Clinical Characteristics of Coexistent Chronic Myeloid Leukemia and BCR::ABL1 Negative Myeloproliferative Neoplasms: A Retrospective Study.

Coexistent chronic myeloid leukemia (CML) and BCR::ABL1-negative myeloproliferative neoplasms (MPN) are rare. We aimed to evaluate their clinical and therapeutic profiles. We retrospectively evaluated 36 institutional patients with coexistent CML and BCR::ABL1-negative MPN (Cohort A) and systematically reviewed 244 published cases (Cohort B). Patients were categorized by diagnostic sequence: prior CML, prior BCR::ABL1-negative MPN, or concurrent presentation. BCR::ABL1 p210 and JAK2V617 F aberrations predominantly co-occurred. Diagnoses in Cohort A were mostly concurrent (77.8%), whereas Cohort B predominantly featured prior BCR::ABL1-negative MPN (43.0%), followed by concurrent diagnoses (35.7%) and prior CML (21.3%). In Cohort B, myelofibrosis was significantly more prevalent in prior BCR::ABL1-negative MPN compared to those with prior CML or concurrent diagnoses (56.2% vs. 26.9% vs. 35.6%, respectively; p = 0.007). Persistent, unexplained cytosis despite active therapy triggered secondary mutation cross-screening in both cohorts. In Cohort A, exploratory survival analysis suggested a potential trend toward shorter overall survival in prior BCR::ABL1-negative MPN compared to concurrent diagnoses (90.5 months vs. not reached, p = 0.032). Multivariable analysis of Cohort B identified prior BCR::ABL1-negative MPN as an independent adverse predictor for major or deeper molecular responses (OR = 0.412, 95% CI: 0.197-0.861, p = 0.018), while tyrosine kinase inhibitor (TKI)-based therapy was favorable (OR = 9.74, 95% CI: 1.108-85.636, p = 0.040). Addition of JAK2 inhibitors to TKI therapy did not significantly improve molecular responses over TKI monotherapy (67.1% vs. 54.8%, p = 0.193). To summarize, prior BCR::ABL1-negative MPN, the most frequent presentation, predicted inferior molecular responses. Clinicians should screen for coexistent mutations if cytosis persisted despite treatment. TKI remained the therapeutic cornerstone, as combined JAK2 inhibition demonstrated limited additional benefit.