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3. Order-Fractal transition in abstract paintings

Author

De la Calleja, E. M., Cervantes, F., and De la Calleja, J.

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

We report the degree of order of twenty-two Jackson Pollock's paintings using \emph{Hausdorff-Besicovitch fractal dimension}. Through the maximum value of each multi-fractal spectrum, the artworks are classify by the year in which they were painted. It has been reported that Pollock's paintings are fractal and it increased on his latest works. However our results show that fractal dimension of the paintings are on a range of fractal dimension with values close to two. We identify this behavior as a fractal-order transition. Based on the study of disorder-order transition in physical systems, we interpreted the fractal-order transition through its dark paint strokes in Pollocks' paintings, as structured lines following a power law measured by fractal dimension. We obtain self-similarity in some specific Pollock's paintings, that reveal an important dependence on the scale of observation. We also characterize by its fractal spectrum, the called \emph{Teri's Find}. We obtained similar spectrums between \emph{Teri's Find} and \emph{Number 5} from Pollock, suggesting that fractal dimension cannot be completely rejected as a quantitative parameter to authenticate this kind of artworks.

Published
2015
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4. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

Author

Hochhaus, A., Baccarani, M., Silver, R. T., Schiffer, C., Apperley, J. F., Cervantes, F., Clark, R. E., Cortes, J. E., Deininger, M. W., Guilhot, F., Hjorth-Hansen, H., Hughes, T. P., Janssen, J. J. W. M., Kantarjian, H. M., Kim, D. W., Larson, R. A., Lipton, J. H., Mahon, F. X., Mayer, J., Nicolini, F., Niederwieser, D., Pane, F., Radich, J. P., Rea, D., Richter, J., Rosti, G., Rousselot, P., Saglio, G., Saußele, S., Soverini, S., Steegmann, J. L., Turkina, A., Zaritskey, A., and Hehlmann, R.

Published
2020
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5. The Gravitational Universe

Author

Consortium, The eLISA, Seoane, P. Amaro, Aoudia, S., Audley, H., Auger, G., Babak, S., Baker, J., Barausse, E., Barke, S., Bassan, M., Beckmann, V., Benacquista, M., Bender, P. L., Berti, E., Binétruy, P., Bogenstahl, J., Bonvin, C., Bortoluzzi, D., Brause, N. C., Brossard, J., Buchman, S., Bykov, I., Camp, J., Caprini, C., Cavalleri, A., Cerdonio, M., Ciani, G., Colpi, M., Congedo, G., Conklin, J., Cornish, N., Danzmann, K., de Vine, G., DeBra, D., Freitag, M. Dewi, Di Fiore, L., Aguilo, M. Diaz, Diepholz, I., Dolesi, R., Dotti, M., Barranco, G. Fernández, Ferraioli, L., Ferroni, V., Finetti, N., Fitzsimons, E., Gair, J., Galeazzi, F., Garcia, A., Gerberding, O., Gesa, L., Giardini, D., Gibert, F., Grimani, C., Groot, P., Cervantes, F. Guzman, Haiman, Z., Halloin, H., Heinzel, G., Hewitson, M., Hogan, C., Holz, D., Hornstrup, A., Hoyland, D., Hoyle, C. D., Hueller, M., Hughes, S., Jetzer, P., Kalogera, V., Karnesis, N., Kilic, M., Killow, C., Klipstein, W., Kochkina, E., Korsakova, N., Krolak, A., Larson, S., Lieser, M., Littenberg, T., Livas, J., Lloro, I., Mance, D., Madau, P., Maghami, P., Mahrdt, C., Marsh, T., Mateos, I., Mayer, L., McClelland, D., McKenzie, K., McWilliams, S., Merkowitz, S., Miller, C., Mitryk, S., Moerschell, J., Mohanty, S., Monsky, A., Mueller, G., Müller, V., Nelemans, G., Nicolodi, D., Nissanke, S., Nofrarias, M., Numata, K., Ohme, F., Otto, M., Perreur-Lloyd, M., Petiteau, A., Phinney, E. S., Plagnol, E., Pollack, S., Porter, E., Prat, P., Preston, A., Prince, T., Reiche, J., Richstone, D., Robertson, D., Rossi, E. M., Rosswog, S., Rubbo, L., Ruiter, A., Sanjuan, J., Sathyaprakash, B. S., Schlamminger, S., Schutz, B., Schütze, D., Sesana, A., Shaddock, D., Shah, S., Sheard, B., Sopuerta, C. F., Spector, A., Spero, R., Stanga, R., Stebbins, R., Stede, G., Steier, F., Sumner, T., Sun, K. -X., Sutton, A., Tanaka, T., Tanner, D., Thorpe, I., Tröbs, M., Tinto, M., Tu, H. -B., Vallisneri, M., Vetrugno, D., Vitale, S., Volonteri, M., Wand, V., Wang, Y., Wanner, G., Ward, H., Ware, B., Wass, P., Weber, W. J., Yu, Y., Yunes, N., and Zweifel, P.

Subjects
Astrophysics - Cosmology and Extragalactic Astrophysics, General Relativity and Quantum Cosmology
Abstract

The last century has seen enormous progress in our understanding of the Universe. We know the life cycles of stars, the structure of galaxies, the remnants of the big bang, and have a general understanding of how the Universe evolved. We have come remarkably far using electromagnetic radiation as our tool for observing the Universe. However, gravity is the engine behind many of the processes in the Universe, and much of its action is dark. Opening a gravitational window on the Universe will let us go further than any alternative. Gravity has its own messenger: Gravitational waves, ripples in the fabric of spacetime. They travel essentially undisturbed and let us peer deep into the formation of the first seed black holes, exploring redshifts as large as z ~ 20, prior to the epoch of cosmic re-ionisation. Exquisite and unprecedented measurements of black hole masses and spins will make it possible to trace the history of black holes across all stages of galaxy evolution, and at the same time constrain any deviation from the Kerr metric of General Relativity. eLISA will be the first ever mission to study the entire Universe with gravitational waves. eLISA is an all-sky monitor and will offer a wide view of a dynamic cosmos using gravitational waves as new and unique messengers to unveil The Gravitational Universe. It provides the closest ever view of the early processes at TeV energies, has guaranteed sources in the form of verification binaries in the Milky Way, and can probe the entire Universe, from its smallest scales around singularities and black holes, all the way to cosmological dimensions., Comment: 20 pages; submitted to the European Space Agency on May 24th, 2013 for the L2/L3 selection of ESA's Cosmic Vision program

Published
2013

6. On-orbit alignment and diagnostics for the LISA Technology Package

Author

Marin, A F Garcia, Wand, V, Steier, F, Cervantes, F Guzman, Bogenstahl, J, Jennrich, O, Heinzel, G, and Danzmann, K

Subjects
Physics - Instrumentation and Detectors, Physics - Space Physics
Abstract

This paper presents a procedure to perform fully autonomous on-orbit alignment of the interferometer on board the LISA Technology Package (LTP). LTP comprises two free-floating test masses as inertial sensors that additionally serve as end mirrors of a set of interferometers. From the output signals of the interferometers, a subset has been selected to obtain alignment information of the test masses. Based on these signals, an alignment procedure was developed and successfully tested on the engineering model of the optical bench. Furthermore, operation procedures for the characterization of critical on-orbit properties of the optical metrology system (e.g. fibre noise) have been established., Comment: 7 pages, 6 figures

Published
2006
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11. A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis

Author

Passamonti, F, Giorgino, T, Mora, B, Guglielmelli, P, Rumi, E, Maffioli, M, Rambaldi, A, Caramella, M, Komrokji, R, Gotlib, J, Kiladjian, J J, Cervantes, F, Devos, T, Palandri, F, De Stefano, V, Ruggeri, M, Silver, R T, Benevolo, G, Albano, F, Caramazza, D, Merli, M, Pietra, D, Casalone, R, Rotunno, G, Barbui, T, Cazzola, M, and Vannucchi, A M

Published
2017
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13. Driver mutations’ effect in secondary myelofibrosis: an international multicenter study based on 781 patients

Author

Passamonti, F, Mora, B, Giorgino, T, Guglielmelli, P, Cazzola, M, Maffioli, M, Rambaldi, A, Caramella, M, Komrokji, R, Gotlib, J, Kiladjian, J J, Cervantes, F, Devos, T, Palandri, F, De Stefano, V, Ruggeri, M, Silver, R, Benevolo, G, Albano, F, Caramazza, D, Rumi, E, Merli, M, Pietra, D, Casalone, R, Barbui, T, Pieri, L, and Vannucchi, A M

Published
2017
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14. High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists

Author

De Stefano, V, Ruggeri, M, Cervantes, F, Alvarez-Larrán, A, Iurlo, A, Randi, M L, Elli, E, Finazzi, M C, Finazzi, G, Zetterberg, E, Vianelli, N, Gaidano, G, Rossi, E, Betti, S, Nichele, I, Cattaneo, D, Palova, M, Ellis, M H, Cacciola, R, Tieghi, A, Hernandez-Boluda, J C, Pungolino, E, Specchia, G, Rapezzi, D, Forcina, A, Musolino, C, Carobbio, A, Griesshammer, M, Sant’Antonio, E, Vannucchi, A M, and Barbui, T

Published
2016
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20. Indication and management of allogeneic stem cell transplantation in primary myelofibrosis: a consensus process by an EBMT/ELN international working group

Author

Kröger, N M, Deeg, J H, Olavarria, E, Niederwieser, D, Bacigalupo, A, Barbui, T, Rambaldi, A, Mesa, R, Tefferi, A, Griesshammer, M, Gupta, V, Harrison, C, Alchalby, H, Vannucchi, A M, Cervantes, F, Robin, M, Ditschkowski, M, Fauble, V, McLornan, D, Ballen, K, Popat, U R, Passamonti, F, Rondelli, D, and Barosi, G

Published
2015
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22. P995: MYELOID NEOPLASMS-ASSOCIATED GENE VARIANTS IN 639 PATIENTS WITH POST-POLYCYTHEMIA VERA AND POST-ESSENTIAL THROMBOCYTHEMIA MYELOFIBROSIS: AN ANALYSIS OF THE MYSEC COHORT

Author

Mora, B., primary, Guglielmelli, P., additional, Kuykendall, A., additional, Maffioli, M., additional, Rotunno, G., additional, Komrokji, R. S., additional, Palandri, F., additional, Kiladjian, J.-J., additional, Iurlo, A., additional, Auteri, G., additional, Cattaneo, D., additional, De Stefano, V., additional, Salmoiraghi, S., additional, Devos, T., additional, Cervantes, F., additional, Merli, M., additional, Campagna, A., additional, Benevolo, G., additional, Brociner, M., additional, Albano, F., additional, Gotlib, J., additional, Caramella, M., additional, Ruggeri, M., additional, Ross, D. M., additional, Orsini, F., additional, Pessina, C., additional, Colugnat, I., additional, Pallotti, F., additional, Barbui, T., additional, Bertù, L., additional, Della Porta, M. G., additional, Vannucchi, A. M., additional, and Passamonti, F., additional

Published
2022
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23. P1041: IMPACT OF FEDRATINIB ON SPLEEN VOLUME AND MYELOFIBROSIS SYMPTOMS IN PATIENTS WITH SUBSTANTIAL SPLENOMEGALY: POST HOC ANALYSES FROM THE JAKARTA AND JAKARTA2 TRIALS

Author

Kiladjian, J.-J., primary, Tefferi, A., additional, Passamonti, F., additional, Vannucchi, A., additional, Talpaz, M., additional, Cervantes, F., additional, Harrison, C. N., additional, Mesa, R. A., additional, Mascarenhas, J., additional, Schaap, N., additional, Verstovsek, S., additional, Devos, T., additional, Rose, S., additional, Zhang, J., additional, Sy, O., additional, and Pardanani, A., additional

Published
2022
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25. P1026: COMPARATIVE GENOMIC PROFILING OF MYELOPROLIFERATIVE NEOPLASMS PRESENTING WITH AND WITHOUT SPLANCHNIC VEIN THROMBOSIS

Author

Garrote, M., primary, López-Guerra, M., additional, Arellano-Rodrigo, E., additional, Magaz, M., additional, Triguero, A., additional, Carbonell, S., additional, Alamo, J. R., additional, Turon, F., additional, Hernandez-Gea, V., additional, Baiges, A., additional, Colomer, D., additional, García-Pagán, J. C., additional, Cervantes, F., additional, and Alvarez-Larrán, A., additional

Published
2022
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26. Impact of Individual Comorbidities on Survival of Patients with Myelofibrosis

Author

Garcia-Fortes M, Hernandez-Boluda J, Alvarez-Larran A, Raya J, Angona A, Estrada N, Fox L, Cuevas B, Garcia-Hernandez M, Gomez-Casares M, Ferrer-Marin F, Saavedra S, Cervantes F, Garcia-Delgado R, and On Behalf Of The Grupo Espanol de Enfermedades Mieloproliferativas Filadelfia Ne

Abstract

The comorbidity burden is an important risk factor for overall survival (OS) in several hematological malignancies. This observational prospective study was conducted to evaluate the impact of individual comorbidities on survival in a multicenter series of 668 patients with primary myelofibrosis (PMF) or MF secondary to polycythemia vera (PPV-MF) or essential thrombocythemia (PET-MF). Hypertension (hazard ratio (HR) = 4.96, p < 0.001), smoking (HR = 5.08, p < 0.001), dyslipidemia (HR = 4.65, p < 0.001) and hepatitis C virus (HCV) (HR = 4.26, p = 0.015) were most adversely associated with OS. Diabetes (HR = 3.01, p < 0.001), pulmonary disease (HR = 3.13, p < 0.001) and renal dysfunction (HR = 1.82, p = 0.037) were also associated with an increased risk of death. Multivariate analysis showed that pulmonary disease (HR = 2.69, p = 0.001), smoking (HR = 3.34, p < 0.001), renal dysfunction (HR = 2.08, p = 0.043) and HCV (HR = 11.49, p = 0.001) had a negative impact on OS. When ruxolitinib exposure was included in the model, the effect of each comorbidity on survival was modified. Therefore, individual comorbidities should be taken into account in determining the survival prognosis for patients with MF.

Published
2022

27. Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)

Author

Barosi, G, Tefferi, A, Besses, C, Birgegard, G, Cervantes, F, Finazzi, G, Gisslinger, H, Griesshammer, M, Harrison, C, Hehlmann, R, Hermouet, S, Kiladjian, J-J, Kröger, N, Mesa, R, Mc Mullin, M F, Pardanani, A, Passamonti, F, Samuelsson, J, Vannucchi, A M, Reiter, A, Silver, R T, Verstovsek, S, Tognoni, G, and Barbui, T

Published
2015
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28. The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: an international study of 797 patients

Author

Guglielmelli, P, Lasho, T L, Rotunno, G, Score, J, Mannarelli, C, Pancrazzi, A, Biamonte, F, Pardanani, A, Zoi, K, Reiter, A, Duncombe, A, Fanelli, T, Pietra, D, Rumi, E, Finke, C, Gangat, N, Ketterling, R P, Knudson, R A, Hanson, C A, Bosi, A, Pereira, A, Manfredini, R, Cervantes, F, Barosi, G, Cazzola, M, Cross, N C P, Vannucchi, A M, and Tefferi, A

Published
2014
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29. Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia: primary results of the phase 4 BYOND study

Author

Hochhaus, A, Gambacorti Passerini, C, Abboud, C, Gjertsen, B, Brummendorf, T, Smith, B, Ernst, T, Giraldo-Castellano, P, Olsson-Stromberg, U, Saussele, S, Bardy-Bouxin, N, Viqueira, A, Leip, E, Russell-Smith, T, Leone, J, Rosti, G, Watts, J, Giles, F, Abruzzese, E, Akard, L, Bosi, A, Cervantes, F, Charbonnier, A, Di Raimondo, F, Etienne, G, Garcia Gutierrez, V, Guerci-Bresler, A, Hjorth-Hansen, H, Karsenti, J, Kelly, K, Le Coutre, P, Martinez Chamorro, C, Oehler, V, Orti Pascual, G, Petzer, A, Pungolino, E, Rege-Cambrin, G, Rigal-Huguet, F, Roboz, G, Rousselot, P, Sanchez-Guijo, F, Sanz Santillana, G, Schafhausen, P, Scheid, C, Schmidt, S, Specchia, G, Steegmann, J, Stenke, L, Hochhaus A., Gambacorti Passerini C., Abboud C., Gjertsen B. T., Brummendorf T. H., Smith B. D., Ernst T., Giraldo-Castellano P., Olsson-Stromberg U., Saussele S., Bardy-Bouxin N., Viqueira A., Leip E., Russell-Smith T. A., Leone J., Rosti G., Watts J., Giles F. J., Abruzzese E., Akard L. P., Bosi A., Cervantes F., Charbonnier A., Di Raimondo F., Etienne G., Garcia Gutierrez V., Guerci-Bresler A. P., Hjorth-Hansen H., Karsenti J. M., Kelly K. R., Le Coutre P., Martinez Chamorro C., Oehler V. G., Orti Pascual G., Petzer A., Pungolino E., Rege-Cambrin G., Rigal-Huguet F., Roboz G. J., Rousselot P., Sanchez-Guijo F. M., Sanz Santillana G., Schafhausen P., Scheid C., Schmidt S., Specchia G., Steegmann J. L., Stenke L., Hochhaus, A, Gambacorti Passerini, C, Abboud, C, Gjertsen, B, Brummendorf, T, Smith, B, Ernst, T, Giraldo-Castellano, P, Olsson-Stromberg, U, Saussele, S, Bardy-Bouxin, N, Viqueira, A, Leip, E, Russell-Smith, T, Leone, J, Rosti, G, Watts, J, Giles, F, Abruzzese, E, Akard, L, Bosi, A, Cervantes, F, Charbonnier, A, Di Raimondo, F, Etienne, G, Garcia Gutierrez, V, Guerci-Bresler, A, Hjorth-Hansen, H, Karsenti, J, Kelly, K, Le Coutre, P, Martinez Chamorro, C, Oehler, V, Orti Pascual, G, Petzer, A, Pungolino, E, Rege-Cambrin, G, Rigal-Huguet, F, Roboz, G, Rousselot, P, Sanchez-Guijo, F, Sanz Santillana, G, Schafhausen, P, Scheid, C, Schmidt, S, Specchia, G, Steegmann, J, Stenke, L, Hochhaus A., Gambacorti Passerini C., Abboud C., Gjertsen B. T., Brummendorf T. H., Smith B. D., Ernst T., Giraldo-Castellano P., Olsson-Stromberg U., Saussele S., Bardy-Bouxin N., Viqueira A., Leip E., Russell-Smith T. A., Leone J., Rosti G., Watts J., Giles F. J., Abruzzese E., Akard L. P., Bosi A., Cervantes F., Charbonnier A., Di Raimondo F., Etienne G., Garcia Gutierrez V., Guerci-Bresler A. P., Hjorth-Hansen H., Karsenti J. M., Kelly K. R., Le Coutre P., Martinez Chamorro C., Oehler V. G., Orti Pascual G., Petzer A., Pungolino E., Rege-Cambrin G., Rigal-Huguet F., Roboz G. J., Rousselot P., Sanchez-Guijo F. M., Sanz Santillana G., Schafhausen P., Scheid C., Schmidt S., Specchia G., Steegmann J. L., and Stenke L.

Abstract

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of cumulative confirmed major cytogenetic response (MCyR) rate by 1 year was 75.8% in Ph+ CP CML patients after one or two prior TKIs and 62.2% after three prior TKIs. Cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) rates by 1 year were 80.6% and 70.5%, respectively, in Ph+ CP CML patients overall. No patient progressed to AP/BP on treatment. Across all patients, the most common treatment-emergent adverse events were diarrhea (87.7%), nausea (39.9%), and vomiting (32.5%). The majority of patients had confirmed MCyR by 1 year and MMR by 1 year, further supporting bosutinib use for Ph+ CP CML patients resistant/intolerant to prior TKIs.

Published
2020

34. Mutations and prognosis in primary myelofibrosis

Author

Vannucchi, A M, Lasho, T L, Guglielmelli, P, Biamonte, F, Pardanani, A, Pereira, A, Finke, C, Score, J, Gangat, N, Mannarelli, C, Ketterling, R P, Rotunno, G, Knudson, R A, Susini, M C, Laborde, R R, Spolverini, A, Pancrazzi, A, Pieri, L, Manfredini, R, Tagliafico, E, Zini, R, Jones, A, Zoi, K, Reiter, A, Duncombe, A, Pietra, D, Rumi, E, Cervantes, F, Barosi, G, Cazzola, M, Cross, N C P, and Tefferi, A

Published
2013
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45. Suspensión del tratamiento con inhibidores de BCR-ABL en los pacientes con leucemia mieloide crónica en respuesta molecular profunda dentro de la práctica clínica asistencial: Experiencia española en un total de 236 casos

Author

Galan, I.P., Larran, A.A., Savchuk, A., Puerta, J.M., Pina, J.M.S., Collado, R., Gonzalez, A.D., Angona, A., Sagues, M., Gutierrez, V.G., Boque, C., Centurion, I.G., Vallansot, R., Palomera, L., Mendizabal, A., Casado, L.F., Encinas, M.P., Lopez, R.P., Marin, F.F., Guijo, F.S., Garcia, C., De las Heras, N., Cervantes, F., Steegmann, J.L., and Boluda, J.C.H.

Abstract

Oral Presentation [CO-092] Introducción: La mitad de los pacientes con leucemia mieloide crónica (LMC) en respuesta molecular profunda no pierde la respuesta molecular mayor (RMM) tras la suspensión del tratamiento con inhibidores de BCR-ABL (ITC). Esta estrategia ha demostrado ser segura en ensayos clínicos pero hay poca información acerca de su aplicabilidad en la práctica clínica asistencial. El objetivo del estudio fue analizar la experiencia con la suspensión del tratamiento fuera de ensayo clínico en España. Métodos: Se analizan los resultados de 236 pacientes con LMC en fase crónica que suspendieron el tratamiento fuera de ensayo clínico en 33 hospitales. Criterios de inclusión: a) tratamiento con ITC >3 años, b) respuesta molecular grado 4.5 durante >2 años (se permitió una única determinación de RM4 durante ese período). Se excluyeron los pacientes trasplantados. Resultados: Las características de la serie se muestran en la tabla 1. Los motivos principales para suspender el tratamiento fueron los efectos secundarios (n=66), lograr la remisión libre de tratamiento (n=166) y el embarazo (n=4). La mediana de seguimiento tras la suspensión fue de 21, 5 meses y 5 pacientes fallecieron por causas no relacionadas con la LMC. Durante este periodo, 67 pacientes reiniciaron el tratamiento por recaída molecular (pérdida de RMM: n=52, aumento de tránscritos >1 log en dos controles sucesivos sin pérdida de RMM: n=12), decisión del paciente (n=2) o síndrome de discontinuación (n=1). Un paciente perdió la RMM a los 20 meses y decidió no tratarse, recuperando la RMM espontáneamente. Cuarenta y nueve recaídas (75% del total) ocurrieron en los primeros 6 meses, 8 entre los meses 7-12, y 8 tras los 12 meses, produciéndose la pérdida de RMM más tardía a los 30 meses. La supervivencia libre de reinicio del tratamiento (figura 1) y de recaída molecular fue del 66, 8% y del 67, 5% a los 3 años, respectivamente. Los factores asociados a mayor supervivencia libre de recaída fueron la duración del tratamiento con ITC >5 años (p=0.01) y la RM4.5 >4 años antes de la suspensión (p=0.017). Un total de 51 pacientes (22%) desarrollaron dolor osteomuscular tras la suspensión. No se registró ningún caso de progresión a fases avanzadas. El valor mediano de la carga de BCR-ABL al reinicio del tratamiento fue del 0, 3% (>5% en 7 casos). La mediana de seguimiento tras reinicio del tratamiento fue de 20 meses; 46 de 52 casos (88%) recuperaron la RMM tras una mediana de tiempo de 3 meses; 50 de 64 recuperaron la RM4 (mediana 3, 5 meses) y 47 de 64 recuperaron la MR4.5 (mediana 5 meses). En el último control, el estado de la respuesta fue: RM4.5 (n=195), RM4 (n=15), RMM (n=14), respuesta citogenética completa (n=10), otros (n=2). Conclusiones: los resultados confirman que la suspensión del tratamiento es factible en la práctica clínica asistencial en España. La duración del tratamiento y de la respuesta molecular profunda se asociaron con la supervivencia libre de recaída. Esta información puede ser útil para establecer recomendaciones generales acerca de la discontinuación del tratamiento de la LMC en nuestro medio.

Published
2020

46. The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview

Author

Baccarani, M, Castagnetti, F, Gugliotta, G, Rosti, G, Soverini, S, Albeer, A, Pfirrmann, M, Bekadja, Ma, Entasoltan, B, Nachi, M, Elghandour, A, El Sorady, M, Abdelfattah, R, El Nahass, Y, Samra, M, Azzazi, M, Elsobki, E, Moussa, M, Fahmy, O, Mattar, M, Shehata, Azmy, Se, (Azmy, E, 9 ), Emad), Bolarinwa, (Bolarinwa, Ra, ( 10 ), Rahman A., Eid, (Eid, S, Samir)( 11, ), Khelif, (Khelif, A, Abderrhaim)( 11, ), Hached, (Hached, F, Farhat)( 11, ), Menif, (Menif, S, Samia)( 12, ), Rahman, (Rahman, H, Hafizur)( 13, ), Huang, (Huang, Xj, Xiaojun)(, 14, 15, ), Jiang, (Jiang, Q, Qian)(, 14, (Ye, Yx, Yuanxin)( 16, ), Zhu, (Zhu, Hl, Huanling)( 16, ), Chen, (Chen, Sn, Suning)( 17, ), Varma, (Varma, N, Neelam)( 18, ), Ganesan, (Ganesan, P, Prasanth)( 19, ), Gundeti, (Gundeti, S, Sadashivudu)( 20, ), Malhotra, (Malhotra, H, Hemant)( 21, ), Radhakrishnan, (Radhakrishnan, Vs, ( 22 ), Vivek S., Kumar, (Kumar, L, Lalit)( 23, ), Sharawat, (Sharawat, Sk, Surender Kumar)( 23, ), Seth, (Seth, T, Tulika)( 24, ), Ausekar, (Ausekar, Bv, ( 25 ), B. V., Balasubramanian, (Balasubramanian, P, Poonkuzhali)( 26, ), Poopak, (Poopak, B, Behzad)(, 27, 28, ), Inokuchi, (Inokuchi, K, Koiti)( 29, ), Kim, (Kim, Dw, Dong-Wook)( 30, ), Kindi, Al, S (Al Kindi, Salam)( 31, ), Mirasol, (Mirasol, A, Angelina)( 32, ), Qari, (Qari, M, Mohammed)( 33, ), Goh, (Goh, Yt, Yeow Tee)( 34, ), Shih, (Shih, Ly, Lee-Yung)(, 35, 36, ), Branford, (Branford, S, Susan)(, 37, 38, ), Lion, (Lion, T, Thomas)( 39, ), Valent, (Valent, P, Peter)( 40, ), Burgstaller, (Burgstaller, S, Sonja)( 41, ), Thaler, (Thaler, J, Joseph)( 41, ), Labar, (Labar, B, Boris)( 42, ), Zadro, (Zadro, R, Renata)( 42, ), Mayer, (Mayer, J, Jiri)(, 43, 44, ), Zackova, (Zackova, D, Daniela)(, 43, Faber, (Faber, E, Edgar)( 45, ), Pallisgaard, (Pallisgaard, N, Niels)( 46, ), Xavier-Mahon, (Xavier-Mahon, F, Francois)( 47, ), Lippert, (Lippert, E, Eric)( 48, ), Cayuela, (Cayuela, Jm, Jean Michel)( 49, ), Rea, (Rea, D, Delphine)( 49, ), Millot, (Millot, F, Frederic)( 50, ), Suttorp, (Suttorp, M, Meinolf)( 51, ), Hochhaus, (Hochhaus, A, Andreas)( 52, ), Niederwieser, (Niederwieser, D, Dietger)( 53, ), Saussele, (Saussele, S, Susanne)( 54, ), Haferlach, (Haferlach, T, Torsten)( 55, ), Jeromine, (Jeromine, S, Sabine)( 55, ), Panayiotidis, (Panayiotidis, P, Panayiotis)(, 56, 57, ), Conneally, (Conneally, E, Eibhlin)( 58, ), Langabeer, (Langabeer, S, Steve)( 58, ), Nagler, (Nagler, A, Arnon)(, 59, 60, ), Rupoli, (Rupoli, S, Serena)( 61, ), Santoro, (Santoro, N, Nicola)( 62, ), Albano, (Albano, F, Francesco)( 63, ), Castagnetti, (Castagnetti, F, Fausto), Ottaviani, (Ottaviani, E, Emanuela)(, 64, 65, ), Rambaldi, (Rambaldi, A, Alessandro)(, 66, 67, ), Stagno, (Stagno, F, Fabio)( 68, ), Molica, (Molica, S, Stefano)( 69, ), Biagiotti, (Biagiotti, C, Caterina)( 70, ), Scappini, (Scappini, B, Barbara)( 70, ), Lemoli, (Lemoli, R, Roberto)( 71, ), Iurlo, (Iurlo, A, Alessandra)(, 72, 73, ), Pungolino, (Pungolino, E, Ester)( 74, ), Menna, (Menna, G, Giuseppe), Pane, (Pane, F, Fabrizio)( 76, ), Gottardi, (Gottardi, E, Enrico)(, 77, 78, ), Rege-Cambrin, (Rege-Cambrin, G, Giovanna)(, 77, Binotto, (Binotto, G, Gianni)( 79, ), Putti, (Putti, Mc, Maria Caterina)( 80, ), Falzetti, (Falzetti, F, Franca)( 81, ), Visani, (Visani, G, Giuseppe)( 82, ), Galimberti, (Galimberti, S, Sara)( 83, ), Musto, (Musto, P, Pellegrino)( 84, ), Abruzzese, (Abruzzese, E, Elisabetta)( 85, ), Breccia, (Breccia, M, Massimo)( 86, ), Giona, (Giona, F, Fiorina)( 86, ), Chiusolo, (Chiusolo, P, Patrizia)( 87, ), Sica, (Sica, S, Simona)( 87, ), Fava, (Fava, C, Carmen)( 88, ), Ferrero, (Ferrero, D, Dario)( 88, ), Tiribelli, (Tiribelli, M, Mario)( 89, ), Bonifacio, (Bonifacio, M, Massimiliano)( 90, ), Griskevicius, (Griskevicius, L, Laimonas)( 91, ), Musteata, (Musteata, V, Vasile)( 92, ), Janssen, (Janssen, J, Jeroen)( 93, ), Prejzner, (Prejzner, W, Witold)( 94, ), Sacha, (Sacha, T, Tomasz)( 95, ), Waclaw, (Waclaw, J, Joanna)( 95, ), Almeida, (Almeida, Am, Antonio Medina)( 96, ), Kulikov, (Kulikov, S, Sergei)( 97, ), Turkina, (Turkina, A, Anna)( 97, ), Bogdanovic, (Bogdanovic, A, Andrija)( 98, ), Zupan, (Zupan, I, Irena)( 99, ), Marce, (Marce, S, Silvia)( 100, ), Cervantes, (Cervantes, F, Francisco)( 101, ), Steegmann, (Steegmann, Jl, Juan Luis)( 102, ), Kotlyarchuk, (Kotlyarchuk, K, Konstyantyn)( 103, ), Milner, (Milner, Bj, ( 104 ), Benedict J., Rose, (Rose, S, Susan)( 105, ), Clench, (Clench, T, Tim)( 106, ), Waits, (Waits, P, Paula)( 107, ), Austin, (Austin, S, Steve)( 108, ), Wickham, (Wickham, C, Caroline)( 109, ), Clark, (Clark, R, Richard)( 110, ), Apperley, (Apperley, J, Jane), Claudiani, (Claudiani, S, Simone)( 111, ), Foroni, (Foroni, L, Letizia)( 111, ), Szydlo, (Szydlo, R, Richard)( 111, ), Burt, (Burt, E, Emma)( 112, ), Bescoby, (Bescoby, R, Ruth)( 113, ), Cork, (Cork, L, Leanne)( 113, ), O'Brien, (O'Brien, S, Stephen)( 113, ), Green, (Green, B, Bethaney)( 114, ), Hawtree, (Hawtree, S, Sarah)( 114, ), Watson, (Watson, M, Mark)( 114, ), Bengio, (Bengio, Rm, Raquel Maria)( 115, ), Larripa, (Larripa, I, Irene)( 115, ), Pavlovsky, (Pavlovsky, C, Carolina)( 116, ), Moiraghi, (Moiraghi, B, Beatriz)( 117, ), Pinna, De, CAR (Requiao de Pinna, Cristiane Almeida)( 118, ), Magalhaes, GHR (Romani Magalhaes, Gustavo Henrique)( 119, ), Pagnano, (Pagnano, K, Katia)( 120, ), Funke, (Funke, V, Vaneuza)( 121, ), Tavares, (Tavares, Rs, Renato Sampaio)( 122, ), Prado, (Prado, A, Adriana)( 123, ), Azevedo, (Azevedo, Aa, Alita Andrade)( 124, ), Fogliatto, (Fogliatto, L, Laura)( 125, ), Bonecker, (Bonecker, S, Simone)( 126, ), Centrone, (Centrone, R, Renato)( 127, ), Moellman, (Moellman, A, Artur)( 128, ), Conchon, (Conchon, M, Monika)( 130, ), Centurion, (Centurion, Me, Maria Elida)( 131, ), (Prado, Ai, Ana-Ines)( 132, ), Lopez, (Lopez, Jl, ( 133 ), J. L., Petruzziello, (Petruzziello, F, Fara)( 75, ), Bendit, (Bendit, I, Israel), Baccarani M., Castagnetti F., Gugliotta G., Rosti G., Soverini S., Albeer A., and Pfirrmann M.

Subjects
Male, 0301 basic medicine, Cancer Research, bcr-abl, Fusion Proteins, bcr-abl, Global Health, 0302 clinical medicine, hemic and lymphatic diseases, 80 and over, Odds Ratio, Prevalence, Age Factor, Chronic, Young adult, Child, MOLECULAR RESPONSE, Leukemic, Aged, 80 and over, Leukemia, Hematology, Gene Expression Regulation, Leukemic, CHRONIC MYELOGENOUS LEUKEMIA, Age Factors, Myeloid leukemia, Middle Aged, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Female, Life Sciences & Biomedicine, Human, Adult, Transcriptional Activation, medicine.medical_specialty, Adolescent, Immunology, IMATINIB MESYLATE, DENDRITIC CELLS, CML PATIENTS, Young Adult, 03 medical and health sciences, Myelogenous, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, medicine, Humans, 1112 Oncology and Carcinogenesis, BCR/ABL TRANSCRIPT, Preschool, CYTOGENETIC RESPONSE, Aged, Science & Technology, CHRONIC-PHASE, business.industry, Infant, Newborn, Fusion Proteins, ABL FUSION PROTEINS, P190 BCR-ABL, Infant, 1103 Clinical Sciences, Odds ratio, Newborn, medicine.disease, International BCR-ABL Study Group, Settore MED/15 - MALATTIE DEL SANGUE, 030104 developmental biology, Imatinib mesylate, Gene Expression Regulation, BCR-ABL Positive, business, Chronic myelogenous leukemia
Abstract

There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia. Their frequency has never been systematically investigated. In a series of 45503 newly diagnosed CML patients reported from 45 countries, it was found that the proportion of e13a2 (also known as b2a2) and of e14a2 (also known as b3a2), including the cases co-expressing e14a2 and e13a2, was 37.9% and 62.1%, respectively. The proportion of these two transcripts was correlated with gender, e13a2 being more frequent in males (39.2%) than in females (36.2%), was correlated with age, decreasing from 39.6% in children and adolescents down to 31.6% in patients ≥ 80 years old, and was not constant worldwide. Other, rare transcripts were reported in 666/34561 patients (1.93%). The proportion of rare transcripts was associatedwith gender (2.27% in females and 1.69% in males) and with age (from 1.79% in children and adolescents up to 3.84% in patients ≥ 80 years old). These data show that the differences in proportion are not by chance. This is important, as the transcript type is a variable that is suspected to be of prognostic importance for response to treatment, outcome of treatment, and rate of treatment-free remission.

Published
2019
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