From Molecular Silence to Lymphoid Blast Phase: Diagnostic and Therapeutic Challenges in a Young Female Patient With Chronic Myeloid Leukemia

TL;DR

A young woman with chronic myeloid leukemia faced diagnostic and treatment challenges due to negative molecular tests and resistance to multiple drugs, but found success with a new therapy.

Contribution

This case highlights the challenges of managing CML with multi-TKI intolerance and the potential of asciminib as a novel therapeutic option.

Findings

Molecular testing remained negative despite CML diagnosis confirmed by FISH.

Patient developed intolerance to first- and second-generation tyrosine kinase inhibitors.

Asciminib was successfully introduced as an alternative therapy.

Abstract

Chronic myeloid leukemia (CML) is a triphasic myeloproliferative neoplasm characterized by the breakpoint cluster region-Abelson BCR::ABL1 fusion gene, typically detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We present a case of a 20-year-old female patient who presented with non-specific constitutional symptoms and was diagnosed with CML based upon detection of the Philadelphia (Ph) chromosome by fluorescence in situ hybridization (FISH), while repeated molecular testing remained negative. Notably, during treatment with tyrosine kinase inhibitors (TKIs), she became intolerant to first- and second-generation TKIs, including the branded and generic imatinib, nilotinib, and dasatinib, followed by progression into lymphoid blast phase. This case highlights the diagnostic challenges and therapeutic complexity of managing CML in the setting of multi-TKI intolerance. Importantly, it underscores the persistent molecular silence despite repeated RT-qPCR testing and the successful introduction of asciminib as a novel therapeutic alternative.

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