Rapid Evolution to Blast Crisis Associated with a Q252HABL1Kinase Domain Mutation in e19a2BCR-ABL1Chronic Myeloid Leukaemia

Abstract

A minority of chronic myeloid leukaemia (CML) patients express variant transcripts of which the e19a2BCR-ABL1fusion is the most common. Instances of tyrosine kinase inhibitor (TKI) resistance in e19a2BCR-ABL1CML patients have rarely been reported. A case of e19a2BCR-ABL1CML is described in whom imatinib resistance, associated with a Q252HABL1kinase domain mutation, became apparent soon after initiation of TKI therapy. The patient rapidly transformed to myeloid blast crisis (BC) with considerable bone marrow fibrosis and no significant molecular response to a second generation TKI. The clinical course was complicated by comorbidities with the patient rapidly succumbing to advanced disease. This scenario of Q252H-associated TKI resistance with rapid BC transformation has not been previously documented in e19a2BCR-ABL1CML. This case highlights the considerable challenges remaining in the management of TKI-resistant BC CML, particularly in the elderly patient.