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Multiparametric Flow Cytometry in Mixed Phenotype Acute Leukemia

  • Sindhura Lakshmi Koulmane LaxminarayanaEmail author
  • Nishika Madireddy
  • Chethan Manohar
  • Karthik Udupa
Original Article

Abstract

Mixed phenotype acute leukaemia (MPAL) is a diverse group of leukemia of ambiguous lineage diagnosed when blasts in peripheral blood and/or bone marrow have antigens of more than one lineage or a mosaic of blasts belonging to more than one lineage. Retrospective analysis of 218 consecutive cases of acute leukaemia diagnosed by multiparametric flow cytometry (FCM) was done. MPAL cases were identified in accordance with European Group for the Immunological Classification of Leukaemias Criteria and World Health Organization 2008/2016 guidelines for lineage assignment. Nine out of 218 (4.1%) cases were classified as MPAL. Eight out of nine patients (88.8%) were male and 4/9 (44.4%) were < 20 years of age. There were three cases of B/T and T/myeloid MPAL each. Two cases were B/myeloid MPAL and one case was chronic myeloid leukaemia (CML) in B/myeloid blast crisis. B/myeloid MPAL and CML in B/myeloid blast crisis cases were Philadelphia chromosome positive. The latter case had a complex karyotype as well. Seven cases were treated with acute lymphoblastic leukaemia treatment regimen; two of them achieved complete remission (CR). The patient with CML in B/myeloid blast crisis was treated with imatinib based regimen, attained CR, underwent allogenic bone marrow stem cell transplantation, but developed graft versus host disease. Five patients died due to complications of febrile neutropenia early in the course of treatment (62.5%). The last patient (B/T MPAL) refused therapy and was lost to follow-up. Early accurate diagnosis of MPAL requires FCM. It may be misdiagnosed if a limited panel of antibodies is used.

Keywords

Mixed phenotype acute leukemia Multiparametric flow cytometry Immunophenotype Leukemia of ambiguous lineage 

Notes

Funding

This study has not received any funding from any agency.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

The study was reviewed and approved by institutional committee at Kasturba Medical College, Manipal. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.

References

  1. 1.
    Bene MC (2009) Biphenotypic, bilineal, ambiguous or mixed lineage: strange leukemia! Haematologica 94(7):891–893CrossRefGoogle Scholar
  2. 2.
    Matutes E, Morilla R, Farahat N, Carbonell F, Swansbury J, Dyer M, Catovsky D (1997) Definition of acute biphenotypic leukemia. Haematologica 82(1):64–66Google Scholar
  3. 3.
    Weinberg OK, Arber DA (2010) Mixed-phenotype acute leukemia: historical overview and a new definition. Leukemia 24(11):1844–1851CrossRefGoogle Scholar
  4. 4.
    Bene MC, Castoldi G, Knapp W et al (1995) Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 9:1783–1786Google Scholar
  5. 5.
    Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Thiele J (eds) (2017) WHO classification of tumours of haematopoietic and lymphoid tissues, revised 4th edn. IARC, Lyon, pp 180–187Google Scholar
  6. 6.
    Arber DA, Orazi A, Hasserjian R et al (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127:2391–2405CrossRefGoogle Scholar
  7. 7.
    Weir EG, Ali Ansari-Lari M, Batista DA, Griffin CA, Fuller S, Smith BD, Borowitz MJ (2007) Acute bilineal leukemia: a rare disease with poor outcome. Leukemia 21(11):2264–2270.  https://doi.org/10.1038/sj.leu.2404848 CrossRefGoogle Scholar
  8. 8.
    Yan L, Ping N, Zhu M, Sun A, Xue Y, Ruan C, Drexler HG, Macleod RA, Wu D, Chen S (2012) Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117 adult patients with mixed-phenotype acute leukemia defined by WHO-2008 classification. Haematologica 97(11):1708–1712CrossRefGoogle Scholar
  9. 9.
    Matutes E, Pickl WF, Van’t Veer M, Morilla R, Swansbury J, Strobl H, Attarbaschi A, Hopfinger G, Ashley S, Bene MC, Porwit A, Orfao A, Lemez P, Schabath R, Ludwig WD (2011) Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 117(11):3163–3171CrossRefGoogle Scholar
  10. 10.
    Pawar RN, Banerjee S, Bramha S, Krishnan S, Bhattacharya A, Saha V et al (2017) Mixed-phenotypic acute leukemia series from tertiary care center. Indian J Pathol Microbiol 60:43–49Google Scholar
  11. 11.
    Sukumaran R, Nair RA, Jacob PM, Nair Anila KA, Prem S, Binitha R, Kusumakumary P (2015) Flow cytometric analysis of mixed phenotype acute leukemia: experience from a tertiary oncology center. Indian J Pathol Microbiol 58(2):181–186CrossRefGoogle Scholar
  12. 12.
    Charles NJ, Boyer DF (2017) Mixed-phenotype acute leukemia: diagnostic criteria and pitfalls. Arch Pathol Lab Med 141(11):1462–1468.  https://doi.org/10.5858/arpa.2017-0218-RA CrossRefGoogle Scholar
  13. 13.
    Serrano J, Roman J, Jimenez A et al (1999) Genetic, phenotypic and clinical features of acute lymphoblastic leukemias expressing myeloperoxidase mRNA detected by RT-PCR. Leukemia 13(2):175–180CrossRefGoogle Scholar
  14. 14.
    Weinberg OK, Seetharam M, Ren L, Alizadeh A, Arber DA (2014) Mixed phenotype acute leukemia: a study of 61 cases using World Health Organization and European Group for the Immunological Classification of Leukaemias criteria. Am J Clin Pathol 142(6):803–808CrossRefGoogle Scholar
  15. 15.
    Wolach O, Stone RM (2015) How I treat mixed-phenotype acute leukemia. Blood 125(16):2477–2485CrossRefGoogle Scholar
  16. 16.
    Yumura-Yagi K, Hara J, Kurahashi H, Nishiura T, Kaneyama Y, Osugi Y, Sakata N, Inoue M, Tawa A, Okada S et al (1992) Mixed phenotype of blasts in acute megakaryocytic leukaemia and transient abnormal myelopoiesis in Down’s syndrome. Br J Haematol 81(4):520–525CrossRefGoogle Scholar
  17. 17.
    Choi W, Kim M, Lim J, Han K, Lee S, Lee JW et al (2014) Four cases of chronic myelogenous leukemia in mixed phenotype blast phase at initial presentation mimicking mixed phenotype acute leukemia with t(9;22). Ann Lab Med 34:60–63CrossRefGoogle Scholar
  18. 18.
    Gao X, Li J, Wang L, Lin J, Jin HB, Xu YB et al (2016) Bilineal extramedullary blast crisis as an initial presentation of chronic myeloid leukemia: a case report and literature review. Am J Case Rep 17:793–798CrossRefGoogle Scholar
  19. 19.
    Nair IM, Feroze M, Aravindan KP (2016) Bilineage T-lymphoblastic/myeloid extramedullary blast crisis in chronic myelogenous leukemia. Indian J Pathol Microbiol 59(1):107–109Google Scholar
  20. 20.
    Shimizu H, Yokohama A, Hatsuni N, Takada S, Handa H, Sakura T, Nojima Y (2014) Philadelphia chromosome-positive mixed phenotype acute leukemia in the imatinib era. Eur J Haematol 93(4):297–301CrossRefGoogle Scholar
  21. 21.
    Takata H, Ikebe T, Sasaki H, Miyazaki Y, Ohtsuka E, Saburi Y, Ogata M, Shirao K (2016) Two elderly patients with Philadelphia chromosome positive mixed phenotype acute leukemia who were successfully treated with dasatinib and prednisolone. Intern Med 55(9):1177–1181CrossRefGoogle Scholar
  22. 22.
    Kiyoi H (2015) FLT3 inhibitors: recent advances and problems for clinical application. Nagoya J Med Sci 77:7–17Google Scholar
  23. 23.
    Pomerantz A, Rodriguez-Rodriguez S, Demichelis-Gomez R et al (2016) Mixed-phenotype acute leukemia: suboptimal treatment when the 2008/2016 WHO classification is used. Blood research. 51(4):233–241.  https://doi.org/10.5045/br.2016.51.4.233 CrossRefGoogle Scholar
  24. 24.
    Mejstrikova E, Volejnikova J, Fronkova E et al (2010) Prognosis of children with mixed phenotype acute leukemia treated on the basis of consistent immunophenotypic criteria. Haematologica 95(6):928–935CrossRefGoogle Scholar
  25. 25.
    Rubnitz JE, Onciu M, Pounds S, Shurtleff S, Cao X, Raimondi SC et al (2009) Acute mixed lineage leukemia in children: the experience of St. Jude Children’s Research Hospital. Blood 113(21):5083–5089CrossRefGoogle Scholar
  26. 26.
    Munker R, Brazauskas R, Wang HL, De Lima M, Khoury HJ, Gale RP, Maziarz RT, Sandmaier BM, Weisdorf D, Saber W (2016) Allogeneic hematopoietic cell transplantation for patients with mixed phenotype acute leukemia. Biol Blood Marrow Transplant 22(6):1024–1029CrossRefGoogle Scholar
  27. 27.
    Mourad YR, Fernandez HF, Kharfan-Dabaja MA (2008) Allogeneic hematopoietic cell transplantation for adult Philadelphia-positive acute lymphoblastic leukemia in the era of tyrosine kinase inhibitors. Biol Blood Marrow Transplant 14:949–958CrossRefGoogle Scholar
  28. 28.
    Wolach O, Stone RM (2017) Mixed-phenotype acute leukemia: current challenges in diagnosis and therapy. Curr Opin Hematol 24(2):139–145.  https://doi.org/10.1097/MOH.0000000000000322 CrossRefGoogle Scholar

Copyright information

© Indian Society of Hematology and Blood Transfusion 2019

Authors and Affiliations

  1. 1.Department of Pathology, Kasturba Medical CollegeManipal Academy of Higher EducationManipal, UdupiIndia
  2. 2.Department of PathologyNizam’s Institute of Medical SciencesHyderabadIndia
  3. 3.Department of Medical Oncology, Kasturba Medical CollegeManipal Academy of Higher EducationManipalIndia

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