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

被引：67

作者：

Chiaretti, Sabina ^{[1
]}

Messina, Monica ^{[1
,2
]}

Della Starza, Irene ^{[1
,2
]}

Piciocchi, Alfonso ^{[2
]}

Cafforio, Luciana ^{[1
]}

Cavalli, Marzia ^{[1
]}

Taherinasab, Akram ^{[1
]}

Ansuinelli, Michela ^{[1
]}

Elia, Loredana ^{[1
]}

Petroni, Guglielmo Albertini ^{[1
]}

La Starza, Roberta ^{[3
]}

Canichella, Martina ^{[1
]}

Lauretti, Alessia ^{[1
]}

Puzzolo, Maria Cristina ^{[1
]}

Pierini, Valentina ^{[3
]}

Santoro, Alessandra ^{[4
]}

Spinelli, Orietta ^{[5
]}

Apicella, Valerio ^{[1
]}

Capria, Saveria ^{[1
]}

Di Raimondo, Francesco ^{[6
]}

De Fabritiis, Paolo ^{[7
]}

Papayannidis, Cristina ^{[8
]}

Candoni, Anna ^{[9
,10
]}

Cairoli, Roberto ^{[11
]}

Cerrano, Marco ^{[12
]}

Fracchiolla, Nicola ^{[13
]}

Mattei, Daniele ^{[14
]}

Cattaneo, Chiara ^{[15
]}

Vitale, Antonella ^{[1
]}

Crea, Enrico ^{[2
]}

Fazi, Paola ^{[2
]}

Mecucci, Cristina ^{[3
]}

Rambaldi, Alessandro ^{[4
]}

Guarini, Anna ^{[16
]}

Bassan, Renato ^{[17
,18
]}

Foa, Robin ^{[1
]}

机构：

[1] Sapienza Univ, Dept Translat & Precis Med, Hematol Unit, Rome, Italy

[2] Fdn GIMEMA Franco Mandelli Onlus, GIMEMA Data Ctr, Rome, Italy

[3] Univ Perugia, Dept Med, Hematol & Bone Marrow Transplantat Unit, Perugia, Italy

[4] Osped Riuniti Villa Sofia Cervello, Hematol & Bone Marrow Transplant Unit, Palermo, Italy

[5] Osped Papa Giovanni XXIII, Hematol & Bone Marrow Transplant Unit, Bergamo, Italy

[6] Univ Catania, Dept Gen Surg & Med Surg Specialties, Haematol Unit, Catania, Italy

[7] S Eugenio Hosp, Hematol Unit, Rome, Italy

[8] Bologna Univ, Seragnoli Inst Hematol, Sch Med, Bologna, Italy

[9] Azienda Sanit Univ Integrata, Clin Ematol, Udine, Italy

[10] Azienda Sanit Univ Integrata, Unita Terapie Cellulari Carlo Melzi, Udine, Italy

[11] Osped Niguarda Ca Granda, Hematol Unit, Milan, Italy

[12] AOU Citta Salute & Sci Torino, Dept Oncol, Hematol Unit, Turin, Italy

[13] Univ Milan, UOC Oncoematol, Fdn IRCCS Ca Granda Osped Maggiore Policlin Milan, Milan, Italy

[14] Osped S Croce, Dept Hematol, Cuneo, Italy

[15] ASST Spedali Civili, Dept Hematol, Brescia, Italy

[16] Sapienza Univ, Dept Mol Med, Rome, Italy

[17] Osped Angelo, Hematol Unit, Venice, Italy

[18] Osped Ss Giovanni & Paolo, Venice, Italy

来源：

HAEMATOLOGICA | 2021年 / 106卷 / 06期

关键词：

MURINE XENOGRAFT MODELS; KINASE; LESIONS;

D O I：

10.3324/haematol.2020.247973

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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-Phlike 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. Clinicaltrials gov. Identifier: 02067143.

引用

页码：1559 / 1568

页数：10

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