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Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)–an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT)


On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor-T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring and disease assessments. To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.

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We acknowledge the critical review of the manuscript and constructive feedback from the American Society for Blood and Marrow Transplant’s (ASBMT) Practice Guideline Committee, ASBMT’s Cellular Therapy committee, and the Acute Leukemia Working Party and Cell Therapy and Immunobiology Working Party of the European Society for Blood and Marrow Transplantation (EBMT).

Author contributions

AK, NVF, MB, and TWL wrote the first draft of the manuscript and are first authors. All authors contributed substantially to the conception, writing, critical review and final approval of the submitted version of the manuscript.

Author information

Correspondence to Mark R. Litzow or Mohamad Mohty or Shahrukh K. Hashmi.

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Conflict of interest

AJK: Scientific Advisory Board–Celgene. NVF: Consultant–Novartis, Servier. TWL: Consultant–Novartis CMB: Scientific Advisory Boards: Cellectis. Stock/ownership: Mana Therapeutics, Torque and Neximmune. KK: Scientific Advisory Boards: Kite/Gilead, Novartis, Juno/Celgene, Atara, Takeda; Clinical Research Site: Kite, Iovance, Juno, Atara. CC: Consultant–Gilead, Research Funding: Gilead, Celgene, Speaker: Terumo BCT, Novartis. MAP: Honorarium: Abbvie, Bellicum, Incyte, Merck, Novartis, Nektar Therapeutics, and Takeda. Data Safety Monitoring Board: Servier and Medigene, Scientific Advisory Boards–MolMed and NexImmune. Research Funding–Incyte, Miltenyi Biotec. LA: Board of director/Scientific Advisory Board: HCLF, Consultant: AstraZeneca. VB: Research Funding–Gamida Cell, GT Biopharma, Scientific Advisory Board - Novartis, Kite, Travel funding–Amgen. CB: Research Funding–Intellia Therapeutics, Scientific Advisory Boards - TxCell, MolMed s.p.a., Travel funding–Miltenyi. SAG: Research Funding–Novartis, Servier and Kite. Consultant/Study Steering Committees/Scientific Advisory Boards–Novartis, Adaptimmune, Eureka, TCR2, Juno, GlaxoSmithKline, Cellectis, Vertex, and Roche. JAH: Consultant–Nohla Therapeutics, inc. and Amplyx, Research Funding–Karius and Shire. SK: Research funding: Humanigen, Tolero, Lentigen. Patents and Royalites: Novartis. DM: Scientific Advisory Board: Janssen, Honoraria: Seattle Genetics, Roche/Genentech, Research Funding: Juno Therapeutics, GlaxoSmithKline. MAK: Consultant–Pharmacyclics, Speaker–Incyte Corp, Seattle Genetics and Alexion Pharmaceuticals. EJ: Scientific Advisory Boards–Novartis. Speaker: Medison. AB: Scientific Advisory Boards–Novartis, Roche, Sanofi, Jazz, Adienne, Pfizer, Amgen. Research Funding: Novartis, Amgen, Takeda, Astellas, Celgene, Pfizer. JFD: Ownership/Equity–WUGEN. DLP: Research Funding–Novartis, Scientific Advisory Boards - Novartis, Kite, Patent and Royalty payments–Novartis. SIG: Research Funding–Novartis; Tmunity Therapeutics. Scientific Advisory Boards–Aileron; Fate Therapeutics; Intellia. Patent and Royalties–Novartis. Ownership/equity–Carisma Therapeutics. MS: Research Funding: Fate Theapeutics Inc, Consultant/Board of Director/Scientific Advisory Board/Patents and Royalties/Research Funding: Juno Therapeutics, MM: Lecture honoraria and Consultant- Novartis, Amgen and Pfizer. SKH: Honorarium: Mallinckrodt

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This paper was originally published in Biology of Blood and Marrow Transplantation Volume 25, Issue 3, e76 - e85

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