Inclusion Criteria:  subjects must have histologically or cytologically confirmed R/R MPAL based on WHO criteria, OR MPAL in CR/CRh/CRi/CRp after at least one chemotherapy block of standard ALL or AML treatment with MRD positivity at a level of ≥ 0.1% using an assay with a minimum sensitivity of 0.01% Age 18 years and older subjects who have undergone allo-HSCT are eligible if they are ≥ 4 weeks post stem cell infusion, have no evidence of GVHD > Grade 2, and are at least ≥ 1 week off all immunosuppressive therapy Previous cytotoxic chemotherapy (except for hydroxyurea) must have been completed at least 2 weeks prior to day 1 of treatment on the study. subjects with hematologic malignancies are expected to have hematologic abnormalities at study entry. ECOG performance status < 3  Subjects must have organ function as below:  Direct bilirubin ≤ 2.5 mg/dL AST/ALT/Alkaline phosphatase ≤ 5 X institutional upper limit of normal Serum creatinine ≤ 3 mg/dL Subjects with a history of CNS leukemia must be clinically stable with a flow cytometric clear CSF in the 2 weeks prior to day 1 of blinatumomab administration. subjects with history of CNS leukemia in Cohort A should have received one dose of intrathecal (IT) 6 chemotherapy in the 4 weeks prior to day 1 of blinatumomab administration. Subject can receive subsequent prophylactic intrathecal chemotherapy. Female subjects of childbearing potential must have a negative pregnancy test Ability to understand and willingness to sign a written informed consent document Agree to comply with the study requirements and agree to come to the clinic/hospital for required study visits  Exclusion Criteria:  Subjects receiving any other investigational agents, or concurrent chemotherapy, radiation therapy, or immunotherapy not including corticosteroids or hydroxyurea  Subjects with acute leukemia with any of the following cytogenetic abnormalities:  t(15;17)(q24;q21) PML/RARA, t(8;21)(q22;q22) RUNX1/RUNX1T1, inv(16)(p13q22)/t(16;16)(p13;q22) CBFB-MYH11  A history or presence of clinically relevant CNS pathology (e.g., as epilepsy, paresis, aphasia, stroke, severe brain injuries, dementia, cerebellar disease, psychosis) Hyperleukocytosis with > 50,000 blasts/µL. Hydroxyurea for blast count control is permitted before starting treatment and up to maximum of 10 days after starting treatment on the study. The WBC need not reach 50,000/µL to start hydroxyurea during protocol; the decision to start hydroxyurea during this time is at the discretion of the treating physician Active, uncontrolled infection; subjects with infection under active treatment and controlled with antimicrobials are eligible Pregnant women Uncontrolled undercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled active seizure disorder, or psychiatric illness/social situations that per site Principal Investigator's judgment would limit compliance with study requirements