The advancement of chronic myeloid leukemia (CML) treatment through tyrosine kinase inhibitors (TKIs) has brought about a revolutionary transformation in patient outcomes, clinical responses, and survival rates. Nevertheless, specific patient subsets exhibit inferior responses to therapy and poor prognosis. Moreover, a small fraction of patients might develop clonal chromosomal anomalies in Philadelphia-negative (Ph-) cells, referred to as CCA/Ph-, which the European Leukemia Net (ELN) designates as having an adverse prognosis. In this study, we present a unique case of a CML patient who underwent CCA/Ph- evolution.

GSB, a 78-year-old male, received a CML diagnosis in 2019 at 74 years old, with an intermediate Sokal risk classification. At diagnosis, 100% of cells were Ph+ (Philadelphia chromosome positive), and p210 BCR-ABL was detected. Due to severe grade 3 skin lesions caused by Imatinib, the patient was switched to Dasatinib in August 2019, exhibiting good tolerance. In December 2021, pleural effusion occurred, accompanied by clinical and radiological deterioration, leading to furosemide treatment in May 2022. Dasatinib was temporarily suspended in November 2022, resulting in progressive clinical improvement. By December, the dose was adjusted to 80 mg/day, maintaining a major molecular response (BCR-ABL1: 0.00375, International Scale). In June 2023, the patient presented with acute malaise, nausea, and diarrhea. Notably, a complete blood count revealed substantial bicytopenia (anemia and thrombocytopenia), prompting the suspension of Dasatinib. A bone marrow evaluation in August 2023 unveiled myeloid blast transformation, with BCR-ABL1 p210 remaining nearly undetectable (0.002%). Immunophenotyping disclosed that 10.2% of myeloblasts were positive for CD4, CD13, CD33, CD34, CD38, CD45, CD117, HLA-DR, and cMPO, while being negative for cCD3, CD7, CD10, CD11b, CD14, CD16, CD19, CD56, CD64, cCD79a, and CD123. Moreover, 59.1% of viable cells were categorized as monocytes/monoblasts and positive for CD4, CD11b, CD13, CD14 (partial, 88,7%), CD33, CD34, CD38, CD45, CD56 (partial, 38,0%), CD64, HLA-DR, cMPO and negative for cCD3, CD7, CD10, CD16, CD19, cCD79a, CD117, CD123. Cytogenetic analysis exhibited a monosomy of chromosome 7 (45, XY, -7[20]) in all metaphases.

In this context, we portray a case of a 74-year-old patient who developed AML, myelodysplasia-related (AML-MR) after four years of a major molecular response to second line TKI treatment. The earliest documented instance of a patient developing monosomy 7, following 12 months of imatinib therapy, with hypoplastic bone marrow and dysplastic features, dates to 2002. Among CML patients treated with TKIs, around 25% with CCA/Ph- exhibit chromosome 7 abnormalities (-7/del(7q)) and derive the greatest benefits from second line TKIs. Drawing from prior descriptions, as well as observations in this case, it is essential to closely examine clinical and laboratory characteristics (morphological, immunophenotypic, cytogenetic, and molecular) in cases where blast counts in the bone marrow increase. This scrutiny is crucial for accurately classifying the AML-MR clone with CCA/Ph- progression in CML.