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Prognosis of children with mixed phenotype acute leukemia treated in accordance with consistent immunophenotypic criteria

¹ CLIP-Childhood Leukemia Investigation Prague
² Department of Pediatric Hematology and Oncology, Charles University, 2^nd Faculty of Medicine and University Hospital Motol, Prague
³ Departments of Pediatric Oncology and Medical Genetics, University Hospital, Brno
⁴ Department of Pediatrics, Regional Hospital, Ceske Budejovice
⁵ Department of Pediatrics, Faculty of Medicine Palacky University and University Hospital, Olomouc
⁶ Department of Pediatrics, Teaching Hospital Ostrava
⁷ Department of Pediatrics, University Hospital Pilsen
⁸ Department of Pediatrics, Masaryk Hospital Usti nad Labem
⁹ Department of Pediatrics, Faculty of Medicine Hradec Kralove
¹⁰ Center of Oncocytogenetics, Institute of Clinical Biochemistry and Laboratory Diagnostics, General University Hospital and 1^st Faculty of Medicine, Charles University, Prague
¹¹ Department of Hemato-oncology, Faculty of Medicine Palacky University and University Hospital, Olomouc
¹² Institute of Hematology and Blood Transfusion, Prague

Address for correspondence: Ondrej Hrusak and Ester Mejstrikova, Dept. of Pediatric Hematology Oncology, V uvalu 84, 150 06 Praha 5, Czech Republic, emails: Ondrej.Hrusak{at}lfmotol.cuni.cz and Ester.Mejstrikova{at}lfmotol.cuni.cz

ABSTRACT

Background: Mixed phenotype acute leukemia (MPAL) represents a diagnostic and therapeutic dilemma. EGIL scoring system unambiguously defines MPAL expressing aberrant lineage markers. Discussions surrounding it have focused on scoring details, and information is limited regarding its biological, clinical and prognostic significance. Recent WHO classification is simpler and can replace the EGIL scoring after transformed into unambiguous guidelines.

Design and Methods: Simple immunophenotypic criteria classified all cases to ALL- or AML-directed therapy. Prognosis, genotype and immunoglobulin/T-cell receptor gene rearrangement (Ig/TCR) status are analyzed.

Results: Incidences of MPAL were 28/582 and 4/107 for children treated as ALL and AML, respectively. In immunophenotypic principal component analysis (PCA), MPAL treated as T-ALL clustered between non-mixed T-ALL and AML cases while other MPAL cases were included in the respective non-mixed BCP-ALL or AML clusters. Analogously, Ig/TCR rearrangements followed the expected pattern in patients treated as AML (non-rearranged, 4/4) or as BCP-ALL (rearranged, 20/20), but were missing in 3/5 analyzed MPAL treated as T-ALL. In patients who received ALL treatment, the 5-year event-free survival was poorer in MPAL compared to non-mixed cases (53±10% and 76±2% at 5 years, respectively, p=0.0075), with a more pronounced difference among B lineage cases. Small numbers of MPAL cases treated as T-ALL or as AML hampered separate statistics. We compared prognosis of all subsets to published cohorts.

Conclusions: Simple immunophenotypic criteria are useful for therapy decisions in MPAL. In B lineage leukemia, MPAL confers poorer prognosis. However, our data did not justify a preferential use of current AML-based therapy in MPAL.

Key words: pediatric acute lymphoblastic leukemia, pediatric acute myeloid leukemia, mixed phenotype leukemia, biphenotypic leukemia, aberrant antigens, cytometry, acute hybrid leukemia.