Children Diagnosed with Acute Leukemia of Ambiguous Lineage (ALAL) Benefit from Acute Myeloid Leukemia (AML) Treatment Protocols: A Retrospective Analysis from a Single Center
Authors: Avgerinou Georgia , Binenbaum Ilona , Glentis Stavros , Tzannoudaki Marianna , Papadhimitriou Stefanos , Rigatou Efthimia , Katsibardi Katerina , Tourkantoni Natalia , Tsipou Haroula , Roka Kleoniki , Vlachou Antonia , Filippidou Maria , Kattamis Antonis 
Published: February 2021

Background:Acute Leukemia of Ambiguous Lineage (ALAL) is a very rare type of leukemia, comprising 2%-5% of Acute Leukemias (AL). There is a lack of a uniform definition, with two different classification systems used (EGIL and WHO 2008/2016), making the optimal chemotherapy approach undetermined.
Patients and Methods:The medical records of newly diagnosed ALAL patients (BAL based on the EGIL criteria or ALAL based on the 2008/2016 WHO criteria), who were admitted to our hospital from January 2012 to August 2020, were retrospectively reviewed. Patients characteristics including age, sex, blood count, blasts in bone marrow and peripheral blood, morphology, immunophenotyping, and cytogenetic/molecular studies were obtained. Treatment methods and outcome data including induction chemotherapy, complete remission (CR), relapse, use of Hematopoietic Stem Cell Transplantation (HSCT) in first CR (CR1), and death were reviewed.
Results:Among a total of 168 newly diagnosed patients with AL, 7 (4.17%) patients (5 male & 2 female), fulfilled prerequisites of ALAL/MPAL. The median age at diagnosis was 5 years (range 1-14 years). Distinct dimorphic lymphoid and myeloid (monocytic) blast populations were present in one case with bilineal leukemia, as well as in two cases of biphenotypic leukemia. The remaining cases had morphologic and cytochemical features of Acute Myeloid Leukemia (AML), French-American-British (FAB): M1, M5 subtypes in two cases and Acute Lymphoblastic Leukemia (ALL) FAB L1-L2 subtype in one case. One case presented with early switch of lineage from ALL at diagnosis to AML M5 at the end of induction treatment. The AML directed regimen was associated with better complete remission rate at the end of induction treatment (CR 100%) compared to the ALL directed regimen (CR 0%). It is of note that the two patients that failed to achieve CR with ALL directed chemotherapy did respond to the AML induction treatment. Six patients underwent HSCT in CR1. One patient relapsed and underwent HSCT in CR2, but succumbed due to treatment related mortality during the transplantation period. At a median follow-up of 3.7 years (range 1-8 years) the 5-year overall survival (OS) and the event free survival (EFS) were 80% and 60%, respectively.
Conclusions:Considering that ALAL is a very rare leukemia, the optimal treatment approach remains a dilemma for many clinicians. Although patient numbers are small and follow-up periods are short, the use of AML treatment protocols for ALAL appears to be promising and efforts need to be made on an international collaborative scale.

Disclosures
Kattamis: Novartis:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Vertex:Membership on an entity's Board of Directors or advisory committees;Genesis Pharma SA:Membership on an entity's Board of Directors or advisory committees;Apopharma/Chiesi:Honoraria, Speakers Bureau;Celgene/BMS:Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Ionis:Membership on an entity's Board of Directors or advisory committees;Agios:Consultancy;Vifor:Membership on an entity's Board of Directors or advisory committees.