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Mixed Phenotype Acute Leukemia: Diagnosis, Treatment, and Prognosis

Learn about a case of mixed phenotype acute leukemia (MPAL), providing clinical history, diagnostic tests, proposed and consensus diagnoses, treatment options, and immunophenotype analysis. Understand the clinical significance of myeloid antigen expression and its implications on prognosis. References to published studies are included for further reading.

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Mixed Phenotype Acute Leukemia: Diagnosis, Treatment, and Prognosis

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  1. CASE 205 Denyo Adjoa Zakhia, MD Kristin Hunt Karner, MDHenry Ford Hospital, Detroit, MI

  2. 61 year-old Caucasian male • Cough, night sweats, low-grade fever • Complete blood count • Hemoglobin – 9.4 gm/dl • White blood cell count – 71.1 K/uL • Platelet count – 135 K/uL • Peripheral blood smear • Leukocytosis with 79% blasts CLINICAL HISTORY

  3. BONE MARROW ASPIRATE Cellularity ->95% Blasts-87% BONE BIOPSY H&E CD1a

  4. FLOW CYTOMETRY cyto CD3

  5. FLOW CYTOMETRY SUMMARY

  6. CHROMOSOMAL ANALYSIS OF BONE MARROW ASPIRATE 46,XY,del(16)(q13)[6]/46,XY[14] FISH ANALYSIS No genetic abnormalities involving: MYC(8q24) BCL6(3q27) IGH-BCL2(14:18) API2-MALT1(11:18) BCR-ABL(9:22) MLL (11q23) Inv 16

  7. WHAT IS THE DIAGNOSIS? EGIL WHO

  8. EGIL T-lineage: Score 3.5 Myeloid: Score 2.5 • Mixed phenotype acute leukemia, favor T/myeloid

  9. WHO table (criteria) • Acute leukemia of T-cell Lineage with • aberrant myeloid differentiation

  10. INITIAL PROPOSED DIAGNOSIS • Mixed phenotype acute leukemia, favor T/myeloid • Acute leukemia of T-cell Lineage with aberrant myeloid differentiation PANEL CONSENSUS DIAGNOSIS EARLY T-CELL PRECURSOR ALL with MYELOID ANTIGEN EXPRESSION

  11. NEED FOR A CONSENSUS IN THE CLASSIFICATION SYSTEM • Provide appropriate treatment • Provide appropriate prognostication

  12. Hyper CVAD therapy Matched unrelated donor stem cell transplant Complications DVT New diagnosis of Hepatitis C infection Clostridium difficile colitis Reactivation of EBV and BK virus Subdural hemorrhage Patient in remission at day 116+ s/p SCT Treatment and Outcome

  13. IMMUNOPHENOTYPE (Adapted from WHO 2008) CD7 CD1a CD2/CD5 CD3 Cytoplasmic | Surface CD4+ CD8+ CD4/CD8 Double + TdT T-ALL Mature Early

  14. Comprises 85-90% of all lymphoblastic lymphoma • Adolescents > Younger children • 15% pediatric ALL • 25% adult ALL • Presentation: • Mediastinal mass with pleura effusions • Bone marrow involvement if present <20% • High peripheral blood blast counts COMMON DIAGNOSTIC FEATURES OF EARLY T-CELL PRECURSOR ALL (ETP-ALL)

  15. CLINICAL SIGNIFICANCE OF ETP-ALL • Clinical, laboratory and biologic characteristics not useful in prognostication • HIGH RISK • INDUCTION FAILURE • EARLY RELAPSE • CNS RELAPSE • Children treated as high risk • 75% 5 yr-event free survival rate (similar to pre B-ALL/LBL)

  16. DOES MYELOID ANTIGEN EXPRESSION OFFER ANY CLINICAL SIGNIFICANCE? Asnafi et al CD13 and CD33 most frequently expressed myeloid-associated antigens 15% of 91 cases reviewed MPO – negative or very rarely <3%

  17. Uckun et al • Not an adverse prognostic factor in childhood ALL

  18. Evaluated c-kit expression in 295 ALL patients and in 977 AML patients • T- ALL, 5.4 % expressed c-kit • In AML 84% expressed c-kit • Concluded • High c-kit expression is an independent predictor of • Lower complete response in ALL • Higher complete response in AML • Not an independent predictor of disease free survival in ALL or AML • T-ALL may benefit from AML type therapy

  19. Improved survival rates • Normal karyotype • T(10:14)(q24:q11) HOX11:TCRα • Overexpression of HOX11 gene

  20. THANK YOUQUESTIONS???

  21. REFERENCES • Goldberg JM, Silverman LB, Levy DE, et al. Childhood T-cell acute lymphoblastic leukemia: the Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium experience. J ClinOncol. 2003;21:3616-3622. • Onciu M, Lai R, Vega F, et al. Precursor T-cell acute lymphoblastic leukemia in adults: age-related immunophenotypic, cytogenetic, and molecular subsets. Am J ClinPathol. 2002;117:252-258. • Brunning R, Borowitz M, Matutes E, et al. Precursor B-cell and T-cell neoplasms. In: Jaffe ES, Harris NL, Stein H, et al, eds. Pathology and Genetics of Tumors of Hematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001:109-117. World Health Organization Classification of Tumors. • Thalhammer-Scherrer R, Mitterbauer G, Simonitsch I, et al. The immunophenotype of 325 adult acute leukemias’: relationship to morphologic and molecular classification and proposal for a minimal screening program highly predictive for lineage discrimination. Am J ClinPathol. 2002;117:380-389. • Asnafi V, Beldjord K, Libura M, et al. Age-related phenotypic and oncogenic differences in T-cell acute lymphoblastic leukemias may reflect thymic atrophy. Blood. 2004;104:4173-4180. • Asnafi V, Buzyn A, Thomas X, et al. Impact of TCR status and genotype on outcome in adult T-cell acute lymphoblastic leukemia: a LALA-94 study. Blood. 2005;105:3072-3078. • Uckun FM, Sather HN, Gaynon PS, et al. Clinical feature and treatment outcome of children with myeloid antigen positive acute lymphoblastic leukemia: a report from the Children’s Cancer Group. Blood. 1997;90:28-35. • Tsao AS, Kantarjian H, Thomas D, et al. C-kit receptor expression in acute leukemias: association with patient and disease characteristics and with outcome. Leuk Res. 2004;28:373-378. • Ferrando AA, Neuberg DS, Dodge RK, et al. Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukaemia. Lancet. 2004;363:535-536. • Schneider NR, Carroll AJ, Shuster JJ, et al. New recurring cytogenetic abnormalities and association of blast cell karyotypes with prognosis in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group report of 343 cases. Blood. 2000;96:2543-2549. • X Han, CE Bueso-Ramos. Precursor T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma and acute biphenotypicleukemias. Am J of clinpathol 2007;127:528-544. • Bene MC, Bernier RO, Casasnovas G, et al. The reliability and specificity of c-kit for the diagnosis of acute myeloid Leukemias and Undifferentiated leukemias. Blood 1998;15:596-599.

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