Research publications

Found 5 publicacions matching the indicated search criteria.
Ribera JM, García-Calduch O, Ribera J, Montesinos P, Cano-Ferri I, Martínez P, Esteve J, Esteban D, García-Fortes M, Alonso N, González-Campos J, Bermúdez A, Torrent A, Genesca E, Mercadal S, Martínez-Lopez J, Garcia-Sanz R

Ponatinib, Chemotherapy, and Transplant in Adults with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.

Blood Adv 8 Jun 2022, . Epub 8 Jun 2022
Promising results have been shown combining ponatinib and chemotherapy in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). The PONALFIL trial combined ponatinib (30 mg/day) with standard induction and consolidation chemotherapy followed by allogeneic hematopoietic stem cell transplant (alloHSCT) in newly diagnosed Ph+ALL patients aged 18-60 years. Ponatinib was only given pre-emptively after alloHSCT. Primary endpoints were hematologic and molecular response before alloHSCT and event-free survival (EFS), including molecular relapse as event. Thirty patients (median age 49 [19-59] years) entered the trial. All showed hematologic response, and alloHSCT was performed in 26 patients (20 in complete molecular response and 6 in major molecular response). Only one patient died by graft-versus-host disease and 5 patients showed molecular relapse after alloHSCT. No tyrosine kinase inhibitor (TKI) was given after HSCT in 18/26 patients. Twenty-nine patients are alive (median follow-up 2.1 years, range 0.2-4.0), with 3-year EFS and overall survival (OS) of 70% (95% CI, 51%-89%) and 96% (89%-100%). Comparison of the PONALFIL and the ALLPh08 trials (same schedule using imatinib as TKI ) by propensity score showed significant improvement in OS for patients in PONALFIL (3-year OS 96% vs. 53%, p=0.002). The most frequent grade 3-4 adverse events were hematologic (42%), infections (17%) and hepatic (22%), with only one vascular occlusive event. The combination of chemotherapy with ponatinib followed by alloHSCT is well tolerated, with encouraging EFS in adults with newly diagnosed Ph+ALL. Cross-trial comparison suggests improvement versus imatinib. (Clinicaltrials.gov NCT02776605).
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Bataller A, Guijarro F, Caye A, Strullu M, Sterin A, Molina O, Chevallier P, Zaliova M, Zuna J, Mozas P, Magnano L, Grardel N, Cornillet-Lefebvre P, Fu JF, Shih LY, Boneva T, Nacheva EP, Beà S, López-Guerra M, Bueno C, Menéndez P, Esteve J, Larghero P, Meyer C, Marschalek R

KMT2A-CBL rearrangements in acute leukemias: clinical characteristics and genetic breakpoints.

Blood Adv 12 Oct 2021, . Epub 12 Oct 2021
No abstract available
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Ribera JM, Morgades M, Ciudad J, Montesinos P, Esteve J, Genescà E, Barba P, Ribera J, García-Cadenas I, Moreno MJ, Martínez-Carballeira D, Torrent A, Martínez-Sánchez P, Monsalvo S, Gil C, Tormo M, Artola MT, Cervera M, González-Campos J, Rodríguez C, Bermúdez A, Novo A, Soria B, Coll R, Amigo ML, López-Martínez A, Fernández-Martín R, Serrano J, Mercadal S, Cladera A, Giménez-Conca A, Peñarrubia MJ, Abella E, Vall-Llovera F, Hernández-Rivas JM, Garcia-Guiñon A, Bergua JM, de Rueda B, Sánchez-Sánchez MJ, Serrano A, Calbacho M, Alonso N, Méndez-Sánchez JÁ, García-Boyero R, Olivares M, Barrena S, Zamora L, Granada I, Lhermitte L, Feliu E, Orfao A

Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome-negative adult lymphoblastic leukemia.

Blood 8 Apr 2021, 137 (14) 1879-1894.
The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph- adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph- adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance. This trial was registered at www.clinicaltrials.gov as # NCT01540812.
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Sitges M, Boluda B, Garrido A, Morgades M, Granada I, Barragan E, Arnan M, Serrano J, Tormo M, Miguel Bergua J, Colorado M, Salamero O, Esteve J, Benavente C, Pérez-Encinas M, Coll R, Martí-Tutusaus JM, Brunet S, Sierra J, Ángel Sanz M, Montesinos P, Ribera JM, Vives S

Scute myeloid leukemia with inv(3)(q21q26.2)/t(3;3)(q21;q26.2). study of 61 patients treated with intensive protocols.

Eur. J. Haematol. 3 Apr 2020, . Epub 3 Apr 2020
Inv(3)(q21q26.2)/t(3;3)(q21;q26.2) is a rare poor prognosis cytogenetic abnormality present in acute myeloid leukemia (AML) and other myeloid neoplasms.
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Ribera J, Zamora L, Morgades M, Vives S, Granada I, Montesinos P, Gómez-Seguí I, Mercadal S, Guàrdia R, Nomdedeu J, Pratcorona M, Tormo M, Martínez-Lopez J, Hernández-Rivas JM, Ciudad J, Orfao A, González-Campos J, Barba P, Escoda L, Esteve J, Genescà E, Solé F, Feliu E, Ribera JM

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

Genes Chromosomes Cancer Nov 2019, 58 (11) 815-819. Epub 7 Aug 2019
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 Español de Tratamientos en Hematología 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.
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