Clinical significance of CD56 expression in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens
Pau Montesinos, Chelo Rayón, Edo Vellenga, Salut Brunet, José González, Marcos González, Aleksandra Holowiecka, Jordi Esteve, Juan Bergua, José D González, Concha Rivas, Mar Tormo, Vicente Rubio, Javier Bueno, Félix Manso, Gustavo Milone, Javier de la Serna, Inmaculada Pérez, Manuel Pérez-Encinas, Isabel Krsnik, Josep M Ribera, Lourdes Escoda, Bob Lowenberg, Miguel A Sanz, PETHEMA, HOVON Groups, J M Beltrán de Heredia, J M Hernández, J Arias, F Ramos, A Román, J de la Serna, S Negri, C Rayón, J Esteve, F J Fernández-Calvo, J Díaz-Mediavilla, C Gil, M Pérez-encinas, M Tormo, M Olave, E Amutio, C Pedro, A Gorosquieta, M Viguria, M Zudaire, T Molero, M J Sayas, R Guardia, F Manso, C Rivas, C Esquembre, R García, A Alcalá, J A López, V Rubio, M L Amigo, M Linares, J M Ribera, J D González San Miguel, G Debén, L Escoda, R de la Cámara, A Molines, C Loureiro, M J Allegue, L Amador, J M Martí, L Madero, A Lassaletta, M Cabezudo, J García-Laraña, R Rojas, F Ortega, M J Peñarrubia, F Puente, B López-Ibor, S Brunet, J M Bergua, J Ibáñez, P Sánchez, A Novo, L L Font, J M Guinea, A Montero, M González, M A Sanz, G Martín, J Martínez, P Montesinos, A Verdeguer, P García, E Conde, J García, F J Capote, I Krsnik, J Bueno, P Bastida, A Rubio, J L Fuster, J González, I Pérez, J Molina, M C Mateos, M A Ardaiz, M Rodríguez-calvillo, C Poderós, M Arnán, R Duarte, J A Hernández, M Díaz-Morfa, E Martín-Chacón, J M Calvo-Villas, D García-Belmonte, D Hernández-Maraver, G J Ossenkoppele, J van der Lelie, B Lowenberg, P Sonneveld, M Zijlmans, E Vellenga, J Maertens, B de Valk, P W Wijermans, M R de Groot, H C Schouten, D H Biesma, M van Marwijk Kooy, Pau Montesinos, Chelo Rayón, Edo Vellenga, Salut Brunet, José González, Marcos González, Aleksandra Holowiecka, Jordi Esteve, Juan Bergua, José D González, Concha Rivas, Mar Tormo, Vicente Rubio, Javier Bueno, Félix Manso, Gustavo Milone, Javier de la Serna, Inmaculada Pérez, Manuel Pérez-Encinas, Isabel Krsnik, Josep M Ribera, Lourdes Escoda, Bob Lowenberg, Miguel A Sanz, PETHEMA, HOVON Groups, J M Beltrán de Heredia, J M Hernández, J Arias, F Ramos, A Román, J de la Serna, S Negri, C Rayón, J Esteve, F J Fernández-Calvo, J Díaz-Mediavilla, C Gil, M Pérez-encinas, M Tormo, M Olave, E Amutio, C Pedro, A Gorosquieta, M Viguria, M Zudaire, T Molero, M J Sayas, R Guardia, F Manso, C Rivas, C Esquembre, R García, A Alcalá, J A López, V Rubio, M L Amigo, M Linares, J M Ribera, J D González San Miguel, G Debén, L Escoda, R de la Cámara, A Molines, C Loureiro, M J Allegue, L Amador, J M Martí, L Madero, A Lassaletta, M Cabezudo, J García-Laraña, R Rojas, F Ortega, M J Peñarrubia, F Puente, B López-Ibor, S Brunet, J M Bergua, J Ibáñez, P Sánchez, A Novo, L L Font, J M Guinea, A Montero, M González, M A Sanz, G Martín, J Martínez, P Montesinos, A Verdeguer, P García, E Conde, J García, F J Capote, I Krsnik, J Bueno, P Bastida, A Rubio, J L Fuster, J González, I Pérez, J Molina, M C Mateos, M A Ardaiz, M Rodríguez-calvillo, C Poderós, M Arnán, R Duarte, J A Hernández, M Díaz-Morfa, E Martín-Chacón, J M Calvo-Villas, D García-Belmonte, D Hernández-Maraver, G J Ossenkoppele, J van der Lelie, B Lowenberg, P Sonneveld, M Zijlmans, E Vellenga, J Maertens, B de Valk, P W Wijermans, M R de Groot, H C Schouten, D H Biesma, M van Marwijk Kooy
Abstract
The expression of CD56 antigen in acute promyelocytic leukemia (APL) blasts has been associated with short remission duration and extramedullary relapse. We investigated the clinical significance of CD56 expression in a large series of patients with APL treated with all-trans retinoic acid and anthracycline-based regimens. Between 1996 and 2009, 651 APL patients with available data on CD56 expression were included in 3 subsequent trials (PETHEMA LPA96 and LPA99 and PETHEMA/HOVON LPA2005). Seventy-two patients (11%) were CD56(+) (expression of CD56 in ≥ 20% leukemic promyelocytes). CD56(+) APL was significantly associated with high white blood cell counts; low albumin levels; BCR3 isoform; and the coexpression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. For CD56(+) APL, the 5-year relapse rate was 22%, compared with a 10% relapse rate for CD56(-) APL (P = .006). In the multivariate analysis, CD56 expression retained the statistical significance together with the relapse-risk score. CD56(+) APL also showed a greater risk of extramedullary relapse (P < .001). In summary, CD56 expression is associated with the coexpression of immaturity-associated and T-cell antigens and is an independent adverse prognostic factor for relapse in patients with APL treated with all-trans-retinoic acid plus idarubicin-derived regimens. This marker may be considered for implementing risk-adapted therapeutic strategies in APL. The LPA2005 trial is registered at http://www.clinicaltrials.gov as NCT00408278.
Source: PubMed