AUTHOR=Salama Maram , Ahmed Sonia , Soliman Sonya , El-Sharkawy Nahla , Salem Sherine , El-Nashar Amr , Khedr Reham , Lehmann Leslie , Sidhom Iman , El-Haddad Alaa 

TITLE=Characteristics, Treatment Complexity, and Outcome of Mixed-Phenotype Acute Leukemia in Children in a Low–Middle-Income Country

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.941885

DOI=10.3389/fonc.2022.941885

ISSN=2234-943X

ABSTRACT=Background: Mixed phenotype acute leukemia (MPAL) in children is an uncommon subtype of acute leukemia that cannot be definitively assigned to a specific lineage. There is no consensus on the best approach to therapy. Management is further complex in low-middle-income countries (LMICs). Aim: To evaluate the clinicopathological characteristics as well as outcomes of patients with MPAL in a developing country. Patients and methods: A retrospective descriptive study of 42 pediatric patients newly diagnosed with MPAL from July 2007 until December 2017. Results: The immunophenotyping was T/Myeloid in 24 patients (57.1%) and B/Myeloid in 16 (38.1%). Three subjects had MLL gene rearrangement, two had Philadelphia positive chromosomes, and eight had FLT3-ITD with a ratio >0.4. Two subjects died before starting chemotherapy. Ten patients (25%) received ALL induction, and all achieved complete remission (CR) with no induction deaths and no shift of therapy. Thirty patients (75%) started therapy with AML induction: five (16.6%) died during induction, 17 (56.7%) achieved CR, and 10 patients received maintenance ALL therapy after ending AML treatment. Four of the eight patients with induction failure were switched to ALL therapy. The 5-year event-free (EFS), as well as overall survival (OS), were 56.7% (standard error [SE]: 8.1%) and 61% (SE: 8%), while the cumulative incidence of relapse was 21.7% (SE: 6.7%), with a median follow-up duration of 5.8 years. Patients treated with ALL directed therapy had a 5-year EFS of 70% (SE: 14%) and OS of 78.8% (SE: 13%). FLT3-ITD mutation showed a significantly lower five-year-EFS of 28.6% (SE: 17%) versus 75% (SE: 9%) for the wild-type, P= .032. Undernourished patients with a BMI z-score -2 at presentation had a significantly lower 5-year EFS of 20% (SE: 17%) compared to 61.8% (SE: 8%) for patients with BMI z-score > -2, p=0.015  Conclusion: This study supports ALL directed therapy for pediatric MPAL in a setting of LMIC. Given the poor outcome of FLT3-ITD, the role of FLT3 inhibitor needs to be explored in this subset of cases.