CASE REPORT: B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (PH+) WITH IMMUNOPHENOTYPIC SHIFT TO MIXED-PHENOTYPE ACUTE LEUKAEMIA B/MYELOID

The shift in immunophenotype from B-cell Acute Lymphoblastic Leukemia (B-ALL) to Acute Myeloid Leukemia (AML) is a rare phenomenon known as a “phenotypic switch.” The aim of this report is to describe a case of B-cell Acute Lymphoblastic Leukemia with an immunophenotypic shift to a Mixed-phenotype Acute Leukaemia B/myeloid. A 37-year-old male patient presented with complaints of lesions on his tongue, right inguinal region, and buttocks, along with red spots on the skin. One day prior to seeking medical attention, he experienced gum bleeding lasting about an hour. The patient was obese (200 kg). Complete blood count: Hb 10.6 g/dL; Leukocytes 120,290/mm³ (80% small-sized cells, high nucleus-to-cytoplasm ratio, loose chromatin, evident nucleoli, and agranular basophilic cytoplasm); Platelets 5,000/mm³. Bone marrow aspiration was not performed due to technical difficulties. Peripheral blood immunophenotyping: Consistent with B-ALL, showing 65.9% low-complexity cells, dim/negative expression of CD45, and positivity for CD19/CD13/CD25/CD33/CD34/CD38/CD58/cyCD79a/CD123/CRFL-2(dim)/TdTnu, with absence of CD3sm/CD3cy/CD10/CD15/CD20/CD22/CD117/cyMPO/cyIgM. Cerebrospinal fluid: 1.6% positive for CD19/CD34/CD38/CD45 and negative for CD3/CD10/CD14/CD20/CD56. FISH: BCR::ABL1 rearrangement t(9;22). Karyotype: 46,XY,t(9;22)(q34;q11.2)[1]/45, idem, -7[19]. Lymphoid panel in peripheral blood: Presence of RUNX1 and BCR::ABL1. The patient was treated with Hyper CVAD + dasatinib and chemotherapy. On Day 20 of treatment, a bone marrow and cerebrospinal fluid reassessment was performed. Bone marrow: 78.0% small to moderately sized cells, high nucleus-to-cytoplasm ratio, nucleus with loose chromatin, and evident nucleoli, occasionally convoluted, basophilic cytoplasm with granules. Immunophenotype: Presence of two cell populations: one with 76.9% myeloid blast cells expressing CD4/CD11b/CD13/CD19/CD33/CD34/CD36/CD38/CD45/CD64/CD71/CD117/CD123/HLA-DR/cyMPO, and negative for CD2/smCD3/cyCD3/CD7/CD10/CD14/CD15/CD20/CD22/CD56/CD61/cyCD79a/IREM-2; and another with 8.3% lymphoid blast cells expressing partial CD10/CD13/CD19/CD22/CD34/CD38/CD58/cyCD79a/CD123/cyIgM (partial), and negative for smCD3/cyCD3/CD117/CD15/CD20/CD25/CD33/CD45/cyMPO/CRFL2. Cerebrospinal fluid immunophenotyping: 13.8% positive for CD34/CD38/CD45/CD64/CD117 and negative for CD3/CD10/CD14/CD19.The patient was treated with FLAG-IDA + Venetoclax + Ponatinib, but developed severe neutropenia, multi-drug-resistant Klebsiella pneumoniae infection, septic shock, and died on Day 17 of the chemotherapy cycle. The shift in the leukemic cell lineage (lymphoid or myeloid) during the disease course is rare, and the mechanisms involved are not fully understood. These shifts may represent the expansion of a pre-existing clone prior to therapy, clonal evolution, or the development of a new clone. According to the International Consensus Classification of Acute Leukemias 2022, B-ALL Ph+ can be subdivided into two subtypes: “multilineage involvement” and “lymphoid-only involvement.” However, there is still no consensus on how to classify these cases. In a large cohort of patients with B-ALL Ph+, Bastian et al. characterized two groups based on transcriptomic and genomic profiles. The "multilineage involvement" group exhibited a genomic pattern of HBS1L deletion and monosomy 7. Conclusion: The occurrence of immunophenotypic shifts in B-ALL Ph+ highlights the need for further studies to establish the prognostic value of molecular classifications in these leukemias. This, in turn, will help define the most appropriate therapeutic approach for each subtype.