Applied Clinical Research in Hematological Malignances

Research group

Group Leader

Carles Besses Raebel

The group is studying molecular markers in chronic myeloproliferative neoplasms, mainly driver mutations but also mutations in epigenetic modifiers and genes involved in the splicing mechanism, and their role in monitoring the response to cytoreductive therapy and in the prognosis of patients. In addition, the group is searching for new mutations using exome sequencing techniques in those patients with essential thrombocythemia unmutated for JAK2, CALR and MPL genes. In addition, the role of circulating DNA as a tool to diagnose and monitor the response to therapy in myeloid neoplasms is an ongoing research project. Another area of research is the effect of new drugs in ex vivo cultures of neoplastic lymphoid cells obtained from lymphoma patients and determining the mechanisms underlying response/resistance, and identification of potential synergistic combinations. The clinical research in lymphoma is focused on the usefulness of natriuretic peptid and cardiovascular risk scales to predict anthracycline-induced cardiomyotoxicity in patients with diffuse large B-cell lymphoma.

 

2017

Members

Eugènia Abella Monreal (Researcher)

Beatriz Bellosillo Paricio (Researcher)

Eva Gimeno Vázquez (Researcher)

Carmen Jiménez Martínez (Researcher)

Antonio Salar Silvestre (Researcher)

Blanca Sánchez González (Researcher)

Anna Angona Figueras (Technician)

Randa Ben Azaiz Ben Lahsen (Technician)

Francesc Garcia Pallarols (Technicican)

Lierni Fernández Ibarrondo (Technician)

María Concepción Fernández Rodríguez (Technician)

María Alicia Senín Magán (Technician)

María Elena Torres Grande (Technician)

Anna Maria Massó Carreras (Research Assistant)

 

Main Publications

• Salar A, Domingo-Domenech E, Panizo C, Nicolás C, Bargay J, Muntañola A, Canales M, Bello JL, Sancho JM, Tomás JF, Rodríguez MJ, Peñalver J, Grande C, Sánchez-Blanco JJ, Palomera L, Arranz R, Conde E, Garcia M, García JF, Caballero D, Montalbán C. Long-term results of a phase II study of rituximab and bendamustine for mucosa-associated lymphoid tissue lymphoma. Blood 2017; 130(15): 1772-1774. IF 13.164. D1.

• Brammeld J, Petljak M, Martincorena I, Williams SP, Alonso LG, Dalmases A, Bellosillo B, Robles-Espinoza CD, Price S, Barthorpe S, Tarpey P, Alifrangis C, Bignell G, Vidal J, Young J, Stebbings L, Beal K, Stratton MR, Saez-Rodriguez J, Garnett M, Montagut C, Iorio F, McDermott U. Genome-wide chemical mutagenesis screens allow unbiased saturation of the cancer genome and identification of drug resistance mutations. Genome Res 2017; 27(4): 613-625. IF 11.922. D1.

• Vidal J, Muinelo L, Dalmases A, Jones F, Edelstein D, Iglesias M, Orrillo M, Abalo A, Rodríguez C, Brozos E, Vidal Y, Candamio S, Vázquez F, Ruiz J, Guix M, Visa L, Sikri V, Albanell J, Bellosillo B, López R, Montagut C. Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients. Ann Oncol 2017; 28(6): 1325-1332. IF 11.855. D1.

• Geyer HL, Kosiorek H, Dueck AC, Scherber R, Slot S, Zweegman S, te Boekhorst PA, Senyak Z, Schouten HC, Sackmann F, Kerguelen-Fuentes A, Hernández-Maraver D, Pahl HL, Griesshammer M, Stegelmann F, Döhner K, Lehmann T, Bonatz K, Reiter A, Boyer F, Etienne G, Ianotto JC, Ranta D, Roy L, Cahn JY, Harrison CN, Radia D, Muxi P, Maldonado N, Besses C, Cervantes F, Johansson PL, Barbui T, Barosi G, Vannucchi AM, Paoli C, Passamonti F, Andreasson B, Ferrari ML, Rambaldi A, Samuelsson J, Cannon K, Birgegard G, Xiao Z, Xu Z, Zhang Y, Sun X, Xu J, Kiladjian JJ, Zhang P, Gale RP, Mesa RA. Associations between gender, disease features and symptom burden in the MPN population: An analysis by the MPN QOL International Working Group. Haematologica 2017; 102(1): 85-93. IF 7.702. D1.

• Granell M, Calvo X, Garcia-Guiñón A, Escoda L, Abella E, Martínez CM, Teixidó M, Gimenez MT, Senín A, Sanz P, Campoy D, Vicent A, Arenillas L, Rosiñol L, Sierra J, Blade J, Fernandez de Larrea C. Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukaemia definition. Haematologica 2017; 102(6): 1099-1104. IF 7.702. D1.

• Peñalver FJ, Sancho JM, de la Fuente A, Olave MT, Martín A, Panizo C, Pérez E, Salar A, Orfao A. Guidelines for diagnosis, prevention and management of central nervous system involvement in diffuse large B-cell lymphoma patients by the Spanish Lymphoma Group (GELTAMO). Haematologica 2017; 102(2): 235-245. IF 7.702. D1.

• Miralpeix E, Genovès J, Sole JM, Mancebo G, Lloveras B, Bellosillo B, Alameda F, Carreras R. Usefulness of p16INK4a staining for managing histological high-grade squamous intraepithelial cervical lesions. Modern Pathol 2017; 30(2): 304-310. IF 5.728. D1.

• Álvarez-Larran A, Senín A, Fernández-Rodríguez MC, Pereira A, Arellano-Rodrigo E, Gómez M, Ferrer-Marin F, Martínez-López J, Camacho L, Colomer D, Angona A, Navarro B, Cervantes F, Besses C, Bellosillo B, Hernández-Boluda JC. Impact of genotype on leukaemic transformation in polycythaemia vera and essential thrombocythaemia. Br J Haematol 2017; 178(5): 764-771. IF 5.67. Q1.

• Gonzalez-Lopez TJ, Alvarez-Roman MT, Pascual C, Sanchez-Gonzalez B, Fernandez-Fuentes F, Perez-Ruz G, Hernandez-Rivas JA, Bernat S, Bastida JM, Martinez-Badas MP, Martinez-Robles V, Soto I, Olivera P, Bolaños E, Alonso R, Entrena L, Gomez-Nuñez M, Alonso A, Yera Cobo M, Caparros I, Tenorio M, Arrieta-Cerdan E, Lopez-Ansoar E, Garcia-Frade J, Gonzalez-Porras JR. Use of eltrombopag for secondary immune thrombocytopenia in clinical practice. Br j Haematol 2017; 178(6): 959-970. IF 5.670. Q1.

Ongoing Research Projects

• Caracterización molecular de las neoplasias mieloides a partir del ADN tumoral circulante

- Fondo de Investigación Sanitaria. ISCIII (PI16/00153)

- From 2017 to 2019

- Principal investigator: Bellosillo Paricio, Beatriz

• Molecular characterization of myeloid malignancies in tumoral circulating free DNA and exosomes

- Gilead España (GLD16/00064)

- From 2016 to 2018

- Principal investigator: Besses Raebel, Carles

• Caracterización mediante secuenciación masiva de las mutaciones asociadas con fallo precoz al tratamiento de primera línea en linfoma folicular

- Fondo de Investigación Sanitaria. ISCIII (PI15/00459)

- From 2016 to 2018

- Principal investigator: Salar Silvestre, Antonio

• Caracterización de la trombocitemia esencial jak2v617f y mpl negativa mediante secuenciación del exoma

- Fondo de Investigación Sanitaria. ISCIII (PI13/00393)

- From 2014 to 2018

- Principal investigator: Bellosillo Paricio, Beatriz

• Molecular characterization of Non-Small Cell Lung Cancer (NSCLC) KRAS mutant tumors: clinical implications of new biomarkers

- Fundació La Marató de TV3 (20130530)

- From 2014 to 2017

- Principal investigator: Bellosillo Paricio, Beatriz

 

Group’s Recognitions

• Officially recognised as a consolidated research group by the Generalitat de Catalunya: Grup de Recerca Aplicada en Hematologia (2017 to 2019)

- Agència de Gestió d’Ajuts Universitaris i de Recerca (SGR 205)

- Principal investigator: Besses Raebel, Carles

 

Clinical Trials Signed in 2017

• Phase 2 Open-label Study Investigating the Safety and Efficacy of Blinatumomab After Frontline R-Chemotherapy in Adult Subjects With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma (DLBCL)

- Register: 20150288

- Principal investigator: Salar Silvestre, Antonio

• Estudio observacional prospectivo para evaluar la precocidad, estabilidad y profundidad de la respuesta molecular en pacientes recién diagnosticados de leucemia mieloide crónica en fase crónica (LMC-FC) tratados con inhibidores de la actividad tirosina-quinasa (ITK) como tratamiento de primera línea en la práctica clínica. Estudio RELMC-NOVA

- Register: FMS-ITK-2016-01

- Principal investigator: Álvarez Larrán, Alberto

• Estudio observacional para valorar la carga de la enfermedad, en términos de Calidad de Vida Relacionada con la Salud y costes sanitarios directos, en pacientes con Mieloma Múltiple de nuevo diagnóstico no candidatos a trasplante autólogo de progenitores hematopoyéticos en España

- Register: CEL-MIE-2016-01

- Principal investigator: Abella Monreal, Eugènia

• An Open-Label, Dose-Finding, and Cohort-Expansion Phase 1 Study Evaluating Safety and Efficacy of INCB050465 in Combination With Bendamustine and Obinutuzumab in Subjects With Relapsed or Refractory Follicular Lymphoma (CITADEL-102)

- Register: 20150288

- Principal investigator: Salar Silvestre, Antonio

• Estudio multicéntrico de fase 1B/fase III con avelumab (MSB0010718C) en politerapias que incluyen un agonista inmunitario, un modulador epigenético, un antagonista del CD20 y/o quimioterapia convencional en pacientes con linfoma difuso de células grandes B (LDCGB) recidivante o resistente al tratamiento

- Register: B9991011

- Principal investigator: Salar Silvestre, Antonio

• Estudio de fase 3, aleatorizado, doble ciego, controlado con placebo y multicéntrico entre Bendamustina con Rituximab (BR) en monoterapia y en combinación con Acalabrutinib (ACP-196) en pacientes con linfoma de células del manto no tratado previamente

- Register: ACE-LY-308

- Principal investigator: Salar Silvestre, Antonio

• A Phase 2, Multicenter, International, Open-Label, Safety and Efficacy Study of INCB050465 in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

- Register: INCB50465-202

- Principal investigator: Sánchez González, Blanca

• A phase II trial addressing feasibility and activity of clarithromycin+ lenalidomide combination: a full oral treatment for patients with relapsed/refractory mucosa-associated lymphoid tissue (MALT) lymphoma

- Register: IELSG40

- Principal investigator: Salar Silvestre, Antonio

• Un estudio multicéntrico, aleatorizado, doble ciego y controlado con placebo de fase 3 del inhibidor de tirosina kinasa de Bruton (BTK) ibrutinib, en combinación con rituximab en comparación con placebo en combinación con rituximab en sujetos sin tratamiento previo con linfoma folicular

- Register: PCYC-1141-CA

- Principal investigator: Salar Silvestre, Antonio

• Ensayo aleatorizado y doble ciego para evaluar la eficacia, la seguridad y la inmunogenicidad de ABP 798 en comparación con rituximab en sujetos con linfoma no Hodgkin (LNH) de células B CD20+

- Register: 20130109

- Principal investigator: Salar Silvestre, Antonio

 

Theses

• Angona A. Caracterización de los progenitores hematopoyéticos CD34+ en las neoplasias mieloproliferativas. Universitat Autònoma de Barcelona

- Directors: Besses Raebel, Carles; Álvarez-Larrán, A

- Date of defense: 26/04/2017

• Ancochea A. Reproducibilidad de los criterios de la OMS en el diagnóstico de la policitemia vera. Universitat Autònoma de Barcelona

- Director: Álvarez-Larrán, A; Besses Raebel, Carles

- Date of defense: 15/06/2017

 

 

 

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