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Relapsed T Cell ALL: Current Approaches and New Directions

  • Acute Lymphocytic Leukemias (K Ballen and M Keng, Section Editors)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Patients with relapsed T cell acute lymphoblastic leukemia (T-ALL) have limited therapeutic options and a poor prognosis. Although a variety of salvage chemotherapy regimens may be used, response rates are unsatisfactory. This article summarizes current approaches and promising emerging strategies for the treatment of relapsed T-ALL.

Recent Findings

Although nelarabine is the only agent approved specifically for T-ALL, recent studies have identified a variety of genetic alterations and signaling pathways that are critical in its pathogenesis. Based on these findings, a number of small-molecule inhibitors and other targeted therapies are being studied for relapsed T-ALL, including gamma-secretase inhibitors, BCL-2 inhibitors, cyclin-dependent kinase inhibitors, and mTOR inhibitors. In addition, pre-clinical studies of chimeric antigen receptor T cells targeting CD5 and CD7 as well as the monoclonal antibody daratumumab have shown promising results for T-ALL.

Summary

Relapsed T-ALL currently remains challenging to treat, but recent pre-clinical studies of targeted and immunotherapeutic agents have shown encouraging results. A number of clinical trials investigating these approaches for T-ALL are currently underway.

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Acknowledgements

We would like to thank Ivan P. Maillard, MD, PhD, for discussion regarding recent advances in T cell ALL biology.

Funding

C.M. is supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number TL1TR001880.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Christine M. McMahon & Selina M. Luger

  2. Perelman Center for Advanced Medicine, 12th Floor South Extension, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA

    Selina M. Luger

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  1. Christine M. McMahon
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  2. Selina M. Luger
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Correspondence to Selina M. Luger.

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This article is part of the Topical Collection on Acute Lymphocytic Leukemias

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McMahon, C.M., Luger, S.M. Relapsed T Cell ALL: Current Approaches and New Directions. Curr Hematol Malig Rep 14, 83–93 (2019). https://doi.org/10.1007/s11899-019-00501-3

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