Mixed-phenotype acute leukemia: suboptimal treatment when the 2008/2016 WHO classification is used

Alan Pomerantz; Sergio Rodriguez-Rodriguez; Roberta Demichelis-Gomez; Georgina Barrera-Lumbreras; Olga Barrales-Benitez; Xavier Lopez-Karpovitch; Alvaro Aguayo-Gonzalez

doi:10.5045/br.2016.51.4.233

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Original Article

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Blood Res 2016; 51(4):

Published online December 23, 2016

https://doi.org/10.5045/br.2016.51.4.233

Mixed-phenotype acute leukemia: suboptimal treatment when the 2008/2016 WHO classification is used

Alan Pomerantz^1,2, Sergio Rodriguez-Rodriguez^1,2, Roberta Demichelis-Gomez¹, Georgina Barrera-Lumbreras¹, Olga Barrales-Benitez¹, Xavier Lopez-Karpovitch¹, and Alvaro Aguayo-Gonzalez^1*

Author Info. +

¹Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico City, Mexico.

²Faculty of Health Sciences, Universidad Anahuac Mexico Norte, Huixquilucan, State of Mexico, Mexico.

Correspondence to : Correspondence to Alvaro Aguayo-Gonzalez, M.D. Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicasy Nutricion Salvador Zubiran, Vasco de Quiroga 15, Col. Belisario Dominguez Seccion XVI, Del. Tlalpan, C.P. 14080, Mexico City, Mexico. alvaroaguayo@hotmail.com

Received: July 14, 2016; Revised: September 20, 2016; Accepted: October 7, 2016

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

Different criteria have been used to diagnose mixed-phenotype acute leukemia (MPAL), which has impacted the number of individuals diagnosed with this pathology. Better outcomes have been reported when using acute lymphoblastic leukemia (ALL)-type chemotherapy in the treatment of MPAL.

Methods

We compared the outcome of 4 groups of patients with MPAL. Group 1 included patients diagnosed using the 2008/2016 World Health Organization (WHO) classification; group 2 included patients diagnosed using the European Group for the Immunological Characterization of Leukemias (EGIL) criteria; group 3 included patients diagnosed using either the EGIL or the 2008/2016 WHO criteria; and group 4 was comprised of patients diagnosed with MPAL using the EGIL classification only.

Results

We found a significantly worse disease-free survival (groups 1-4) and overall survival (OS) (groups 2 and 3) when comparing MPAL patients to other acute leukemia (AL) patients. A significantly better OS was obtained in patients (groups 2-4) treated with ALL-type chemotherapy compared to acute myeloid leukemia (AML)-type regimens.

Conclusion

In light of these results, and because a trend (P=0.06) was found with regard to a better OS in group 4 when compared to other AL patients, an argument can be made that the 2008/2016 WHO classification is underpowered to diagnose all MPAL cases, potentially resulting in the suboptimal treatment of some individuals with AL.

Keywords Mixed-phenotype acute leukemia, WHO classification, EGIL classification, Suboptimal treatment

Article

Original Article

Blood Res 2016; 51(4): 233-241

Published online December 23, 2016 https://doi.org/10.5045/br.2016.51.4.233

Mixed-phenotype acute leukemia: suboptimal treatment when the 2008/2016 WHO classification is used

Alan Pomerantz^1,2, Sergio Rodriguez-Rodriguez^1,2, Roberta Demichelis-Gomez¹, Georgina Barrera-Lumbreras¹, Olga Barrales-Benitez¹, Xavier Lopez-Karpovitch¹, and Alvaro Aguayo-Gonzalez^1*

¹Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico City, Mexico.

²Faculty of Health Sciences, Universidad Anahuac Mexico Norte, Huixquilucan, State of Mexico, Mexico.

Correspondence to: Correspondence to Alvaro Aguayo-Gonzalez, M.D. Department of Hematology and Oncology, Instituto Nacional de Ciencias Medicasy Nutricion Salvador Zubiran, Vasco de Quiroga 15, Col. Belisario Dominguez Seccion XVI, Del. Tlalpan, C.P. 14080, Mexico City, Mexico. alvaroaguayo@hotmail.com

Received: July 14, 2016; Revised: September 20, 2016; Accepted: October 7, 2016

Abstract

Background

Methods

Results

Conclusion

Keywords: Mixed-phenotype acute leukemia, WHO classification, EGIL classification, Suboptimal treatment

Abstract

Fig 1.

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Figure 1.

Overall survival of mixed-phenotype acute leukemia patients versus individuals with other acute leukemias in group 1 (A), group 2 (B), group 3 (C) and group 4 (D).

Blood Research 2016; 51: 233-241https://doi.org/10.5045/br.2016.51.4.233

Fig 2.

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Figure 2.

Disease-free survival of mixed-phenotype acute leukemia patients versus individuals with other acute leukemias in group 1 (A), group 2 (B), group 3 (C) and group 4 (D).

Blood Research 2016; 51: 233-241https://doi.org/10.5045/br.2016.51.4.233

Table 1 . 1998 EGIL classification for biphenotypic acute leukemias (BAL)..

To establish a BAL diagnosis, a score >2 must be established for at least two lineages..

Abbreviations: EGIL, European Group for the Immunological Characterization of Leukemias; TCR, T-cell receptor; MPO, myeloperoxidase; TdT, terminal deoxynucleotidyl transferase..

Table 2 . 2008/2016 WHO criteria for the classification of mixed-phenotype acute leukemia (MPAL)..

To establish an MPAL diagnosis, two or more lineages must be positive for the indicated antigens..

Abbreviations: WHO, World Health Organization; NSE, non–specific esterase..

Table 3 . Clinical characteristics and endpoints of individual patients with MPAL..

Abbreviations: EGIL, European Group for the Immunologic Characterization of Leukemias; WHO, World Health Organization; FISH, Fluorescence In Situ Hybridization; HSCT, allogenic hematopoietic stem cell transplantation; OS, overall survival; DFS, disease-free survival; CR, complete remission; MPAL, mixed-phenotype acute leukemia; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; B-L, B-lymphoid markers; T-L, T-lymphoid markers; M, myeloid markers; CVAD, Cyclophosphamide+Vincristine+Adriamycin+Dexamethasone; 7+3, Cytarabine+idarubicin; PMHP, Princess Margaret Hospital Protocol; NA, not available..

Table 4 . Demographic and clinical characteristics of patients with MPAL (Group 1 and 2)..

Abbreviations: WHO, World Health Organization; EGIL, European Group for the Immunological characterization of Leukemias; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; MPAL, mixed-phenotype acute leukemia; PB, peripheral blood; BM, bone marrow; CR, complete remission; OS, overall survival; DFS, disease-free survival..

Table 5 . Demographic and clinical characteristics of patients with MPAL (Group 3 and 4)..

Table 6 . Clinical endpoints of MPAL patients according to different treatment regimens..

Abbreviations: EGIL, European Group for the Immunologic Characterization of Leukemias; WHO, World Health Organization; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CR, complete remission; OS, overall survival; DFS, disease-free survival..