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. 2021 Jun 1;106(6):1559-1568.
doi: 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

Sabina Chiaretti  1 , Monica Messina  2 , Irene Della Starza  2 , Alfonso Piciocchi  3 , Luciana Cafforio  4 , Marzia Cavalli  4 , Akram Taherinasab  4 , Michela Ansuinelli  4 , Loredana Elia  4 , Guglielmo Albertini Petroni  4 , Roberta La Starza  5 , Martina Canichella  4 , Alessia Lauretti  4 , Maria Cristina Puzzolo  4 , Valentina Pierini  5 , Alessandra Santoro  6 , Orietta Spinelli  7 , Valerio Apicella  8 , Saveria Capria  8 , Francesco Di Raimondo  9 , Paolo De Fabritiis  10 , Cristina Papayannidis  11 , Anna Candoni  12 , Roberto Cairoli  13 , Marco Cerrano  14 , Nicola Fracchiolla  15 , Daniele Mattei  16 , Chiara Cattaneo  17 , Antonella Vitale  4 , Enrico Crea  3 , Paola Fazi  3 , Cristina Mecucci  18 , Alessandro Rambaldi  7 , Anna Guarini  19 , Renato Bassan  20 , Robin Foà  4
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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 et al. Haematologica. .

Abstract

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.

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Figures

Figure 1.
Figure 1.
Distribution of the genetic lesions in the Philadelphia-like (Ph-like) and non-Ph-like cases study. Only the samples evaluated for the BCR/ABL1-like predictor and mutational status are depicted.
Figure 2.
Figure 2.
Survival curves of Philadelphia-like (Ph-like) and non-Ph-like patients. event-free survival and disease-free survival.
See this image and copyright information in PMC

Comment in

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