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.

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 / Chiaretti, S.; Messina, M.; Starza, I. D.; Piciocchi, A.; Cafforio, L.; Cavalli, M.; Taherinasab, A.; Ansuinelli, M.; Elia, L.; Petroni, G. A.; la Starza, R.; Canichella, M.; Lauretti, A.; Puzzolo, M. C.; Pierini, V.; Santoro, A.; Spinelli, O.; Apicella, V.; Capria, S.; Di Raimondo, F.; de Fabritiis, P.; Papayannidis, C.; Candoni, A.; Cairoli, R.; Cerrano, M.; Fracchiolla, N.; Mattei, D.; Cattaneo, C.; Vitale, A.; Crea, E.; Fazi, P.; Mecucci, C.; Rambaldi, A.; Guarini, A.; Bassan, R.; Foa, R.. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 106:6(2021), pp. 1559-1568. [10.3324/haematol.2020.247973]

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

Candoni A.;
2021

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.
2021
106
6
1559
1568
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 / Chiaretti, S.; Messina, M.; Starza, I. D.; Piciocchi, A.; Cafforio, L.; Cavalli, M.; Taherinasab, A.; Ansuinelli, M.; Elia, L.; Petroni, G. A.; la Starza, R.; Canichella, M.; Lauretti, A.; Puzzolo, M. C.; Pierini, V.; Santoro, A.; Spinelli, O.; Apicella, V.; Capria, S.; Di Raimondo, F.; de Fabritiis, P.; Papayannidis, C.; Candoni, A.; Cairoli, R.; Cerrano, M.; Fracchiolla, N.; Mattei, D.; Cattaneo, C.; Vitale, A.; Crea, E.; Fazi, P.; Mecucci, C.; Rambaldi, A.; Guarini, A.; Bassan, R.; Foa, R.. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 106:6(2021), pp. 1559-1568. [10.3324/haematol.2020.247973]
Chiaretti, S.; Messina, M.; Starza, I. D.; Piciocchi, A.; Cafforio, L.; Cavalli, M.; Taherinasab, A.; Ansuinelli, M.; Elia, L.; Petroni, G. A.; la Starza, R.; Canichella, M.; Lauretti, A.; Puzzolo, M. C.; Pierini, V.; Santoro, A.; Spinelli, O.; Apicella, V.; Capria, S.; Di Raimondo, F.; de Fabritiis, P.; Papayannidis, C.; Candoni, A.; Cairoli, R.; Cerrano, M.; Fracchiolla, N.; Mattei, D.; Cattaneo, C.; Vitale, A.; Crea, E.; Fazi, P.; Mecucci, C.; Rambaldi, A.; Guarini, A.; Bassan, R.; Foa, R.
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