Lineage switch in acute leukemias is considered a rare event, especially in what concerns adult disease compared to pediatric patients. Differential diagnosis between biphenotypic/bilineal leukemias, de novo leukemias, therapy-related and phenotype switch variants, stands as an intricate challenge. Complementary laboratory studies and complex laboratory assays (conventional karyotyping, FISH- fluorescence in situ hybridization, molecular biology, immunophenotyping, etc.) represent one of the crucial resources regarding the process of establishing an accurate diagnosis, thus having a firm ground for the most beneficial treatment choice. Aim: To emphasize the diagnostic and therapeutic particularities regarding the case of a female patient with acute lymphoblastic leukemia (ALL) who later developed a phenotype switch towards an intermediary form of acute myeloid leukemia (AML), sharing features of both AML with maturation and atypical acute promyelocytic leukemia (AML M2/M3/APL). Material and methods: We hereby present the case of a 66 year old female, diagnosed with B- ALL, who underwent both classical chemotherapy (adequate protocol related to age, genetic profile, commorbidites) and bispecific monoclonal antibody therapy at first early relapse (Blinatumomab), followed by phenotype switch at second early relapse towards atypical APL. Combined ATRA and anthracycline therapy followed, yet laboratory work-up shows refractory disease. Complications during treatment were comprised of severe DIC (disseminated intravascular coagulation) and infections- sepsis followed by exitus. Results and conclusions: This is the case of a phenotype switch in a patient with ALL, who underwent both classical chemotherapy and Blinatumomab, towards myeloid lineage-refractory APL atypical variant. Availability of flow cytometry and cytogenetics during morphology evaluation represents a key aspect in the management of such hematologic malignancies.
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