120 results on '"Dulucq, S."'
Search Results
2. Standardization of molecular monitoring of CML : results and recommendations from the European treatment and outcome study
- Author
-
White HE, Salmon M, Albano F, Andersen CSA, Balabanov S, Balatzenko G, Barbany G, Cayuela JM, Cerveira N, Cochaux P, Colomer D, Coriu D, Diamond J, Dietz C, Dulucq S, Engvall M, Franke GN, Gineikiene-Valentine E, Gniot M, Gómez-Casares MT, Gottardi E, Hayden C, Hayette S, Hedblom A, Ilea A, Izzo B, Jiménez-Velasco A, Jurcek T, Kairisto V, Langabeer SE, Lion T, Meggyesi N, Mešanović S, Mihok L, Mitterbauer-Hohendanner G, Moeckel S, Naumann N, Nibourel O, Oppliger Leibundgut E, Panayiotidis P, Podgornik H, Pott C, Rapado I, Rose SJ, Schäfer V, Touloumenidou T, Veigaard C, Venniker-Punt B, Venturi C, Vigneri P, Vorkinn I, Wilkinson E, Zadro R, Zawada M, Zizkova H, Müller MC, Saussele S, Ernst T, Machova Polakova K, Hochhaus A, Cross NCPa 62, Andreas Hochhaus 52, Nicholas C P Cross, White, He, Salmon, M, Albano, F, Andersen, Csa, Balabanov, S, Balatzenko, G, Barbany, G, Cayuela, Jm, Cerveira, N, Cochaux, P, Colomer, D, Coriu, D, Diamond, J, Dietz, C, Dulucq, S, Engvall, M, Franke, Gn, Gineikiene-Valentine, E, Gniot, M, Gómez-Casares, Mt, Gottardi, E, Hayden, C, Hayette, S, Hedblom, A, Ilea, A, Izzo, B, Jiménez-Velasco, A, Jurcek, T, Kairisto, V, Langabeer, Se, Lion, T, Meggyesi, N, Mešanović, S, Mihok, L, Mitterbauer-Hohendanner, G, Moeckel, S, Naumann, N, Nibourel, O, Oppliger Leibundgut, E, Panayiotidis, P, Podgornik, H, Pott, C, Rapado, I, Rose, Sj, Schäfer, V, Touloumenidou, T, Veigaard, C, Venniker-Punt, B, Venturi, C, Vigneri, P, Vorkinn, I, Wilkinson, E, Zadro, R, Zawada, M, Zizkova, H, Müller, Mc, Saussele, S, Ernst, T, Machova Polakova, K, Hochhaus, A, Cross NCPa, 62, Andreas Hochhaus, 52, and Nicholas C, P Cross
- Subjects
Cancer Research ,Cancer och onkologi ,Fatigue Syndrome, Chronic ,Fusion Proteins, bcr-abl ,610 Medicine & health ,Hematology ,Reference Standards ,Treatment Outcome ,Oncology ,hemic and lymphatic diseases ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Cancer and Oncology ,Humans ,Hematologi - Abstract
Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1IS and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.
- Published
- 2022
3. S157: BCR::ABL1 DIGITAL PCR IDENTIFIES CHRONIC PHASE CML PATIENTS SUITABLE FOR AN EARLY TKI DISCONTINUATION ATTEMPT: A PATIENT-LEVEL META-ANALYSIS
- Author
-
Kockerols, C., primary, Dulucq, S., additional, Bernardi, S., additional, Farina, M., additional, Civettini, I., additional, Colafigli, G., additional, Mori, S., additional, Valk, P., additional, Mahon, F.-X., additional, Gambacorti-Passerini, C., additional, Nicolini, F.-E., additional, Breccia, M., additional, Russo, D., additional, and Westerweel, P. E., additional
- Published
- 2022
- Full Text
- View/download PDF
4. Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia
- Author
-
Cross, N CP, White, H E, Colomer, D, Ehrencrona, H, Foroni, L, Gottardi, E, Lange, T, Lion, T, Polakova, K Machova, Dulucq, S, Martinelli, G, Leibundgut, E Oppliger, Pallisgaard, N, Barbany, G, Sacha, T, Talmaci, R, Izzo, B, Saglio, G, Pane, F, Müller, M C, and Hochhaus, A
- Published
- 2015
- Full Text
- View/download PDF
5. A certified plasmid reference material for the standardisation of BCR-ABL1 mRNA quantification by real-time quantitative PCR
- Author
-
White, H, Deprez, L, Corbisier, P, Hall, V, Lin, F, Mazoua, S, Trapmann, S, Aggerholm, A, Andrikovics, H, Akiki, S, Barbany, G, Boeckx, N, Bench, A, Catherwood, M, Cayuela, J-M, Chudleigh, S, Clench, T, Colomer, D, Daraio, F, Dulucq, S, Farrugia, J, Fletcher, L, Foroni, L, Ganderton, R, Gerrard, G, Gineikiene, E, Hayette, S, El Housni, H, Izzo, B, Jansson, M, Johnels, P, Jurcek, T, Kairisto, V, Kizilors, A, Kim, D-W, Lange, T, Lion, T, Polakova, K M, Martinelli, G, McCarron, S, Merle, P A, Milner, B, Mitterbauer-Hohendanner, G, Nagar, M, Nickless, G, Nomdedéu, J, Nymoen, D A, Leibundgut, E O, Ozbek, U, Pajic, T, Pfeifer, H, Preudhomme, C, Raudsepp, K, Romeo, G, Sacha, T, Talmaci, R, Touloumenidou, T, Van der Velden, V HJ, Waits, P, Wang, L, Wilkinson, E, Wilson, G, Wren, D, Zadro, R, Ziermann, J, Zoi, K, Müller, M C, Hochhaus, A, Schimmel, H, Cross, N CP, and Emons, H
- Published
- 2015
- Full Text
- View/download PDF
6. From in vitro to in vivo: intracellular determination of imatinib and nilotinib may be related with clinical outcome
- Author
-
Bouchet, S, Dulucq, S, Pasquet, J-M, Lagarde, V, Molimard, M, and Mahon, F-X
- Published
- 2013
- Full Text
- View/download PDF
7. Combining several polymorphisms of thymidylate synthase gene for pharmacogenetic analysis
- Author
-
Krajinovic, M, Costea, I, Primeau, M, Dulucq, S, and Moghrabi, A
- Published
- 2005
- Full Text
- View/download PDF
8. Combinatorial properties of smooth infinite words
- Author
-
Brlek, S., Dulucq, S., Ladouceur, A., and Vuillon, L.
- Published
- 2006
- Full Text
- View/download PDF
9. Analyse de l’impact budgétaire de l’arrêt des inhibiteurs de la tyrosine kinase chez les patients atteints de leucémie myéloïde chronique en rémission moléculaire profonde et durable
- Author
-
Astrugue, C., primary, Mahon, F.-X., additional, Dulucq, S., additional, Bosco-Lévy, P., additional, Yon, E., additional, Lassalle, R., additional, Droz, C., additional, Hayes, N., additional, and Bénard, A., additional
- Published
- 2018
- Full Text
- View/download PDF
10. Colourings of planar maps and the equality of two languages
- Author
-
Cori, R., Dulucq, S., Goos, G., editor, Hartmanis, J., editor, Barstow, D., editor, Brauer, W., editor, Brinch Hansen, P., editor, Gries, D., editor, Luckham, D., editor, Moler, C., editor, Pnueli, A., editor, Seegmüller, G., editor, Stoer, J., editor, Wirth, N., editor, and Franchi-Zannettacci, Paul, editor
- Published
- 1986
- Full Text
- View/download PDF
11. Development and evaluation of a secondary reference panel for BCR-ABL1 quantification on the International Scale
- Author
-
Cross, N.C.P. White, H.E. Ernst, T. Welden, L. Dietz, C. Saglio, G. Mahon, F.-X. Wong, C.C. Zheng, D. Wong, S. Wang, S.-S. Akiki, S. Albano, F. Andrikovics, H. Anwar, J. Balatzenko, G. Bendit, I. Beveridge, J. Boeckx, N. Cerveira, N. Cheng, S.-M. Colomer, D. Czurda, S. Daraio, F. Dulucq, S. Eggen, L. El Housni, H. Gerrard, G. Gniot, M. Izzo, B. Jacquin, D. Janssen, J.J.W.M. Jeromin, S. Jurcek, T. Kim, D.-W. Machova-Polakova, K. Martinez-Lopez, J. McBean, M. Mesanovic, S. Mitterbauer-Hohendanner, G. Mobtaker, H. Mozziconacci, M.-J. Pajič, T. Pallisgaard, N. Panagiotidis, P. Press, R.D. Qin, Y.-Z. Radich, J. Sacha, T. Touloumenidou, T. Waits, P. Wilkinson, E. Zadro, R. Müller, M.C. Hochhaus, A. Branford, S.
- Subjects
hemic and lymphatic diseases - Abstract
Molecular monitoring of chronic myeloid leukemia patients using robust BCR-ABL1 tests standardized to the International Scale (IS) is key to proper disease management, especially when treatment cessation is considered. Most laboratories currently use a time-consuming sample exchange process with reference laboratories for IS calibration. A World Health Organization (WHO) BCR-ABL1 reference panel was developed (MR 1 -MR 4), but access to the material is limited. In this study, we describe the development of the first cell-based secondary reference panel that is traceable to and faithfully replicates the WHO panel, with an additional MR 4.5 level. The secondary panel was calibrated to IS using digital PCR with ABL1, BCR and GUSB as reference genes and evaluated by 44 laboratories worldwide. Interestingly, we found that >40% of BCR-ABL1 assays showed signs of inadequate optimization such as poor linearity and suboptimal PCR efficiency. Nonetheless, when optimized sample inputs were used, >60% demonstrated satisfactory IS accuracy, precision and/or MR 4.5 sensitivity, and 58% obtained IS conversion factors from the secondary reference concordant with their current values. Correlation analysis indicated no significant alterations in %BCR-ABL1 results caused by different assay configurations. More assays achieved good precision and/or sensitivity than IS accuracy, indicating the need for better IS calibration mechanisms. © 2016 Macmillan Publishers Limited, part of Springer Nature.
- Published
- 2016
12. Pièges de la mesure de la saturation de l’hémoglobine en oxygène : à propos d’un cas de désaturation chronique
- Author
-
Eguienta, S., Martigne, L., Dulucq, S., and Fayon, M.
- Published
- 2015
- Full Text
- View/download PDF
13. Présentation atypique d’un lymphome pédiatrique : hypermétabolisme ostéo-médullaire isolé en TEP/TDM au 18F-FDG
- Author
-
Schollhammer, R., primary, Meyer, M., additional, De Clermont, H., additional, Aladjidi, N., additional, Parrens, M.C., additional, Dulucq, S., additional, Jubert, C., additional, Tiphaine, A., additional, Perel, Y., additional, and Fernandez, P., additional
- Published
- 2017
- Full Text
- View/download PDF
14. Development and evaluation of a secondary reference panel for BCR-ABL1 quantification on the International Scale
- Author
-
Cross, N C P, primary, White, H E, additional, Ernst, T, additional, Welden, L, additional, Dietz, C, additional, Saglio, G, additional, Mahon, F-X, additional, Wong, C C, additional, Zheng, D, additional, Wong, S, additional, Wang, S-S, additional, Akiki, S, additional, Albano, F, additional, Andrikovics, H, additional, Anwar, J, additional, Balatzenko, G, additional, Bendit, I, additional, Beveridge, J, additional, Boeckx, N, additional, Cerveira, N, additional, Cheng, S-M, additional, Colomer, D, additional, Czurda, S, additional, Daraio, F, additional, Dulucq, S, additional, Eggen, L, additional, El Housni, H, additional, Gerrard, G, additional, Gniot, M, additional, Izzo, B, additional, Jacquin, D, additional, Janssen, J J W M, additional, Jeromin, S, additional, Jurcek, T, additional, Kim, D-W, additional, Machova-Polakova, K, additional, Martinez-Lopez, J, additional, McBean, M, additional, Mesanovic, S, additional, Mitterbauer-Hohendanner, G, additional, Mobtaker, H, additional, Mozziconacci, M-J, additional, Pajič, T, additional, Pallisgaard, N, additional, Panagiotidis, P, additional, Press, R D, additional, Qin, Y-Z, additional, Radich, J, additional, Sacha, T, additional, Touloumenidou, T, additional, Waits, P, additional, Wilkinson, E, additional, Zadro, R, additional, Müller, M C, additional, Hochhaus, A, additional, and Branford, S, additional
- Published
- 2016
- Full Text
- View/download PDF
15. Colourings of planar maps and the equality of two languages
- Author
-
Cori, R., primary and Dulucq, S., additional
- Full Text
- View/download PDF
16. A certified plasmid reference material for the standardisation of BCR–ABL1 mRNA quantification by real-time quantitative PCR
- Author
-
White, H, primary, Deprez, L, additional, Corbisier, P, additional, Hall, V, additional, Lin, F, additional, Mazoua, S, additional, Trapmann, S, additional, Aggerholm, A, additional, Andrikovics, H, additional, Akiki, S, additional, Barbany, G, additional, Boeckx, N, additional, Bench, A, additional, Catherwood, M, additional, Cayuela, J-M, additional, Chudleigh, S, additional, Clench, T, additional, Colomer, D, additional, Daraio, F, additional, Dulucq, S, additional, Farrugia, J, additional, Fletcher, L, additional, Foroni, L, additional, Ganderton, R, additional, Gerrard, G, additional, Gineikienė, E, additional, Hayette, S, additional, El Housni, H, additional, Izzo, B, additional, Jansson, M, additional, Johnels, P, additional, Jurcek, T, additional, Kairisto, V, additional, Kizilors, A, additional, Kim, D-W, additional, Lange, T, additional, Lion, T, additional, Polakova, K M, additional, Martinelli, G, additional, McCarron, S, additional, Merle, P A, additional, Milner, B, additional, Mitterbauer-Hohendanner, G, additional, Nagar, M, additional, Nickless, G, additional, Nomdedéu, J, additional, Nymoen, D A, additional, Leibundgut, E O, additional, Ozbek, U, additional, Pajič, T, additional, Pfeifer, H, additional, Preudhomme, C, additional, Raudsepp, K, additional, Romeo, G, additional, Sacha, T, additional, Talmaci, R, additional, Touloumenidou, T, additional, Van der Velden, V H J, additional, Waits, P, additional, Wang, L, additional, Wilkinson, E, additional, Wilson, G, additional, Wren, D, additional, Zadro, R, additional, Ziermann, J, additional, Zoi, K, additional, Müller, M C, additional, Hochhaus, A, additional, Schimmel, H, additional, Cross, N C P, additional, and Emons, H, additional
- Published
- 2014
- Full Text
- View/download PDF
17. Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib front-line therapy
- Author
-
Etienne, G., primary, Dulucq, S., additional, Nicolini, F.-E., additional, Morisset, S., additional, Fort, M.-P., additional, Schmitt, A., additional, Etienne, M., additional, Hayette, S., additional, Lippert, E., additional, Bureau, C., additional, Tigaud, I., additional, Adiko, D., additional, Marit, G., additional, Reiffers, J., additional, and Mahon, F.-X., additional
- Published
- 2013
- Full Text
- View/download PDF
18. Paroxysmal nocturnal hemoglobinuria and pregnancy before the eculizumab era: the French experience
- Author
-
de Guibert, S., primary, Peffault de Latour, R., additional, Varoqueaux, N., additional, Labussiere, H., additional, Rio, B., additional, Jaulmes, D., additional, Eveillard, J.-R., additional, Dulucq, S., additional, Stoppa, A.-M., additional, Bouscary, D., additional, Girodon, F., additional, Bonnotte, B., additional, Laskri, D., additional, Socie, G., additional, and Lamy, T., additional
- Published
- 2011
- Full Text
- View/download PDF
19. Persistence of complete molecular remission in chronic myeloid leukemia after imatinib discontinuation: Interim analysis of the STIM trial
- Author
-
Mahon FX, F., primary, Rea, D., additional, Guilhot, F., additional, Legros, L., additional, Guilhot, J., additional, Aton, E., additional, Dulucq, S., additional, Reiffers, J., additional, and Rousselot, P., additional
- Published
- 2009
- Full Text
- View/download PDF
20. A combinatorial proof of J. West's conjecture
- Author
-
Dulucq, S., primary, Gire, S., additional, and Guibert, O., additional
- Published
- 1998
- Full Text
- View/download PDF
21. Baxter permutations
- Author
-
Dulucq, S., primary and Guibert, O., additional
- Published
- 1998
- Full Text
- View/download PDF
22. Stack words, standard tableaux and Baxter permutations
- Author
-
Dulucq, S., primary and Guibert, O., additional
- Published
- 1996
- Full Text
- View/download PDF
23. Permutations with forbidden subsequences and nonseparable planar maps
- Author
-
Dulucq, S., primary, Gire, S., additional, and West, J., additional
- Published
- 1996
- Full Text
- View/download PDF
24. Complexité d'algorithmes et opérations sur les arbres
- Author
-
Dulucq, S, primary and Gire, S, additional
- Published
- 1993
- Full Text
- View/download PDF
25. Sur les facteurs des suites de sturm
- Author
-
Dulucq, S, primary and Gouyou-Beauchamps, D, additional
- Published
- 1990
- Full Text
- View/download PDF
26. A certified plasmid reference material for the standardisation of BCR-ABL1 mRNA quantification by real-time quantitative PCR
- Author
-
Van Der Velden, V H J, Cayuela, J-M, McCarron, S, Sacha, T, Fletcher, L, Ziermann, J, Müller, M C, Schimmel, H, El Housni, H, White, H, Farrugia, J, Boeckx, N, Romeo, G, Johnels, P, Zoi, K, Chudleigh, S, Lion, T, Kairisto, V, Deprez, L, Ganderton, R, Merle, P A, Dulucq, S, Pajič, T, Gerrard, G, Martinelli, G, Trapmann, S, Hall, V, Nagar, M, Colomer, D, Hochhaus, A, Kizilors, A, Mitterbauer-Hohendanner, G, Talmaci, R, Gineikienė, E, Oppliger Leibundgut, Elisabeth, Mazoua, S, Cross, N C P, Milner, B, Zadro, R, Lin, F, Foroni, L, Waits, P, Kim, D-W, Nickless, G, Jansson, M, Pfeifer, H, Wilson, G, Raudsepp, K, Clench, T, Daraio, F, Preudhomme, C, Wang, L, Emons, H, Bench, A, Nomdedéu, J, Wilkinson, E, Hayette, S, Jurcek, T, Aggerholm, A, Izzo, B, Lange, T, Akiki, S, Andrikovics, H, Polakova, K M, Corbisier, P, Ozbek, U, Nymoen, D A, Wren, D, Barbany, G, Catherwood, M, and Touloumenidou, T
- Subjects
hemic and lymphatic diseases ,610 Medicine & health ,3. Good health - Abstract
Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 10(6), 1.08±0.11 × 10(5), 1.03±0.10 × 10(4), 1.02±0.09 × 10(3), 1.04±0.10 × 10(2) and 10.0±1.5 copies/μl. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR-ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR-ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/; CRM code ERM-AD623a-f).
27. Cordes, arbres et permutations
- Author
-
Dulucq, S. and Penaud, J.-G.
- Published
- 1993
- Full Text
- View/download PDF
28. La correspondance de Robinson-Schensted pour les tableaux oscillants gauches
- Author
-
Dulucq, S. and Sagan, B. E.
- Published
- 1995
- Full Text
- View/download PDF
29. Development and evaluation of a secondary reference panel for BCR-ABL1 quantification on the International Scale
- Author
-
T. Pajič, J. Anwar, J. Beveridge, T Touloumenidou, Dolors Colomer, P. Waits, Tomáš Jurček, S. Czurda, Andreas Hochhaus, L. Welden, Israel Bendit, M J Mozziconacci, Jeroen Janssen, Tomasz Sacha, Francesco Albano, Dong-Kee Kim, M. Gniot, Jerry Radich, D. Zheng, E. Wilkinson, L. Eggen, Christian Dietz, S. M. Cheng, K. Machova-Polakova, S. Wong, Martin C. Müller, Gareth Gerrard, Stéphanie Dulucq, Nuno Cerveira, H El Housni, Barbara Izzo, Francois-Xavier Mahon, Filomena Daraio, Helen E. White, G. Mitterbauer-Hohendanner, D. Jacquin, Susanna Akiki, G. Balatzenko, Renata Zadro, Susan Branford, Niels Pallisgaard, Nicholas C.P. Cross, Ya-Zhen Qin, S. Jeromin, H. Mobtaker, M. McBean, S. S. Wang, S. Mesanovic, Panagiotis Panagiotidis, Wong Connie C, Nancy Boeckx, Richard D. Press, Thomas Ernst, Hajnalka Andrikovics, Joaquin Martinez-Lopez, Giuseppe Saglio, Cross, NCP, White, HE, Ernst, T, Welden, L, Branford, Susan, Cancer Center Amsterdam, Hematology, CCA - Biomarkers, Cross, N. C. P, White, H. E, Dietz, C, Saglio, G, Mahon, F. X, Wong, C. C, Zheng, D, Wong, S, Wang, S. S, Akiki, S, Albano, F, Andrikovics, H, Anwar, J, Balatzenko, G, Bendit, I, Beveridge, J, Boeckx, N, Cerveira, N, Cheng, S. M, Colomer, D, Czurda, S, Daraio, F, Dulucq, S, Eggen, L, El Housni, H, Gerrard, G, Gniot, M, Izzo, Barbara, Jacquin, D, Janssen, J. J. W. M, Jeromin, S, Jurcek, T, Kim, D. W, Machova Polakova, K, Martinez Lopez, J, Mcbean, M, Mesanovic, S, Mitterbauer Hohendanner, G, Mobtaker, H, Mozziconacci, M. J, Pajič, T, Pallisgaard, N, Panagiotidis, P, Press, R. D, Qin, Y. Z, Radich, J, Sacha, T, Touloumenidou, T, Waits, P, Wilkinson, E, Zadro, R, Müller, M. C, Hochhaus, A, and Branford, S.
- Subjects
0301 basic medicine ,Cancer Research ,International scale ,bcr-abl ,Fusion Proteins, bcr-abl ,Genes, abl ,Bioinformatics ,World Health Organization ,Polymerase Chain Reaction ,World health ,Anesthésiologie ,03 medical and health sciences ,Bcr abl1 ,0302 clinical medicine ,Reference genes ,hemic and lymphatic diseases ,Statistics ,Calibration ,Secondary reference ,Medicine ,Humans ,Digital polymerase chain reaction ,business.industry ,Proto-Oncogene Proteins c-bcr ,Reference Standards ,Hematology ,Oncology ,abl ,leukemia ,Fusion Proteins ,BCR-ABL1 tests ,Cancérologie ,030104 developmental biology ,Genes ,molecular monitoring ,030220 oncology & carcinogenesis ,Correlation analysis ,Original Article ,business ,Hématologie - Abstract
Molecular monitoring of chronic myeloid leukemia patients using robust BCR-ABL1 tests standardized to the International Scale (IS) is key to proper disease management, especially when treatment cessation is considered. Most laboratories currently use a time-consuming sample exchange process with reference laboratories for IS calibration. A World Health Organization (WHO) BCR-ABL1 reference panel was developed (MR 1 -MR 4), but access to the material is limited. In this study, we describe the development of the first cell-based secondary reference panel that is traceable to and faithfully replicates the WHO panel, with an additional MR 4.5 level. The secondary panel was calibrated to IS using digital PCR with ABL1, BCR and GUSB as reference genes and evaluated by 44 laboratories worldwide. Interestingly, we found that >40% of BCR-ABL1 assays showed signs of inadequate optimization such as poor linearity and suboptimal PCR efficiency. Nonetheless, when optimized sample inputs were used, >60% demonstrated satisfactory IS accuracy, precision and/or MR 4.5 sensitivity, and 58% obtained IS conversion factors from the secondary reference concordant with their current values. Correlation analysis indicated no significant alterations in %BCR-ABL1 results caused by different assay configurations. More assays achieved good precision and/or sensitivity than IS accuracy, indicating the need for better IS calibration mechanisms., 0, SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2016
30. A certified plasmid reference material for the standardisation of BCR-ABL1 mRNA quantification by real-time quantitative PCR
- Author
-
J M Cayuela, BJ Milner, Stéphane Mazoua, Elisabeth Oppliger Leibundgut, Linda Fletcher, Heike Pfeifer, Tomáš Jurček, E Gineikienė, P. Waits, Susanna Akiki, G Wilson, J Farrugia, H El Housni, Ugur Ozbek, D Wren, F. Lin, Tomasz Sacha, Hajnalka Andrikovics, S Chudleigh, Letizia Foroni, Stefanie Trapmann, Petra Johnels, Gareth Gerrard, Thomas Lion, M. Jansson, Katerina Zoi, Hendrik Emons, K. Raudsepp, Gisela Barbany, D A Nymoen, H Schimmel, J Ziermann, Nancy Boeckx, Mark Catherwood, Sandrine Hayette, G Romeo, Helen E. White, R Ganderton, Filomena Daraio, G. Mitterbauer-Hohendanner, Philippe Corbisier, Claude Preudhomme, Andreas Hochhaus, Martin C. Müller, P A Merle, V H J van der Velden, M Nagar, Victoria J. Hall, Lihui Wang, Theis Lange, Tim Clench, T Pajič, Stéphanie Dulucq, D-W Kim, Nicholas C.P. Cross, Josep F. Nomdedeu, Rodica Talmaci, Kateřina Machová Poláková, A Bench, Liesbet Deprez, T Touloumenidou, G Nickless, Veli Kairisto, Barbara Izzo, Dolors Colomer, Aytug Kizilors, Giovanni Martinelli, Renata Zadro, Anni Aggerholm, S McCarron, E Wilkinson, Hematology, CCA - Disease profiling, White, H, Deprez, L, Corbisier, P, Hall, V, Lin, F, Mazoua, S, Trapmann, S, Aggerholm, A, Andrikovics, H, Akiki, S, Barbany, G, Boeckx, N, Bench, A, Catherwood, M, Cayuela, Jm, Chudleigh, S, Clench, T, Colomer, D, Daraio, F, Dulucq, S, Farrugia, J, Fletcher, L, Foroni, L, Ganderton, R, Gerrard, G, Gineikienė, E, Hayette, S, El Housni, H, Izzo, Barbara, Jansson, M, Johnels, P, Jurcek, T, Kairisto, V, Kizilors, A, Kim, Dw, Lange, T, Lion, T, Polakova, Km, Martinelli, G, Mccarron, S, Merle, Pa, Milner, B, Mitterbauer Hohendanner, G, Nagar, M, Nickless, G, Nomdedéu, J, Nymoen, Da, Leibundgut, Eo, Ozbek, U, Pajič, T, Pfeifer, H, Preudhomme, C, Raudsepp, K, Romeo, G, Sacha, T, Talmaci, R, Touloumenidou, T, Van der Velden, Vh, Waits, P, Wang, L, Wilkinson, E, Wilson, G, Wren, D, Zadro, R, Ziermann, J, Zoi, K, Müller, Mc, Hochhaus, A, Schimmel, H, Cross, Nc, Emons, H., Immunology, Radiology & Nuclear Medicine, Izzo, B, and Mitterbauer-Hohendanner, G
- Subjects
EMTREE drug terms: plasmid DNA EMTREE medical terms: Article ,Cancer Research ,Fusion Proteins, bcr-abl ,Gene Dosage ,Membrane Transport Protein ,Plasmid ,RECOMMENDATIONS ,real time quantitative polymerase chain reaction ,K562 cell line ,law.invention ,law ,hemic and lymphatic diseases ,Escherichia coli Protein ,CANCER PROGRAM ,Digital polymerase chain reaction ,Cloning, Molecular ,Polymerase chain reaction ,MOLECULAR RESPONSE ,Medicine (all) ,Escherichia coli Proteins ,copy number variation ,breakpoint cluster region ,gene control ,Hematology ,Reference Standards ,gusb gene ,3. Good health ,Real-time polymerase chain reaction ,Certified reference materials ,priority journal ,Oncology ,real time polymerase chain reaction ,Calibration ,Proto-Oncogene Proteins c-bcr ,Original Article ,Life Sciences & Biomedicine ,Medical Genetics ,Plasmids ,EUROPE ,POLYMERASE-CHAIN-REACTION ,610 Medicine & health ,Biology ,Real-Time Polymerase Chain Reaction ,IMATINIB ,Gene dosage ,Anesthésiologie ,chronic myeloid leukemia ,TRANSCRIPTS ,TYROSINE KINASE INHIBITORS ,bcr abl gene ,Humans ,controlled study ,human ,ddc:610 ,RNA, Messenger ,CHRONIC MYELOID-LEUKEMIA ,gene ,certified plasmid reference material ,bcr-abl1 ,Medicinsk genetik ,freeze thawing ,Messenger RNA ,Science & Technology ,human cell ,reference value ,Membrane Transport Proteins ,HL 60 cell line ,DNA ,ta3122 ,Molecular biology ,Cancérologie ,Anesthesiology and Pain Medicine ,certified reference material ,minimal residual disease ,Reference Standard ,Hématologie - Abstract
Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 10 6, 1.08±0.11 × 10 5, 1.03±0.10 × 10 4, 1.02±0.09 × 10 3, 1.04±0.10 × 10 2 and 10.0±1.5 copies/μl. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR-ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR-ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/; CRM code ERM-AD623a-f)., 0, SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2015
31. Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia
- Author
-
Thoralf Lange, K Machova Polakova, Enrico Gottardi, Tomasz Sacha, Nicholas C.P. Cross, Stéphanie Dulucq, Hans Ehrencrona, Fabrizio Pane, Letizia Foroni, Gisela Barbany, Rodica Talmaci, E. Oppliger Leibundgut, Andreas Hochhaus, Helen E. White, Martin C. Müller, Niels Pallisgaard, Barbara Izzo, Dolors Colomer, Giuseppe Saglio, Giovanni Martinelli, Thomas Lion, Cross, N C P, White, H E, Colomer, D, Ehrencrona, H, Foroni, L, Gottardi, E, Lange, T, Lion, T, Machova Polakova, K, Dulucq, S, Martinelli, G, Oppliger Leibundgut, E, Pallisgaard, N, Barbany, G, Sacha, T, Talmaci, R, Izzo, B, Saglio, G, Pane, F, Müller, M C, Hochhaus, A, Bristol Myers Squibb, N. C. P., Cro, H., White, D., Colomer, H., Ehrencrona, L., Foroni, E., Gottardi, T., Lange, T., Lion, K. M., Polakova, S., Dulucq, G., Martinelli, E. O., Leibundgut, N., Pallisgaard, G., Barbany, T., Sacha, R., Talmaci, Izzo, Barbara, G., Saglio, Pane, Fabrizio, M. C., Muller, and A., Hochhaus
- Subjects
Oncology ,Cancer Research ,bcr-abl ,Fusion Proteins, bcr-abl ,Disease ,Review ,Bioinformatics ,Polymerase Chain Reaction ,Limit of Detection ,hemic and lymphatic diseases ,Protein-Tyrosine Kinase ,CANCER PROGRAM ,Chronic ,610 Medicine & health ,MINIMAL RESIDUAL DISEASE POLYMERASE-CHAIN-REACTION HARMONIZING CURRENT METHODOLOGY CHRONIC MYELOGENOUS LEUKEMIA BCR-ABL TRANSCRIPTS INTERNATIONAL SCALE CANCER PROGRAM PCR IMATINIB STANDARDIZATION ,Leukemic ,Leukemia ,Hematology ,Gene Expression Regulation, Leukemic ,HARMONIZING CURRENT METHODOLOGY ,CHRONIC MYELOGENOUS LEUKEMIA ,Myeloid leukemia ,Protein-Tyrosine Kinases ,BCR-ABL TRANSCRIPTS ,Europe ,PCR ,Treatment Outcome ,Calibration ,Life Sciences & Biomedicine ,medicine.drug ,Human ,medicine.medical_specialty ,POLYMERASE-CHAIN-REACTION ,Immunology ,MINIMAL RESIDUAL DISEASE ,Reproducibility of Result ,IMATINIB ,Myelogenous ,chronic myeloid leukemia ,Internal medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,medicine ,Humans ,Science & Technology ,INTERNATIONAL SCALE ,business.industry ,Gene Expression Profiling ,Fusion Proteins ,Reproducibility of Results ,Genetic Variation ,1103 Clinical Sciences ,Imatinib ,STANDARDIZATION ,medicine.disease ,Minimal residual disease ,Anesthesiology and Pain Medicine ,Gene Expression Regulation ,Cancer and Oncology ,BCR-ABL Positive ,business ,1112 Oncology And Carcinogenesis ,Chronic myelogenous leukemia - Abstract
Treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors has advanced to a stage where many patients achieve very low or undetectable levels of disease. Remarkably, some of these patients remain in sustained remission when treatment is withdrawn, suggesting that they may be at least operationally cured of their disease. Accurate definition of deep molecular responses (MRs) is therefore increasingly important for optimal patient management and comparison of independent data sets. We previously published proposals for broad standardized definitions of MR at different levels of sensitivity. Here we present detailed laboratory recommendations, developed as part of the European Treatment and Outcome Study for CML (EUTOS), to enable testing laboratories to score MR in a reproducible manner for CML patients expressing the most common BCR-ABL1 variants.Leukemia advance online publication, 27 February 2015; doi:10.1038/leu.2015.29.
- Published
- 2015
32. Mémoires coloniales
- Author
-
Christine Deslaurier, Aurélie Roger, Dulucq, S. (dir.), Klein, J.F. (dir.), Stora, B. (dir.), Deslaurier, Christine, Dulucq S., Klein J.F. et Stora B., Intervention publique, espaces, sociétés, Centre de Recherche sur les Pouvoirs Locaux dans la Caraibe (CRPLC), and Université des Antilles et de la Guyane (UAG)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
SYSTEME DE REPRESENTATIONS ,LIEU DE MEMOIRE ,[SHS.HIST] Humanities and Social Sciences/History ,HISTOIRE COLONIALE ,[SHS.HIST]Humanities and Social Sciences/History ,LEXIQUE THEMATIQUE ,MEMOIRE COLLECTIVE ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
33. European Stop Tyrosine Kinase Inhibitor Trial (EURO-SKI) in Chronic Myeloid Leukemia: Final Analysis and Novel Prognostic Factors for Treatment-Free Remission.
- Author
-
Mahon FX, Pfirrmann M, Dulucq S, Hochhaus A, Panayiotidis P, Almeida A, Mayer J, Hjorth-Hansen H, Janssen JJWM, Mustjoki S, Martinez-Lopez J, Vestergaard H, Ehrencrona H, Machová Poláková K, Olsson-Strömberg U, Ossenkoppele G, Berger MG, Etienne G, Dengler J, Brümmendorf TH, Burchert A, Réa D, Rousselot P, Nicolini FE, Hofmann WK, Richter J, and Saussele S
- Subjects
- Humans, Female, Middle Aged, Male, Adult, Aged, Prognosis, Imatinib Mesylate therapeutic use, Fusion Proteins, bcr-abl genetics, Fusion Proteins, bcr-abl antagonists & inhibitors, Pyrimidines therapeutic use, Europe, Young Adult, Aged, 80 and over, Treatment Outcome, Tyrosine Kinase Inhibitors, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Protein Kinase Inhibitors therapeutic use, Remission Induction
- Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The European Stop Kinase Inhibitors (EURO-SKI) study is the largest clinical trial for investigating the cessation of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia in stable deep molecular remission (DMR). Among 728 patients, 434 patients (61%; 95% CI, 57 to 64) remained in major molecular response (MMR) at 6 months and 309 patients of 678 (46%; 95% CI, 42 to 49) at 36 months. Duration of TKI treatment and DMR before TKI stop were confirmed as significant factors for the prediction of MMR loss at 6 months. In addition, the type of BCR::ABL1 transcript was identified as a prognostic factor. For late MMR losses after 6 months, TKI treatment duration, percentage of blasts in peripheral blood, and platelet count at diagnosis were significant factors in multivariate analysis. For the entire study period of 36 months, multiple logistic regression models confirmed duration of treatment, blasts, and transcript type as independent factors for MMR maintenance. In addition to the duration of treatment, transcript type as well as blasts in peripheral blood at diagnosis should be considered as important factors to predict treatment-free remission.
- Published
- 2024
- Full Text
- View/download PDF
34. BCR::ABL1 digital PCR for treatment-free remission prediction in chronic myeloid leukemia patients: An individual participant data meta-analysis.
- Author
-
Kockerols C, Valk PJM, Dulucq S, Nicolini FE, Mahon FX, Atallah E, Mauro MJ, Radich JP, Bernardi S, Russo D, Farina M, Mori S, Gambacorti-Passerini C, Civettini I, Lu L, Yeung D, Branford S, Colafigli G, Breccia M, Hogenbirk P, van Rosmalen J, Cornelissen JJ, and Westerweel PE
- Subjects
- Humans, Polymerase Chain Reaction methods, Male, Female, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Fusion Proteins, bcr-abl genetics, Remission Induction
- Published
- 2024
- Full Text
- View/download PDF
35. Kinetics of molecular recurrence after tyrosine kinase inhibitor cessation in chronic phase chronic myelogenous leukaemia patients.
- Author
-
Alcazer V, Morisset S, Rea D, Legros L, Dulucq S, Hayette S, Cayuela JM, Huguet F, Mahon FX, Etienne G, and Nicolini FE
- Subjects
- Humans, Protein Kinase Inhibitors therapeutic use, Imatinib Mesylate, Tyrosine Kinase Inhibitors, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
- Published
- 2024
- Full Text
- View/download PDF
36. Efficacy and safety of nilotinib in chronic myeloid leukaemia patients who failed to achieve a treatment-free remission period after imatinib discontinuation: Results of the French Nilo post-STIM study.
- Author
-
Dulucq S, Rigal-Huguet F, Nicolini FE, Cony-Makhoul P, Escoffre-Barbe M, Gardembas M, Legros L, Rousselot P, Liu J, Rea D, De Mas V, Hayette S, Raynaud S, Lacoste-Roussillon C, Robbesyn F, Klein E, Morisset S, Mahon FX, and Etienne G
- Subjects
- Humans, Imatinib Mesylate adverse effects, Pyrimidines adverse effects, Treatment Outcome, Protein Kinase Inhibitors adverse effects, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
- Abstract
Molecular recurrence (MRec) occurs in about half of all patients with chronic myeloid leukaemia (CML) who discontinue tyrosine kinase inhibitors (TKI) in sustained deep molecular response. A second TKI discontinuation has been attempted in some patients who regain the discontinuation criteria after resuming treatment. Nilotinib treatment affords faster and deeper molecular responses than imatinib as first-line therapy. We prospectively evaluated the efficacy and safety of nilotinib (300 mg twice daily) in chronic-phase CML patients who experienced MRec, after imatinib discontinuation and analysed the probability of TFR after a new attempt in patients treated for 2 years with sustained MR
4.5 for at least 1 year. A total of 31 patients were included in the study between 2013 and 2018. Seven (23%) patients experienced serious adverse events after a median of 2 months of nilotinib treatment leading to discontinuation of treatment. One patient was excluded from the study for convenience. Among the 23 patients treated for 2 years with nilotinib, 22 maintained their molecular response for at least 1 year (median: 22 months) and stopped nilotinib. The TFR rates at 24 and 48 months after nilotinib discontinuation were 59.1% (95% confidence interval [CI]: 41.7%-83.7%) and 42.1% (95% CI: 25%-71%) respectively (NCT #01774630)., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2023
- Full Text
- View/download PDF
37. Specific High-Sensitivity Enzymatic Reporter UnLOCKing-Mediated Detection of Oncogenic BCR::ABL1 and EGFR Rearrangements.
- Author
-
Cullot G, Amintas S, Karembé L, Prouzet-Mauléon V, Rébillard J, Boureau L, Cappellen D, Bedel A, Moreau-Gaudry F, Dulucq S, Dabernat S, and Turcq B
- Subjects
- Humans, Fusion Proteins, bcr-abl genetics, CRISPR-Cas Systems, Gene Editing, ErbB Receptors genetics, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms diagnosis, Lung Neoplasms genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
- Abstract
Advances in molecular medicine have placed nucleic acid detection methods at the center of an increasing number of clinical applications. Polymerase chain reaction (PCR)-based diagnostics have been widely adopted for their versatility, specificity, and sensitivity. However, recently reported clustered regularly interspaced short palindromic repeats-based methods have demonstrated equivalent to superior performance, with increased portability and reduced processing time and cost. In this study, we applied Specific High-Sensitivity Enzymatic Reporter UnLOCKing (SHERLOCK) technology to the detection of oncogenic rearrangements. We implemented SHERLOCK for the detection of BCR::ABL1 mRNA, a hallmark of chronic myeloid leukemia (CML), and EGFR DNA oncogenic alleles, frequently detected in glioblastoma and non-small cell lung cancer (NSCLC). SHERLOCK enabled rapid, sensitive, and variant-specific detection of BCR::ABL1 and EGFR alterations. Compared with the gold-standard PCR-based methods currently used in clinic, SHERLOCK achieved equivalent to greater sensitivity, suggesting it could be a new tool in CML and NSCLC, to detect low level of molecular residual disease.
- Published
- 2023
- Full Text
- View/download PDF
38. Onset of blast crisis in chronic myeloid leukemia patients in treatment-free remission.
- Author
-
Dulucq S, Hayette S, Cayuela JM, Bauduer F, Chabane K, Chevallier P, Cony-Makhoul P, Flandrin-Gresta P, Jeune CL, Bris YL, Legros L, Maisonneuve H, Roy L, Mahon FX, Sloma I, Rea D, and Nicolini FE
- Subjects
- Humans, Imatinib Mesylate, Remission Induction, Blast Crisis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
- Published
- 2022
- Full Text
- View/download PDF
39. Kinetics of early and late molecular recurrences after first-line imatinib cessation in chronic myeloid leukemia: updated results from the STIM2 trial.
- Author
-
Dulucq S, Nicolini FE, Rea D, Cony-Makhoul P, Charbonnier A, Escoffre-Barbe M, Coiteux V, Lenain P, Rigal-Huguet F, Liu J, Guerci-Bresler A, Legros L, Ianotto JC, Gardembas M, Turlure P, Dubruille V, Rousselot P, Martiniuc J, Jardel H, Johnson-Ansah H, Joly B, Henni T, Cayssials E, Zunic P, Berger MG, Villemagne B, Robbesyn F, Morisset S, Mahon FX, and Etienne G
- Subjects
- Humans, Fusion Proteins, bcr-abl genetics, Imatinib Mesylate therapeutic use, Protein Kinase Inhibitors therapeutic use, Remission Induction, Stromal Interaction Molecule 2, Treatment Outcome, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myeloid, Chronic-Phase drug therapy
- Abstract
Discontinuation of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia is feasible in clinical practice based on recently published international recommendations. Nevertheless, factors predictive of molecular recurrence have not been fully elucidated and long-term follow-up of patients enrolled in clinical studies are required in order to update knowledge on discontinuation attempts particularly in terms of the safety and durability of treatment-free remission (TFR). In the current study, we updated results from the STIM2 study in the light of the consensual criterion of molecular recurrence reported in different international recommendations. Among the 199 patients included in the perprotocol study, 108 patients lost a major molecular response. With a median follow-up of 40.8 months (5.5-111 months), the probability of treatment-free remission was 43.4% [36.3-50.4] at 5 years, 40.9% [32.8-47.3] at 7 years and 34.5% [25.6- 43.3] at 9 years. Molecular recurrence occurred between 0 to 6 months, 6 to 24 months and after 24 months in 75 patients (69%), 15 patients (14%) and 18 patients (17%), respectively. Notably, the kinetics of molecular recurrence differed significantly between these three subgroups with a median time from loss of MR4 (BCR::ABL1 IS≤0.01%) to loss of major molecular response of 1, 7 and 22 months, respectively. Predictive factors of molecular recurrence differed according to the time of occurrence of the molecular recurrence. Durations of imatinib treatment and deep molecular response as well as BCR::ABL1/ABL1 levels at cessation of tyrosine kinase inhibitor treatment, as quantified by reverse transcriptase droplet digital polymerase chain reaction, are involved in molecular recurrence occurring up to 24 months but not beyond. (ClinicalTrial. gov Identifier NCT#0134373).
- Published
- 2022
- Full Text
- View/download PDF
40. Acquired glucose 6-phosphate dehydrogenase (G6PD) deficiency in a patient with Chronic Myelomonocytic Leukemia.
- Author
-
Naville AS, Lazaro E, Boutin J, Prot-Leurent C, Mansier O, Richard E, Augis V, Weinmann L, Fuster V, Vial JP, Ged C, and Dulucq S
- Subjects
- Erythrocytes, Glucose, Glucosephosphate Dehydrogenase, Humans, Oxidoreductases, Phosphates, Glucosephosphate Dehydrogenase Deficiency complications, Glucosephosphate Dehydrogenase Deficiency genetics, Leukemia, Myelomonocytic, Chronic complications, Leukemia, Myelomonocytic, Juvenile
- Published
- 2022
- Full Text
- View/download PDF
41. Assessment of droplet digital polymerase chain reaction for measuring BCR-ABL1 in chronic myeloid leukaemia in an international interlaboratory study.
- Author
-
Scott S, Cartwright A, Francis S, Whitby L, Sanzone AP, Mulder A, Galimberti S, Dulucq S, Mauté C, Lauricella C, Salmon M, Rose S, Willoughby J, Boeckx N, Pallisgaard N, Maier J, Leibundgut EO, Zizkova H, Ling Goh L, Duong C, Tang WF, Ma E, Shivakumar Y, Beppu L, Bhagavatula P, and Chantry A
- Subjects
- Asia, Biomarkers, Tumor blood, Europe, HL-60 Cells chemistry, Humans, K562 Cells chemistry, Laboratories, Clinical, Linear Models, North America, Reagent Kits, Diagnostic, Reproducibility of Results, Fusion Proteins, bcr-abl blood, Laboratory Proficiency Testing, Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood, Reverse Transcriptase Polymerase Chain Reaction methods
- Abstract
Measurement of BCR activator of RhoGEF and GTPase -ABL proto-oncogene 1, non-receptor tyrosine kinase (BCR-ABL1) mRNA levels by reverse transcription quantitative polymerase chain reaction (RTqPCR) has been critical to treatment protocols and clinical trials in chronic myeloid leukaemia; however, interlaboratory variation remains a significant issue. Reverse transcriptase droplet digital PCR (RTddPCR) has shown potential to improve testing but a large-scale interlaboratory study is required to definitively establish this. In the present study, 10 BCR-ABL1-positive samples with levels ranging from molecular response (MR)
1·0 -MR5·0 were tested by 23 laboratories using RTddPCR with the QXDX BCR-ABL %IS kit. A subset of participants tested the samples using RTqPCR. All 23 participants using RTddPCR detected BCR-ABL1 in all samples to MR4·0 . Detection rates for deep-response samples were 95·7% at MR4·5 , 78·3% at MR4·7 and 87·0% at MR5·0 . Interlaboratory coefficient of variation was indirectly proportional to BCR-ABL1 level ranging from 29·3% to 69·0%. Linearity ranged from 0·9330 to 1·000 (average 0·9936). When results were compared for the 11 participants who performed both RTddPCR and RTqPCR, RTddPCR showed a similar limit of detection to RTqPCR with reduced interlaboratory variation and better assay linearity. The ability to detect deep responses with RTddPCR, matched with an improved linearity and reduced interlaboratory variation will allow improved patient management, and is of particular importance for future clinical trials focussed on achieving and maintaining treatment-free remission., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2021
- Full Text
- View/download PDF
42. Relevance of treatment-free remission recommendations in chronic phase chronic leukemia patients treated with frontline tyrosine kinase inhibitors.
- Author
-
Etienne G, Faberes C, Bauduer F, Adiko D, Lifermann F, Dagada C, Lenoir C, Schmitt A, Klein E, Fort MP, Bijou F, Turcq B, Robbesyn F, Durrieu F, Versmée L, Madene S, Moldovan M, Katsahian S, Charles-Nelson A, Lascaux A, Mahon FX, and Dulucq S
- Subjects
- Adult, Aged, Aged, 80 and over, Female, France, Fusion Proteins, bcr-abl analysis, Guidelines as Topic, Humans, Leukemia, Myeloid, Chronic-Phase genetics, Male, Middle Aged, Progression-Free Survival, Recurrence, Remission Induction, Young Adult, Imatinib Mesylate therapeutic use, Leukemia, Myeloid, Chronic-Phase drug therapy, Patient Selection, Protein Kinase Inhibitors therapeutic use, Withholding Treatment statistics & numerical data
- Abstract
Background: Tyrosine kinase inhibitors (TKI) can be safely discontinued in chronic phase chronic myeloid leukemia (CP-CML) patients who had achieved a sustained deep molecular response. Based on the results of discontinuation trials, recommendations regarding patient selection for a treatment-free remission (TFR) attempt had been proposed. The aims of this study were to evaluate the rate of patients eligible for TKI discontinuation and molecular recurrence-free survival (MRFS) after stop according to recommendations., Methods: Over a 10-year period, newly diagnosed CP-CML patients and treated with first-line TKI in the nine French participating centers were included. Eligibility to treatment discontinuation and MRFS were analyzed and compared according to selection criteria defined by recommendations and first-line treatments., Results: From January 2006 to December 2015, 398 patients were considered. Among them, 73% and 27% of patients received imatinib or either second or third generation tyrosine kinase inhibitors as frontline treatment, respectively. Considering the selection criteria defined by recommendations, up to 55% of the patients were selected as optimal candidates for treatment discontinuation. Overall 95/398 (24%) discontinued treatment. MRFS was 51.8% [95% CI 41.41-62.19] at 2 years and 43.8% [31.45-56.15] at 5 years. Patients receiving frontline second-generation TKI and fulfilling the eligibility criteria suggested by recommendations had the lowest probability of molecular relapse after TKI stop when compare to others., Conclusion: One third of CP-CML patients treated with TKI frontline fulfilled the selection criteria suggested by European LeukemiaNet TFR recommendations. Meeting selection criteria and second-generation TKI frontline were associated with the highest MRFS., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
43. Budget Impact of Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia With Sustained Deep Molecular Response.
- Author
-
Astrugue C, Bénard A, Bosco-Levy P, Dulucq S, Rouyer M, Lassalle R, Hayes N, and Mahon FX
- Subjects
- France, Humans, Insurance Claim Review economics, Models, Statistical, Remission Induction, Costs and Cost Analysis economics, Delivery of Health Care economics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Protein Kinase Inhibitors economics, Protein Kinase Inhibitors therapeutic use, Quality of Life psychology, Withholding Treatment economics
- Abstract
Objectives: Tyrosine kinase inhibitors (TKIs) account for the vast majority of healthcare expenditure on patients with chronic myeloid leukemia (CML), and it has been demonstrated that TKI discontinuation in patients in long-term deep molecular remission (DMR) is safe and improves quality of life. Our objective was to estimate the budget impact of TKI discontinuation in CML patients in long-term DMR from the perspective of the French healthcare system., Methods: This analysis was conducted over a 5-year time horizon using a Markov model with cycles of 6 months. Transition probabilities were estimated through systematic reviews and meta-analyses. Costs were estimated from the French National Claims Database. Monte Carlo simulations were performed to take into account the uncertainty surrounding model parameters. Sensitivity analyses were carried out by varying the size of the target population and the cost of TKIs., Results: Over a 5-year period and for a target population of 100 patients each year eligible and agreeing to stop TKI, the TKI discontinuation strategy would save €25.5 million (95% confidence interval -39.3 to 70.0). In this model, the probability that TKI discontinuation would be more expensive than TKI continuation was 12.0%. In sensitivity analyses, mean savings ranged from €14.9 million to €62.9 million., Conclusions: This study provides transparent, reproducible, and interpretable results for healthcare professionals and policy makers. Our results clearly show that innovative healthcare strategies can benefit both the healthcare system and patients. Savings from generalizing TKI discontinuation in CML patients in sustained DMR should yield health gains for other patients., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
44. Incidences of Deep Molecular Responses and Treatment-Free Remission in de Novo CP-CML Patients.
- Author
-
Etienne G, Dulucq S, Bauduer F, Adiko D, Lifermann F, Dagada C, Lenoir C, Schmitt A, Klein E, Madene S, Fort MP, Bijou F, Moldovan M, Turcq B, Robbesyn F, Durrieu F, Versmée L, Katsahian S, Faberes C, Lascaux A, and Mahon FX
- Abstract
Background: Tyrosine Kinase Inhibitors (TKIs) discontinuation in patients who had achieved a deep molecular response (DMR) offer now the opportunity of prolonged treatment-free remission (TFR). Patients and Methods: Aims of this study were to evaluate the proportion of de novo chronic-phase chronic myeloid leukemia (CP-CML) patients who achieved a sustained DMR and to identify predictive factors of DMR and molecular recurrence-free survival (MRFS) after TKI discontinuation. Results: Over a period of 10 years, 398 CP-CML patients treated with first-line TKIs were included. Median age at diagnosis was 61 years, 291 (73%) and 107 (27%) patients were treated with frontline imatinib (IMA) or second- or third-generation TKIs (2-3G TKI), respectively. With a median follow-up of seven years (range, 0.6 to 13.8 years), 182 (46%) patients achieved a sustained DMR at least 24 months. Gender, BCR-ABL1 transcript type, and Sokal and ELTS risk scores were significantly associated with a higher probability of sustained DMR while TKI first-line (IMA vs. 2-3G TKI) was not. We estimate that 28% of CML-CP would have been an optimal candidate for TKI discontinuation according to recent recommendations. Finally, 95 (24%) patients have entered in a TFR program. MRFS rates at 12 and 48 months were 55.1% (95% CI, 44.3% to 65.9%) and 46.9% (95% CI, 34.9% to 58.9%), respectively. In multivariate analyses, first-line 2-3G TKIs compared to IMA and TKI duration were the most significant factors of MRFS. Conclusions: Our results suggest that frontline TKIs have a significant impact on TFR in patients who fulfill the selection criteria for TKI discontinuation.
- Published
- 2020
- Full Text
- View/download PDF
45. Model-Based Inference and Classification of Immunologic Control Mechanisms from TKI Cessation and Dose Reduction in Patients with CML.
- Author
-
Hähnel T, Baldow C, Guilhot J, Guilhot F, Saussele S, Mustjoki S, Jilg S, Jost PJ, Dulucq S, Mahon FX, Roeder I, Fassoni AC, and Glauche I
- Subjects
- Humans, Protein Kinase Inhibitors, Recurrence, Remission Induction, Fusion Proteins, bcr-abl, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Abstract
Recent clinical findings in patients with chronic myeloid leukemia (CML) suggest that the risk of molecular recurrence after stopping tyrosine kinase inhibitor (TKI) treatment substantially depends on an individual's leukemia-specific immune response. However, it is still not possible to prospectively identify patients that will remain in treatment-free remission (TFR). Here, we used an ordinary differential equation model for CML, which explicitly includes an antileukemic immunologic effect, and applied it to 21 patients with CML for whom BCR-ABL1/ABL1 time courses had been quantified before and after TKI cessation. Immunologic control was conceptually necessary to explain TFR as observed in about half of the patients. Fitting the model simulations to data, we identified patient-specific parameters and classified patients into three different groups according to their predicted immune system configuration ("immunologic landscapes"). While one class of patients required complete CML eradication to achieve TFR, other patients were able to control residual leukemia levels after treatment cessation. Among them were a third class of patients that maintained TFR only if an optimal balance between leukemia abundance and immunologic activation was achieved before treatment cessation. Model simulations further suggested that changes in the BCR-ABL1 dynamics resulting from TKI dose reduction convey information about the patient-specific immune system and allow prediction of outcome after treatment cessation. This inference of individual immunologic configurations based on treatment alterations can also be applied to other cancer types in which the endogenous immune system supports maintenance therapy, long-term disease control, or even cure. SIGNIFICANCE: This mathematical modeling approach provides strong evidence that different immunologic configurations in patients with CML determine their response to therapy cessation and that dose reductions can help to prospectively infer different risk groups. See related commentary by Triche Jr, p. 2083 ., (©2020 American Association for Cancer Research.)
- Published
- 2020
- Full Text
- View/download PDF
46. A single center evaluation of cost savings related to treatment-free remission in chronic myeloid leukemia patients: the prerequisites of a pharmaco-economy larger study.
- Author
-
Etienne G, Dulucq S, Faberes C, Bijou F, Schmitt A, Klein E, Fort MP, Durrieu F, Toulza E, and Mahon FX
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Male, Middle Aged, Cost Savings methods, Leukemia, Myelogenous, Chronic, BCR-ABL Positive economics, Remission Induction methods
- Published
- 2020
- Full Text
- View/download PDF
47. Risk of molecular recurrence after tyrosine kinase inhibitor discontinuation in chronic myeloid leukaemia patients: a systematic review of literature with a meta-analysis of studies over the last ten years.
- Author
-
Dulucq S, Astrugue C, Etienne G, Mahon FX, and Benard A
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Male, Middle Aged, Neoplasm Recurrence, Local, Protein Kinase Inhibitors pharmacology, Time Factors, Treatment Outcome, Young Adult, Protein Kinase Inhibitors therapeutic use
- Abstract
More than 10 years ago, the first pilot observational study of imatinib discontinuation was reported in chronic myeloid leukaemia (CML) patients in deep molecular response (DMR). Several studies have been published since then, in patients treated with frontline imatinib, or second-generation tyrosine kinase inhibitors (TKI) in first or second line but also on second attempt of TKI discontinuation. Our objective was to estimate, through meta-analyses of the literature data, the probability of molecular recurrence (MolRec) in the time periods of 0-6, 6-12, 12-18 and 18-24 months after a first and second TKI discontinuation and the probability of re-acquisition of DMR after MolRec. The Medline and Scopus databases were searched up to April 2019. The studies were selected by three independent reviewers. Random-effect meta-analyses were conducted using the MetaXL software. The probability of MolRec in the time periods 0-6, 6-12, 12-18 and 18-24 months after the first attempt was respectively 35%, 8%, 3% and 3%, whereas the probability of MolRec in the time periods 0-6, 6-12 and 12-18 after the second attempt was 48%, 27% and 12% respectively. Re-acquisition of a DMR was observed in 90% of patients. Most of the MolRec occur during the first six months in case of a first attempt, whereas the second MolRec occurs over a larger window of time., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2020
- Full Text
- View/download PDF
48. [Recommendations from the French CML Study Group (Fi-LMC) for BCR-ABL1 kinase domain mutation analysis in chronic myeloid leukemia].
- Author
-
Cayuela JM, Chomel JC, Coiteux V, Dulucq S, Escoffre-Barbe M, Etancelin P, Etienne G, Hayette S, Millot F, Nibourel O, Nicolini FE, and Réa D
- Subjects
- Antineoplastic Agents therapeutic use, Catalytic Domain, Clinical Decision-Making, DNA, Neoplasm analysis, Drug Resistance, Neoplasm genetics, Drug Substitution, Fusion Proteins, bcr-abl antagonists & inhibitors, High-Throughput Nucleotide Sequencing, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive enzymology, Molecular Biology, Protein Domains, Protein Kinase Inhibitors therapeutic use, Role, DNA Mutational Analysis methods, DNA, Neoplasm genetics, Fusion Proteins, bcr-abl genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Mutation, Missense, Point Mutation
- Abstract
In the context of chronic myeloid leukemia (CML) resistant to tyrosine kinase inhibitors (TKIs), BCR-ABL1 tyrosine kinase domain (TKD) mutations still remain the sole biological marker that directly condition therapeutic decision. These recommendations aim at updating the use of BCR-ABL1 mutation testing with respect to new available therapeutic options and at repositioning different testing methods at the era of next generation sequencing (NGS). They have been written by a panel of experts from the French Study Group on CML (Fi-LMC), after a critical review of relevant publications. TKD mutation testing is recommended in case of treatment failure but not in case of optimal response. For patients in warning situation, mutation testing must be discussed depending on the type of TKI used, lasting of the treatment, kinetic evolution of BCR-ABL1 transcripts along time and necessity for switching treatment. The kind and the frequency of TKD mutations occasioning resistance mainly depend on the TKI in use and disease phase. Because of its better sensitivity, NGS methods are recommended for mutation testing rather than Sanger's. Facing a given TKD mutation, therapeutic decision should be taken based on in vitro sensitivity and clinical efficacy data. Identification by sequencing of a TKD mutation known to induce resistance must lead to a therapeutic change. The clinical value of testing methods more sensitive than NGS remains to be assessed., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
49. [Accreditation strategy for rare somatic molecular abnormalities detected or quantified by polymerase chain reaction: GBMHM recommendations].
- Author
-
Sujobert P, Dulucq S, Alary AS, Etancelin P, Bouvier A, Boureau L, Chauveau A, Kosmider O, and Flandrin P
- Subjects
- France, Gene Frequency, Hematologic Neoplasms blood, Humans, Laboratories organization & administration, Laboratories standards, Medical Oncology organization & administration, Medical Oncology standards, Molecular Diagnostic Techniques methods, Molecular Diagnostic Techniques standards, Practice Guidelines as Topic, Quality Control, Reproducibility of Results, Sensitivity and Specificity, Societies, Scientific organization & administration, Societies, Scientific standards, Accreditation methods, DNA Mutational Analysis methods, DNA Mutational Analysis standards, Hematologic Neoplasms diagnosis, Hematologic Neoplasms genetics, Real-Time Polymerase Chain Reaction methods, Real-Time Polymerase Chain Reaction standards
- Abstract
In 2020, accreditation of molecular tests according to ISO 15189 is a requirement for all French medical laboratories. For many years, the GBMHM group (French Group of Molecular Biologists in Hematology) supports this approach through organization of external quality evaluation campaigns, and by publishing recommendations that have allowed the accreditation of the most frequent molecular tests for most laboratories. However, some molecular abnormalities concerns very few patients (and sometimes a single patient), and therefore cannot be evaluated in the same way, because of the lack of external quality controls or inter-laboratory comparisons. In order to allow the accreditation of these rare analyzes, the GBMHM proposes recommendations, based on the fact that analyzes using the same methodology than those already accredited by an extensive validation process, may be accredited without the need for full analytical validation. In particular, assays based on quantitative PCR or endpoint PCR may be accredited after verification of primer specificity, repeatability and/or reproducibility, and the determination of detection or linearity limits. These recommendations, by defining the validation approach for rare molecular abnormalities, make it possible to extend the requirement of accreditation for rare tests, to provide the best patient care.
- Published
- 2019
- Full Text
- View/download PDF
50. Evaluation of Residual Disease and TKI Duration Are Critical Predictive Factors for Molecular Recurrence after Stopping Imatinib First-line in Chronic Phase CML Patients.
- Author
-
Nicolini FE, Dulucq S, Boureau L, Cony-Makhoul P, Charbonnier A, Escoffre-Barbe M, Rigal-Huguet F, Coiteux V, Varet B, Dubruille V, Lenain P, Rousselot P, Rea D, Guerci-Bresler A, Legros L, Liu J, Gardembas M, Ianotto JC, Turlure P, Johnson-Ansah H, Martiniuc J, Jardel H, Joly B, Zunic P, Henni T, Villemagne B, Berger MG, Cayssials E, Guilhot F, Larosa F, Guilhot J, Etienne G, and Mahon FX
- Subjects
- Adult, Aged, Drug Administration Schedule, Female, Fusion Proteins, bcr-abl genetics, Gene Expression Regulation, Leukemic, Humans, Leukemia, Myeloid, Chronic-Phase genetics, Leukemia, Myeloid, Chronic-Phase pathology, Male, Middle Aged, Neoplasm Recurrence, Local, Prognosis, Prospective Studies, Remission Induction, Survival Analysis, Treatment Outcome, Imatinib Mesylate therapeutic use, Leukemia, Myeloid, Chronic-Phase drug therapy, Neoplasm, Residual diagnosis, Protein Kinase Inhibitors therapeutic use
- Abstract
Purpose: Tyrosine kinase inhibitor (TKI) discontinuation is an emerging goal in chronic myelogenous leukemia (CML) management and several studies have demonstrated the feasibility of safely stopping imatinib. A sustained deep molecular response on long-term TKI is critical prior to attempting treatment-free remission. Reproducible results from several studies reported recently, failed to identify robust and reproducible predictive factors for the selection of the best candidates for successful TKI cessation., Patients and Methods: We conducted a prospective national phase II study evaluating the cessation of imatinib after at least 2 years of MR4.5 obtained on imatinib first-line in patients with chronic phase CML., Results: A total of 218 patients with de novo chronic phase CML were involved in the study. The median follow-up after imatinib cessation was 23.5 (1-64) months, 2 patients died from unrelated causes, and 107 experienced a confirmed increase in BCR-ABL1 levels defined as molecular recurrence. The molecular recurrence-free survival was 52% [95% confidence interval (CI), 45%-59%] at 6 months, and 50% (95% CI, 43%-57%) at 24 months. Droplet digital PCR (ddPCR) was used to evaluate more accurately low levels of BCR-ABL1 in 175 of 218 patients at imatinib cessation. To apply positive BCR-ABL1/ABL1 ratios on the international scale (IS), a conversion factor was calculated for ddPCR and the significant cut-off point was established at 0.0023%
IS . In a multivariate analysis, the duration of TKI (≥74.8 months) and ddPCR (≥0.0023%IS ) were the two identified predictive factors of molecular recurrence, with P = 0.0366 (HR, 0.635; 95% CI, 0.415-0.972] and P = 0.008 (HR, 0.556; 95% CI, 0.360-0.858), respectively., Conclusions: We conclude that the duration of TKI and residual leukemic cell load as determined by ddPCR are key factors for predicting successful treatment-free remission for patients with de novo chronic phase CML. See related commentary by Yan et al., p. 6561 ., (©2019 American Association for Cancer Research.)- Published
- 2019
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.