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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Simple Summary

Recent advances in genomic analyses of acute lymphoblastic leukemia (ALL) have identified novel prognostic markers associated with patient outcome. In this frame, copy number alterations (CNAs) are constantly gaining relevance as potential risk stratification markers. Herein, we present our data of a proposed CNA-profile risk-index applied on a Greek ALLIC-BFM cohort. The results of our study demonstrate that EFS for GR(good-risk)-CNA-profile patients was 96.0% versus 57.6% of PR(poor-risk)-CNA-profile ones (p < 0.001) in the whole cohort. EFS within the IR-group for the GR-CNA vs. PR-CNA subgroups was 100.0% vs. 60.0% (p < 0.001), and within the HR-group, 88.2% vs. 55.6% (p = 0.047), respectively. The above results indicate that the application of the proposed CNA-profile classifier is feasible in BFM-based protocols, adding prognostic value to the existing prognostic markers and successfully stratifying patients within prognostic subgroups. This novel genomic risk index can be incorporated in future risk-stratification algorithms, further refining MRD-based stratification and possibly reassigning optimal treatment strategies.

Abstract

We present our data of a novel proposed CNA-profile risk-index, applied on a Greek ALLIC-BFM-treated cohort, aiming at further refining genomic risk-stratification. Eighty-five of 227 consecutively treated ALL patients were analyzed for the copy-number-status of eight genes (IKZF1/CDKN2A/2B/PAR1/BTG1/EBF1/PAX5/ETV6/RB1). Using the MLPA-assay, patients were stratified as: (1) Good-risk(GR)-CNA-profile (n = 51), with no deletion of IKZF1/CDKN2A/B/PAR1/BTG1/EBF1/PAX5/ETV6/RB1 or isolated deletions of ETV6/PAX5/BTG1 or ETV6 deletions with a single additional deletion of BTG1/PAX5/CDKN2A/B. (2) Poor-risk(PR)-CNA-profile (n = 34), with any deletion of ΙΚΖF1/PAR1/EBF1/RB1 or any other CNA. With a median follow-up time of 49.9 months, EFS for GR-CNA-profile and PR-CNA-profile patients was 96.0% vs. 57.6% (p < 0.001). For IR-group and HR-group patients, EFS for the GR-CNA/PR-CNA subgroups was 100.0% vs. 60.0% (p < 0.001) and 88.2% vs. 55.6% (p = 0.047), respectively. Among FC-MRDd15 + patients (MRDd15 ≥ 10−4), EFS rates were 95.3% vs. 51.7% for GR-CNA/PR-CNA subjects (p < 0.001). Similarly, among FC-MRDd33 + patients (MRDd33 ≥ 10−4), EFS was 92.9% vs. 27.3% (p < 0.001) and for patients FC-MRDd33 − (MRDd33 < 10−4), EFS was 97.2% vs. 72.7% (p = 0.004), for GR-CNA/PR-CNA patients, respectively. In a multivariate analysis, the CNA-profile was the most important outcome predictor. In conclusion, the CNA-profile can establish a new genomic risk-index, identifying a distinct subgroup with increased relapse risk among the IR-group, as well as a subgroup of patients with superior prognosis among HR-patients. The CNA-profile is feasible in BFM-based protocols, further refining MRD-based risk-stratification.

Details

Title
Copy Number Alteration Profile Provides Additional Prognostic Value for Acute Lymphoblastic Leukemia Patients Treated on BFM Protocols
Author
Αmpatzidou, Μirella 1   VIAFID ORCID Logo  ; Florentin, Lina 2 ; Papadakis, Vassilios 1 ; Paterakis, Georgios 3 ; Tzanoudaki, Marianna 4 ; Bouzarelou, Dimitra 2 ; Papadhimitriou, Stefanos I 5 ; Polychronopoulou, Sophia 1 

 Department of Pediatric Hematology-Oncology, “Aghia Sophia” Children’s Hospital, 11527 Athens, Greece; [email protected] (V.P.); [email protected] (S.P.) 
 Alfa Laboratory Diagnostic Center, YGEIA Hospital, 11524 Athens, Greece; [email protected] (L.F.); [email protected] (D.B.) 
 Laboratory of Flow Cytometry, Department of Immunology, “G.Gennimatas” General Hospital, 11527 Athens, Greece; [email protected] 
 Department of Immunology, “Aghia Sophia” Children’s Hospital, 11527 Athens, Greece; [email protected] 
 Laboratory of Hematology, Department of Molecular Cytogenetics, “G.Gennimatas” General Hospital, 11527 Athens, Greece; [email protected] 
First page
3289
Publication year
2021
Publication date
2021
Publisher
MDPI AG
e-ISSN
20726694
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2549278177
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.