Adverse prognostic impact of complex karyotype (≥3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL)

© 2021 The Author(s).The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients.This project was supported by the AECC (GC16173697BIGA); ISCIII (PI19/01828) co-funded by ERDF/ESF "A way to make Europe"/ "Investing in your future", CERCA/Generalitat de Catalunya SGR 2017 288 (GRC)/ “La Caixa” P. Barba was supported by the Instituto de Salud Carlos III FIS16/01433 and PERIS 2018-2020 from Generalitat de Catalunya (BDNS357800)

Adverse prognostic impact of complex karyotype (≥3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL)

The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients

Feasibility and Outcome of Allogeneic Hematopoietic Stem-Cell Transplantation in High-Risk AML: Real-Life Perspective from a Single Institution

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Unique clinico-biological, genetic and prognostic features of adult early T-cell precursor acute lymphoblastic leukemia

Early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL), was first identified within cases of childhood T-ALL based on its unique immunophenotypic and genetic features of limited (early) T-cell differentiation associated with (some) myeloid and stem cell features.1 Thus ETP-ALL blasts express CD7, dim CD5 (<75% positive cells), in the absence of CD1a and CD8, and positivity for ≥1 myeloid/stem cell related markers (i.e., CD34, CD13 or CD33).21 In turn, ETP-ALL frequently shows myeloid-associated gene alterations such as FLT3, NRAS/KRAS, DNMT3A, IDH1 and IDH2 mutations,43 with lower frequencies of other T-ALL-associated mutations (e.g., NOTCH1 and CDKN2A/B gene mutations).65 The World Health Organization (WHO) 2016 classification of ALL included ETP-ALL for the first time, as a provisional entity,7 but it failed to establish robust diagnostic criteria. Thus, after the first immunophenotypic characterization of ETP-ALL by Coustan-Smith et al.1 the proposed criteria did not allow identification of all ETP-ALL cases as detected by gene expression profiling.2 In addition, the “partial CD5 expression” criterion had a negative impact on the reproducibility of ETP-ALL diagnoses because of the lack of standardization of the method used for its assessment. Because of this, Zuubier et al. proposed refined immunophenotypic criteria by excluding CD5 expression while adding negativity for CD4.2Funding: this project was supported by the Asociación Española Contra el Cáncer (project ref: GC16173697BIGA), PI14/01971 FIS, Instituto Carlos III, CERCA Program/Generalitat de Catalunya, 2014-SGR225 (GRE), Obra Social “La Caixa” . This work was also partially supported by FEDER funds from the ISCIII (PT13/0010/0026, CIBERONC (CB16/12/00284 and CB16/12/00400), Madrid, Spain). P. Barba was supported by the Instituto de Salud Carlos III FIS16/01433 and PERIS 2018-2020 from Generalitat de Catalunya (BDNS357800) grant

sj-docx-1-tah-10.1177_20406207221127547 – Supplemental material for Relevance of infections on the outcomes of patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia treated with hypomethylating agents: a cohort study from the GESMD

Supplemental material, sj-docx-1-tah-10.1177_20406207221127547 for Relevance of infections on the outcomes of patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia treated with hypomethylating agents: a cohort study from the GESMD by Laura Vilorio-Marqués, Christelle Castañón Fernández, Elvira Mora, Lorena Gutiérrez, Beatriz Rey Bua, Maria José Jiménez Lorenzo, Marina Díaz Beya, Miriam Vara Pampliega, Antonieta Molero, Joaquín Sánchez-García, Marisa Calabuig, Maria Teresa Cedena, Tzu Chen-Liang, Johana Alejandra Díaz Santa, Irene Padilla, Francisca Hernández, Rosana Díez, Pedro Asensi, Blanca Xicoy, Guillermo Sanz, David Valcárcel, María Diez-Campelo and Teresa Bernal in Therapeutic Advances in Hematology</p