Clinical Characteristics And Outcome Of Biphenotypic Acute Leukemia: 10 Case Reports And Literature Review

BACKGROUND: Biphenotypic acute leukemia (BAL), or mixed-phenotype acute leukemia (MPAL) represents a rare subgroup of acute leukemia which co-expresses markers for either more than one lineage in a homogenous blast population or the coexistence of two blast populations of different lineages. Proper diagnosis and classification of BAL are extremely important for patients’ outcome since BAL usually has a poor prognosis. PURPOSE: The objective of this study was to identify the incidence of biphenotypic acute leukemia, their clinical characteristics and outcome of BAL patients with the chemotherapy treatment and Hematopoietic Stem Cell Transplantation (HSCT) after initial complete remission. PATIENTS AND METHODS: Ten cases of biphenotypic acute leukemia were analyzed for their clinical characteristics, immunological phenotypes, chemotherapy methods for induction initial complete remission and outcome data, including induction chemotherapy, complete remission (CR) and the overall survival time, relapse and death. This study was an observational, retrospective, and descriptive study of the clinical aspects of BAL. Cytogenetics and fusion genes analysis were also done with bone marrow samples using G-banding analysis and karyotyped according to the International System for Human Cytogenetic Nomenclature. The fusion genes’ mutational status was determined by real-time PCR (RT-PCR). Gene mutation analyses were conducted with next-generation sequencing method. RESULTS: Among 10 BAL patients, 4 cases carried B/Myeloid phenotype, 4 cases carried T/Myeloid phenotype and 2 cases carried T/B phenotype. Cytogenetic analysis showed that 3 of the 10 cases had clonal abnormalities. Of the four cases of fusion gene aberration, two patients had RUNX1 gene mutation, one patient had BCR/ABL fusion gene mutation, and one patient had JAK1, JAK3, FBXW7 mutation. Overall, 5 of 8 (62.5%) BAL patients with chemotherapy achieved complete remission (CR) after their initial induction therapy. In the AML-directed therapy group, 1 of 2 (50%) patients achieved CR. Meanwhile, 4 of 6 (66.7%) patients achieved CR after ALL-directed induction chemotherapy. Two patients received Hematopoietic Stem Cell Transplantation (HSCT) after initial CRs, one patient died two months after transplantation due to pulmonary infection, and another patient is still alive. With an average of 14.3 (4.0–42.0) months’ follow-ups, the median survival time was 7 months. Although patients achieved CR after initial chemotherapy, the relapse rate was very high and the CR rate after relapse was very low. CONCLUSION: Our results confirmed that BAL is a rare malignancy with a very poor prognosis. Patients with ALL-directed chemotherapy achieved a better CR rate compared to those with AML-directed chemotherapy. Patients should receive HSCT after initial CR whenever it is possible.