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1. An analysis of the impact of CD56 expression in de novo acute promyelocytic leukemia patients treated with upfront all-trans retinoic acid and anthracycline-based regimens

Author

Sobas M, Montesinos P, Boluda B, Bernal T, Vellenga E, Nomdedeu J, Gonzalez-Campos J, Chillon M, Holowiecka A, Esteve J, Bergua J, Gonzalez-Sanmiguel J, Gil-Cortes C, Tormo M, Salamero O, Manso F, Fernandez I, de la Serna J, Moreno M, Perez-Encinas M, Krsnik I, Ribera J, Escoda L, Lowenberg B, Sanz M, de Heredia J, Hernandez J, Arias J, Ramos F, Roman A, Negri S, Rayon C, Fernandez-Calvo F, Diaz-Mediavilla J, Gil C, Olave M, Amutio E, Pedro C, Gorosquieta A, Viguria M, Zudaire M, Molero T, Sayas M, Guardia R, Esquembre C, Garcia R, Alcala A, Lopez J, Rubio V, Amigo M, Linares M, San Miguel J, Coruna A, Deben G, de la Camara R, Molines A, Loureiro C, Allegue M, Amador L, Marti J, Madero L, Lassaletta A, Cabezudo M, Garcia-Larana J, Rojas R, Ortega F, Penarrubia M, Puente F, Lopez-Ibor B, Brunet S, Ibanez J, Sanchez P, Novo A, Guinea J, Montero A, Gonzalez M, Martin G, Martinez J, Verdeguer A, Garcia P, Conde E, Garcia J, Capote F, Bueno J, Bastida P, Rubio A, Fuster J, Gonzalez J, Perez I, Molina J, Mateos M, Ardaiz M, Rodriguez-calvillo M, Poderos C, Arnan M, Duarte R, Diaz-Morfa M, Martin-Chacon E, Calvo-Villas J, Garcia-Belmonte D, Hernandez-Maraver D, Ossenkoppele G, van der Lelie J, Sonneveld P, Zijlmans M, Maertens J, de Valk B, Wijermans P, de Groot M, Schouten H, Biesma D, van Marwijk M, de Lisa E, Golos A, Ejduk A, Armatys A, Zarzycka E, Knopinska W, Miskiewicz W, Jastrzab B, Pluta A, Paluszewska M, Podhorecka M, Gromek T, Jakubas B, Majcherek M, Skret A, Watek M, Charlinski G, Calbecka M, Becht R, Gadomska A, Rzenno E, Piszcz J, Grosicki S, Palmer L, Ciarlo S, Bezares F, Rojas F, Longoni H, Gelemur M, Fazio P, Canepa C, Saba S, Balladares G, Negri P, Giunta M, Milone J, Lafalse D, Sossa C, Jaramillo F, Mayer J, Protivankova M, Scwarz J, PETHEMA Cooperative Grp, HOVON Cooperative Grp, PALG Cooperative Grp, and GATLA Cooperative Grp

Subjects
relapse, Acute promyelocytic leukemia, CD56, ATRA, chemotherapy, prognostic
Abstract

Out of 956, there were 95 (10%) CD56+ APL patients treated with PETHEMA ATRA and chemotherapy. CD56+ expression was associated with high WBC, BCR3 isoform, and co-expression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. CD56+ vs CD56- APL presented higher induction death rate (16% vs 8%, p = .02) and 5-years cumulative incidence of relapse (33% versus 10%, p = .006), irrespectively of the Sanz score (low-risk 47% versus 5%, p < .001; intermediate 23% versus 7%, p < .001; and high-risk 42% versus 21%, p = .007). In the multivariate analysis, CD56 + (p < .0001), higher relapse-risk score (p = .001), and male gender (p = .05) retained the independent predictive value. CD56+ APL also showed a greater risk of CNS relapse (6% versus 1%, p < .001) and lower 5-year OS (75% versus 83%, p = .003). The AIDA-based LPA2012 trial, with an intensified consolidation schedule for CD56+ APL, will elucidate whether an intensified consolidation schedule could mitigate the relapse rate in this setting.

Published
2019

2. An analysis of the impact of CD56 expression in de novo acute promyelocytic leukemia patients treated with upfront all-trans retinoic acid and anthracycline-based regimens

Author

Sobas, M, Montesinos, P, Boluda, B, Bernal, T, Vellenga, E, Nomdedeu, J, Gonzalez-Campos, J, Chillon, M, Holowiecka, A, Esteve, J, Bergua, J, Gonzalez-Sanmiguel, J, Gil C, Tormo, M, Salamero, O, Manso, F, Fernandez, I, de la Serna, J, Moreno, M, Perez-Encinas, M, Krsnik, I, Ribera, J, Escoda, L, Lowenberg, B, Sanz, M, de Heredia, J, Hernandez, J, Arias, J, Ramos, F, Roman, A, Negri, S, Rayon, C, Fernandez-Calvo, F, Diaz-Mediavilla, J, Gil, C, Olave, M, Amutio, E, Pedro, C, Gorosquieta, A, Viguria, M, Zudaire, M, Molero, T, Sayas, M, Guardia, R, Esquembre, C, Garcia, R, Alcala, A, Lopez, J, Rubio, V, Amigo, M, Linares, M, San Miguel, J, Coruna, A, Deben, G, de la Camara, R, Molines, A, Loureiro, C, Allegue, M, Amador, L, Marti, J, Madero, L, Lassaletta, A, Cabezudo, M, Garcia-Larana, J, Rojas, R, Ortega, F, Penarrubia, M, Puente, F, Lopez-Ibor, B, Brunet, S, Ibanez, J, Sanchez, P, Novo, A, Guinea, J, Montero, A, Gonzalez, M, Martin, G, Martinez, J, Verdeguer, A, Garcia, P, Conde, E, Garcia, J, Capote, F, Bueno, J, Bastida, P, Rubio, A, Fuster, J, Gonzalez, J, Perez, I, Molina, J, Mateos, M, Ardaiz, M, Rodriguez-calvillo, M, Poderos, C, Arnan, M, Duarte, R, Diaz-Morfa, M, Martin-Chacon, E, Calvo-Villas, J, Garcia-Belmonte, D, Hernandez-Maraver, D, Ossenkoppele, G, van der Lelie, J, Sonneveld, P, Zijlmans, M, Maertens, J, de Valk, B, Wijermans, P, de Groot, M, Schouten, H, Biesma, D, van Marwijk, M, de Lisa, E, Golos, A, Ejduk, A, Armatys, A, Zarzycka, E, Knopinska, W, Miskiewicz, W, Jastrzab, B, Pluta, A, Paluszewska, M, Podhorecka, M, Gromek, T, Jakubas, B, Majcherek, M, Skret, A, Watek, M, Charlinski, G, Calbecka, M, Becht, R, Gadomska, A, Rzenno, E, Piszcz, J, Grosicki, S, Palmer, L, Ciarlo, S, Bezares, F, Rojas, F, Longoni, H, Gelemur, M, Fazio, P, Canepa, C, Saba, S, Balladares, G, Negri, P, Giunta, M, Milone, J, Lafalse, D, Sossa, C, Jaramillo, F, Mayer, J, Protivankova, M, Scwarz, J, PETHEMA Cooperative Grp, HOVON Cooperative Grp, PALG Cooperative Grp, and GATLA Cooperative Grp

Subjects
relapse, Acute promyelocytic leukemia, CD56, ATRA, chemotherapy, prognostic
Abstract

Out of 956, there were 95 (10%) CD56+ APL patients treated with PETHEMA ATRA and chemotherapy. CD56+ expression was associated with high WBC, BCR3 isoform, and co-expression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. CD56+ vs CD56- APL presented higher induction death rate (16% vs 8%, p = .02) and 5-years cumulative incidence of relapse (33% versus 10%, p = .006), irrespectively of the Sanz score (low-risk 47% versus 5%, p < .001; intermediate 23% versus 7%, p < .001; and high-risk 42% versus 21%, p = .007). In the multivariate analysis, CD56 + (p < .0001), higher relapse-risk score (p = .001), and male gender (p = .05) retained the independent predictive value. CD56+ APL also showed a greater risk of CNS relapse (6% versus 1%, p < .001) and lower 5-year OS (75% versus 83%, p = .003). The AIDA-based LPA2012 trial, with an intensified consolidation schedule for CD56+ APL, will elucidate whether an intensified consolidation schedule could mitigate the relapse rate in this setting.

Published
2019

3. Clinical significance of complex karyotype at diagnosis in pediatric and adult patients with de novo acute promyelocytic leukemia treated with ATRA and chemotherapy

Author

Labrador J, Luno E, Vellenga E, Brunet S, Gonzalez-Campose J, Chillon M, Holowiecka A, Esteve J, Bergua J, Gonzalez-Sanmiguel J, Gil C, Tormo M, Salamero O, Manso F, Fernandez I, de laSerna J, Moreno M, Perez-Encinas M, Krsnik I, Ribera J, Cervera J, Calasanz M, Boluda B, Sobas M, Lowenberg B, Sanz M, Montesinos P, Palmer L, Ciarlo S, Bezares F, Rojas F, Longoni H, Gelemur M, Fazio P, Canepa C, Saba S, Balladares G, Negri P, Giunta M, Milone J, Prates M, Lafalse D, Sossa C, Jaramillo F, Mayer J, Protivankova M, Scwarz J, Holowiecka-Goral A, Jakubas B, Skret-Norwicz A, Bizgalska-Skrzypek P, Pluta A, Becht R, Kielbinski M, Watek M, Paluszewska M, Gadomska A, Rzenno E, Piszcz J, Ejduk A, Dobrzanska J, Calbecka M, Kostyra A, Malek M, Grosicki S, Knopinska W, Beltran de Heredia J, Hernandez J, Arias J, Ramos F, Roman A, de la Serna J, Negri S, Rayon C, Fernandez-Calvo F, Diaz-Mediavilla J, Olave M, Amutio E, Pedro C, Gorosquieta A, Viguria M, Zudaire M, Molero T, Sayas M, Guardia R, Rivas C, Esquembre C, Garcia R, Alcala A, Lopez J, Rubio V, Amigo M, Linares M, Gonzalez San Miguel J, Deben G, Escoda L, de la Camara R, Molines A, Loureiro C, Allegue M, Amador L, Marti J, Madero L, Lassaletta A, Cabezudo M, Garcia-Larana J, Rojas R, Ortega F, Penarrubia M, Puente F, Lopez-Ibor B, Ibanez J, Sanchez P, Novo A, Font L, Guinea J, Montero A, Gonzalez M, Martin G, Martinez J, Verdeguer A, Garcia P, Conde E, Garcia J, Capote F, Bueno J, Bastida P, Rubio A, Fuster J, Gonzalez J, Perez I, Molina J, Mateos M, Ardaiz M, Rodriguez-calvillo M, Poderos C, Arnan M, Duarte R, Diaz-Morfa M, Martin-Chacon E, Calvo-Villas J, Garcia-Belmonte D, Hernandez-Maraver D, Ossenkoppele G, van der Lelie J, Sonneveld P, Zijlmans M, Maertens J, de Valk B, Wijermans P, de Groot M, Schouten H, Biesma D, Kooy M, de Lisa E, PETHEMA Grp, HOVON Grp, PALG Grp, and GATLA Grp

Subjects
relapse, complex karyotype, Acute promyelocytic leukemia, ATRA, chemotherapy, prognostic
Abstract

Although additional cytogenetic abnormalities (ACA) do not affect the prognosis of patients with t(15;17) acute promyelocytic leukemia (APL), the role of a complex karyotype (CK) is yet to be clarified. We aimed to investigate the relationship of CK with relapse incidence in 1559 consecutive APL patients enrolled in three consecutive trials. Treatment consisted of AIDA induction followed by risk-adapted consolidation. A CK (CK) was defined as the presence of >= 2 ACA, and a very CK (CK+) as >= 3 ACA. Eighty-nine patients (8%) had a CK, of whom 41 (4%) had CK+. The 5-year cumulative incidence of relapse (CIR) in patients with CK was 18%, and 12% in those with

Published
2019

4. Clinical significance of complex karyotype at diagnosis in pediatric and adult patients with de novo acute promyelocytic leukemia treated with ATRA and chemotherapy

Author

Labrador, J, Luno, E, Vellenga, E, Brunet, S, Gonzalez-Campose, J, Chillon, MC, Holowiecka, A, Esteve, J, Bergua, J, Gonzalez-Sanmiguel, JD, Gil, C, Tormo, M, Salamero, O, Manso, F, Fernandez, I, de laSerna, J, Moreno, MJ, Perez-Encinas, M, Krsnik, I, Ribera, JM, Cervera, J, Calasanz, MJ, Boluda, B, Sobas, M, Lowenberg, B, Sanz, MA, Montesinos, P, Palmer, L, Ciarlo, S, Bezares, F, Rojas, F, Longoni, H, Gelemur, M, Fazio, P, Canepa, C, Saba, S, Balladares, G, Negri, P, Giunta, M, Milone, J, Prates, MV, Lafalse, D, Sossa, C, Jaramillo, F, Mayer, J, Protivankova, M, Scwarz, J, Holowiecka-Goral, A, Jakubas, B, Skret-Norwicz, A, Bizgalska-Skrzypek, P, Pluta, A, Becht, R, Kielbinski, M, Watek, M, Paluszewska, M, Gadomska, A, Rzenno, E, Piszcz, J, Ejduk, A, Dobrzanska, J, Calbecka, M, Kostyra, A, Malek, M, Grosicki, S, Knopinska, W, de Heredia, JMB, Hernandez, JM, Arias, J, Ramos, F, Roman, A, de la Serna, J, Negri, S, Rayon, C, Fernandez-Calvo, FJ, Diaz-Mediavilla, J, Olave, M, Amutio, E, Pedro, C, Gorosquieta, A, Viguria, M, Zudaire, M, Molero, T, Sayas, MJ, Guardia, R, Rivas, C, Esquembre, C, Garcia, R, Alcala, A, Lopez, JA, Rubio, V, Amigo, ML, Linares, M, San Miguel, JDG, Deben, G, Escoda, L, de la Camara, R, Molines, A, Loureiro, C, Allegue, MJ, Amador, L, Marti, JM, Madero, L, Lassaletta, A, Cabezudo, M, Garcia-Larana, J, Rojas, R, Ortega, F, Penarrubia, MJ, Puente, F, Lopez-Ibor, B, Bergua, JM, Ibanez, J, Sanchez, P, Novo, A, Font, LL, Guinea, JM, Montero, A, Gonzalez, M, Martin, G, Martinez, J, Verdeguer, A, Garcia, P, Conde, E, Garcia, J, Capote, FJ, Bueno, J, Bastida, P, Rubio, A, Fuster, JL, Gonzalez, J, Perez, I, Molina, J, Mateos, MC, Ardaiz, MA, Rodriguez-calvillo, M, Poderos, C, Arnan, M, Duarte, R, Hernandez, JA, Diaz-Morfa, M, Martin-Chacon, E, Calvo-Villas, JM, Garcia-Belmonte, D, Hernandez-Maraver, D, Ossenkoppele, GJ, van der Lelie, J, Sonneveld, P, Zijlmans, M, Maertens, J, de Valk, B, Wijermans, PW, de Groot, MR, Schouten, HC, Biesma, DH, Kooy, MV, and de Lisa, E

Subjects
relapse, complex karyotype, Acute promyelocytic leukemia, ATRA, chemotherapy, prognostic
Abstract

Although additional cytogenetic abnormalities (ACA) do not affect the prognosis of patients with t(15;17) acute promyelocytic leukemia (APL), the role of a complex karyotype (CK) is yet to be clarified. We aimed to investigate the relationship of CK with relapse incidence in 1559 consecutive APL patients enrolled in three consecutive trials. Treatment consisted of AIDA induction followed by risk-adapted consolidation. A CK (CK) was defined as the presence of >= 2 ACA, and a very CK (CK+) as >= 3 ACA. Eighty-nine patients (8%) had a CK, of whom 41 (4%) had CK+. The 5-year cumulative incidence of relapse (CIR) in patients with CK was 18%, and 12% in those with

Published
2019

5. An analysis of the impact of CD56 expression in de novo acute promyelocytic leukemia patients treated with upfront all-trans retinoic acid and anthracycline-based regimens

Author

Sobas, M, Montesinos, P, Boluda, B, Bernal, T, Vellenga, E, Nomdedeu, J, Gonzalez-Campos, J, Chillon, M, Holowiecka, A, Esteve, J, Bergua, J, Gonzalez-Sanmiguel, JD, Gil-Cortes, C, Tormo, M, Salamero, O, Manso, F, Fernandez, I, de la Serna, J, Moreno, MJ, Perez-Encinas, M, Krsnik, I, Ribera, JM, Escoda, L, Lowenberg, B, Sanz, MA, de Heredia, JMB, Hernandez, JM, Arias, J, Ramos, F, Roman, A, Negri, S, Rayon, C, Fernandez-Calvo, FJ, Diaz-Mediavilla, J, Gil, C, Olave, M, Amutio, E, Pedro, C, Gorosquieta, A, Viguria, M, Zudaire, M, Molero, T, Sayas, MJ, Guardia, R, Esquembre, C, Garcia, R, Alcala, A, Lopez, JA, Rubio, V, Amigo, ML, Linares, M, San Miguel, JDG, Coruna, A, Deben, G, de la Camara, R, Molines, A, Loureiro, C, Allegue, MJ, Amador, L, Marti, JM, Madero, L, Lassaletta, A, Cabezudo, M, Garcia-Larana, J, Rojas, R, Ortega, F, Penarrubia, MJ, Puente, F, Lopez-Ibor, B, Brunet, S, Ibanez, J, Sanchez, P, Novo, A, Guinea, JM, Montero, A, Gonzalez, M, Martin, G, Martinez, J, Verdeguer, A, Garcia, P, Conde, E, Garcia, J, Capote, FJ, Bueno, J, Bastida, P, Rubio, A, Fuster, JL, Gonzalez, J, Perez, I, Molina, J, Mateos, MC, Ardaiz, MA, Rodriguez-calvillo, M, Poderos, C, Arnan, M, Duarte, R, Diaz-Morfa, M, Martin-Chacon, E, Calvo-Villas, JM, Garcia-Belmonte, D, Hernandez-Maraver, D, Ossenkoppele, GJ, van der Lelie, J, Sonneveld, P, Zijlmans, M, Maertens, J, de Valk, B, Wijermans, PW, de Groot, MR, Schouten, HC, Biesma, DH, van Marwijk, M, de Lisa, E, Golos, A, Ejduk, A, Armatys, A, Zarzycka, E, Knopinska, W, Miskiewicz, W, Jastrzab, B, Pluta, A, Paluszewska, M, Podhorecka, M, Gromek, T, Jakubas, B, Majcherek, M, Skret, A, Watek, M, Charlinski, G, Calbecka, M, Becht, R, Gadomska, A, Rzenno, E, Piszcz, J, Grosicki, S, Palmer, L, Ciarlo, S, Bezares, F, Rojas, F, Longoni, H, Gelemur, M, Fazio, P, Canepa, C, Saba, S, Balladares, G, Negri, P, Giunta, M, Milone, J, Lafalse, D, Sossa, C, Jaramillo, F, Mayer, J, Protivankova, M, and Scwarz, J

Subjects
relapse, Acute promyelocytic leukemia, CD56, ATRA, chemotherapy, prognostic
Abstract

Out of 956, there were 95 (10%) CD56+ APL patients treated with PETHEMA ATRA and chemotherapy. CD56+ expression was associated with high WBC, BCR3 isoform, and co-expression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. CD56+ vs CD56- APL presented higher induction death rate (16% vs 8%, p = .02) and 5-years cumulative incidence of relapse (33% versus 10%, p = .006), irrespectively of the Sanz score (low-risk 47% versus 5%, p < .001; intermediate 23% versus 7%, p < .001; and high-risk 42% versus 21%, p = .007). In the multivariate analysis, CD56 + (p < .0001), higher relapse-risk score (p = .001), and male gender (p = .05) retained the independent predictive value. CD56+ APL also showed a greater risk of CNS relapse (6% versus 1%, p < .001) and lower 5-year OS (75% versus 83%, p = .003). The AIDA-based LPA2012 trial, with an intensified consolidation schedule for CD56+ APL, will elucidate whether an intensified consolidation schedule could mitigate the relapse rate in this setting.

Published
2019

6. Clinical significance of complex karyotype at diagnosis in pediatric and adult patients with de novo acute promyelocytic leukemia treated with ATRA and chemotherapy

Author

Labrador, J, Luno, E, Vellenga, E, Brunet, S, Gonzalez-Campose, J, Chillon, MC, Holowiecka, A, Esteve, J, Bergua, J, Gonzalez-Sanmiguel, JD, Gil, C, Tormo, M, Salamero, O, Manso, F, Fernandez, I, de laSerna, J, Moreno, MJ, Perez-Encinas, M, Krsnik, I, Ribera, JM, Cervera, J, Calasanz, MJ, Boluda, B, Sobas, M, Lowenberg, B, Sanz, MA, Montesinos, P, Palmer, L, Ciarlo, S, Bezares, F, Rojas, F, Longoni, H, Gelemur, M, Fazio, P, Canepa, C, Saba, S, Balladares, G, Negri, P, Giunta, M, Milone, J, Prates, MV, Lafalse, D, Sossa, C, Jaramillo, F, Mayer, J, Protivankova, M, Scwarz, J, Jakubas, B, Skret-Norwicz, A, Bizgalska-Skrzypek, P, Pluta, A, Becht, R, Kielbinski, M, Watek, M, Paluszewska, M, Gadomska, A, Rzenno, E, Piszcz, J, Ejduk, A, Dobrzanska, J, Calbecka, M, Kostyra, A, Malek, M, Grosicki, S, Knopinska, W, de Heredia, JMB, Hernandez, JM, Arias, J, Ramos, F, Roman, A, Negri, S, Rayon, C, Fernandez-Calvo, FJ, Diaz-Mediavilla, J, Olave, M, Amutio, E, Pedro, C, Gorosquieta, A, Viguria, M, Zudaire, M, Molero, T, Sayas, MJ, Guardia, R, Rivas, C, Esquembre, C, Garcia, R, Alcala, A, Lopez, JA, Rubio, V, Amigo, ML, Linares, M, San Miguel, JDG, Deben, G, Escoda, L, de la Camara, R, Molines, A, Loureiro, C, Allegue, MJ, Amador, L, Marti, JM, Madero, L, Lassaletta, A, Cabezudo, M, Garcia-Larana, J, Rojas, R, Ortega, F, Penarrubia, MJ, Puente, F, Lopez-Ibor, B, Ibanez, J, Sanchez, P, Novo, A, Font, LL, Guinea, JM, Montero, A, Gonzalez, M, Martin, G, Martinez, J, Verdeguer, A, Garcia, P, Conde, E, Garcia, J, Capote, FJ, Bueno, J, Bastida, P, Rubio, A, Fuster, JL, Perez, I, Molina, J, Mateos, MC, Ardaiz, MA, Rodriguez-calvillo, M, Poderos, C, Arnan, M, Duarte, R, Hernandez, JA, Diaz-Morfa, M, Martin-Chacon, E, Calvo-Villas, JM, Garcia-Belmonte, D, Hernandez-Maraver, D, Ossenkoppele, GJ, van der Lelie, J, Sonneveld, P, Zijlmans, M, Maertens, J, de Valk, B, Wijermans, PW, de Groot, MR, Schouten, HC, Biesma, DH, Kooy, MV, and de Lisa, E

Subjects
relapse, complex karyotype, Acute promyelocytic leukemia, ATRA, chemotherapy, prognostic
Abstract

Although additional cytogenetic abnormalities (ACA) do not affect the prognosis of patients with t(15;17) acute promyelocytic leukemia (APL), the role of a complex karyotype (CK) is yet to be clarified. We aimed to investigate the relationship of CK with relapse incidence in 1559 consecutive APL patients enrolled in three consecutive trials. Treatment consisted of AIDA induction followed by risk-adapted consolidation. A CK (CK) was defined as the presence of >= 2 ACA, and a very CK (CK+) as >= 3 ACA. Eighty-nine patients (8%) had a CK, of whom 41 (4%) had CK+. The 5-year cumulative incidence of relapse (CIR) in patients with CK was 18%, and 12% in those with

Published
2019

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