Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017, 161(3):234-241 | DOI: 10.5507/bp.2017.013

Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification and treatment

Martin Cernan, Tomas Szotkowski, Zuzana Pikalova
Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic.

Mixed-phenotype acute leukemia (MPAL) is a heterogeneous group of hematopoietic malignancies in which blasts show markers of multiple developmental lineages and cannot be clearly classified as acute myeloid or lymphoblastic leukemias. Historically, various names and classifications were used for this rare entity accounting for 2-5% of all acute leukemias depending on the diagnostic criterias used. The currently valid classification of myeloid neoplasms and acute leukemia published by the World Health Organization (WHO) in 2016 refers to this group of diseases as MPAL. Because adverse cytogenetic abnormalities are frequently present, MPAL is generally considered a disease with a poor prognosis. Knowledge of its treatment is limited to retrospective analyses of small patient cohorts. So far, no treatment recommendations verified by prospective studies have been published. The reported data suggest that induction therapy for acute lymphoblastic leukemia followed by allogeneic hematopoietic cell transplantation is more effective than induction therapy for acute myeloid leukemia or consolidation chemotherapy. The establishment of cooperative groups and international registries based on the recent WHO criterias are required to ensure further progress in understanding and treatment of MPAL. This review summarizes current knowledge on the diagnosis, classification, prognosis and treatment of MPAL patients.

Keywords: mixed-phenotype acute leukemia, MPAL, diagnosis, classification, prognosis, treatment

Received: November 15, 2016; Accepted: March 21, 2017; Prepublished online: April 18, 2017; Published: September 26, 2017  Show citation

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Cernan, M., Szotkowski, T., & Pikalova, Z. (2017). Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification and treatment. Biomedical papers, 161(3), 234-241. doi: 10.5507/bp.2017.013
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    References

    1. Trněný M, Čermák J, Klamová H, Šálek C, Cieslar P, Salaj P, Kvasnička J, Písačka M, Gašová Z. Acute leukemias. In: Češka R, et al. Interna. Prague: Triton; 2010. p. 683-8.
    2. Weinberg OK, Arber DA. Mixed-phenotype acute leukemia: historical overview and a new definition. Leukemia 2010;24:1844-51. Go to original source... Go to PubMed...
    3. Deffis-Court M, Alvarado-Ibarra M, Ruiz-Argüelles GJ, Rosas-López A, Barrera-Lumbreras G, Aguayo-Gonzáles Á, López-Karpovitch X, López-Hernándes M, Velázquez-Sánchez S, Zamora-Ortiz G, Crespo-Solís E. Diagnosing and treating mixed phenotype acute leukemia: a multicenter 10-year experience in México. Ann Hematol 2014;93(4):595-601. Go to original source... Go to PubMed...
    4. Borowitz MJ, Bene MC, Harris NL, Porwit A, Matutes E. Acute leukemias of ambiguous lineage. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardinan JW. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2008. p. 150-5.
    5. Arber DA, Orazi A, Hassejian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardinan JW. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood 2016;127(20):2391-405. Go to original source... Go to PubMed...
    6. Matutes E, Pickl WF, Veer MV, Morilla R, Swansbury J, Strobl H, Attarbaschi A, Hopfinger G, Ashley S, Bene MC, Porwit A, Orfao A, Lemez P, Schabath R, Ludwig WD. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 2011;117(11):3163-71. Go to original source... Go to PubMed...
    7. Bene MC. Biphenotypic, bilineal, ambiguous or mixed lineage: strange leukemias! Haematologica 2009;94(7):891-3. Go to original source... Go to PubMed...
    8. Catovsky D, Matutes E, Buccheri V, Shetty V, Hanslip J, Yoshida N, Morilla R. A classification of acute leukemia for the 1990s. Ann Hematol 1991;62:16-21. Go to original source... Go to PubMed...
    9. Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, Veer MB. Proposal for immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 1995;9:1783-6. Go to PubMed...
    10. Bene MC, Bernier M, Casasnovas RO, Castoldi G, Knapp W, Lanza F, Ludwig WD, Matutes E, Orfao A, Sperling C, Veer MB. The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. Blood 1998;92:596-9. Go to original source...
    11. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med 1985;103:620-5. Go to original source... Go to PubMed...
    12. Weir EG, Ansari-Lari AM, Batista DA, Griffin CA, Fuller S, Smith BD, Borowitz MJ. Acute bilineal leukemia: a rare disease with poor outcome. Leukemia 2007;21:2264-70. Go to original source... Go to PubMed...
    13. Marinov I, Mikulenková D, Luxová A, Tkáčová V. Immunophenotypic characterization of acute leukemias of ambiguous lineage - new diagnostic entity of the revised WHO classification 2008. Transfuze Hematol. dnes 2010;16(3):166-71.
    14. Yan L, Ping N, Zhu M, Sun A, Xue Y, Ruan C, Drexler HG, Macleod RA, Wu D, Chen S. Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117 adult patients with mixed-phenotype acute leukemia defined by WHO-2008 classification. Haematologica 2012;97(11):1708-12. Go to original source... Go to PubMed...
    15. Al-Seraihy AS, Owaidah TM, Ayas M, El-Solh H, Al-Mahr M, Al-Ahmari A, Belgaumi AF. Clinical characteristics and outcome of children with biphenotypic acute leukemia. Haematologica 2009;94(12):1682-90. Go to original source... Go to PubMed...
    16. Rubnitz JE, Onciu M, Pounds S, Shurtleff S, Cao X, Raimondi SC, Behm FG, Campana D, Razzouk BI, Ribeiro RC, Downing JR, Pui CH. Acute mixed lineage leukemia in children: the experience of St Jude Children's Research Hospital. Blood 2009;113(21):5083-9. Go to original source... Go to PubMed...
    17. Bar M, Tong W, Othus M, Loeb RK, Estey EH. Central nervous system involvement in acute myeloid leukemia patients undergoing hematopoietic cell transplantation. Biol Blood Marrow Transplant 2015;21:546-51. Go to original source... Go to PubMed...
    18. Lazarus HM, Richards SM, Chopra R, Litzow MR, Burnett AK, Wiernik PH, Franklin IM, Tallman MS, Cook L, Buck G, Durrant IJ, Rowe JM, Goldstone AH. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993. Blood 2006;108(2):465-72. Go to original source... Go to PubMed...
    19. Xu XQ, Wang JM, Lü SG, Chen L, Yang JM, Zhang WP, Song XM, Hou J, Ni X, Qiu HY. Clinical and biological characteristics of adult biphenotypic acute leukemia in comparison with that of acute myeloid leukemia and acute lymphoblastic leukemia: a case series of a Chinese population. Haematologica 2009;94:919-27. Go to original source... Go to PubMed...
    20. Tong H, Liu Z, Lu C, Wang Q. Clinical and laboratory features of adult biphenotypic acute leukemia. Asia Pac J Clin Oncol 2013;9(2):146-54. Go to original source... Go to PubMed...
    21. Weinberg OK, Seetharam M, Ren L, Alizadeh A, Arber DA. 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 2014;142(6):803-8. Go to original source... Go to PubMed...
    22. Tian H, Xu Y, Liu L, Yan L, Jin Z, Tang X, Han Y, Fu Z, Qiu H, Sun A, Wu D. Comparison of outcomes in mixed phenotype acute leukemia patients treated with chemotherapy and stem cell transplantation versus chemotherapy alone. Leuk Res 2016;45:40-6. Go to original source... Go to PubMed...
    23. Manola KN. Cytogenetic abnormalities in acute leukaemia of ambiguous lineage: an overview. Br J Haematol 2013;163(1):24-39. Go to original source... Go to PubMed...
    24. Hoehn D, Medeiros LJ, Chen SS, Tian T, Jorgensen JL, Ahmed Y, Lin P. CD117 expression is a sensitive but nonspecific predictor of FLT3 mutation in T acute lymphoblastic leukemia and T/myeloid acute leukemia. Am J Clin Pathol 2012;137(2):213-19. Go to original source... Go to PubMed...
    25. Wolach O, Stone RM. How I Treat: Mixed phenotype acute leukemia. Blood 2015;125(16):2477-85. Go to original source... Go to PubMed...
    26. Killick S, Matutes E, Powles RL, Hamblin M, Swansbury J, Treleaven JG, Zomas A, Atra A, Catovsky D. Outcome of biphenotypic acute leukemia. Haematologica 1999;84(8):699-706. Go to PubMed...
    27. Munker R, Brazauskas R, Wang HL, De Lima M, Khoury HJ, Gale RP, Maziarz RT, Sandmaier BM, Weisdorf D, Saber W. Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia. Biol Blood Marrow Transplant 2016;22(6):1024-9. Go to original source... Go to PubMed...
    28. Mourad YR, Fernandez HF, Kharfan-Dabaja MA. Allogeneic hematopoietic cell transplantation for adult Philadelphia-positive acute lymphoblastic leukemia in the era of tyrosine kinase inhibitors. Biology of Blood and Marrow Transplantation 2008;14:949-58. Go to original source... Go to PubMed...
    29. Shimizu H, Yokohama A, Hatsuni N, Takada S, Handa H, Sakura T, Nojima Y. Philadelphia chromosome-positive mixed phenotype acute leukemia in the imatinib era. Eur J Haematol 2014;93(4):297-301. Go to original source... Go to PubMed...
    30. Foa R, Vitale A, Vignetti M, Meloni G, Guarini A, De Propris MS, Elia L, Paoloni F, Fazi P, Cimino G, Nobile F, Ferrara F, Castagnola C, Sica S, Leoni P, Zuffa E, Fozza C, Luppi M, Candoni A, Iacobucci I, Soverini S, Mandelli F, Martinelli G, Baccarani M. Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 2011;118(25):6521-8. Go to original source... Go to PubMed...
    31. Shi R, Munker R. Survival of patients with mixed phenotype acute leukemias: A large population-based study. Leuk Res 2015;39(6):606-16. Go to original source... Go to PubMed...
    32. Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM. Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. Blood 2012;119:34-43. Go to original source... Go to PubMed...
    33. Takata H, Ikebe T, Sasaki H, Miyazaki Y, Ohtsuka E, Saburi Y, Ogata M, Shirao K. Two Elderly Patients with Philadelphia Chromosome Positive Mixed Phenotype Acute Leukemia Who Were Successfully Treated with Dasatinib and Prednisolone. Intern Med 2016;55(9):1177-81. Go to original source... Go to PubMed...
    34. Kiyoi H. FLT3 inhibitors: recent advances and problems for clinical application. Nagoya J Med Sci 2015;77:7-17.

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