Challenges and Opportunities in Management of Adult Mixed Phenotype Acute Leukaemia

Background & Objectives: Mixed-phenotype leukemia (MPAL) is a type of acute leukemia in which the blast population shows mixed features of myeloid, T-lymphoid, and/or B-lymphoid differentiation. MPALs are rare and carry a poor prognosis because of both diagnostic and therapeutic challenge. Conventionally, the diagnosis of MPAL requires either a single blast population with a lineage-defining phenotypic expression of multiple lineages (myeloid, B-cell and/or T-cell) (biphenotypic) or two distinct blast populations that each independently satisfy criteria for designation as AML, B-ALL, and/or T-ALL (bilineage). This retrospective study was designed to study the clinicopathological presentation and treatment outcome of MPAL cases in a tertiary care hospital in western India.

Aim: To evaluate the clinicopathological characteristics and treatment outcomes of patients with MPAL in a developing Low–middle–income country.

Methods: A retrospective study of 24 adult patients newly diagnosed with MPAL from January 2005 to December 2017.

Results: There were 8 females and 16 males. The average age was 35 years old (range = 19–78). Nine cases were bilineage and fifteen were biphenotypic. There were 21 adult and 3 geriatric patients. We found 8 T/Myeloid (33.3%) and 16 B/Myeloid (66.7%) patients. MLL gene rearrangement was detected in Two (8.3%) patients. Philadelphia-positive chromosomes were detected in four (16.7%) patients, and FMS-like tyrosine kinase 3 (FLT3-ITD) internal tandem duplication (FLT3-ITD) was detected in two (8.3%) patients. CNS involvement was found at presentation in 3 (12.5%) cases among 24 MPAL patients. MPAL patients were treated with either ALL or AML protocol combined with tyrosine kinase inhibitor (TKI). Eighteen patients (75%) received acute lymphoblastic leukemia (ALL) induction and thirteen patients (72.2%) achieved complete remission (CR) with no induction deaths. Therapy for four Ph1+ MPALs is based on an ALL or AML protocol combined with tyrosine kinase inhibitor (TKI). Six patients (25%) started therapy with acute myeloid leukemia (AML) induction: 3(50%) achieved CR. Five patients with ALL induction failure were switched to AML therapy. 5-year EFS 79.2% overall, 83.3% with ALL directed treatment and 66.7% with AML directed treatment. Five patients relapsed, three after ALL-directed treatment and two after AML-directed treatment.

Conclusion: ALL-directed therapy is associated with better outcomes than AML directed therapy in adult MPAL patients in our study.