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5. Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia

Author

Genescà, E., Lazarenkov, A., Morgades, M., Berbis, G., Ruíz-Xivillé, N., Gómez-Marzo, P., Ribera, J., Juncà, J., González-Pérez, A., Mercadal, S., Guardia, R., Artola, M. T., Moreno, M. J., Martínez-López, J., Zamora, L., Barba, P., Gil, C., Tormo, M., Cladera, A., Novo, A., Pratcorona, M., Nomdedeu, J., González-Campos, J., Almeida, M., Cervera, J., Montesinos, P., Batlle, M., Vives, S., Esteve, J., Feliu, E., Solé, F., Orfao, A., and Ribera, J. M.

Published
2018
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9. 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, Marta, Montesinos, Pau, Boluda, Blanca, Bernal, Teresa, Vellenga, Edo, Nomdedeu, Josep, Gonzalez-Campos, Jose, Chillon, Maria, Holowiecka, Aleksandra, Esteve, Jordi, Bergua, Juan, David Gonzalez-Sanmiguel, Jose, Gil-Cortes, Cristina, Tormo, M., Salamero, Olga, Manso, Felix, Fernandez, Isolda, de la Serna, Javier, Moreno, Maria-Jose, Perez-Encinas, Manuel, Krsnik, Isabel, Ribera, Josep-Maria, Escoda, Lourdes, Lowenberg, Bob, Angel Sanz, Miguel, Beltran de Heredia, J. M., Hernandez, J. M., Arias, J., Ramos, F., Roman, A., de la Serna, J., Negri, S., Rayon, C., Esteve, J., Fernandez-Calvo, F. J., Diaz-Mediavilla, J., Gil, C., Olave, M., Amutio, E., Pedro, C., Gorosquieta, A., Viguria, M., Zudaire, M., Molero, T., Sayas, M. J., Guardia, R., Martinez, J., de Groot, M. R., Schouten, H. C., Hematology, Radiotherapy, Erasmus MC other, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), Interne Geneeskunde, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and MUMC+: MA Hematologie (9)

Subjects
Male, Cancer Research, medicine.medical_treatment, Retinoic acid, CD34, Gene Expression, Kaplan-Meier Estimate, chemotherapy, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, PROGNOSTIC-FACTORS, Leukemia, Promyelocytic, Acute, Recurrence, Acute promyelocytic leukemia, Antineoplastic Combined Chemotherapy Protocols, FAILURE, Anthracyclines, Cumulative incidence, ATRA, Child, CONSOLIDATION, relapse, RISK, Hematology, Middle Aged, Prognosis, CD56 Antigen, Leukemia, Treatment Outcome, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Female, CD56, medicine.medical_specialty, Adolescent, Anthracycline, Tretinoin, Young Adult, 03 medical and health sciences, ADULT, Internal medicine, medicine, Humans, INDICATOR, Aged, Chemotherapy, business.industry, De novo acute, medicine.disease, chemistry, business, prognostic, 030215 immunology
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

Published
2019
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21. Current drive methods to extend the range of travel of electrostatic microactuators beyond the voltage pull-in point

Author

Nadal-Guardia, R., Dehe, A., Aigner, R., and Castaner, L.M.

Subjects
Microelectromechanical systems -- Research, Electrostatics -- Research, Engineering and manufacturing industries, Science and technology
Abstract

When a voltage source drives an electrostatic parallel plate actuator, the well-known pull-in instability limits the range of displacement to 1/3 of the gap. Different strategies have been reported to overcome this limitation. More recently, experimental results [1] have been presented using a capacitor in series with the actuator [2]. Nevertheless, this strategy requires higher voltage than the pull-in voltage value to achieve full range of travel. In order to reduce the operating voltage, a switched-capacitor configuration has been also proposed [3]. In this paper, two different approaches are introduced to control charge in the actuator by means of current driving. Theoretical equations derived for each method show that full range of travel can be achieved without voltage penalty. Both approaches are based on the use of current pulses injecting the required amount of charge to fix the position of the movable plate. However, the first method uses a series capacitance to sense the voltage drop produced by the injected charge [4]. Depending on the sensed voltage more charge is injected, switching on the driving current source, or removed, with the current sink. The second approach operates in open loop configuration [5]. The current source is switched off after injecting the required charge to fix the movable electrode to the desired position. The position shift, due to the leakage currents, is eliminated by a refresh cycle. Experimental measurements, showing that displacement beyond the pull-in point can be achieved, are in good agreement with the theoretical and the predicted simulated behavior. [707] Index Terms--Electrostatic actuators, extended travel, position control, pull-in actuators.

Published
2002

23. Silent ribosomal cistrons are located at the pairing segment of the postreductional sex chromosomes of Apodemus sylvaticus (Rodentia, Muridae)

Author

Stitou, S., Jimenez, R., Guardia, R. Diaz de la, and Burgos, M.

Subjects
Heredity -- Research, Ribosomes -- Research, Rodents -- Genetic aspects, Meiosis -- Research, Sex chromosomes -- Research, Biological sciences
Abstract

Silent ribosomal cistrons have been found to be at the pairing segment of the postreductional sex chromosomes of Apodemus sylvaticus (Rodentia, Muridae). The karyotype of the species was analyzed by G- and C-banding, Ag-nucleolar-organizer regions (NOR)-staining and in situ hydridization, with special attention to sex chromosomes.

Published
2001

28. Norgestomet implants prevent pregnancy in beef heifers on pasture

Author

Geary, T.W., Reeves, J.J., Schafer, D.W., Evans, R.R., Randel, R.D., Rutter, L.M., Sasser, R.G., Guardia, R., Alexander, B., Holcombe, D., Hanks, D.R., and Faulkner, D.B.

Subjects
Beef cattle -- Breeding, Heifers -- Research, Progestational hormones -- Usage, Zoology and wildlife conservation
Abstract

The efficacy of erodible norgestomet implants for preventing pregnancy in postpubertal heifers was evaluated in two experiments at five locations each. Heifers (n = 896) within each study location were stratified by weight and allotted randomly to receive an ear implant containing either 0, 24, 36, or 48 mg of norgestomet (d 0). Heifers were exposed to fertile bulls immediately after implantation for 75 d (d 0 to 74) in Exp. 1 (n = 476) or for 80 d (d 75 to 154) in Exp. 2 (n = 420). Weights were recorded on d 0 and 74 (Exp. 1 and 2) and d 154 (Exp. 2). Each heifer was palpated rectally for pregnancy at the end of each experiment. Pregnancy rates were higher (P < .01) for control heifers (0 mg implant) than for heifers that received 24, 36, or 48 mg of norgestomet. In Exp. 1, pregnancy rates were 96, 29, 6, and 4% for heifers that received 0, 24, 36, and 48 mg implants of norgestomet, respectively. In Exp. 2, pregnancy rates were 85, 36, 19, and 9% for heifers that received 0, 24, 36, and 48 mg implants of norgestomet, respectively. Estrous activity during the first 3 wk of bull exposure was reduced (P < .05) among heifers that received norgestomet implants compared to control heifers but was not completely abolished at any dosage in Exp. 1. During the first 75 d of Exp. 1 and 2, heifers treated with 36 or 48 mg norgestomet implants gained weight faster (P < .05) than control heifers. Combined across both experiments, ADG during the first 74 d were .53, .56, .59, and .60 kg/d for heifers treated with 0, 24, 36, and 48 mg implants of norgestomet, respectively. These data indicate that norgestomet implants increased rate of weight gain, reduced estrous activity, and reduced the occurrence of pregnancy in heifers on pasture. Key Words: Beef Cattle, Progestogens, Heifers, Females, Fertility, Pastures

Published
1997

29. 41BB-based and CD28-based CD123-redirected T-cells ablate human normal hematopoiesis in vivo

Author

Baroni, M.L. (Matteo Libero), Sanchez Martinez, D. (Diego), Gutierrez Aguera, F. (Francisco), Roca Ho, H. (Heleia), Castella, M. (Maria), Zanetti, S. (Samanta), Velasco Hernandez, T. (Talia), Diaz de la Guardia, R. (Rafael), Castaño, J. (Julio), Anguita, E. (Eduardo), Vives, S. (Susana), Nomdedéu, J. (J), Lapillone, H. (H.), Bras, A.E. (Anne), Velden, V.H.J. (Vincent) van der, Junca, J. (Jordi), Marin, P. (Pedro), Bataller, A. (Alex), Esteve, J. (Jordi), Vick, B. (Binje), Jeremias, I. (Irmela), Lopez, A. (Angel), Sorigue, M. (Marc), Bueno, C. (Clara), Menéndez, P. (Pablo), Baroni, M.L. (Matteo Libero), Sanchez Martinez, D. (Diego), Gutierrez Aguera, F. (Francisco), Roca Ho, H. (Heleia), Castella, M. (Maria), Zanetti, S. (Samanta), Velasco Hernandez, T. (Talia), Diaz de la Guardia, R. (Rafael), Castaño, J. (Julio), Anguita, E. (Eduardo), Vives, S. (Susana), Nomdedéu, J. (J), Lapillone, H. (H.), Bras, A.E. (Anne), Velden, V.H.J. (Vincent) van der, Junca, J. (Jordi), Marin, P. (Pedro), Bataller, A. (Alex), Esteve, J. (Jordi), Vick, B. (Binje), Jeremias, I. (Irmela), Lopez, A. (Angel), Sorigue, M. (Marc), Bueno, C. (Clara), and Menéndez, P. (Pablo)

Abstract

BACKGROUND: Acute myeloid leukemia (AML) is a hematopoietic malignancy which is biologically, phenotypically and genetically very heterogeneous. Outcome of patients with AML remains dismal, highlighting the need for improved, less toxic therapies. Chimeric antigen receptor T-cell (CART) immunotherapies for patients with refractory or relapse (R/R) AML are challenging because of the absence of a universal pan-AML target antigen and the shared expression of target antigens with normal hematopoietic stem/progenitor cells (HSPCs), which may lead to life-threating on-target/off-tumor cytotoxicity. CD33-redirected and CD123-redirected CARTs for AML are in advanced preclinical and clinical development, and they exhibit robust antileukemic activity. However, preclinical and clinical controversy exists on whether such CARTs are myeloablative. METHODS: We set out to comparatively characterize in vitro and in vivo the efficacy and safety of 41BB-based and CD28-based CARCD123. We analyzed 97 diagnostic and relapse AML primary samples to investigate whether CD123 is a suitable immunotherapeutic target, and we used several xenograft models and in vitro assays to assess the myeloablative potential of our second-generation CD123 CARTs. RESULTS: Here, we show that CD123 represents a bona fide target for AML and show that both 41BB-based and CD28-based CD123 CARTs are very efficient in eliminating both AML cell lines and primary cells in vitro and in vivo. However, both 41BB-based and CD28-based CD123 CARTs ablate normal human hematopoiesis and prevent the establishment of de novo hematopoietic reconstitution by targeting both immature and myeloid HSPCs. CONCLUSIONS: This study calls for caution when clinically implementing CD123 CARTs, encouraging its preferential use as a bridge to allo-HSCT in patients with R/R AML.

Published
2020
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39. Real life outcomes of patients aged >= 75 years old with acute promyelocytic leukemia: experience of the PETHEMA registry

Author

Salamero O, Mart?nez-Cuadr?n D, Sobas M, Benavente C, Vives S, De la Serna J, P?rez-Encinas M, Escoda L, Gil C, Brunet S, Ramos F, Esteve J, Amigo M, Krsnik I, Manso F, Arias J, Gonz?lez-Campos J, Serrano J, Oleksiuk J, Barrios M, Garc?a-Boyero R, Novo A, Sanz M, Montesinos P, Helbig G, Holowiecka A, Armatys A, Hawrylecka D, Golos A, Ejduk A, Majcherek M, Skret A, Czyzewska J, Grosicki S, Zarzycka E, Watek M, Piatkowska-Jakubas B, Holojda J, Pluta A, Podhorecka M, Gromek T, Guzicka E, Charlinski G, Paluszewska M, de Heredia J, Hern?ndez J, Rom?n A, de la Serna J, Negri S, Ray?n C, Fern?ndez-Calvo F, D?az-Mediavilla J, Tormo M, Olave M, Amutio E, Pedro C, Gorosquieta A, Viguria M, Zudaire M, Molero T, Sayas M, Guardia R, Rivas C, Esquembre C, Garc?a R, Alcal? A, L?pez J, Rubio V, Linares M, Ribera J, San Miguel J, Deb?n G, de la C?mara R, Molines A, Loureiro C, Allegue M, Amador L, Mart? J, Madero L, Lassaletta A, Cabezudo M, Garc?a-Larana J, Rojas R, Ortega F, Pe?arrubia M, Puente F, Lopez-Ibor B, Bergua J, Ib??ez J, S?nchez P, Font L, Guinea J, Montero A, Gonz?lez M, Mart?n G, Mart?nez J, Verdeguer A, Garc?a P, Conde E, Garc?a J, Capote F, Bueno J, Bastida P, Rubio A, Fuster J, Gonz?lez J, P?rez I, Molina J, Mateos M, Ardaiz M, Rodr?guez-Calvillo M, Poder?s C, Arn?n M, Duarte R, D?az-Morfa M, Mart?n-Chac?n E, Calvo-Villas J, Garc?a-Belmonte D, Hern?ndez-Maraver D, Miskiewicz W, PETHEMA Grp, and PALG Grp

Subjects
induction mortality in APL, APL real life outcomes, Elderly APL, APL prognostic factors, neoplasms
Abstract

Acute promyelocytic leukemia is infrequent among patients aged >= 75 years old, a population that is rarely eligible for clinical protocols. This study aims to analyze the treatment strategies and clinical outcomes of very old APL patients reported to the international PETHEMA registry. Between 1997 and 2017, among 2501 APL cases registered 120 were >= 75 years old. Treatment approaches were: AIDA regimen, 79 patients; ATRA alone, 23; 16, supportive care (SC) and 2, other strategies. Patients treated with AIDA were younger, had better ECOG and lower leukocytes. Complete remission (CR) was achieved in 65% of AIDA-group vs. 45% in the ATRA-group, being infections followed by bleeding the most frequent causes of induction death. Patients in CR after AIDA showed 3-year DFS of 73%. Our real-life series of very old APL patients provides a reference basis for future treatment strategies aiming to improve clinical outcomes in this challenging population.

Published
2019

40. Molecular profiling refines minimal residual disease-based prognostic assessment in adults with Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia

Author

Ribera J, Zamora L, Morgades M, Vives S, Granada I, Montesinos P, Gomez-Segui I, Mercadal S, Guardia R, Nomdedeu J, Pratcorona M, Tormo M, Martinez-Lopez J, Hernandez-Rivas J, Ciudad J, Orfao A, Gonzalez-Campos J, Barba P, Escoda L, Esteve J, Genesca E, Sole F, Feliu E, Spanish PETHEMA Grp, and Spanish Soc Hematology

Subjects
hemic and lymphatic diseases
Abstract

Minimal residual disease (MRD) assessment is an essential tool in contemporary acute lymphoblastic leukemia (ALL) protocols, being used for therapeutic decisions such as hematopoietic stem cell transplantation in high-risk patients. However, a significant proportion of adult ALL patients with negative MRD still relapse suggesting that other factors (ie, molecular alterations) must be considered in order to identify those patients with high risk of disease progression. We have identified partial IKZF1 gene deletions and CDKN2A/B deletions as markers of disease recurrence and poor survival in a series of uniformly treated adolescent and adult Philadelphia chromosome-negative B-cell progenitor ALL patients treated according to the Programa Espanol de Tratamientos en Hematologia protocols. Importantly, CDKN2A/B deletions showed independent significance of MRD at the end of induction, which points out the need for treatment intensification in these patients despite being MRD-negative after induction therapy.

Published
2019

41. 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

44. Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Author

Urdinguio, RG, Lopez, V, Bayon, GF, Diaz de la Guardia, R, Sierra, MI, Garcia-Torano, E, Perez, RF, Garcia, MG, Carella, A, Pruneda, PC, Prieto, C, Dmitrijeva, M, Santamarina, P, Belmonte, T, Mangas, C, Diaconu, E, Ferrero, C, Ramon Tejedor, J, Luis Fernandez-Morera, J, Bravo, C, Bueno, C, Sanjuan-Pla, A, Rodriguez, RM, Suarez-Alvarez, B, Lopez-Larrea, C, Bernal, T, Colado, E, Balbin, M, Garcia-Suarez, O, Dolores Chiara, M, Saenz-de-Santa-Maria, I, Rodriguez, F, Pando-Sandoval, A, Rodrigo, L, Santos, L, Salas, A, Vallejo-Diaz, J, Carrera, AC, Rico, D, Hernandez-Lopez, I, Vaya, A, Ricart, JM, Seto, E, Sima-Teruel, N, Vaquero, A, Valledor, L, Jesus Canal, M, Pisano, D, Grana-Castro, O, Thomas, T, Voss, AK, Menendez, P, Villar-Garea, A, Deutzmann, R, Fernandez, AF, Fraga, MF, Urdinguio, RG, Lopez, V, Bayon, GF, Diaz de la Guardia, R, Sierra, MI, Garcia-Torano, E, Perez, RF, Garcia, MG, Carella, A, Pruneda, PC, Prieto, C, Dmitrijeva, M, Santamarina, P, Belmonte, T, Mangas, C, Diaconu, E, Ferrero, C, Ramon Tejedor, J, Luis Fernandez-Morera, J, Bravo, C, Bueno, C, Sanjuan-Pla, A, Rodriguez, RM, Suarez-Alvarez, B, Lopez-Larrea, C, Bernal, T, Colado, E, Balbin, M, Garcia-Suarez, O, Dolores Chiara, M, Saenz-de-Santa-Maria, I, Rodriguez, F, Pando-Sandoval, A, Rodrigo, L, Santos, L, Salas, A, Vallejo-Diaz, J, Carrera, AC, Rico, D, Hernandez-Lopez, I, Vaya, A, Ricart, JM, Seto, E, Sima-Teruel, N, Vaquero, A, Valledor, L, Jesus Canal, M, Pisano, D, Grana-Castro, O, Thomas, T, Voss, AK, Menendez, P, Villar-Garea, A, Deutzmann, R, Fernandez, AF, and Fraga, MF

Abstract

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death.

Published
2019

46. Frequency and prognostic significance of additional cytogenetic abnormalities to the Philadelphia chromosome in young and older adults with acute lymphoblastic leukemia

Author

Motllo C, Ribera JM, Morgades M, Granada I, Montesinos P, Mercadal S, Gonzalez-Campos J, Moreno MJ, Barba P, Cervera M, Barrios M, Novo A, Bernal T, Hernandez-Rivas JM, Abella E, Amigo ML, Tormo M, Martino R, Lavilla E, Bergua J, Serrano A, Garcia-Belmonte D, Guardia R, Grau J, Feliu E, and PETHEMA Group, Spanish Society of Hematology

Subjects
prognosis, Acute lymphoblastic leukemia, Philadelphia chromosome, additional cytogenetic alterations, monosomies
Abstract

About 25-35% of adult patients with acute lymphoblastic leukemia show the Philadelphia (Ph) chromosome. Few series have evaluated the prognosis of additional cytogenetic alterations (ACA) to the Ph chromosome. We analyzed the frequency, type and prognostic significance ofACA in adults (18-60 years) treated in the ALL-Ph-08 trial. Fifty-two out of 74 patients (70%) showed ACA and 19 (26%) presented monosomies associated with t(9; 22) (monosomal karyotype, MK). Similar complete response (CR) rate, CR duration, overall survival and event-free survival (EFS) were observed in patients with or without ACA, but patients with MK showed shorter CR duration and EFS than the remaining. On multivariate analysis, the only variable with prognostic impact for CR duration and EFS was the presence of MK (p = .003 and p = .036, respectively). Although ACA associated with the Ph chromosome are frequent, only monosomies were associated with poor prognosis in this group of patients.

Published
2018

47. Comparison of intensive, pediatric-inspired therapy with non-intensive therapy in older adults aged 55-65 years with Philadelphia chromosome-negative acute lymphoblastic leukemia

Author

Ribera, JM, Garcia, O, Gil, C, Mercadal, S, Garcia-Cadenas, I, Montesinos, P, Barba, P, Vives, S, Gonzalez-Campos, J, Tormo, M, Esteve, J, Lopez, A, Moreno, MJ, Ribera, J, Alonso, N, Bermudez, A, Amigo, ML, Genesca, E, Garcia, D, Vall-Llovera, F, Bergua, JM, Guardia, R, Monteserin, MC, Bernal, T, Calbacho, M, Martinez, MP, Feliu, E, and PETHEMA Grp

Subjects
Older adults, Philadelphia chromosome-negative, Chemotherapy, Acute lymphoblastic leukemia
Abstract

Background and objective: The standardization of treatment of older adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) is challenging, especially in the age range of 55-65 years. This study aimed to compare intensive, pediatric-inspired therapy with non-intensive therapy in this population of patients. Patients and methods: The outcomes of 67 patients prospectively included in two consecutive pediatric-inspired intensive protocols (ALL-HR03 and ALL-HR11) from the Spanish PETHEMA Group were compared with those from 44 patients included in a contemporary semi-intensive protocol (ALL-OLD07). Results: Baseline patient and ALL characteristics were similar in both groups, except for a younger median age in the intensive group (medians: 58 vs. 62 years). Patients treated intensively had a higher complete remission rate (85% vs. 64%, p = 0.005), a lower cumulative incidence of relapse (39% [95% CI, 25% to 52%] vs. 60% [95% CI, 38% to 77%], p =. 003), a similar cumulative incidence of treatment-related mortality (28% [95% CI, 18%, 40%] vs. 21% [95% CI, 10%, 34%]) and superior event-free survival at 2 years (37% [95% CI, 25%-49%) vs. 21% [8%-34%], p = 0.002). On multivariable analysis the type of protocol was the only variable with independent significance for event-free survival (HR [95% CI]: 2 [1.3, 3], p =. 002). Conclusions: Compared with less intensive chemotherapy, pediatric-inspired intensive chemotherapy significantly improves the outcome of older adults with Ph-negative ALL in the age range of 55-65 years.

Published
2018

50. PROFILING OF RECURRENT COPY NUMBER ALTERATIONS IN RELAPSED ADULT B CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA

Author

Ribera, J., Morgades, M., Zamora, L., Mallo, M., Solanes, N., Vives, S., Batlle, M., Cabezon, M., Marce, S., Dominguez, D., Granada, I., Junca, J., Malinverni, R., Ruiz, R., Gomez, P., Guardia, R., Mercadal, S., Escoda, L., Vall-Llovera, F., Martinez Lopez, J., Tormo, M., Esteve, J., Nomdedeu, J., Pratcorona, M., Sanchez, J., Genesca, E., Sole, F., Feliu, E., and Ribera, J. M.

Published
2017

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