Nouveau! Un pot-pourri d’articles sur la LMC

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Nouveau! Un pot-pourri d’articles sur la LMC - New! A pot-pourri of articles about CML

Vous avez trouvé des nouveaux articles sur la LMC et ses traitements. Il n’est pas nécessaire de les classer. Il est important cependant de spécifier le titre, l’auteur et la date. Seules les articles en français ou en anglais sont acceptables pour la compréhension de la majorité des lecteurs.

You've found some new articles on CML and its treatment. It is not necessary to classify them. It is important however to specify the title, author and date. Only articles in French or English are acceptable to the understanding of most readers.

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Nilotinib versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia
Giuseppe Saglio, M.D., Dong-Wook Kim, M.D., Ph.D., Surapol Issaragrisil, M.D., Philipp le Coutre, M.D., Gabriel Etienne, M.D., Clarisse Lobo, M.D., Ricardo Pasquini, M.D., Richard E. Clark, M.D., Andreas Hochhaus, M.D., Timothy P. Hughes, M.D., M.B., B.S., Neil Gallagher, M.D., Ph.D., Albert Hoenekopp, M.D., Mei Dong, M.D., Ariful Haque, M.S., Richard A. Larson, M.D., Hagop M. Kantarjian, M.D
The New England Journal of Medecine, June 5, 2010
http://content.nejm.org/cgi/content/full/NEJMoa0912614

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Dasatinib versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia
Hagop Kantarjian, M.D., Neil P. Shah, M.D., Ph.D., Andreas Hochhaus, M.D., Jorge Cortes, M.D., Sandip Shah, M.D., Manuel Ayala, M.D., Beatriz Moiraghi, M.D., Zhixiang Shen, M.D., Jiri Mayer, M.D., Ricardo Pasquini, M.D., Hirohisa Nakamae, M.D., Ph.D., Françoise Huguet, M.D., Concepción Boqué, M.D., Charles Chuah, M.R.C.P., M.D., Eric Bleickardt, M.D., M. Brigid Bradley-Garelik, M.D., Chao Zhu, Ph.D., Ted Szatrowski, M.D., David Shapiro, M.D., and Michele Baccarani, M.D.
M.D., Hagop M. Kantarjian, M.D.,
The New England Journal of Medecine, June 5, 2010
http://content.nejm.org/cgi/content/full/NEJMoa1002315

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Two Drugs Appear to Surpass Landmark Novartis Leukemia Treatment
By PETER LOFTUS , The Wall Street Journal. June 6, 2010
''CHICAGO—Novartis AG's Gleevec is one of the closest things to a miracle drug to come out of the battle against cancer in recent years. But new research suggests two newer drugs are even more effective for the form of leukemia whose treatment Gleevec has transformed.
In separate studies published Saturday, Bristol-Myers Squibb Co.'s Sprycel and Novartis's Tasigna each were superior to Gleevec in treating people with newly diagnosed chronic myeloid leukemia. The two newer drugs are currently approved to treat patients whose disease persisted after trying Gleevec. ''
Extrait de http://online.wsj.com/article/SB1000142 ... TWhatsNews

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Dasatinib compared to imatinib (IM) in patients (pts) with newly diagnosed chronic-phase chronic myelogenous leukemia in chronic phase (CML-CP): Twelve-month efficacy and safety from the phase III DASISION study.
June 7, 2010
Author(s): H. Kantarjian, N. P. Shah, A. Hochhaus, J. E. Cortes, S. Shah, M. Ayala, B. Moiraghi, M. Bradley-Garelik, C. Zhu, M. Baccarani; University of Texas M. D. Anderson Cancer Center, Houston, TX; University of California, San Francisco, San Francisco, CA; Universitätsklinikum Jena, Jena, Germany; Vedanta Institute of Medical Sciences, Ahmedabad, India; Institututo Mexicano del Seguro Social, Mexico City, Mexico; Hospital General De Agudos J. M. Ramos Mejia, Buenos Aires, Argentina; Bristol-Myers Squibb, Wallingford, CT; University of Bologna Istituto di Ematologia, Bologna, Italy

'Abstract:
Background: Dasatinib is a highly potent BCR-ABL kinase inhibitor. Once daily dasatinib demonstrated high rates of durable complete cytogenetic response (CCyR) with 73% progression-free survival and 87% overall survival at 3 yrs in pts with CML-CP post IM failure. DASISION compares efficacy and safety of dasatinib and IM as initial treatment of CML-CP. Methods: 519 pts with Ph(+) newly diagnosed CML-CP stratified by Hasford risk were randomized to dasatinib 100 mg QD (n = 259) or IM 400 mg QD (n = 260). The primary endpoint was 12-mo rate of confirmed CCyR (cCCyR; CCyR on 2 consecutive analyses; any # of metaphases). Other endpoints were rates of and times to CCyR and major molecular response (MMR). Results: Pts characteristics were well balanced. Minimum follow-up was 12 mos; median treatment duration was 14 mos. 85% of dasatinib and 81% of IM pts remained on study. Median dose intensity was 99 mg/d for dasatinib and 400 mg/d for IM. cCCyR rate was superior for dasatinib vs IM (77% vs 66%, P = 0.0067). 12-mo CCyR and MMR rates (Table) were higher for dasatinib vs IM (CCyR: 83% vs 72%; MMR: 46% vs. 28%). MMR was obtained significantly faster with dasatinib (HR 2.0, P < 0.0001) as was CCyR (HR 1.5, P < 0.0001). Rates of transformation to AP/BC were 1.9% for dasatinib and 3.5% for IM. Grade 3/4 anemia (10% vs 7%) and neutropenia (21% vs 20%) were similar across arms; thrombocytopenia was more common for dasatinib (19% vs. 10%). Non-hematologic adverse drug reactions (all grades) in ?10% of pts (dasatinib vs. IM) were fluid retention (19% vs 42%; including pleural effusion, all grade 1 or 2, 10% vs. 0%), nausea (8% vs. 20%), vomiting (5% vs. 10%), myalgia (6% vs.12%), muscle inflammation (4% vs. 17%) and rash (11% vs. 17%). Conclusions: Dasatinib showed significantly higher and faster rates of CCyR and MMR vs IM. Given the predictive value of 12-mo CCyR and MMR and the favorable tolerability of dasatinib, dasatinib may improve long-term outcomes in pts with newly diagnosed CML-CP. '

Extrait de http://abstract.asco.org/AbstView_74_50536.html

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In search of the original leukemic clone in chronic myeloid leukemia patients in complete molecular remission after stem cell transplantation or imatinib
Manuel Sobrinho-Simões, Vicki Wilczek, Joannah Score, Nicholas C. P. Cross, Jane F. Apperley and Junia V. Melo
Blood First Edition Paper, prepublished online May 12, 2010; DOI 10.1182/blood-2009-11-255109.
Abstract
It is not clear if absence of BCR-ABL transcripts - complete molecular response (CMR) - is synonymous with, or required for, cure of chronic myeloid leukemia (CML). Some patients achieve CMR with imatinib (IM), but most relapse shortly after treatment discontinuation. Furthermore, most patients in long-term remission (LTR) post stem cell transplantation (SCT) are considered 'functionally cured', although some remain occasionally positive for low level BCR-ABL mRNA. Interpretation of the latter is complicated since it has been observed in healthy individuals. We designed a patient-specific, highly sensitive, DNA quantitative PCR to test follow-up samples for the original leukemic clone, identified by its unique genomic BCR-ABL fusion (gBCR-ABL). In 5 IM-treated patients in CMR, gBCR-ABL was detected in transcript-negative samples; 4 patients became gBCR-ABL-negative with continuing IM therapy. In contrast, out of 9 patients in LTR (13-27 years) post-SCT, gBCR-ABL was detected in only 1, despite occasional transcript-positive samples in 8 of them. In conclusion, in IM-treated patients, absence of transcripts should not be interpreted as absence of the leukemic clone, although continuing IM after achievement of CMR may lead to further reduction of residual disease. Post-SCT, we found little evidence that the transcripts occasionally detected originate from the leukemic clone
http://bloodjournal.hematologylibrary.o ... type=HWCIT

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Chromosome abnormalities additional to the Philadelphia chromosome at the diagnosis of chronic myelogenous leukemia: pathogenetic and prognostic implications.
Zaccaria A, Testoni N, Valenti AM, Luatti S, Tonelli M, Marzocchi G, Cipriani R, Baldazzi C, Giannini B, Stacchini M, Gamberini C, Castagnetti F, Rosti G, Azzena A, Cavazzini F, Cianciulli AM, Dalsass A, Donti E, Giugliano E, Gozzetti A, Grimoldi MG, Ronconi S, Santoro A, Spedicato F, Zanatta L, Baccarani M; GIMEMA Working Party on CML.
Cancer Genetics and Cytogenetics, Volume 199, Issue 2, Pages 76-80 (June 2010)
Abstract
'Additional chromosome abnormalities (ACAs) occur in less than 10% of cases at diagnosis of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). In some cases, on the basis of the persistence of the ACAs in Ph-negative cells after response to imatinib, a secondary origin of the Ph chromosome has been demonstrated. In this study, the possible prognostic value of this phenomenon was evaluated. Thirty-six Ph-positive CML patients were included in the study. In six patients, ACAs persisted after the disappearance of the Ph. A complete cytogenetic response (CCR) was obtained in five of these six patients, and five of six also had a high Sokal score. In all the other cases, ACAs disappeared together (in cases of response to therapy with imatinib) or persisted with the Ph (in cases of no response to imatinib). In the former cases, the primary origin of the Ph was demonstrated. CCR was obtained in 22 cases (17 with low to intermediate Sokal scores), while no response was observed in 8 patients (5 with a high Sokal score). Sokal score seems to maintain its prognostic value for patients in whom the Ph occurs as a primary event, but not in those in whom it occurs as a secondary one.'

Extrait de http://www.cancergeneticsjournal.org/ar ... 9/abstract

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Successful treatment using omacetaxine for a patient with CML and BCR-ABL2 35INS
Kris M. Mahadeo and Peter D. Cole
Blood, 6 May 2010, Vol. 115, No. 18, pp. 3852.
http://bloodjournal.hematologylibrary.o ... 15/18/3852

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Even Better Kinase Inhibitors for Chronic Myeloid Leukemia
Charles L. Sawyers, M.D.
The New England Journal of Medecine, June 5, 2010
http://content.nejm.org/cgi/content/ful ... 0?query=OF

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La chimiothérapie ciblée
INFOCANCER - Mise à jour 5 juin 2010
http://www.arcagy.org/infocancer/locali ... iblee.html

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UK patient group makes case for CML drugs Sprycel and Tasigna given initial “thumbs down” by the NICE
Thepharmaletter - 24 February 2010
‘Following the latest draft guidance from the UK’s National Institute for Health and Clinical Excellence (NICE) on drugs for the treatment of chronic myeloid leukemia, which took a somewhat negative, cost-related, stance on the use of Novartis’ Tasigna (nilotinib) and Bristol-Myers Squibb’s Sprycel (dasatinib) for use under the National Health Service in patients who are intolerant to Glivec (imatinib), also from Novartis (The Pharma Letter February 9), the patient group, the Chronic Myeloid Leukemia Support group, has put up a strong argument for the two drugs’
Extrait de http://www.thepharmaletter.com/file/918 ... -nice.html

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New Discoveries in CML Treatment
http://www.everydayhealth.com/cancer/we ... ipt-1.aspx

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Preliminary studies show cancer vaccine may reduce tumor cells in CML patients
8. January 2010
http://www.news-medical.net/news/201001 ... ients.aspx

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BioSante says small leukemia vaccine trial successful
by Rita Uplend on March 11, 2010
http://vaccinenewsdaily.com/news/212336 ... successful

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Contact Persons in Project 4: Chronic myeloblastic leukemia (CML)
The European LeukemiaNet is an EU-funded organisation of physicians, scientists and patients with interest in leukemia. It aims to improve the treatment and knowledge about Leukemia in Europe and spread excellence. The website delivers information for physicians, patients (e.g. patient organisations in Europe), ongoing clinical trials and further information about the disease. You can get information about the European LeukemiaNet in various european languages. The European LeukemiaNet is funded by the 6th Framework Program of the European Community.
http://www.leukemia-net.org/content/leu ... l/contact/

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Research Highlights
Nature Reports Stem Cells
Published online: 5 February 2009 |
Self-renewing blood and leukaemia cells need hedgehog
http://www.nature.com/stemcells/2009/09 ... 09.26.html

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Initial treatment for patients with CML
John M. Goldman, Hematology 2009
'For adult patients who present with chronic myeloid leukemia (CML) in chronic phase it is now generally agreed that initial treatment should start with the tyrosine kinase inhibitor (TKI) imatinib at 400 mg daily. Five years after starting imatinib about 60% of these patients will be in complete cytogenetic response (CCyR), still taking imatinib; an appreciable proportion of these will have achieved a major molecular response, defined as a 3-log reduction in the level of BCR-ABL1 transcripts in their blood. The patients in CCyR seem to have a very low risk of relapse to chronic phase or of progression to advanced phase. Other patients may be resistant to imatinib or may experience significant side effects that require change of therapy. The best method of monitoring responding patients is to enumerate Philadelphia chromosome–positive marrow metaphases at 3-month intervals until CCyR and to perform RQ-PCR for BCR-ABL1 transcripts at 3-month intervals after starting imatinib. The recommendations for defining "failure" and "sub-optimal response" proposed by the European LeukemiaNet in 2006 have proved to be a major contribution to assessing responses in individual patients and are now being updated. Patients who fail imatinib may respond to second-generation TKIs, but allogeneic stem cell transplantation still plays an important role for eligible patients who fare badly with TKIs. Patients who present in advanced phases of CML should be treated initially with TKI alone or with TKI in conjunction with cytotoxic drugs, but their overall prognosis is likely to be much inferior to that of those presenting in early chronic phase. '
http://asheducationbook.hematologylibra ... 2009/1/453

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BioSante says small leukemia vaccine trial successful
by Rita Uplend on March 11, 2010
'LINCOLNSHIRE, Ill. — BioSante Pharmaceuticals Inc. on March 11 announced positive results of a human clinical study that show that its GVAX leukemia vaccine may be able to reduce or eliminate the last remaining cancer cells in some chronic myeloid leukemia patients taking the drug Gleevec (imatinib mesylate).'
http://vaccinenewsdaily.com/news/212336 ... successful

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Au cours des prochaines années...
La LMC en 2020 : un regard sur l'avenir
La revue Source, 10 mai 2010
http://cmlsource.ca/fr/reportages/233-i ... rs-to-come

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L'anti-cancéreux Sprycel plus efficace que le Gleevec contre la leucémie
La Chaîne Santé - 06/06/2010
'L'anti-cancéreux Sprycel serait plus efficace que le Gleevec, traitement actuel de choix, contre la leucémie myéloïde chronique (LMC), forme rare de cancer du sang et de la moelle osseuse, selon les résultats d'un essai clinique publiés samedi.'
http://femmes.fr.msn.com/sante/article. ... =153668362

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Cancer : les pilules de la controverse De nouveaux médicaments contre le cancer prolongent l’espérance de vie… au prix fort. Le Québec a-t-il seulement les moyens de payer la note ?
Octobre 2010, Revue l’Actualité, Québec
http://www.lactualite.com/sante/cancer- ... page=0%2C0
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Les chiffres du cancer aux Etats-Unis ; estimations pour l’année 2010
Septembre 2010, Revue de Presse, France Hemato
http://www.france-hemato.net/?ze=2&zg=2 ... &spec=mato
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Interview de François-Xavier Mahon (Bordeaux) - LMC : vers de plus en plus de guérisons...
Juin 2010, EHA (European Hematology Association), Barcelone
http://www.edimark.fr/ejournaux/eha2010 ... php?id=383
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