Childhood Mixed Lineage Leukemia: The St. Jude Experience.
Authors: Onciu Mihaela , Pui Ching-Hon , Behm Fred G. , Razzouk Bassem I. , Ribeiro Raul C. , Rubnitz Jeffrey E. 
Published: April 2020

Abstract
PURPOSE: To report a single institutional experience with presenting features, therapeutic approach and outcomes in pediatric mixed lineage acute leukemias, as defined by the WHO classification (including biphenotypic, bilineal and poorly differentiated leukemias).
PATIENTS AND METHODS: Retrospective study of all pediatric patients with acute leukemias fulfilling the EGIL/WHO criteria for mixed-lineage leukemia, treated at St. Jude Children’s Research Hospital from 1985–2006. Features analyzed included morphology, cytochemistry, immunophenotype (flow cytometry), cytogenetics, therapy, response to therapy (including minimal residual disease level as detected by flow cytometry) and outcome.
RESULTS: Of 1500 patients with newly diagnosed acute leukemia, 35 (21 boys and 14 girls), were diagnosed to have mixed lineage leukemia. They ranged in age between 2 days and 19 years (median, 10 years) and had a median leukocyte count of 18 × 109/L (range, 1 to 150 × 109/L). Morphologic and flow cytometric studies identified these leukemias as biphenotypic T-lymphoid/myeloid (20 cases), B-lymphoid/myeloid (10 cases), B/T-lymphoid/myeloid (2 cases), bilineal (2 cases) and undifferentiated (1 case). Sixteen cases showed cytochemical positivity for myeloperoxidase (1% to 90%, median 5%) and 9 cases had Auer rods. Twenty-three patients initially received standard induction therapy for AML (cytarabine, daunorubicin, and etoposide) and 12 patients received ALL-directed remission induction [prednisone, vincristine, L-asparaginase (PVA), and daunomycin]. Of the former group, 12 (52%) achieved complete remission (CR), 2 attained partial remission (PR), 8 had no response (NR), and 1 died of toxicity. Ten of the 12 patients (83%) who first received ALL therapy achieved CR and only 2 had NR. Thus, after initial induction therapy, 22 of the 35 patients (63%) achieved CR. However, 8 of the 10 patients who had NR or PR to AML therapy attained CR after receiving standard ALL induction therapy with only PVA, and 1 of 2 patients who had NR to ALL therapy achieved CR after receiving AML therapy, resulting in an overall CR rate of 91% (32 of 35 patients). Notably, of the 8 patients who did not respond to AML therapy but achieved CR after PVA, all 4 tested were MRD-negative after PVA and all 6 who received multiagent chemotherapy without transplantation are alive and in long-term remission for 1.1 to 16.4 years. Seven of these 8 patients had T-lymphoid/myeloid biphenotypic leukemia with expression of CD2, CD7, cytoplasmic CD3, and low MPO positivity (1% to 3.5%). Overall, among patients who achieved CR, 15 of 20 patients treated with chemotherapy alone are alive in remission, compared to only 4 of 11 patients who underwent transplantation.
CONCLUSIONS: Pediatric patients with mixed lineage leukemia may benefit from a therapeutic approach directed against both AML and ALL. We suggest that patients who respond well to myeloid-directed therapy should continue to receive this therapy, whereas those who require lymphoid-directed induction should receive prolonged continuation treatment directed against both ALL and AML. Furthermore, our results indicate that patients with mixed lineage leukemias who achieve remission do not require stem cell transplantation to achieve long term survival.