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      Acute lymphoblastic leukemia: a comprehensive review and 2017 update

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      Author(s): 1 , 1 , 2 , *
      Publication date (Electronic):
      Journal: Blood Cancer Journal
      Publisher: Nature Publishing Group

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          Abstract

          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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          Proposals for the Classification of the Acute Leukaemias French-American-British (FAB) Co-operative Group

          J M Bennett, D Catovsky, Marie-Theregse Daniel … (1976)
          A uniform system of classification and nomenclature of the acute leukaemias, at present lacking, should permit more accurate recording of the distribution of cases entered into clinical trials, and could provide a reference standard when newly developed cell-surface markers believed to characterize specific cell types are applied to cases of acute leukaemia. Proposals based on conventional morphological and cytochemical methods are offered following the study of peripheral blood and bone-marrow films from some 200 cases of acute leukaemia by a group of seven French, American and British haematologists. The slides were examined first independently, and then by the group working together. Two groups of acute leukaemia, 'lymphoblastic' and myeloid are further subdivided into three and six groups. Dysmyelopoietic syndromes that may be confused with acute myeloid leukaemia are also considered. Photomicrographs of each of the named conditions are presented.
          Article 0 comments Cited 275 times – based on 0 reviews     Review now
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            Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia.

            Waleed M. Haso, Daniel Lee, Nirali Shah … (2013)
            Immune targeting of B-cell malignancies using chimeric antigen receptors (CARs) is a promising new approach, but critical factors impacting CAR efficacy remain unclear. To test the suitability of targeting CD22 on precursor B-cell acute lymphoblastic leukemia (BCP-ALL), lymphoblasts from 111 patients with BCP-ALL were assayed for CD22 expression and all were found to be CD22-positive, with median CD22 expression levels of 3500 sites/cell. Three distinct binding domains targeting CD22 were fused to various TCR signaling domains ± an IgG heavy chain constant domain (CH2CH3) to create a series of vector constructs suitable to delineate optimal CAR configuration. CARs derived from the m971 anti-CD22 mAb, which targets a proximal CD22 epitope demonstrated superior antileukemic activity compared with those incorporating other binding domains, and addition of a 4-1BB signaling domain to CD28.CD3 constructs diminished potency, whereas increasing affinity of the anti-CD22 binding motif, and extending the CD22 binding domain away from the membrane via CH2CH3 had no effect. We conclude that second-generation m971 mAb-derived anti-CD22 CARs are promising novel therapeutics that should be tested in BCP-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.

              Max Topp, Peter Kufer, Nicola Gökbuget … (2011)
              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
                Journal ID (nlm-ta): Blood Cancer J
                Journal ID (iso-abbrev): Blood Cancer J
                Title: Blood Cancer Journal
                Publisher: Nature Publishing Group
                ISSN (Electronic): 2044-5385
                Publication date (Print): June 2017
                Publication date (Electronic): 30 June 2017
                Publication date PMC-release: 1 June 2017
                Volume: 7
                Issue: 6
                Page: e577
                Affiliations
                [1 ]New York University School of Medicine , New York, USA
                [2 ]Department of Hematology, New York University Perlmutter Cancer Center , New York, USA
                Author notes
                [* ]New York University School of Medicine , 240 East 38th street, 19 Floor, New York 10016, USA. E-mail: Maher.Abdulhay@ 123456nyumc.org
                Article
                Publisher Item ID: bcj201753
                DOI: 10.1038/bcj.2017.53
                PMC ID: 5520400
                PubMed ID: 28665419
                SO-VID: 2b8fa3d3-2828-4c61-8c79-fcc65e82b7ff
                Copyright © Copyright © 2017 The Author(s)
                License:

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                Date received : 28 March 2017
                Date accepted : 21 April 2017
                Categories
                Subject: Review

                ScienceOpen disciplines: Oncology & Radiotherapy
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy

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