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Myeloma

Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t(4;14) is the most relevant adverse prognostic factor, whereas RB deletion as a unique abnormality is not associated with adverse prognosis

Abstract

Fluorescence in situ hybridization (FISH) has become a powerful technique for prognostic assessment in multiple myeloma (MM). However, the existence of associations between cytogenetic abnormalities compels us to re-assess the value of each abnormality. A total of 260 patients with MM at the time of diagnosis, enrolled in the GEM-2000 Spanish transplant protocol, have been analyzed by FISH in order to ascertain the independent influence on myeloma prognosis of IGH translocations, as well as RB and P53 deletions. Survival analyses showed that patients with t(4;14), RB or P53 deletions had a significantly shorter survival than patients without these abnormalities. However, patients with RB deletions without other abnormalities in FISH analysis, displayed a similar outcome to those patients without genetic changes by FISH (46 vs 54 months, P=0.3). In the multivariate analysis the presence of t(4;14), RB deletion associated with other abnormalities, age >60 years, high proportion of S-phase cells and advanced stage of the disease according to the International Staging System retained their independent prognostic influence. In summary, RB deletion as a sole abnormality does not lead to a shortening in the survival of MM patients, whereas t(4;14) confers the worst prognosis in MM patients treated with high-dose chemotherapy.

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Acknowledgements

We thank Arturo Touchard and Manuel Delgado for data managing; Belén González, M Ángeles Hernández and Isabel Isidro for technical assistance; and Mark Anderson from the University Technology Transfer Office. This study was partially supported by Spanish Myeloma Network Program (G03/136) and ‘Ministerio de Ciencia y Tecnologia’ grant (SAF 04/06587).

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Correspondence to J F San Miguel.

Appendix

Appendix

List of the members of GEM 2000 group: Hospital General de Albacete (Ángela Ibáñez, Félix Manso, Juan Carlos Gómez García); Hospital General Universitario de Alicante (Concepción Rivas González, Pascual Fernández Abellán); Hospital General Universitario Marina Alta Alicante (Rosa Ferrer Marco); Hospital Nuestra Señora de Sonsoles Ávila (Abelardo Bárez García); Complejo Asistencial Son Dureta Palma de Mallorca (Joan Besalduch Vidal, Mariana Canaro); Hospital Verge del Toro Mahon (Pilar Galán Alvarez); Hospital Son Llatzer Palma de Mallorca (Joan Bargay LLeonart); Hospital del Mar Barcelona (Eugenia Abella Monreal); Hospital Clínic Universitari Barcelona (Joan Bladé Creixenti, Laura Rosiñol Dach); Hospital Sant Pau Barcelona (Anna Sureda Balari); Clínica Corachan Barcelona (Alfons Modolell Roig); Hospital de Badalona Germans Trias i Pujol Barcelona (Josep María Ribera Santasusana); Hospital General de Manresa (Maricel Subirá); Complejo Hospitalario del Parc Tauli Barcelona (Juan Alfonso Soler Campos); Hospital del Espíritu Santo (Albert Altes); Hospital General de Mataró (Luis Rodríguez Fernández); Hospital Val D’Hebron Barcelona (Manuel Callis de Nadal); Hospital San Pedro de Alcántara Cáceres (Juan Miguel Bergua Burgués, Maria Luz Amigo Lozano); Hospital Punta de Europa Algeciras (Rosario Butrón Vila); Hospital General de Jerez de la Frontera (Ángel León Lara, José Luís Guzmán Zamudio, Patricio Leiva); Hospital General de Castellón (Maria Guinot Martinez, Raimundo García Boyero); Hospital Nuestra Señora de Alarcos Ciudad Real(Belén Hernández Ruiz); Hospital Clínico Universitario de Santiago de Compostela (José Luís Bello López, Natalia Alonso Vicente); Hospital Virgen de la Luz Cuenca (José Luís Guerra Moyano, María José Busto Medina); Hospital de Girona Josep Trueta (Santiago Gardella Company, Yolanda González Montes); Hospital General de Guadalajara (Félix Fuentes Galván, Miguel Díaz Morfa); Hospital de San Jorge Huesca (Fernando Puente Mangirón); Complejo Hospitalario de Jaén (Antonio Alcalá Muñoz); Hospital de Jaén (Pilar Mesa Valle); Hospital del Bierzo Ponferrada (Josefina Galende del Canto); Hospital Ramón y Cajal Madrid (José García Laraña); Hospital 12 de Octubre Madrid (Carlos Grande García, Juan José Lahuerta); Complejo Universitario San Carlos Madrid (Rafael Martínez Martínez); Hospital Universitario La Princesa Madrid (Adrián Alegre Amor, Beatriz Aguado Bueno, Flor Lara García-Escribano); Fundación Jiménez Díaz Madrid (Elena Prieto Pareja); Hospital Príncipe de Asturias Madrid (Carmen Burgaleta, Gemma Moreno Jiménez); Hospital Severo Ochoa Madrid (Pedro Sánchez Godoy); Hospital de Fuenlabrada Madrid (José Ángel Hernández Rivas); Hospital Universitario de Getafe (María del Carmen Monteserín); Hospital Universitario Virgen de la Victoria Málaga (Inmaculada Pérez Fernández, María José Moreno); Hospital General Morales Messeguer Murcia (Felipe de Arriba de la Fuente, José María Moraleda Jiménez); Hospital Nuestra señora del Rosell Cartagena (Jerónima Ibáñez García); Clínica Universitaria de Navarra Pamplona (Elena Carrascal, Felipe Prosper Cardoso, José Rifon); Hospital de Jarrio Oviedo (Ana Díaz Trapiella, Manuel Vargas Pabón); Hospital Central de Asturias Gijón (Consuelo Rayón Suárez, Dolores Carrera); Hospital Río Carrión Palencia (Fernando Ortega Rivas, José María Alonso Alonso); Complejo Hospitalario Materno-insular Las Palmas (José David González San Miguel ); Complejo Hospitalario Xeral-Cies Vigo (Carmen Albo López, Concha Poderos Baeta); Hospital Clínico de Salamanca (Jesús San Miguel Izquierdo); Hospital Universitario de Canarias Santa Cruz de Tenerife (Miguel Hernández García); Hospital Universitario Marques de Valdecilla Santander (Eulogio Conde García); Hospital General de Segovia (José Mariano Hernández Martín); Hospital Joan XXIII Tarragona (Andrés Llorente, Lourdes Escoda Teigell); Hospital Virgen de la Cinta Tortosa (Llorenç Font Ferré ); Hospital Nuestra Señora del Prado Talavera de la Reina (Fernando Solano Ramos); Hospital Virgen de la Salud Toledo (Felipe Casado Montero); Hospital Universitario La Fe Valencia (Isidro Jarque, Javier de la Rubia Comos); Hospital Doctor Peset Valencia (María José Sayas LLoris, Paz Ribas García); Hospital Arnau de Vilanova Valencia (Aurelio López Martínez, Encarna Monzó Castellano, José Mayans Ferrer); Hospital Clínico Universitario de Valencia (Inmaculada Blasco Blasco, Juan Carlos Hernández Boluda, Mará José Terol Casterá); Hospital General Universitario de Valencia (Félix Carbonell Ramón, Maite Otero Castelló); Fundación Instituto Valenciano de Oncología Valencia (Pablo Llorente Alegre); Hospital Francesc de Borja Gandia (María José Fernández, María Ángeles Ruiz Guinaldo); Hospital de Sagunto (Ana Carral Tatay, Isabel Navarro Gonzalo); Hospital Río Hortera Valladolid (Javier García Frade, María Jesús Peñarrubia); Hospital Clínico Universitario de Valladolid (Francisco Javier Fernández Calvo, Rebeca Cuello García); Hospital de Cruces Barakaldo (Elena Amutio Díez, Juan Carlos García Ruiz); Hospital de Galdakao (Jesús María Ojanguren Bergaz., Koldo Atutxa Aresti); Hospital Virgen de la Concha Zamora (Alejandro Martín García); Hospital Clínico Universitario Lozano Blesa Zaragoza (Luís Palomera Bernal); Hospital Miguel Server Zaragoza (Pilar Giraldo).

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Gutiérrez, N., Castellanos, M., Martín, M. et al. Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t(4;14) is the most relevant adverse prognostic factor, whereas RB deletion as a unique abnormality is not associated with adverse prognosis. Leukemia 21, 143–150 (2007). https://doi.org/10.1038/sj.leu.2404413

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