LAUSR

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 [1–3] 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 [4–7]. Here, we describe a patient who initially presented with chronic phase CML (CP-CML) that quickly progressed to bilineal CML blast crisis with separate lineage-defining translocations arising from a common Philadelphia-positive (Ph+) clone. The patient’s clinical course was unique as his disease concurrently displayed myeloid and lymphoid variants, characterized by evolution of the Ph+ clone with development of inv(16) and del(9p), both of which demonstrated differential sensitivity to TKI therapy. Although co-existence of t(9;22) and inv(16) has been described previously [8, 9], additional 9p loss has not. Despite disease relapse following TKI/chemotherapy, consolidative allogeneic stem cell transplant (SCT), and induction of graft-versus-leukemia (GVL) via early cessation of immunosuppression, he was successfully treated with CD19-specific chimeric antigen receptor T-cell (CART/Tisagenlecleucel) therapy. This patient represents a population not included in the pivotal ELIANA study of tisagenlecleucel and remains in a complete molecular (CMR) and PET response 6 months after CD19 CAR-T [10]. His case emphsasis the importance of detailed molecular and phenotypic profiling when devising novel treatment strategies. In addition, given recent data suggesting impairment of T-cell function by dasatinib [11], this was achieved without TKI maintenance post CAR-T. Written informed consent for treatment and sample analysis was obtained. This analysis was approved by the Dana Farber/Harvard Cancer Center Institutional Review Board. Treatment consisted of standard institutional protocols for CML and commercially available CAR-T. Molecular profiling, FISH, and immunophenotyping were performed previously described [12, 13]. A laboratorydeveloped algorithm was used for fusion transcript and mutation detection and annotation. A previously healthy, 23-year-old male presented with 15-pound weight loss, fatigue, and splenomegaly. Complete blood count (CBC) showed WBC 568,000 cells/μL, and bone marrow biopsy (BMBx) was consistent with Sokal intermediate risk, CP-CML. Cytogenetics at the time demonstrated 46,XY,t(9;22)(q34;q11.2) in 20 metaphases, and BCR–ABL Taqman PCR detected BCR–ABL/GUS * Gabriela S. Hobbs [email protected]