober 7, 2021 12:48 pm
Can activation induced cytidine deaminase (AID) have also a role in leukemia stem cell development in CML?
Akif Selim Yavuz
Istanbul, TurkeyPosted onOctober 7, 2021 12:47 pm
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samia menif tunisiaPosted onOctober 7, 2021 8:41 am
What time are you going to start?
Dr Hamid Al-Jamal (Malaysia)Posted onOctober 7, 2021 8:10 am
test1Posted onOctober 6, 2021 5:33 pm
helloPosted onOctober 6, 2021 4:32 pm
live generalPosted onOctober 6, 2021 4:32 pm
hiPosted onOctober 6, 2021 4:08 pm
testing123Posted onOctober 6, 2021 2:12 pm
Vignir Helgason (Glasgow): Feedback/Comment: Another fantastic meeting - many thanks Jorge, Tim and Daniela!!! Posted onOctober 10, 2021 4:31 pm
Mike Mauro, New York; 1 question 1 comment, question- thoughts on the effects of IGFR from imatinib on the results regarding insulin differences with NIL and IM; comment, any thoughts on pleural effusion on bosutinib being an effect still ongoing from prior exposure despite differences in the TKI at switch after DAS? great talks great session!Posted onOctober 10, 2021 4:23 pm
Vignir Helgason (Glasgow). Q for Pavel: Following drug treatment, did you check if HTB-153 try to compensate for the reduction in carnitine input by increasing glucose consumption? Posted onOctober 10, 2021 4:21 pm
does high doses of carnitine decrease intracellular activity of imatinib in leukemic cells?Posted onOctober 10, 2021 4:15 pm
what was the real incidence rate per dose dasatinib? correcting for the number of patients using a specific dose Posted onOctober 10, 2021 3:44 pm
Did you check if treatment induce stress? Any agent that brake homeostasis lead to stressful conditions. Did you check it? If it is true, than it is better to avoid traditional chemical drugs, but turn into how to teach our immunological system to fight cancer? One of such drug, this is interferonPosted onOctober 10, 2021 3:33 pm
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No role for transplant in young patients with good donors with reversible CV side -effects on ponatinib? Posted onOctober 10, 2021 3:29 pm
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In his experience, he has seen the complication of hemorrhagic pericardial effusion secondary to some TKI? M. Ayala MEX.Posted onOctober 10, 2021 3:28 pm
Clearly drug toxicity impacts compliance and TFR. Many of us tend to taper doses of TKI in the real-world, to maintain MMR, but this is not included in NCCN or ELN guidelines. How do we optimize our efforts to include this in future guidelines? Tariq Mughal (Boston)Posted onOctober 10, 2021 3:27 pm
With regard to your question - when is it acceptable to have an irreversible AE- Do you think it is acceptable to continue on ponatinib if a young patient ( age 30) develops ponatinib induced hypertension? Definitely related to low dose ponatinib , bp 160/100, symptomatic ,would require anti hypertensive treatment, resolves on ponatinib interruption. Posted onOctober 10, 2021 3:22 pm
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Question to Katia Pagano: Did you know that to avoid Covid or to decrease symptoms everybody on this earth should supplement probiotics and quercetin (induce immune cells expression and lead to increase the number of leukocytes, important for defense from every pathogen, viruses and bacteria). There are scientific papers that confirm probiotic bacteria activity on immune system strength. Posted onOctober 10, 2021 1:46 pm
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QoL clearly matters and impacts compliance. In this regards it is noteable that many CML experts tend to utilize the lowest dose of TKI to maintain MMR and this is not in the ELN or NCCN guidelines. In this regard how do suggest we address this issue in the QoL studies in CML? Tariq Mughal (Boston)Posted onOctober 10, 2021 1:25 pm
Jeroen Janssen (Amsterdam NL) I can imagine that in the first year after stopping TKI QoL is suboptimal in view of the withdrawal syndrome and stress because of fear of relapse. But how is this > 1 yr after stopping?Posted onOctober 10, 2021 1:23 pm
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Can you explain the term copy number? Does copy number mutation affect BCR-ABL 1? If so, what is the implication? From Dr Augustine N Duru (Nigeria).Posted onOctober 10, 2021 12:57 pm
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Are you able to detect in sample from resistant patient if there are some mutations that coexistance usually with resistancePosted onOctober 10, 2021 12:56 pm
In pts who have mulyiple CHIP muts, does the order in which you acquire them impacts risks for subsequent myeloid or lymphois malignacies and perhaps their phenotypes? Tariq Mughal (Boston)Posted onOctober 10, 2021 12:55 pm
it seems that the presence of CHIP is quite rare in CML... Is this your experience? What is your interpretation? (Marc Berger, France) Posted onOctober 10, 2021 12:55 pm
Is there any any predictive hematologic parameters when there is M-CHIP for CML? High platelet count? high basophil count? Posted onOctober 10, 2021 12:54 pm
B-cell CLL has a lower in incidence in East Asia. Have you looked in these populations for lymphoid CH? Tiong Ong, Singapore. Posted onOctober 10, 2021 12:54 pm
Peter van Galen, Boston: is there any new insight into why the effects of different blood cell mutations on cardiovascular disease phenotypes converge to some extent, despite the different epigenetic fundctions?Posted onOctober 10, 2021 12:50 pm
Question to round table: What do you think: will choosing active drug and monitoring of its activity will be more profitable for patients, then application for treatment for example interferon, a known drug directed towards IL-2, so strictly directing on immunological system modifications, not strictly on cancer cells.Posted onOctober 10, 2021 12:46 pm
********* Special lecture 7 ********Posted onOctober 10, 2021 12:45 pm
Great discussion, thank you !Posted onOctober 10, 2021 12:34 pm
question to Mahon: how did you first think about possibility to stop TKI at teh STIM? Posted onOctober 10, 2021 12:27 pm
Maybe we need a change in terminalogy? Like 'treatment-free holiday'? Holidays can be short, long, or event permanent!Posted onOctober 10, 2021 12:26 pm
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What about Treatment-dependent remission instead of "relaspe"? Delphine ReaPosted onOctober 10, 2021 12:24 pm
some patients present without splenomegaly and with low WBC counts. These patients get MRD negativity earlier. Are these patients candidate for cure?Posted onOctober 10, 2021 12:20 pm
Are withdrow symptoms better when you stop gradually? Posted onOctober 10, 2021 12:10 pm
AS only about 5 % of all CML patients around the world can reach successful TFR, even if we double this number how can it become the ultinate goal? what about the 90 % ?Posted onOctober 10, 2021 12:06 pm
***************** Round***********Posted onOctober 10, 2021 11:32 am
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Maaike Luesink, Utrecht, The Netherlands Why do the lymphocytes stay BCR-ABL positive? Posted onOctober 10, 2021 11:23 am
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Thank you for great presentation. Have you studied granulocyte PCR during TKI therapy after the start of TKI therapy after the diagnosis; how fast it is decreasing and how that is correlating with various BCR-ABL IS levels? and similarly regarding other leukocyte fractions as well? Posted onOctober 10, 2021 11:23 am
Why do you think it is the PCR-positivity in granulocytes and not in dendritic cells or lymphocytes considering CML is a stem cell disease and BCR-ABL1 should be equally distributed amongst all cell types? Thanks, Daniela Krause, Frankfurt, Germany Posted onOctober 10, 2021 11:22 am
Mike Mauro, New York; Great talk! have you noted any difference in granulocyte PCR (+) between different Tkis as of yet? Posted onOctober 10, 2021 11:21 am
Claudio Sorio, Verona : granulocytes in CML are different from granulocytes in healthy donors based on surface and morphological features? Could this interfere with purification methods?Posted onOctober 10, 2021 11:20 am
@Ilaria: great talk, congratulations. From your data, it seems as if the NK cell PCR would be just as good if not better to discriminate TFR from relapse after TKI cessation. Why did you choose granulocytes for the further analysis ? Tim BrümmendorfPosted onOctober 10, 2021 11:20 am
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Question to Rebekka Schneider: What is your opinion: Could we use TLR4 as a target to block its function to stop fibrosis? Could it be some natural agent with less or non side effect?Posted onOctober 10, 2021 10:10 am
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Question to Goran Karlsson: Could you do this analysis for patient bone marrow in low disease development, later in more aggression, and after treatment when is resistant to treatment to find out what has happened in their expression that might be important for patient resistance? Is it possible to analyze for each patient what is changed in gene expression, because in our body one genes are switch on and others switch off for some reason, what we currently do not know how it worksPosted onOctober 10, 2021 9:52 am
Unlike, imatinib, dasatinib and ponatinib, bosutinib does not inhibit KIT. Did you assess emergence of KIT -ve cells in bosutinib treated pts? Manley, SwitzerlandPosted onOctober 10, 2021 9:45 am
With enhancers could you look at BM (or peripheral blood) cells from patients at the stage of losing MMR for upregulation of efflux transporters (e.g. P-gp)? Manley, SwitzerlandPosted onOctober 10, 2021 9:41 am
Ram Thakur (Lund, Sweden) To the speaker Ana Cevijc: 1. Do the intermediate states such as MEMPs and LMPs contain truly oligolineage cells that express genes of more than one lineage simultaneously or, are these heterogenous populations containing indidual cells with unilineage priming? 2. It is intriguing that transcriptional heterogeneity is observed at the level of chromatin accessibility but not gene expression. Why so?Posted onOctober 10, 2021 9:23 am
Question to Ana Cvejic: You told that in stem cells the low expression is genes usually related to differentiation genes, but what about cell cycle? Because of high potential for this cells to proliferation to grow a body, genes related to cell cycle should be more expressed. If is variable, it is interesting how in detail this works, because it could be some logical explanationPosted onOctober 10, 2021 9:19 am
Can we differentiate cells from stem cell into different cell line? Posted onOctober 10, 2021 9:08 am
********** Day 4 **********Posted onOctober 10, 2021 7:30 am
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Thanks a lot. What would be your recommendations to prevent ischemic events (besides adapting ponatinib doses) ?Posted onOctober 9, 2021 4:42 pm
**************** Poster walk **************Posted onOctober 9, 2021 4:04 pm
To what extend data from Ph ALL will bring insights into the unrdtsanding of TFR in CML????? Posted onOctober 9, 2021 3:58 pm
Richard Clark (Liverpool, UK): Question to Margarita: Most relapses happen within 6 months of stopping and even more within 12 months. What proportion of your patients have been followed for at least 12 months of stopping?Posted onOctober 9, 2021 3:42 pm
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TFR bosutinib question Toni Montserrat (Patient)Posted onOctober 9, 2021 2:49 pm
As patient, who relapsed after only 4 months, having before had DMR on bosutinib for more than 3 years, any recommendations to have a chance on TFR2? Is asciminib a new way? ThanksPosted onOctober 9, 2021 2:48 pm
Does adding another treatment like IFN really increase the chance of successful TFR? Doesn't the kinetics show the biology of the cells and achieving sufficiently low level by adding another medication may not produce TFR necessarily???Posted onOctober 9, 2021 2:48 pm
For the halving time, did you use ABL or GUS for your control? (Soledad Undurraga, Chile)Posted onOctober 9, 2021 2:47 pm
Q to D. Ross: Is there something known, whether the halving time effect (early response) is related to the described group (STIM) of patients loosing CMR after TKI stop but not experiencing a molecular relaspe in term of loosing MMR?Posted onOctober 9, 2021 2:42 pm
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Any data about using a combination of demethylating agent such as 5-Aza and TKI for patients who are resistant to TKI (Hamid AL-Jamal, Malaysia)Posted onOctober 9, 2021 2:13 pm
Prof G-P: Good and interesting Byond data. Considering the deaths noted during the study (in total 17) - did you detect any pattern? Posted onOctober 9, 2021 2:04 pm
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Question to Carlo Gambarcorti: I understand that 88 % of patients respond to treatment. My question is: What is your strategy for 12% of patients who did not respond to therapy? Posted onOctober 9, 2021 2:03 pm
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I have seen in last 3 lectures that patients in cancer react like medical doctors wants, but this is not true. When patient walk through the door you do not know how patient will react, if it is well tolerability t this moment it will change in time. Only patients with strong immunological system will react like you show. My question is: Do you know that most drugs induce in human body stress, and human body wants to revert this staus to bring homeostasis? Posted onOctober 9, 2021 1:56 pm
Were any patients P190 or all P210? Posted onOctober 9, 2021 1:47 pm
Question to Ingo Roeder: This models and simulations will work on statisticaly reactive pateints. What's about peoples resistant to treatment and additionally react not similarly like other patients.?Posted onOctober 9, 2021 1:38 pm
When you treat patient, have you seen previously patient sensitive who have to have lower dose? Posted onOctober 9, 2021 1:29 pm
(Jeroen Janssen Amsterdam NL) In the end overall survival is most important. This is the same for all three arms. Would you recommend then to still use the 45 to 15 mg strategy instead of 15 mg continuously? Especially in view of the AOE rate, which is 3x as high in the 45 --> 15 mg arm?Posted onOctober 9, 2021 1:28 pm
Could you explain a little more about the advantage of reducing TKI dose progressively for TFR (Soledad Undurraga, Chile) Posted onOctober 9, 2021 1:10 pm
Are prognostic markers effective for all patients? What is your opinion, is it better to choose therapy using molecular markers, or better to incubate cells with anticancer drugs and check if this therapy will be effective before therapy administration to patient?Posted onOctober 9, 2021 1:10 pm
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Did all patients who were transferred NK cells positively responded to therapy? Posted onOctober 9, 2021 12:46 pm
Could your strategy be used for MRD?Question from a non-clinicianPosted onOctober 9, 2021 12:45 pm
Paulo Rodrigues-Santos (Coimbra, Portugal): Outstanding talk, congratulations. Do you see a role for KIR alloreactivity in your studies?Posted onOctober 9, 2021 12:44 pm
Excellent talk, thank you. 1. Do you think the antigenic targets may be the same as described in CML, i.e. WT1, Proteinase 3 etc? 2nd question: Are some HLAtypes more responsive to NK cell therapy than others? Thanks, Daniela Krause, Frankfurt, GermanyPosted onOctober 9, 2021 12:44 pm
Outstanding talk, congratulations. Do you see a role for KIR alloreactivity in your studies? Posted onOctober 9, 2021 12:42 pm
Brilliant work. Thank you. Posted onOctober 9, 2021 12:42 pm
@Todd Fehninger: are you certain that memory-like NK cells are being rejected after allo SCT or could they simply exhaust ? Tim BrümmendorfPosted onOctober 9, 2021 12:40 pm
Could NK cells kill also Covid virus? How we can regulate the number of NK cells in the human body?Posted onOctober 9, 2021 12:33 pm
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Comment: Thank you for a remarkable and insightful talk on the potential to target LSC in CML using a novel mechanistic approach. A challenge will be how to integrate the emerging approaches into the clinics a future JMG awardee) (Tariq Mughal, Boston)Posted onOctober 9, 2021 12:22 pm
(danilo, Baltimore MD) Beppe, great talk. I have a question. You showed apoptosis in CML-BC cell lines who have p53 mutated. This means that there are other apoptotic pathways induced by your drugs. Do you have any idea of which pathways maybe involved. Second question: did you investigate the effect of this drug on the TKI-resistant quiescent LSCs?Posted onOctober 9, 2021 12:19 pm
Jeroen Janssen Amsterdam is there any in vivo (mice) data on Meds433 already available? Is it orally available for example?Posted onOctober 9, 2021 12:10 pm
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*************** prize *********Posted onOctober 9, 2021 11:26 am
Is it possible to combine affords and foe example all person who had lecture will study ALL on different way (mutations mtDNA, mutations in general, changes in metabolism, cell cycle, alterations in methylotransferases, apoptosis and response to treatment? I can for examle incubate MCL or ALL cells with drugs, reed the viability, do lysate and send lysates for other analyses, alternatively we can also frise cells for other studies. Is it possible to organize such studies? This is important a specially for patients resistant to treatment.Posted onOctober 9, 2021 10:46 am
Q for Deborah: Could the additional genetic aberrations (del in IKZF1,...) be connected to the chemotherapyPosted onOctober 9, 2021 10:35 am
Excellent session and discussion Thanks to all!Posted onOctober 9, 2021 10:34 am
@Dr Pagani. Great talk, thank you. What do you think is the relevance of mutations in COX1 and COX, i.e. possibly the generation of an inflammatory phenotype via cyclooxyrgenase and prostaglandins?Posted onOctober 9, 2021 10:18 am
@Dr Kamachi: How specific is OR21, i.e. does it also have an effect on DNMT3A? Also, I was surprised at the high percentage of Lin- GFP+ cells in the BM the retroviral model. Is it really 60%?? Thanks, Daniela Krause, Frankfurt, GermanyPosted onOctober 9, 2021 10:16 am
Question to Kazuharu Kamachi: Did you compared result based on MT methylation with analysis of cell cycle and metabolism? Posted onOctober 9, 2021 10:13 am
Claudio Sorio, Italy: Have you evaluated the modulation of the TSG PTPRG, whose expression is known to be increased by demethylating agents, following treatment with OR21 ?Posted onOctober 9, 2021 10:08 am
Did you combine results based on deletions in ALL with metabolism changes and epigenetic alterations? Posted onOctober 9, 2021 10:05 am
Question for Ilaria Pagani: Could you say that mutations in mtDNA are a reason of resistance to treatment? Question for Carolyn Busch: Could apoptosis level be important in analysis of CML response to treatment? Posted onOctober 9, 2021 9:52 am
Vignir Helgason (Glasgow): Q to Ilaria: Do you think mitochondria mutations can be used as a predictive marker for Treatment Free Remission (TRF)?Posted onOctober 9, 2021 9:45 am
Did you analyze mitochondrial DNA from non leukemic cells in these same patients and if so, were there mutation? How frequent are mitochrondrial DNA mutations in the general population? Thanks a lot D Rea ParisPosted onOctober 9, 2021 9:37 am
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Can you say anything about brain penetration of asciminib?Posted onOctober 9, 2021 9:21 am
Vignir (Glasgow): Q to Oliver. Thanks for a great talk. How is myristate binding to the myristate pocket regulated under normal situation in wild type c-Abl? Posted onOctober 9, 2021 9:21 am
Tim Hughes, Australia: Great talk Oliver. How potently does asciminib inhibit the kinase activity of native cABL? How does this compare to ATP competitive TKIs?Posted onOctober 9, 2021 9:16 am
Good morning I couldn't access to the record or get the livePosted onOctober 9, 2021 8:50 am
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************* Day 3 **********Posted onOctober 9, 2021 8:16 am
Dr Abdullah Al-wajeehPosted onOctober 9, 2021 7:27 am
Posted onOctober 8, 2021 6:10 pm
I think I was not really clear. What I meant was to do deep WGS on the bulk, then use all somatic mutations to infer clonal attribution of single cells based on mutation calls that you pick up by RNAseq. I did not mean WGS on single cells. Or are there not enough somatic mutations in hematologic malignancies? Mike DeiningerPosted onOctober 8, 2021 5:40 pm
To Peter: have you tried to use WGS identified non-driver mutation to infer clonal attribution to single cells - Mike Deininger/MilwaukeePosted onOctober 8, 2021 5:25 pm
are there any workshops on techniques presented by Peter?Posted onOctober 8, 2021 5:25 pm
Question for Peter: Do you see clonal hematopoiesis and in general tumor evolution field as a more bioinformatic field nowadays? Posted onOctober 8, 2021 5:20 pm
Technical question: Are there any differences in performing CutTag protocol in hematopoietic stem cell progenitors and other (adherent) cell lines?Posted onOctober 8, 2021 5:10 pm
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(Danilo, Baltimore, MD) Claudio, great work. Did you try to use phosphatase inhibitors to prevent the PMN effect on BCR-ABL1?Posted onOctober 8, 2021 2:48 pm
Please comment on the cytogenetic abnormalities in these leukemiasPosted onOctober 8, 2021 2:18 pm
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Excellent symposium thank you Posted onOctober 8, 2021 1:57 pm
To Dr. Ong: For the clinical application of epigenetic/genetic information in the clinical practice, what do you think is the bottle neck?Posted onOctober 8, 2021 1:46 pm
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@Mhairi and/or Aleksandar Could you please comment on the choice and timing of post-allo TKI maintenance therapy ? Tim BrümmendorfPosted onOctober 8, 2021 1:41 pm
Not only achieving second CP, is there a role of achieving MRD prior to BMT as seen in ALL and AML? Is there any data? Nobuko Hijiya, New YorkPosted onOctober 8, 2021 1:40 pm
Not only achieving second CP, is there a role of negative MRD (e.g. flow cytometry) prior to BMT as seen in ALL and AML? Is there any data? Nobuko Hijiya, New YorkPosted onOctober 8, 2021 1:36 pm
Jeroen Janssen (Amsterdam) have you looked at the impact of conditioning regimens on OS/PFS/Relapse rate (RIC vs myeloablative)?Posted onOctober 8, 2021 1:35 pm
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how did you define CMR? Did I understood you do not transplant when CMR at 3 months? Posted onOctober 8, 2021 1:20 pm
@Koji: was there a difference in response, PFS and OS and outcome after SCT for patients with p190 vs. p210 in the Hyper-CVAD-Pona trial ? Tim BrümmendorfPosted onOctober 8, 2021 1:17 pm
We currently have a 47A patient with CNS extramedullary myeloid blast crisis. It culminated: induction(7+3) + 2 consolidations(HD- AraC) + new TKI(Dasatinib)+ intrathecal chemotherapy and pending Allo HSCT. What other therapeutic alternatives do you suggest in this case? Thank you for the great opportunity. Dr. López Sacerio, Cuba.Posted onOctober 8, 2021 1:12 pm
Jeroen Janssen, Amsterdam: What conditioning regimens for alloSCT do you recommend for BC CML once patients are in CR? myeloablative/RIC? Would you try to reach MMR? Or CCyR, before alloSCT?Posted onOctober 8, 2021 1:07 pm
@Robert (again) What is the frequency of overt bone marrow fibrosis in BC-CML and is it different for Lymphoid vs. Myeloid BP ? Tim BrümmendorfPosted onOctober 8, 2021 12:57 pm
@Robert Hasserjian: In the cases discussed, have you been able to look whether BCR-ABL+ Inv(16)-negative subclones existed in the patient at diagnosis argueing for the acquisition of inv(16) as a secondary event following BCR-ABL ? Tim Brümmendorf Posted onOctober 8, 2021 12:55 pm
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Live feed is not working.Posted onOctober 8, 2021 11:40 am
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****** Symposium ************Posted onOctober 8, 2021 11:11 am
Thank you for the nice and valuable presentations!Posted onOctober 8, 2021 10:41 am
Samuel (Addis Ababa University, Ethiopia), What is your view with regard to HLA of host and heterogeneity of mutation accumulation? do you think some potential "neogenetics" has impact? Thank youPosted onOctober 8, 2021 10:21 am
Amazing and lovely. Gianantonio Rosti Posted onOctober 8, 2021 10:21 am
Not a question Just wanted to thank you for this wonderful lecture and for your work and that of your team You deserve this price Kind regards Delphine Rea and Franck NicoliniPosted onOctober 8, 2021 10:20 am
Does the F359V mutation confer resistance to asciminib, and if so , what is the mechanism?Posted onOctober 8, 2021 10:19 am
************* Janet Rowley ************* Posted onOctober 8, 2021 9:56 am
Thank you Valeria for your response. I think it still would be of interest to treat mice with TKIs as they might also have some direct effects on NK cells and those would be great to follow. Best regards from Satu to all great presenters and chair!Posted onOctober 8, 2021 9:48 am
Could I ask questions about MDSC, are they BCR-ABL positive and if yes Gr or M-MDSC? Thank you! How they interract with different types of T regs?Posted onOctober 8, 2021 9:46 am
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Q from Kasia Piwocka to Virginia: Have you compared the Treg activity and level together with immunosupression in your mouse model at the stage of blastic phase not early chronic phase?Posted onOctober 8, 2021 9:30 am
Question to Valeriya: Thank you for nice presentation. In your mouse model, have you treated them with TKIs and followed what happens during therapy to NK cell phenotype and function? How does the leukemia microenvironment change during the treatment and in remission? Question by Satu Mustjoki, Finland Posted onOctober 8, 2021 9:18 am
Question for Valeriya Kuznetsove: Could we induce production of NK cells in human body to increase the number of cell that are able to find and destroy metastatic cancer cells?Posted onOctober 8, 2021 9:12 am
Question for Julian Swalter: Is it possible that in vessicle are transported some factors important for Leukemia development?Posted onOctober 8, 2021 9:10 am
Did you observed maybe the role of T reg and also NK cells in leukemia development?Posted onOctober 8, 2021 8:59 am
Thank you Dominik for a terrific talk!Posted onOctober 8, 2021 8:52 am
Tim Hughes Australia Great talk! What is driving the inflammatory response at diagnosis seen on some patients but not others? More aggressive disease? patient specific factors?Posted onOctober 8, 2021 8:49 am
TKI's are being explored in treatment of autoimmune diseases including refractory ITP. What are the clinical results so far?Posted onOctober 8, 2021 8:48 am
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Do you seen an opening for any immune-based therapeutic approaches in patients who already doing very well with TKIs, e.g. in MMR/DMR? Tiong Ong, Singapore.Posted onOctober 8, 2021 8:45 am
Mhairi Copland, UK. Do you think there may be a inflammatory protein signature within the bone marrow microenvironment that will be predictive for successful TFR? Posted onOctober 8, 2021 8:44 am
Thank you Dominik for great presentation. What do you think of antigen specific immune responses in CML; how important are for example LAA specific T cells in comparison to NK cells or other cell types? (Satu Mustjoki, Finland)Posted onOctober 8, 2021 8:43 am
What about immun-senescence - how is that inked to TKI and inflammation? NK cell anergy or senescence in particular? Posted onOctober 8, 2021 8:43 am
can you elude to the various potential roles IFN alpha may have in this context given its past and present applications in treatment? Christoph Klade, AustriaPosted onOctober 8, 2021 8:41 am
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Update treatment options for a child with CML living in developing country, the patient is now in chronic phase, being treated with imatinib. Dr.ferdousi begum, NICRH, Bangladesh.Posted onOctober 8, 2021 5:45 am
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Question is already answered - Mike Deininger Posted onOctober 7, 2021 4:57 pm
For Catherine Smith, How are you planning to add the patient specific primers into the single cell seq system? Do you need to order special barcoding reagents from the supplier company?Posted onOctober 7, 2021 4:56 pm
Did you check simultaneously cell signaling, metabolism, presence of CD, and genetic alterations i the same cells? I think that what we see in cells that is a sume of several pathways, and even one difference could lead to unspecific changesPosted onOctober 7, 2021 4:56 pm
Great work Catherine: How do you estimate the false negative rate for BCR-ABL1 expression? Adam Mead struggled with this a lot. Have you tried to include junction-specific fusion (DNA) primers? Mike Deininger, Milwaukee, USPosted onOctober 7, 2021 4:52 pm
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Ahmed from Glasgow, UK Do you think the effect of TNT is specific to HS5 cells? Posted onOctober 7, 2021 4:36 pm
For Wei Liu: do you see differences in expression of cytokine receptors? Is the reduction in cycling cells LSCs after TKI exposure related to an intrinsic signal or to non-response to an extrinsic signal? Mike DPosted onOctober 7, 2021 4:34 pm
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Question to Prof. Naka: How we can explain FL function and involvement with cellular metabolism?Posted onOctober 7, 2021 4:29 pm
(Perrotti, Baltimore MD) question for W. Liu: if your data indicate that MYC and its signature are highly expressed in quiescent LSCs, how do you fit your data with the knowledge that MYC is an inducer of G1/S cell cycle progression as it induces cyclin Ds, CDK6 and E2F1/3, and with the fact that work from different groups indicate that Cyclin D and CDK6 are down regulated and essential for normal and CML LSC quiescence?Posted onOctober 7, 2021 4:28 pm
Ahmed from Dr Helgason, Glasgow, UK For Prof Ravi For complete free remission of CML through targeting stromal cells, Do you think CML will be affected in terms of homing to bone marrow and may infiltrate into CNS? Posted onOctober 7, 2021 4:22 pm
How would modifying the Gdpd3 expression affect pathways unrelated to CML? Posted onOctober 7, 2021 4:21 pm
Vignir (Glasgow): Q for Piotr: Q1:Does mitochondrial respiration (oxygen consumption rate) chance in the stromal cells when co-cultured with CML cells? Q2: Can you inhibit oxygen consumption rate in CML cells in the co-culture by inhibiting tunneling nanotubes? Posted onOctober 7, 2021 4:08 pm
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Great work. Just confirm that p53 is relatively low in quiescent LSCs, and further downregulated by TKIs - Mike Deininger/Milwaukee/USPosted onOctober 7, 2021 3:55 pm
What was the reason, why some LSC cells was cycling, and some other Go. Is it possible to make upcycling cells to become cycling? Posted onOctober 7, 2021 3:50 pm
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Vignir (Glasgow) Are c-Kit low less metabolically active? Do they have lower ROS?Posted onOctober 7, 2021 3:39 pm
Could we add all necessary factors to stem cells cultures to study development of these cells. do we know currently which factors are important? If factors are known, how we can say that these results are similar to present in the human body? Posted onOctober 7, 2021 3:38 pm
The importance of the vasculature in CML has been suggested. In your studies, have you evaluated if there are alteration in the CML endothelium?Posted onOctober 7, 2021 3:34 pm
Great talk. What's the relative proportion of KITlow LSCs and is there a large variation across different newly dx pts? Mike Deininger, Milwaukee, USPosted onOctober 7, 2021 3:33 pm
Samuel (Addis Ababa, Ethiopia), Your view on host hormonal effect on microenvironment of LSC? Thank you for your comprehenive presentation. Posted onOctober 7, 2021 3:32 pm
outside of discovery research - is there a routine role for DNA based PCR in the monitoring of patients in TFR. Sean Young - vancouverPosted onOctober 7, 2021 3:32 pm
************** session 2 *********Posted onOctober 7, 2021 3:19 pm
To what extent would metabolite from Leukemia cell affect itself (auto-modification)? Posted onOctober 7, 2021 3:09 pm
Do you think altered metabolism is the cause or consequence of LSC? Therefore, can the strategy of inhibiting metabolism be a method to just stop leukemia development or eradicate LSC? Thanks. Shaowei. BirminghamPosted onOctober 7, 2021 3:07 pm
... and by the way: Tessa would have loved Craig Jordan's talk !!! Tim BrümmendorfPosted onOctober 7, 2021 3:01 pm
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How important is 5-aza in the triple etoxomir/venetoclax/5-aza regimen? Especially in pts who have failed a 5-aza containing regimen? Mike Deininger/Milwaukee/USPosted onOctober 7, 2021 2:58 pm
@Craig Jordan: Super talk ! Have you had a chance to check whether Azazytidine potentially inhibits FA oxidation and thereby sensitizes relapse AML cells to Venetoclax ? Tim BrümmendorfPosted onOctober 7, 2021 2:58 pm
Have you got maybe some data confirming that all drugs could interact with many different targets leading to cell signaling, changes in metabolism, or as you show also changes in energy (if caused changes on mitochondria)?Posted onOctober 7, 2021 2:56 pm
Peter van Galen, Boston, USA (repeating question): when treating with azacytidine + venetoclax, do the drugs target different cancer cell populations or synergize to target LSCs?Posted onOctober 7, 2021 2:55 pm
Vignir (Glasgow). Q1: Is the effect of Venetoclax on Oxphos independent on it's effect on Bax/Bak activation on mitochondria and cytochrome C release? Q2: Do you think CML stem cells are different from AML stem cells in terms of their ability to cope with ROS?Posted onOctober 7, 2021 2:55 pm
When treating with venetoclax and azacytidine, do the drugs target different tumor cell populations or synergize in LSCs?Posted onOctober 7, 2021 2:54 pm
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Ahmed (Glasgow, UK) Do you think inhibiting CaSR in AML may lead to infeltiration into CNS due to loss of homing to BM?Posted onOctober 7, 2021 2:35 pm
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Danilo Perrotti (Baltimore, MD USA) question for Martha: Is modulation of SHIN1 and AMPK altering BCR-ABL1 expression and activity in CD34+ CML and/or K562 cells? Posted onOctober 7, 2021 2:28 pm
Some reported data have shown that combining TKI with asciminib is effective against mutant forms of BCR-ABL1 in CML and Ph+ALL, my question is that if there is any interest in combinational therapy with TKI and asciminib for TKI-resistant CML in clinics and even in clinical trials for developing such novel therapeutic strategies?Posted onOctober 7, 2021 2:26 pm
For Dr. Copland: Our practice has been to treat lymphoid BP with an ALL regimen. Based on you data, would you advocate for Flag-Ida irrespective of immunophenotype? Mike Deininger/Milwaukee/USPosted onOctober 7, 2021 2:23 pm
Question for Martha M. Zarou, From- Rahul Kumar, Frankfurt Germany Thank you for the talk, very interesting data. Stroma is a contributor to leukemia chemoresistance. Did you try your double inhibition experiment, with Imatinib, in a co-culture system with stroma cells? and can you comment if 1 carbon inhibition could also affect the stromal population? Posted onOctober 7, 2021 2:23 pm
Could you see some differences in disease development in CML patients affected with covid virus? Posted onOctober 7, 2021 2:17 pm
Vignir (Glasgow). Question for Raquel: Do you know if intracellular concentration (i.e. in endoplasmic reticulum) of Ca2 is different in CML and AML cells? Posted onOctober 7, 2021 2:15 pm
For Dr. Pereira: please speculate on the differential function of CaSR in CML vs. AML. Also I missed which AML model(s) you used for the in vivo experiments. - Mike Deininger/MilwaukeePosted onOctober 7, 2021 2:13 pm
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@Katia Pagnano: were the access death in AP/BC patients really due to COVID19 or CML ? Tim BrümmendorfPosted onOctober 7, 2021 2:09 pm
For Ms Copeland. What were the TI/TIi variants identified in your cohort? Would any predict response to open or compassionate access to alternative treatment (eg IDH1/2). Sean Young - Vancouver, canadaPosted onOctober 7, 2021 2:06 pm
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is there experience in AP/BC with T315I mutation treatment with combining asciminib and ponatinib?Posted onOctober 7, 2021 1:48 pm
Jeroen Janssen Amsterdam: was ponatinib continued during chemo and conditioning regimen? Posted onOctober 7, 2021 1:46 pm
Tim Hughes Australia. Question for Mhairi: Great study. I wasn't clear about what determined whether patients received a second cycle of ponatinib plus chemotherapy.Posted onOctober 7, 2021 1:46 pm
The clinical behavior of a de novo or progressive blast crisis, in our experience is different and it may not be necessary in the first place, to perform a transplant if there is an adequate response to chemotherapy + TKI in the de novo BC. M. Ayala MexPosted onOctober 7, 2021 1:46 pm
@Mhairi Copland: great presentation ! Would you recommed only one cycle of PON-FLAG_IDA now before allo based on your results ? Thanks Tim BrümmendorfPosted onOctober 7, 2021 1:45 pm
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Tim Hughes Australia: For Johan Richter: it's really surprising that duration of MR4 has lost its pre-eminence as a predictor of TFR success. TKI duration is now the only variable that matters with longer follow up. Do you have an explanation?Posted onOctober 7, 2021 1:30 pm
Out of the total death on the study how many were CML related? Posted onOctober 7, 2021 1:19 pm
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what happens to the 5-10 % of patients who went on TFR and needed to restart treatment and did not regain the molecular response level they had before stoping?Posted onOctober 7, 2021 1:13 pm
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Superb talk, Catriona, congratuklations !!! Have you been able to check telomere length in the astronaut longitudinally ? Are telomeres elongated as a result of telomerase activation or vice versa, is telomerase activation a result of accelerated telomere shortening happening in space ? Tim BrümmendorfPosted onOctober 7, 2021 12:49 pm
Do you have any idea on how ADAR1 activates Beta catenin?Posted onOctober 7, 2021 12:48 pm
Can activation induced cytidine deaminase (AID) have also a role in leukemia stem cell development in CML? Akif Selim Yavuz Istanbul, TurkeyPosted onOctober 7, 2021 12:47 pm
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samia menif tunisiaPosted onOctober 7, 2021 8:41 am
What time are you going to start? Dr Hamid Al-Jamal (Malaysia)Posted onOctober 7, 2021 8:10 am
test1Posted onOctober 6, 2021 5:33 pm
helloPosted onOctober 6, 2021 4:32 pm
live generalPosted onOctober 6, 2021 4:32 pm
hiPosted onOctober 6, 2021 4:08 pm
testing123Posted onOctober 6, 2021 2:12 pm