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Meta-Analysis
. 2020 Dec 18;15(12):e0243657.
doi: 10.1371/journal.pone.0243657. eCollection 2020.

Role of BCR-ABL1 isoforms on the prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: A meta-analysis

Wanhua Zhang  1 , Pu Kuang  1 , Ting Liu  1
Affiliations
Meta-Analysis

Role of BCR-ABL1 isoforms on the prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: A meta-analysis

Wanhua Zhang et al. PLoS One. .

Abstract

BCR-ABL1 fusion gene is the driver mutation of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Although the prognostic value of BCR-ABL1 isoforms in Ph+ ALL patients has been investigated in numerous studies in the tyrosine kinase inhibitor (TKI) era, the results were still conflicting. Hence we performed herein the meta-analysis to comprehensively assess the impact of BCR-ABL1 isoforms on the clinical outcomes of Ph+ ALL patients. Systematic literature review was conducted in PubMed, Embase, and Cochrane databases with the data access date up to June 15, 2020. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Furthermore, subgroup analyses were performed to assess the robustness of the associations. Nine studies with a total number of 1582 patients were eligible for this meta-analysis. Combined HRs suggested that p210 was slightly associated with inferior event-free survival (EFS) (HR = 1.34, 95% CI 1.05-1.72). The overall survival (OS) was not significantly affected (HR = 1.15, 95% CI 0.92-1.45). In subgroup analyses, the HRs showed a trend toward adverse impact of p210 on clinical outcomes. However, the confidence intervals were not crossing the null value only in a minority of subgroups including Caucasian studies, first-generation TKI treated cohort and transplant cohort. Our findings suggested that p210 might pose a mild adverse impact on the EFS of Ph+ ALL patients. This effect might be compromised by the use of second- or third-generation TKIs. Further studies are needed to verify our conclusions.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. PRISMA flow diagram for study review and inclusion.
Fig 2
Fig 2. Forest plot for the impact of BCR-ABL1 isoforms on the clinical outcomes of Ph+ ALL patients.
(a) Forest plot for event-free survival (EFS). (b) Forest plot for overall survival (OS).
Fig 3
Fig 3. Begg's test of publication bias for (a) event-free survival (EFS) and (b) overall survival (OS).
Fig 4
Fig 4. Sensitivity analysis for event-free survival (EFS).
See this image and copyright information in PMC

References

    1. Burmeister T, Schwartz S, Bartram CR, Gökbuget N, Hoelzer D, Thiel E. Patients' age and BCR-ABL frequency in adult B-precursor ALL: a retrospective analysis from the GMALL study group. Blood. 2008; 112(3): 918–919. 10.1182/blood-2008-04-149286 - DOI - PubMed
    1. Moorman AV, Chilton L, Wilkinson J, Ensor HM, Bown N, Proctor SJ. A population-based cytogenetic study of adults with acute lymphoblastic leukemia. Blood. 2010; 115(2): 206–214. 10.1182/blood-2009-07-232124 - DOI - PubMed
    1. Dombret H, Gabert J, Boiron JM, Rigal-Huguet F, Blaise D, Thomas X, et al. Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia—results of the prospective multicenter LALA-94 trial. Blood. 2002; 100(7): 2357–2366. 10.1182/blood-2002-03-0704 - DOI - PubMed
    1. Gleissner B, Gökbuget N, Bartram CR, Janssen B, Rieder H, Janssen JW, et al. Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood. 2002; 99(5): 1536–1543. 10.1182/blood.v99.5.1536 - DOI - PubMed
    1. Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, et al. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009; 113(19): 4489–4496. 10.1182/blood-2009-01-199380 - DOI - PMC - PubMed

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