Blood Res.  2019 Mar;54(1):63-73. 10.5045/br.2019.54.1.63.

Biphenotypic acute leukemia or acute leukemia of ambiguous lineage in childhood: clinical characteristics and outcome

• Lee HG
• Baek HJ
• Kim HS
• Park SM
• Hwang TJ
• Kook H

• KMID: 2451058
• DOI: http://doi.org/10.5045/br.2019.54.1.63

Abstract

BACKGROUND
Acute leukemia (AL), not clearly assigned to myeloid, B-lymphoid, or T-lymphoid lineage, is classified as either biphenotypic acute leukemia (BAL) based on the European Group for Immunological Classification of Leukemias (EGIL) or acute leukemia of ambiguous lineage (ALAL) encompassing acute undifferentiated leukemia (AUL) and mixed-phenotype acute leukemia (MPAL) based on the World Health Organization (WHO) criteria.
METHODS
Medical records of children newly diagnosed with BAL or ALAL, based on the EGIL or the 2008/2016 WHO criteria, respectively, admitted at Chonnam National University Hospital in 2001-2017 were retrospectively reviewed.
RESULTS
Twelve (3.2%) of 377 AL patients satisfied the BAL or ALAL definitions based on the EGIL or the WHO criteria, respectively. Among 12 patients including 11 with BAL and another with undefined case based on the EGIL criteria, 7 (1.9%) had ALAL based on more stringent 2016 WHO criteria (AUL, 2; MPAL, 5). One patient had MPAL with t(9;22)(q34;q11.2), BCR-ABL+, and two had MLL gene abnormality. ALL-directed regimen was associated with better complete remission rate compared with AML-directed regimen (100.0% vs. 16.7%; P=0.015). The 5-year overall survival (OS) and event-free survival (EFS) were 51.1±15.8% and 51.9±15.7%, respectively. AUL was associated with poor OS and EFS compared with MPAL (0.0% vs. 75.0±21.7%; P=0.008).
CONCLUSION
Due to the rarity of the cases, future multicenter, prospective studies incorporating large number of cases are urgently warranted to identify the clinical, biologic, and molecular markers for the prediction of prognosis and determine the best tailored therapy for each patient.

Keyword

Biphenotypic acute leukemia; Acute leukemia of ambiguous lineage; Mixed-phenotype acute leukemia; Children; Immunophenotyping

MeSH Terms

Child
Classification
Disease-Free Survival
Humans
Immunophenotyping
Jeollanam-do
Leukemia*
Leukemia, Biphenotypic, Acute*
Medical Records
Prognosis
Prospective Studies
Retrospective Studies
World Health Organization

Figure

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  Fig. 1 Flow diagram of the classification, treatment and outcome. Abbreviations: CR, complete remission; MPAL, mixed-phenotype acute leukemia; NR, non-responders; PR, partial remission; SCT, stem cell transplantation.

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  Fig. 2 The 5-year Kaplan-Meier plot for (A) OS and (B) EFS for all biphenotypic acute leukemia patients. Abbreviations: BAL, biphenotypic acute leukemia; EFS, event-free survival; OS, overall survival.

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  Fig. 3 The 5-year Kaplan-Meier plot of (A) OS and (B) EFS of AUL and MPAL by 2016 WHO classification. Abbreviations: AUL, acute undifferentiated leukemia; EFS, event-free survival; MPAL, mix-phenotype acute leukemia; OS, overall survival.

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  Fig. 4 The 5-year Kaplan-Meier plot of (A) OS and (B) EFS according to initial leukocyte count. Abbreviations: EFS, event-free survival; OS, overall survival.

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  Fig. 5 The 5-year Kaplan-Meier plot of (A) OS and (B) EFS for patients with T/myeloid and B/myeloid biphenotypic leukemia. Abbreviations: EFS, event-free survival; OS, overall survival.

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  Fig. 6 The 5-year Kaplan-Meier plot for (A) OS and (B) EFS for biphenotypic acute leukemia patients treated with ALL-directed induction therapy and AML-directed induction therapy. Abbreviations: EFS, event-free survival; OS, overall survival.

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  Fig. 7 The 5-year Kaplan-Meier plot for (A) OS and (B) EFS for biphenotypic acute leukemia patients treated with chemotherapy alone and those treated with HSCT in first remission. Abbreviations: EFS, event-free survival; HSCT, hematopoietic stem cell transplantation; OS, overall survival.

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  Fig. 8 The 5-year Kaplan-Meier plot for (A) OS and (B) EFS for biphenotypic acute leukemia patients treated with HSCT in first remission and those treated with HSCT in the second remission after relapse. Abbreviations: EFS, event-free survival; HSCT, hematopoietic stem cell transplantation; OS, overall survival.

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