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BPX-501 T cells interfere with minimal residual disease evaluation of B-cell acute lymphoblastic leukemia

Bone Marrow Transplantation volume 53, pages 651–653 (2018)Cite this article

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Cellular therapies are increasingly used to treat hematologic malignancies requiring providers to recognize and learn to treat newly prominent complications of therapy such as cytokine release syndrome as well as adapting their practice to incorporate the special requirements for working with cellular therapies. Here we present an unusual complication of BPX-501 T cells affecting the clinical workflow and emphasizing the need for good communication between providers and the laboratory.

The patient is a 24-year-old female with Philadelphia chromosome positive precursor B-cell acute lymphoblastic leukemia (pre-B-ALL) in first complete remission who received an alpha beta T-cell depleted, CD34+ selected haploidentical peripheral blood hematopoietic stem cell transplant (HSCT) after myeloablative conditioning with fludarabine, cyclophosphamide, anti-thymocyte globulin, rituximab, and total body irradiation. The patient received a planned infusion of BPX-501 T cells on day 13 as a part of clinical trial (ClinicalTrials.gov identifier: NCT0174423). BPX-501 T cells are allogeneic donor T cells that have been modified with an inducible apoptosis safety switch based on the fusion of human caspase 9 to human FK506-binding protein (FKBP12). Upon binding of remiducid (AP1903), a bioinert agent with high affinity to FKBP12, caspase 9 dimerizes and is activated, inducing apoptosis. The development of acute graft versus host disease can be abrogated in recipients of haploidentical transplants who have received infusions of BPX-501 T cells upon exposure to remiducid [1].

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References

  1. Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. New Engl J Med. 2011;365:1673–83. https://doi.org/10.1056/NEJMoa1106152.

    Article  Google Scholar 

  2. Borowitz MJ, Wood BL, Devidas M, Loh ML, Raetz EA, Salzer WL, et al. Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children’s Oncology Group study AALL0232. Blood. 2015;126:964–71. https://doi.org/10.1182/blood-2015-03-633685.

    Article  CAS  Google Scholar 

  3. Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children’s Oncology Group study. Blood. 2008;111:5477–85. https://doi.org/10.1182/blood-2008-01-132837.

    Article  CAS  Google Scholar 

  4. Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17:e328–346. https://doi.org/10.1016/s1470-2045(16)30206-6.

    Article  Google Scholar 

  5. Paiva B, Vidriales MB, Cervero J, Mateo G, Perez JJ, Montalban MA, et al. Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. Blood. 2008;112:4017–23. https://doi.org/10.1182/blood-2008-05-159624.

    Article  CAS  Google Scholar 

  6. 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. https://doi.org/10.1056/NEJMoa1407222.

    Article  Google Scholar 

  7. Grupp SA, Maude SL, Shaw PA, Aplenc R, Barrett DM, Callahan C, et al. Durable remissions in children with relapsed/refractory ALL treated with T cells engineered with a CD19-targeted chimeric antigen receptor (CTL019). Blood. 2015;126:681–681.

    Google Scholar 

  8. Cherian S, Miller V, McCullouch V, Dougherty K, Fromm JR, Wood BL A novel flow cytometric assay for detection of residual disease in patients with B-lymphoblastic leukemia/lymphoma post anti-CD19 therapy. Cytometry B Clin Cytom. 2016. https://doi.org/10.1002/cyto.b.21482.

  9. Philip B, Kokalaki E, Mekkaoui L, Thomas S, Straathof K, Flutter B, et al. A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Blood. 2014;124:1277–87.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from Bellicum Pharmaceuticals to GLC. This work was supported by Roswell Park Cancer Institute and National Cancer Institute (NCI) grant P30CA016056.

Authors contributions

A.E., P.K.W., M.J.B., and G.L.C. designed the research, performed the research, analyzed the data, and wrote the paper. A.K., C.C., C.H., S.B., M.R., T.H., V.O., and P.L.M. performed the research.

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Authors and Affiliations

  1. Department of Medicine, Blood and Marrow Transplant Program, Roswell Park Cancer Institute, Buffalo, NY, USA

    Amro Elshoury, Angela Kader, Christine Ho, Sophia Balderman, Maureen Ross, Theresa Hahn, Philip L. McCarthy & George L. Chen

  2. Department of Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA

    Paul K. Wallace

  3. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Michael J. Borowitz

  4. Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA

    Chris Choi

  5. Bellicum Pharmaceuticals, Houston, TX, USA

    Vince O’Neill

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  1. Amro Elshoury
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Correspondence to George L. Chen.

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Conflict of interest

G.L.C. receives funding from Bellicum Pharmaceuticals to conduct clinical research. V.O. is employed by Bellicum Pharmaceuticals. The remaining authors declare that they have no conflict of interest.

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Amro Elshoury, Wallace, P.K., Borowitz, M.J. et al. BPX-501 T cells interfere with minimal residual disease evaluation of B-cell acute lymphoblastic leukemia. Bone Marrow Transplant 53, 651–653 (2018). https://doi.org/10.1038/s41409-017-0036-x

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