Relapsed T Cell ALL: Current Approaches and New Directions

Curr Hematol Malig Rep. 2019 Apr;14(2):83-93. doi: 10.1007/s11899-019-00501-3.

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. 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.

Keywords: Refractory; Relapse; T cell acute lymphoblastic leukemia; T-ALL; Treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / therapeutic use
  • Arabinonucleosides / therapeutic use*
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Liposomes / chemistry
  • Neoplasm Recurrence, Local
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Salvage Therapy / methods
  • Vincristine / chemistry
  • Vincristine / therapeutic use*

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Arabinonucleosides
  • Liposomes
  • daratumumab
  • Vincristine
  • nelarabine