Abstract
Introduction: Mixed phenotype acute leukemia (MPAL) is a rare subset of acute leukemia where the blasts exhibit lineage specific antigens of more than one lineage. Flow cytometric immunephenotyping is essential for the diagnosis of MPAL and the accurate diagnosis highly depends on the panel of markers used. The aim of the study is to study the incidence, clinical presentation, haematological parameters, immunophenotypic, molecular features of MPAL and their correlation to the treatment and prognostic significance.
Materials and Methods: Cases of Acute Leukemia consisting of both the paediatric and adult age group admitted to the department of Haematology S C B Medical College and Hospital Cuttack, Odisha from September 2015 to November 2016 were analysed.
Results: During the study period, flow cytometric analysis of 680 cases was performed. B lymphoblastic leukemia was the most common subtype of acute leukemia. A diagnosis of MPAL was made in 24 cases, which accounted for 3.5% of all leukemias. 13 cases were diagnosed as B/myeloid, 10 cases as T/myeloid and 1 case as B/T/myeloid.19 of 24 cases received induction chemotherapy and 10 cases achieved complete remission. The overall median survival of all patients in our study was 10 months and the survival at 15 months was 38 %.. The survival of pediatric patients at the end of 15 months was 62% and that of adults was 32%.
Conclusion: Mixed phenotype acute leukemia is a rare subset of acute leukemia. Flow cytometry is critical in establishing a diagnosis of MPAL. Outcome-related prognostic factors include age, HLA-DR, CD34 negativity. BCR-ABL fusion and MLL rearrangement are associated with poor prognosis. Complete remission is achieved more in cases of ALL directed therapy than AML regimen and more in cases of paediatric patients than in adult cases.
Keywords: B/myeloid, T/myeloid and B/T/myeloid.
References
- Matutes E et al. Mixed phenotype acute leukemia : clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 2011;.117(11):.3163-3171.
- Weinberg OK et al. Mixed phenotype acute leukemia: historical overview and a new definition. Leukemia 2010; 24:1844-1851.
- Daniel AA et al. Hematopoietic tumors: Principles of pathologic diagnosis. Wintrobe’s clinical hematology: Twelfth edition 2009:1663-1668.
- Gao C et al. Mixed phenotype acute leukemias. NAJ Med Sci 2012; 5:119-122.
- Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H etal. World Health Organization of Classification of Tumours: Pathology and Genetics of Tumours of Haematopoetic and Lymphoid Tissues. Lyon, France: IARC Press; 2008.
- Borowitz M, 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 etal., editors. World Health Organization of Classification of Tumours: Pathology and Genetics of Tumours of Haematopoetic and Lymphoid Tissues. Lyon, France: IARC Press 2008; PP: 150-5.
- Mirro J et al. Acute mixed lineage leukemia: clinicopathologic correlation and prognostic significance. Blood 1985; 66: 1115-23
- Khalidi HS etal Acute lymphoblastic leukemias. Survey of immunophenotype, FAB classification, frequency of myeloid antigen expression and karyotypic abnormalities in 210 pediatric and adult cases Am J clin pathol 1999 ; 111: 467-476.
- Catovsky D et al. A classification of acute leukemia for the 1990’s. Ann Hematol 1991; 62: 16-21.
- Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, et al.Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 1995; 9: 1783-6.
- Bene MC, Bernier M, Casasnovas RO, Castoldi G, Knapp W, Lanza F, et al.The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. (EGIL). Blood 1998; 92: 596-9.
- Owaidah TM et al. Cytogenetics, molecular and ultra structural characteristics of biphenotypic acute leukemia identified by the EGIL scoring system. Leukemia 2006; 20: 620–626.
- Killick S et al. Outcome of biphenotypic acute leukemia. Haematologica 1999; 84: 699–706.
- Yan L et al. Clinical, immunophenotypic, cytogenetic and molecular genetics features in 117 adult patients with mixed phenotype acute leukemia defined by WHO 2008 classification. Hematologica 2012; 97(11): 1708-1712.
- Gujral S, Polampalli S, Badrinath Y, Kumar A, Subramanian PG, Raje G, et al.Clinico-hematological profile in biphenotypic acute leukemia. Indian J Cancer 2009; 46: 160-8.
- Thomas DA, Faderl S, Cortes J, O'Brien S, Giles F, Garcia G, et al . Update of the hyper CVAD and imatinib mesylate regimen in Philadelphia (Ph) positive acute lymphocytic leukemia (ALL). Blood 2004; 104: 2738..
- Towatari M, Yanada M, Usui N, Takeuchi J, Sugiura I, Takeuchi M, et al. Combination of intensive chemotherapy and imatinib can rapidly induce high quality complete remission in majority of patients with newly diagnosed BCR-ABL positive acute lymphoblastic leukemia. Blood 2004; 104: 3507-12.
- Ribera JM, Oriol A, Gonzalez M, Vidriales MB, Xicoy B, Grau J, et al. Treatment of Philadelphia chromosome (Ph) positive acute lymphoblastic leukemia with concurrent chemotherapy and imatinib mesylate. Blood 2002; 102:4483.
- Béné MC. Biphenotypic, bilineal, ambiguous or mixed lineage: Strange leukemias! Haematologica 2009; 94: 891-3.
- Aribi A, Bueso-Ramos C, Estey E, Estrov Z, O'Brien S, Giles F, et al.Biphenotypic acute leukaemia: A case series. Br J Haematol 2007; 138: 213-6.
- Rubnitz JE, Onciu M, Pounds S, Shurtleff S, Cao X, Raimondi SC, et al.Acute mixed lineage leukemia in children: The experience of St Jude Children's Research Hospital. Blood 2009; 113: 5083-9.
- Sukumaran R et al. Flow cytometric analysis of mixed phenotype acute leukemia: experience from a tertiary oncology center. Indian J Pathol Microbial 2015; 58:181-6
- P Amare et al. Clinico-hematological profile in biphenotypic acute leukemia Indian Journal of Cancer. April-June, 2009; 46(2): 160-168.
Corresponding Author
Dharma Niranjan Mishra
Department of Anatomy SCB Medical College, Cuttack, Odisha, India