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

Sabina Chiaretti, Monica Messina, Irene Della Starza, Alfonso Piciocchi, Luciana Cafforio, Marzia Cavalli, Akram Taherinasab, Michela Ansuinelli, Loredana Elia, Guglielmo Albertini Petroni, Roberta la Starza, Martina Canichella, Alessia Lauretti, Maria Cristina Puzzolo, Valentina Pierini, Alessandra Santoro, Orietta Spinelli, Valerio Apicella, Saveria Capria, Francesco Di RaimondoPaolo de Fabritiis, Cristina Papayannidis, Anna Candoni, Roberto Cairoli, Marco Cerrano, Nicola Fracchiolla, Daniele Mattei, Chiara Cattaneo, Antonella Vitale, Enrico Crea, Paola Fazi, Cristina Mecucci, Alessandro Rambaldi, Anna Guarini, Renato Bassan, Robin Foà

Research output: Contribution to journalArticlepeer-review

Abstract

Early recognition of Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) cases could impact on the management and outcome of this subset of B-lineage ALL. In order 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 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 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, decisional for transplant allocation, 52.9% of Ph-like cases versus 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 time point 2 (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 complete remission rate, event-free survival and disease-free survival, 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.

Original languageEnglish
Pages (from-to)1559-1568
Number of pages10
JournalHaematologica
Volume106
Issue number6
DOIs
Publication statusPublished - Jun 2021

ASJC Scopus subject areas

  • Hematology

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