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

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2021-06-08

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Genescà, Eulàlia
Morgades, Mireia
González-Gil, Celia
Fuster-Tormo, Francisco
Haferlach, Claudia
Meggendorfer, Manja
Montesinos, Pau
Barba, Pere
Gil, Cristina
Coll, Rosa

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Abstract

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.

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MeSH Terms

Adolescent
Adult
Chromosome Aberrations
Female
Humans
Karyotype
Male
Middle Aged
Neoplasm, Residual
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Young Adult

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Keywords

Adult T-ALL, Cytogenetics, NGS, Prognosis, Therapy

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