TY - JOUR AU - Sabina Chiaretti, AU - Monica Messina, AU - Irene Della Starza, AU - Alfonso Piciocchi, AU - Luciana Cafforio, AU - Marzia Cavalli, AU - Akram Taherinasab, AU - Michela Ansuinelli, AU - Loredana Elia, AU - Guglielmo Albertini Petroni, AU - Roberta La Starza, AU - Martina Canichella, AU - Alessia Lauretti, AU - Maria Cristina Puzzolo, AU - Valentina Pierini, AU - Alessandra Santoro, AU - Orietta Spinelli, AU - Valerio Apicella, AU - Saveria Capria, AU - Francesco Di Raimondo, AU - Paolo De Fabritiis, AU - Cristina Papayannidis, AU - Anna Candoni, AU - Roberto Cairoli, AU - Marco Cerrano, AU - Nicola Fracchiolla, AU - Daniele Mattei, AU - Chiara Cattaneo, AU - Antonella Vitale, AU - Enrico Crea, AU - Paola Fazi, AU - Cristina Mecucci, AU - Alessandro Rambaldi, AU - Anna Guarini, AU - Renato Bassan, AU - Robin FoĆ , PY - 2021/06/01 Y2 - 2024/03/29 TI - Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimal residual disease-oriented GIMEMA LAL1913 JF - Haematologica JA - haematol VL - 106 IS - 6 SE - Articles DO - 10.3324/haematol.2020.247973 UR - https://haematologica.org/article/view/9764 SP - 1559-1568 AB - Early recognition of Ph-like acute lymphoblastic leukemia cases could impact on the management and outcome of this subset of B-lineage ALL. To assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)-driven trial, we screened 88 B-lineage ALL cases negative for the major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR/ABL1-negative ALL. The screening - performed using the BCR/ABL1-like predictor - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the complete remission (CR) rate was significantly lower in Ph-like compared to non-Ph-like cases (74.1% vs 91.5%, p=0.044); ii) at time point 2 (TP2), decisional for transplant allocation, 52.9% of Ph-like cases vs 20% of non-Ph-like were MRD-positive (p=0.025); iii) the Ph-like profile was the only parameter associated with a higher risk of being MRD-positive at TP2 (p=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs 66.2%, p=0.005 and 45.5% vs 72.3%, p=0.062, respectively). This study documents that Ph-like patients have a lower CR rate, EFS and DFS, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies. ER -