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Immunotherapy

Remission of acute myeloid leukemia with t(8;21) following CD19 CAR T-cells

Leukemia volume 34, pages 1939–1942 (2020)Cite this article

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Relapsed acute myeloid leukemia (AML) is associated with a dismal prognosis, especially when relapse occurs after an allogeneic hematopoietic stem cell transplantation (alloHSCT) [1]. Great hope resides in CAR T-cells, after demonstrating superb remission induction rates in B-cell malignancies including acute lymphoblastic leukemia, non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma [2]. This is based on targeting cell-surface antigens that are restricted to malignant (and normal) B-cells, such as CD19, CD22, CD20, BCMA, and others. Challenges with designing CAR T-cells for myeloid neoplasms are greater, given most cell-surface antigens expressed on AML that are potentially CAR targets are also expressed on hematopoietic stem and progenitor cells [3]. Successful single-targeting CAR T-cells for AML may induce immunologic ablation of hematopoiesis as well as other substantial toxicities [3]. Aberrant cell surface expression is a hallmark of leukemia. Thus, potentially targeting an aberrantly expressed antigen may result in leukemia clearance without associated myelotoxicity.

We report on an adult male diagnosed in April 2018 with AML with t(8;21)(q22;q22.1) confirmed by cytogenetic and fluorescence-in-situ hybridization (FISH) studies. Molecular studies confirmed negativity of fms-related tyrosine kinase 3 (FLT3) mutation or internal-tandem duplication and of nucleophosmin-1 mutation. The patient had failed to achieve morphologic remission following standard 3+7 induction and re-induction. Following a third regimen of high-dose cytosine arabinoside and mitoxantrone the patient’s bone marrow showed disease remission, and he was referred to an alloHSCT from his HLA-matched sister. AlloHSCT conditioning was with busulfan and cyclophosphamide, and the course was uneventful. Six months post-transplant the patient had a relapse. Re-induction with fludarabine, high-dose cytarabine, and idarubicin failed to induce remission and he was referred to our center.

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Fig. 1: Molecular detection of t(8;21) in the bone marrow.

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Authors and Affiliations

  1. Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel

    Ivetta Danylesko, Ronit Yerushalmi, Noga Shem-Tov, Avichai Shimoni, Abraham Avigdor & Arnon Nagler

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Ivetta Danylesko, Elad Jacoby, Ronit Yerushalmi, Noga Shem-Tov, Michal J. Besser, Avichai Shimoni, Abraham Avigdor & Arnon Nagler

  3. Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, Israel

    Elad Jacoby

  4. Ella Institute of Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel

    Michal J. Besser

  5. Institute of Hematology, Sheba Medical Center, Ramat Gan, Israel

    Helly Vernitsky & Victoria Marcu-Malina

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  1. Ivetta Danylesko
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Contributions

Data collection: ID, EJ, MJB, HV, VM-M, AA, and AN; Patient care: ID, RY, NS-T, AS, AA, AN. Analysis and interpretation of data: ID, EJ, HV, VM-M, AA, and AN. Drafting the manuscript: ID, EJ, and AN. All authors approved the manuscript.

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Correspondence to Arnon Nagler.

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EJ received honoraria in from Novartis. All other authors report no conflict of interest.

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Danylesko, I., Jacoby, E., Yerushalmi, R. et al. Remission of acute myeloid leukemia with t(8;21) following CD19 CAR T-cells. Leukemia 34, 1939–1942 (2020). https://doi.org/10.1038/s41375-020-0719-y

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