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CD19 CAR T Cells for the Treatment of Pediatric Pre-B Cell Acute Lymphoblastic Leukemia

  • Holly L. Pacenta
  • Theodore W. LaetschEmail author
  • Samuel John
Leading Article

Abstract

The development of cluster of differentiation (CD)-19-targeted chimeric antigen receptor (CAR) T cells for the treatment of pre-B-cell acute lymphoblastic leukemia (B-ALL) is an exciting new advancement in the field of pediatric oncology. Tisagenlecleucel and axicabtagene ciloleucel are the first US FDA-approved CD19-targeted CAR T cells. While various different CD19 CAR T cells are in development, tisagenlecleucel is the only CAR T cell approved for pediatric patients. The multicenter phase II trial that led to the approval of tisagenlecleucel demonstrated excellent responses in individuals with highly refractory disease. Other high-risk groups of patients with B-ALL who experience poor outcomes with standard therapy may also benefit from treatment with tisagenlecleucel. After receiving CAR T cells, patients must be closely monitored for unique toxicities, including cytokine release syndrome, neurotoxicity, and B-cell aplasia. The management of patients with relapsed or refractory disease after administration of CD19 CAR T cells can be challenging, and treatment options vary according to the characteristics of the disease present at relapse. In the many patients who experience a complete response, CAR T cells can lead to a durable remission. This review describes the current design and manufacturing of CAR T cells. Data in the selection and management of pediatric patients are highlighted, as are areas where further studies are needed.

Notes

Compliance with Ethical Standards

Funding

Theodore W. Laetsch is a Eugene P. Frenkel Scholar in Clinical Medicine and is supported by the Norma and Jim Smith Professorship in Clinical Excellence. No other sources of funding were used to conduct this study or prepare this manuscript.

Conflict of interest

Theodore W. Laetsch is the institutional principal investigator of clinical trials funded by Novartis and has consulted for Novartis. Holly L. Pacenta and Samuel John have no conflicts of interest that are directly relevant to the content of this study.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Pediatric Hematology-OncologyUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.The Pauline Allen Gill Center for Cancer and Blood Disorders, Children’s HealthDallasUSA
  3. 3.Harold C. Simmons Comprehensive Cancer CenterUniversity of Texas Southwestern Medical CenterDallasUSA

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