CML – Prospects for the 21st century

CML – Prospects for the 21st century

Mandelieu, France, 27-30 September 2007

Organisers: Angelo M. Carella, Jorge Cortes, George Daley, John M. Goldman,

Francois Guilhot, Rüdiger Hehlmann, Junia Melo, Giuseppe Saglio

DRAFT PROGRAM 11-08-07

Friday, 28 September

08.30 – 08.35 Welcome John Goldman and Angelo Carella

08.35 – 10.30 Session 1 Basic studies / Mechanisms

Chair: Alan Gewirtz

Keynote: O Hantschel (Vienna) (20)

The Bcr-Abl molecular machine as the target for imatinib/dasatinib/nilotinib

NCP Cross (Salisbury) (10)

New recurrent abnormalities in BCR-ABL negative CML

C Eaves (Vancouver) (10)

Unique features of chronic phase CML stem cells

T Holyoake (Glasgow) (10)

Inducing apoptosis of CML stem cells

F Frassoni (Genoa) (10)

Impact of imatinib on leukemic stem cell burden in CML patients

A Turhan (Poitiers) (10)

STAT3 activation in CML

Discussion

11.00- 13.00 Session 2 Animal Models

Chair: Barney Clarkson

Keynote : R van Etten (Boston) (20)

Targeting the survival and engraftment of CML stem cells

E Passegue (San Francisco) (10)

Understanding JunB function in hematopoietic stem cell maintenance and leukemic stem cell generation

D Cilloni (Torino) (10)

BCR-ABL transgenic drosophila

Session 3 Basis and effects of Genomic Instability

Chair: Giuseppe Saglio

Keynote: T Skorski (Philadelphia) (20)

BCR/ABL kinase induces DNA damage and impairs DNA repair, cell cycle checkpoints, and apoptosis, leading to genomic instability

F Rassool (Baltimore) (10)

Error-prone repair of double strand breaks by “back-up” non homologous end-joining (NHEJ): a model for creating genomic instability in CML?

Annelie Abrahamsson (San Diego) (10)

A molecular mechanism of blastic transformation

Panel Discussion (1)

N. von Bubnoff, S. Kamel-Reid, J. Kuroda, G. Rosti, C. Preudhomme.

14.00 – 16.30 Session 4 Profiling, progression, BCR-ABL effectors

Chair: Pierre Laneuville

X Jiang (Vancouver) (10)

AHI-1, a novel signaling protein, interacts with BCR-ABL and modulates BCR-ABL transforming activity and imatinib sensitivity of primitive CML cells

P Vigneri (Catania) (10)

BCR-ABL modifies the expression and function of the IRF-5 transcription factor

JV Melo (London) (10)

Biomarkers for prognosis in CML

J Radich (Seattle) (10)

Regulation of progression and response

J Duyster (Munich) (10)

Retroviral insertional mutagenesis for identification of genes contributing to persistence of CML cells

D Perrotti (Columbus) (10)

Molecular defects responsible for progression of CML: targeting phosphatases as new and alternative therapeutic approach for imatinib/dasatinib- sensitive and -resistant Ph-positive leukemias

C Gambacorti-Passerini (Monza) (10)

Beta-catenin and Bcr/Abl: a dangerous liaison

T Brummendorf (Hamburg) (10)

Identification of novel targets for BCR-ABL by proteomics

Discussion

17.00 - 18.30 Session 5 Imatinib updated (molecular, clinical toxicity)

Chair: Steve O’Brien

Keynote: C Schiffer (20)

TKIs: What problems remain?

F Guilhot (Poitiers) (10)

Does imatinib really increase survival of patients in previously untreated chronic phase:

a comprehensive review of large phase III trials

M Molimard (Bordeaux) (10)

Through plasma imatinib concentrations are associated with responses to imatinib in CML and improve the standard management

A. Quintas-Cardama (Houston) (10)

High dose imatinib - still an option?

J Reiffers (Bordeaux) 10)

Dose escalation for CML-CP patients with suboptimal response or resistance to imatinib

A Reiter (Mannheim) (10)

Tyrosine kinase inhibition in eosinophilia-associated myeloproliferative disorders

F-X Mahon (10)

Imatinib mesylate discontinuation in patients with CML in complete molecular remission: an update

Panel Discussion (2) – What are the challenges today?

J. Kaeda, L. Foroni, E. Jabbour, Ph. Rousselot, J.J. Cornelissen

Saturday, 29 September

08.00–10.00 Session 6 Mechanisms of resistance

Chair: Junia Melo

Keynote: M. Deininger (Portland) (20)

Combinatorial kinase inhibitor strategies to eliminate mutation-based drug resistance in BCR-ABL-positive leukemia

M Azam (Boston) (10)

Mechanism of action of various drug-resistant forms of BCR/ABL

S. Soverini (Bologna) (10)

Resistance to tyrosine kinase inhibitors: mutations ... and more?

F. Nicolini (Lyon) (10)

Retrospective analysis of T315I KD mutations and future therapeutic options

G. Martinelli (Bologna) (10)

New mechanisms of resistance in Ph+ leukemia and new drugs to overcome it

Discussion

10.30 – 12.30 Session 7 How to predict response to imatinib and then monitor patients?

Chair: Richard Stone

Keynote: T. Hughes (Adelaide) (20)

Predictive tests for imatinib response

RE Clark (Liverpool) (10)

Drug transporters as a critical determinant of the efficacy of imatinib and other TKI

G Saglio (Torino) (10)

Molecular monitoring of CML patients undergoing imatinib therapy: evidence and shadows

JM Goldman (London) (10)

Interpreting transcript levels

Panel Discussion (3) - What issues are still important?

F. Cervantes, D. Marin, T. Mughal, G. Ossenkoppele, B. Simonsson, JL. Steegmann, J. Tanzer

14.00 - 16.00 Session 8 - Second generation tyrosine kinase inhibitors

Chair: Rüdiger Hehlmann

Keynote: N Shah (Los Angeles) (20)

Improving molecular treatment using dasatinib as a single agent or in combination TKI therapy

J Cortes (Houston) (10)

Nilotinib

S. Kimura (Kyoto) (10)

INNO-406, a Bcr-Abl/Lyn inhibitor from bench to clinic

J. Cortes (Houston) (10)

Bosutinib (SKI-606): the new kid on the block

F Cervantes (10)

Complications associated with newer TKIs

A. Quintas Cardama (Houston) (10)

Next generation agents for resistant CML, including MK-0457

Ph Rousselot (Paris) (10)

TKI plus chemotherapy for blastic phase CML and Ph-positive acute leukemia

Discussion

16.30–18.30 Session 9 Immunological aspects of stem cell transplantation

Chair: Alois Gratwohl

A Fefer (Seattle) (10)

Syngeneic BMT for CML in chronic phase: an update of the Seattle data

JF Apperley (London) (10)

Syngeneic transplants – EBMT data

C Crawley (Cambridge, UK) (10)

Reduced intensity or myeloablative transplants?

AM Carella (Genoa) (10)

RIC SCT for older patients

A Devergie (Paris) (10)

Treating CML in relapse after allo-SCT with imatinib

Panel Discussion: SCT in 2007 (40)

Opening presentation: A Gratwohl (10)

Risk adapted strategies for SCT

Panel members:
A Gratwohl, R Hehlmann, F Guilhot, J Apperley, C Crawley, AM Carella, JGoldman

Conference Gala Dinner

Sunday 30 September

8.30-10.00 Session 10 - Immune targets for CML

Chair: Richard Clark

Keynote : F. Dazzi (London) (20)

Exploiting GvL without transplant

D Smith (Baltimore) (10)

Vaccination with K562/GM-CSF

M Bocchia (Sienna) (10)

Bcr-Abl peptide vaccination - an update

K Rezvani (London) (10)

WT1/Pr3 peptide vaccination for leukemia

Panel Discussion

Dazzi, Bocchia, Clark, Saglio, Smith, Rezvani, others.

10.00- 10.30 Coffee

10.30 – 11.45 Session 11 - Future initiatives

Chair: J Goldman

M Baccarani (15)

Defining response and failure - 2007

NCP Cross (Salisbury) (15)

Standardization of RQ-PCR

SG O’Brien (Newcastle) (15)

Future of prospective clinical studies

R Hehlmann (Mannheim) (15)

Leukemia-Net – Prospects for the next 5 years

11.45 – 12.00 Concluding remarks (J Goldman)