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

Hyun Gyung Lee; Hee Jo Baek; Ho Sung Kim; Soo Min Park; Tai Ju Hwang; Hoon Kook

doi:10.5045/br.2019.54.1.63

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Blood Res 2019; 54(1):

Published online March 31, 2019

https://doi.org/10.5045/br.2019.54.1.63

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

Hyun Gyung Lee¹, Hee Jo Baek^1,2, Ho Sung Kim¹, Soo Min Park¹, Tai Ju Hwang¹, and Hoon Kook^1,2*

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¹Department of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.

²Environmental Health Center for Childhood Leukemia and Cancer, Chonnam National University Hwasun Hospital, Hwasun, Korea.

Correspondence to : Correspondence to Hoon KooK, M.D., Ph.D. Department of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, 322 Seoyang-ro, Hwasun-eup, Hwasun 58128, Korea. hoonkook@chonnam.ac.kr

Received: September 7, 2018; Revised: October 8, 2018; Accepted: November 13, 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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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.

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

Article

Original Article

Blood Res 2019; 54(1): 63-73

Published online March 31, 2019 https://doi.org/10.5045/br.2019.54.1.63

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

Hyun Gyung Lee¹, Hee Jo Baek^1,2, Ho Sung Kim¹, Soo Min Park¹, Tai Ju Hwang¹, and Hoon Kook^1,2*

¹Department of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.

²Environmental Health Center for Childhood Leukemia and Cancer, Chonnam National University Hwasun Hospital, Hwasun, Korea.

Correspondence to:Correspondence to Hoon KooK, M.D., Ph.D. Department of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, 322 Seoyang-ro, Hwasun-eup, Hwasun 58128, Korea. hoonkook@chonnam.ac.kr

Received: September 7, 2018; Revised: October 8, 2018; Accepted: November 13, 2018

Abstract

Background

Methods

Results

Conclusion

Keywords: Biphenotypic acute leukemia, Acute leukemia of ambiguous lineage, Mixed-phenotype acute leukemia, Children, Immunophenotyping

Abstract

Fig 1.

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Figure 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.

Blood Research 2019; 54: 63-73https://doi.org/10.5045/br.2019.54.1.63

Fig 2.

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Figure 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.

Blood Research 2019; 54: 63-73https://doi.org/10.5045/br.2019.54.1.63

Fig 3.

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Figure 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.

Blood Research 2019; 54: 63-73https://doi.org/10.5045/br.2019.54.1.63

Fig 4.

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Figure 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.

Blood Research 2019; 54: 63-73https://doi.org/10.5045/br.2019.54.1.63

Fig 5.

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Figure 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.

Blood Research 2019; 54: 63-73https://doi.org/10.5045/br.2019.54.1.63

Fig 6.

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Figure 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.

Blood Research 2019; 54: 63-73https://doi.org/10.5045/br.2019.54.1.63

Fig 7.

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Figure 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.

Blood Research 2019; 54: 63-73https://doi.org/10.5045/br.2019.54.1.63

Fig 8.

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Figure 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.

Blood Research 2019; 54: 63-73https://doi.org/10.5045/br.2019.54.1.63

Table 1 Characteristics of the BAL or ALAL patients.

Abbreviations: ALAL, acute leukemia of ambiguous lineage; B, B lymphoblastic; BAL, biphenotypic acute leukemia; BM, bone marrow; My, myeloid; T, T lymphoblastic; UPN, unique patient number; WBC, white blood cell..

Table 2 EGIL or WHO diagnosis based on cytochemical and immunophenotype data.

Abbreviations: B, B lymphoid; BAL, biphenotypic acute leukemia; EGIL, european group for immunological classification of leukemias; neg, negative; pos, positive; T, T lymphoid; UPN, unique patient number; WHO, World Health Organization..

Table 3 Characteristics of the patients according to immunophenotype.

Abbreviations: B, B lymphoid; My, myeloid; T, T lymphoid..

Table 4 Expression of cytochemical and immunological markers in BAL.

Abbreviations: B, B lymphoid; BAL, biphenotypic acute leukemia; MPO, myeloperoxidase; T, T lymphoid..

Table 5 Initial treatment, additional therapy and outcome.

Abbreviations: AKI, acute kidney injury; B, B lymphoblastic; Con, consolidation chemotherapy; CR, complete remission; GVHD, graft versus host disease; hepatic VOD, hepatic venous occlusive disease; HSCT, hematopoietic stem cell transplantation; ICH, intracerebral hemorrhage; Main, maintenance chemotherapy; MRSA, methicillin-resistant Staphylococcus aureus; My, myeloid; NA, not applicable; NR, non-responders; PR, partial remission; T, T lymphoblastic; UCBT, umbilical cord blood transplantation; UPN, unique patient number; +, alive as of the end of 2017..