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CAR T cells induce a complete response in refractory Burkitt Lymphoma

Bone Marrow Transplantation volume 53, pages 1583–1585 (2018)Cite this article

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We describe a 32-year-old male who presented with lymphadenopathy in December 2016. Morphology and immunohistochemistry from a lymph node biopsy were compatible with Burkitt Lymphoma (BL). Next-generation sequencing identified a TP53 mutation. Fluorescence in situ hybridization confirmed the presence of MYC translocation. The disease was refractory to rituximab, cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate, ifosfamide, cytarabine, etoposide, and intrathecal methotrexate (R-CODOX-M/R-IVAC), etoposide, methylprednisolone, cytarabine, and cisplatin (ESHAP), as well as CY/TBI (cyclophosphamide 120 mg/kg and total body irradiation 12 Gy) conditioning followed by an allogeneic haemopoietic stem cell transplantation (HSCT) from an Human-Leukocyte-Antigen (HLA)-matched sibling donor. Within 3 weeks of transplantation, the disease progressed to a leukemic phase, refractory to high dose cytarabine and mitoxantrone, and donor lymphocyte infusion.

Following lymphodepletion with fludarabine (30 mg/m2/day on days 1–3) and cyclophosphamide (900 mg/m2 on day 3), 1 × 106 autologous CAR T cells/kg (i.e., donor-engrafted T cells) were infused. The patient developed grade II cytokine release syndrome and grade II CAR T cell-related encephalopathy syndrome (Fig. 1e) [1]. He was treated with broad-spectrum antibiotics and low-dose norepinephrine. Anti-interleukin 6 and steroids were not administered. On day +13 the patient was afebrile and neurological symptoms had resolved. One month after cell infusion, the PET–CT showed significant improvement with resolution of previous FDG-avid lesions consistent with a complete metabolic response (Fig. 1c, d). Three weeks later the patient was treated with a haploidentical HSCT followed by post-transplantation cyclophosphamide. The conditioning regimen included thiotepa (5 mg/kg), fludarabine (120 mg/m2), IV busulfan (6.4 mg/kg), and thymoglobulin (2.5 mg/kg). The transplantation was complicated by sinusoidal obstruction syndrome (SOS), treated with defibrotide, and sepsis resulting in the patient’s death 9 days following the graft infusion.

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References

  1. Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2017. https://doi.org/10.1038/nrclinonc.2017.148

    Article  Google Scholar 

  2. Sweetenham JW, Pearce R, Taghipour G, Blaise D, Gisselbrecht C, Goldstone AH. Adult Burkitt’s and Burkitt-like non-Hodgkin’s lymphoma--outcome for patients treated with high-dose therapy and autologous stem-cell transplantation in first remission or at relapse: results from the European Group for Blood and Marrow Transplantation. J Clin Oncol. 1996;14:2465–72. https://doi.org/10.1200/JCO.1996.14.9.2465

    Article  CAS  PubMed  Google Scholar 

  3. Short NJ, Kantarjian HM, Ko H, Khoury JD, Ravandi F, Thomas DA, et al. Outcomes of adults with relapsed or refractory Burkitt and high-grade B-cell leukemia/lymphoma. Am J Hematol. 2017;92:E114–17. https://doi.org/10.1002/ajh.24720

    Article  PubMed  PubMed Central  Google Scholar 

  4. Jacobson C, LaCasce A. How I treat Burkitt lymphoma in adults. Blood. 2014;124:2913–20. https://doi.org/10.1182/blood-2014-06-538504

    Article  CAS  PubMed  Google Scholar 

  5. Maramattom LV, Hari PN, Burns LJ, Carreras J, Arcese W, Cairo MS, et al. Autologous and allogeneic transplantation for burkitt lymphoma outcomes and changes in utilization: a report from the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2013;19:173–9. https://doi.org/10.1016/j.bbmt.2012.11.016

    Article  PubMed  Google Scholar 

  6. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531–44. https://doi.org/10.1056/NEJMoa1707447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak Ö, et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med. 2017;377:2545–54. https://doi.org/10.1056/NEJMoa1708566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Primary analysis of juliet: a global, pivotal, phase 2 trial of CTL019 in adult patients with relapsed or refractory diffuse large B-cell lymphoma. Blood 2017; 130:577.

  9. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–17.

    Article  Google Scholar 

  10. Brudno JN, Kochenderfer JN. Chimeric antigen receptor T-cell therapies for lymphoma. Nat Rev Clin Oncol. 2018;15:31–46. https://doi.org/10.1038/nrclinonc.2017.128

    Article  CAS  PubMed  Google Scholar 

  11. Lee DW, Stetler-Stevenson M, Yuan CM, Shah NN, Delbrook C, Yates B, et al. Long-term outcomes following CD19 CAR T cell therapy for B-ALL are superior in patients receiving a fludarabine/cyclophosphamide preparative regimen and post-CAR hematopoietic stem cell transplantation. Blood 2016;128:218.

  12. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385:517–28. https://doi.org/10.1016/S0140-6736(14)61403-3

    Article  CAS  PubMed  Google Scholar 

  13. Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014;6:224-5 https://doi.org/10.1126/scitranslmed.3008226

    Article  CAS  Google Scholar 

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  1. These authors contributed equally: Abraham Avigdor, Roni Shouval.

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  1. The Chaim Sheba Medical Center, Tel-Hashomer, Affiliated with the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Abraham Avigdor, Roni Shouval, Elad Jacoby, Tima Davidson, Avichai Shimoni, Michal Besser & Arnon Nagler

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Avigdor, A., Shouval, R., Jacoby, E. et al. CAR T cells induce a complete response in refractory Burkitt Lymphoma. Bone Marrow Transplant 53, 1583–1585 (2018). https://doi.org/10.1038/s41409-018-0235-0

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