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.
Highlights
Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) is one of the most commonly encountered genetic subtypes of adult ALL, with the occurrence of about 25% in ALL patients
A systematic literature search was conducted in the PubMed, Embase and Cochrane databases with the data access date up to June 15, 2020 with free-style words and Medical Subjects Headings (MeSH): (("Philadelphia Chromosome"[Mesh] OR breakpoint cluster region (BCR)-ABL1) AND "Precursor Cell Lymphoblastic Leukemia-Lymphoma"[Mesh]) OR Ph positive acute lymphoblastic leukemia OR BCR-ABL1 positive acute lymphoblastic leukemia
Initial literature searches in PubMed, Embase and Cochrane databases identified 5427 articles published till June 15, 2020
Summary
Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) is one of the most commonly encountered genetic subtypes of adult ALL, with the occurrence of about 25% in ALL patients. Ph+ ALL was considered as the most dismal subtype of ALL, with long-term survival of less than 20%, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) was the mainstay of post-remission therapy [3,4,5]. Role of BCR-ABL1 isoforms on prognosis of Ph+ ALL inhibitors (TKIs) targeting the BCR-ABL1 oncoprotein has revolutionized the treatment response and long-term survival of Ph+ ALL patients, making the outcome equivalent to or better than that of Ph- ALL patients [6,7,8,9,10]. Despite the dramatic outcome improvement in this group of patients, the long-term disease-free survival of 40–50% is still less than satisfactory. Recognition of potential risk factors for relapse and mortality could help inform clinical decisions for this heterogeneous disease entity. As allo-HSCT might be dispensable in some patients, and some patients might need intensified treatment regimens including allo-HSCT
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
