Adverse prognostic impact of complex karyotype (≥3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL)
Eulàlia Genescà, Mireia Morgades, Celia González‐Gil, Francisco Fuster‐Tormo, Claudia Haferlach, Manja Meggendorfer, Pau Montesinos, Pere Barba, Cristina Gil, Rosa Coll, María‐José Moreno, Daniel Martínez‐Carballeira, Irene García‐Cadenas, Susana Vives, Jordi Ribera, José González‐Campos, Marina Díaz‐Beyá, Santiago Mercadal, María‐Teresa Artola, Antònia Cladera, Mar Tormo, Arancha Bermúdez, Ferran Vall‐Llovera, Pilar Martínez‐Sánchez, María‐Luz Amigo, Silvia Monsalvo, Andrés Novo, Marta Cervera, Antonio García-Guiñón, Juana Ciudad, José Cervera, Jesús María Hernández‐Rivas, Isabel Granada, Torsten Haferlach, Alberto Órfão, Françesc Solé, Josep‐María Ribera
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.