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Chronic myelogenous leukemia

Long: molecular tracking of CML with bilineal inv(16) myeloid and del(9) lymphoid blast crisis and durable response to CD19-directed CAR-T therapy

Leukemia volume 34, pages 3050–3054 (2020)Cite this article

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Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), allowing most patients to remain in deep remission with an associated near normal life expectancy. Despite these advances, five to ten percent of patients will progress to accelerated or blast phase CML, which is associated with significantly poorer long-term outcomes despite next-generation TKI therapy [1,2,3]

Although advanced disease commonly presents with either a myeloid or lymphoid morphology, rare reports describe simultaneous occurrence of mixed populations of both myeloid and lymphoid variants; myeloid clones are typically identified in bone marrow and lymphoid clones in extramedullary sites [4,5,6,7].

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Fig. 1: Detection of BCR–ABL, CBFB rearrangements, and del(9p) by in situ hybridization.
Fig. 2: Evolution of tumor population and clinical response post CAR-T.

References

  1. Talati C, Isenalumhe LL, Shams SR, Kuykendall AT, Chavez JC, Shah BD. et al. Outcomes of blast phase chronic myeloid leukemia (BP-CML) in the tyrosine kinase inhibitor (TKI) era. J Clin Oncol. 2017;35 Suppl 15:e18546 .

    Article  Google Scholar 

  2. Cortes JE, Saglio G, Kantarjian HM, Baccarani M, Mayer J, Boque C, et al. Final 5-Year study results of DASISION: the dasatinib versus imatinib study in treatment-naive chronic myeloid leukemia patients trial. J Clin Oncol. 2016;34:2333–40.

    Article  CAS  Google Scholar 

  3. Hochhaus A, Saglio G, Hughes TP, Larson RA, Kim DW, Issaragrisil S, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia. 2016;30:1044–54.

    Article  CAS  Google Scholar 

  4. Kantarjian HM, Keating MJ, Talpaz M, Walters RS, Smith TL, Cork A, et al. Chronic myelogenous leukemia in blast crisis. Analysis of 242 patients. Am J Med. 1987;83:445–54.

    Article  CAS  Google Scholar 

  5. Chen X, Rutledge JC, Wu D, Fang M, Opheim KE, Xu M. Chronic myelogenous leukemia presenting in blast phase with nodal, bilineal myeloid sarcoma and T-lymphoblastic lymphoma in a child. Pediatr Dev Pathol. 2013;16:91–6.

    Article  Google Scholar 

  6. Gao X, Li J, Wang L, Lin J, Jin H, Xu Y, et al. Bilineal extramedullary blast crisis as an initial presentation of chronic myeloid leukemia: a case report and literature review. Am J Case Rep. 2016;17:793–8.

    Article  Google Scholar 

  7. Akashi K, Mizuno S, Harada M, Kimura N, Kinjyo M, Shibuya T, et al. T lymphoid/myeloid bilineal crisis in chronic myelogenous leukemia. Exp Hematol. 1993;21:743–8.

    CAS  PubMed  Google Scholar 

  8. Ruiz S, Chen YH. Acute myeloid leukemia with coexistence of t(9;22) and inv(16). Blood. 2018;131:1263.

    Article  CAS  Google Scholar 

  9. Han E, Lee H, Kim M, Kim Y, Han K, Lee SE, et al. Characteristics of hematologic malignancies with coexisting t(9;22) and inv(16) chromosomal abnormalities. Blood Res. 2014;49:22–8.

    Article  Google Scholar 

  10. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439–48.

    Article  CAS  Google Scholar 

  11. Mestermann K, Giavridis T, Weber J, Rydzek J, Frenz S, Nerreter T, et al. The tyrosine kinase inhibitor dasatinib acts as a pharmacologic on/off switch for CAR T cells. Sci Transl Med. 2019;11:eaau5907.

    Article  Google Scholar 

  12. Zheng Z, Liebers M, Zhelyazkova B, Cao Y, Panditi D, Lynch KD, et al. Anchored multiplex PCR for targeted next-generation sequencing. Nat Med. 2014;20:1479–84.

    Article  CAS  Google Scholar 

  13. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25:1754–60.

    Article  CAS  Google Scholar 

  14. Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25:625–38.

    Article  CAS  Google Scholar 

  15. Marinelli Busilacchi E, Costantini A, Viola N, Costantini B, Olivieri J, Butini L, et al. Immunomodulatory effects of tyrosine kinase inhibitor in vitro and in vivo study. Biol Blood Marrow Transplant. 2018;24:267–75.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank the patient and family, as well as the MGH nurses, advanced practitioners, research, and support staff. This retrospective analysis was approved by the Dana Farber/Harvard Cancer Center Institutional Review Board.

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Authors and Affiliations

  1. Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    Vinayak Venkataraman, Keagan S. Casey, Philip C. Amrein, Meghan K. Bergeron, Andrew M. Brunner, Amir T. Fathi, Julia E. Foster, Jenna Moran, Timothy A. Graubert, Hanno Hock, Chrisa Hunnewell, Matthew J. Frigault, Steven McAfee & Gabriela S. Hobbs

  2. Department of Pathology, Massachusetts General Hospital, Boston, MA, USA

    Maristela Onozato & Valentina Nardi

  3. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA

    Paola Dal Cin

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  1. Vinayak Venkataraman
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Contributions

VV, MO, PDC, VN, JEF, CH, PCA, KSC, MJF, MKB, AMB, ATF, HH, JM, SM, TAG, and GH designed the research, analyzed results, made the figures, and wrote the paper; MO, PDC, TAG, and VN performed experiments. Vineet Sharma provided technical assistance with figure generation.

Corresponding author

Correspondence to Gabriela S. Hobbs.

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Conflict of interest

VV, KSC, MO, PDC, VN, PCA, MKB, JEF, JM, HH, CH, SM, and AMB, have no interests to disclose. ATF does scientific consulting for Celgene/BMS, Novartis, Agios, Astellas, Pfizer, Takeda, Amgen, Daiichi Sankyo, Kite, Trovagene, Forty-Seven, NewLink Genetics, and Abbvie, and receives research funding from Celgene and Abbvie. MF does scientific consulting for Novartis, Gilead, Celgene, Arcellx and is funded by the NIH K12CA087723. TG receives research support from Janssen and Calico. GH does scientific consulting for Incyte, Agios, Celgene, BMS, and Jazz as well as receives research support from Bayer, Incyte, Merck, Constellation and research grants in the form of NIH K12 CA087723 Paul Calabresi Award, ASH-AMFDP, and Sanchez Ferguson Research Award.

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Venkataraman, V., Casey, K.S., Onozato, M. et al. Long: molecular tracking of CML with bilineal inv(16) myeloid and del(9) lymphoid blast crisis and durable response to CD19-directed CAR-T therapy. Leukemia 34, 3050–3054 (2020). https://doi.org/10.1038/s41375-020-0983-x

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