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      Impact of timely BCR-ABL1 monitoring before allogeneic stem cell transplantation among patients with BCR-ABL1-positive B-acute lymphoblastic leukemia

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          Abstract

          Background

          With the emergence of tyrosine kinase inhibitors and the incorporation of stringent measurable residual disease (MRD) monitoring, risk stratification for BCR-ABL1-positive acute lymphoblastic leukemia (ALL) patients has changed significantly. However, whether this monitoring can replace conventional risk factors in determining whether patients need allogeneic stem cell transplantation is still unclear. This study aimed to determine the impact of BCR-ABL1 monitoring on the outcome of patients with BCR-ABL1-positive ALL after allogeneic stem cell transplantation.

          Methods

          We retrospectively analyzed the survival outcome of patients with BCR-ABL1-positive ALL based on the quantification of BCR-ABL1 at 3 timepoints the end of induction (timepoint 1), post-consolidation week 16 (timepoint 2), and the end of treatment for patients who were either transplant-eligible or non-transplant eligible (timepoint 3).

          Results

          From 2006 to 2018, a total of 96 patients newly diagnosed with BCR-ABL1-positive ALL were treated with chemotherapy and tyrosine kinase inhibitors. Thirty-eight (41.3%) patients achieved complete remission, and 33 patients underwent allogeneic stem cell transplantation. Our data showed that pre-transplant MRD monitoring by real-time quantitative polymerase chain reaction had the highest correlation with survival in patients with BCR-ABL1-positive ALL, especially for those who underwent allogeneic stem cell transplantation.

          Conclusion

          Patients without MRD pre-transplantation had superior survival compared with those who had MRD, and they had excellent long-term outcomes after allogeneic stem cell transplantation.

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          Most cited references28

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          The 2016 revision of the World Health Organization classification of lymphoid neoplasms.

          A revision of the nearly 8-year-old World Health Organization classification of the lymphoid neoplasms and the accompanying monograph is being published. It reflects a consensus among hematopathologists, geneticists, and clinicians regarding both updates to current entities as well as the addition of a limited number of new provisional entities. The revision clarifies the diagnosis and management of lesions at the very early stages of lymphomagenesis, refines the diagnostic criteria for some entities, details the expanding genetic/molecular landscape of numerous lymphoid neoplasms and their clinical correlates, and refers to investigations leading to more targeted therapeutic strategies. The major changes are reviewed with an emphasis on the most important advances in our understanding that impact our diagnostic approach, clinical expectations, and therapeutic strategies for the lymphoid neoplasms.
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            Acute lymphoblastic leukemia: a comprehensive review and 2017 update

            Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from precursors of the B-cell lineage, with the remainder of cases consisting of malignant T-cell precursors. Traditionally, risk stratification has been based on clinical factors such age, white blood cell count and response to chemotherapy; however, the identification of recurrent genetic alterations has helped refine individual prognosis and guide management. Despite advances in management, the backbone of therapy remains multi-agent chemotherapy with vincristine, corticosteroids and an anthracycline with allogeneic stem cell transplantation for eligible candidates. Elderly patients are often unable to tolerate such regimens and carry a particularly poor prognosis. Here, we review the major recent advances in the treatment of ALL.
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              Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival.

              Blinatumomab, a bispecific single-chain antibody targeting the CD19 antigen, is a member of a novel class of antibodies that redirect T cells for selective lysis of tumor cells. In acute lymphoblastic leukemia (ALL), persistence or relapse of minimal residual disease (MRD) after chemotherapy indicates resistance to chemotherapy and results in hematologic relapse. A phase II clinical study was conducted to determine the efficacy of blinatumomab in MRD-positive B-lineage ALL. Patients with MRD persistence or relapse after induction and consolidation therapy were included. MRD was assessed by quantitative reverse transcriptase polymerase chain reaction for either rearrangements of immunoglobulin or T-cell receptor genes, or specific genetic aberrations. Blinatumomab was administered as a 4-week continuous intravenous infusion at a dose of 15 μg/m2/24 hours. Twenty-one patients were treated, of whom 16 patients became MRD negative. One patient was not evaluable due to a grade 3 adverse event leading to treatment discontinuation. Among the 16 responders, 12 patients had been molecularly refractory to previous chemotherapy. Probability for relapse-free survival is 78% at a median follow-up of 405 days. The most frequent grade 3 and 4 adverse event was lymphopenia, which was completely reversible like most other adverse events. Blinatumomab is an efficacious and well-tolerated treatment in patients with MRD-positive B-lineage ALL after intensive chemotherapy. T cells engaged by blinatumomab seem capable of eradicating chemotherapy-resistant tumor cells that otherwise cause clinical relapse.
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                Author and article information

                Journal
                Blood Res
                Blood Res
                Blood research
                Korean Society of Hematology; Korean Society of Blood and Marrow Transplantation; Korean Society of Pediatric Hematology-Oncology; Korean Society on Thrombosis and Hemostasis
                2287-979X
                2288-0011
                30 September 2021
                30 September 2021
                30 September 2021
                : 56
                : 3
                : 175-183
                Affiliations
                [1 ]Department of Haematology, Hospital Ampang, Selangor, Malaysia
                [2 ]Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Nilai, Malaysia
                [3 ]Department of Haematology, Hospital Umum Sarawak, Kuching, Malaysia
                [4 ]Department of Medicine, Hospital Taiping, Taiping, Malaysia
                [5 ]Institute for Clinical Research, National Institutes of Health (NIH), Shah Alam, Malaysia
                [6 ]Department of Medicine, Hospital Melaka, Melaka, Malaysia
                [7 ]Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Malaysia
                Author notes
                Correspondence to Asral Wirda Ahmad Asnawi, M.D., Ph.D., Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Persiaran Ilmu, Putra Nilai, Nilai, Negeri Sembilan 71800, Malaysia, E-mail: wirda@ 123456usim.edu.my
                Article
                br-56-3-175
                10.5045/br.2021.2021045
                8478615
                34462403
                63b596ed-6375-4b89-8532-e2b5d046a466
                © 2021 Korean Society of Hematology

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 March 2021
                : 27 May 2021
                : 30 July 2021
                Categories
                Original Article

                all,bcr-abl1,philadelphia,survival,tki
                all, bcr-abl1, philadelphia, survival, tki

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