Clinical and Biological Characteristics of Phenotypically Poorly Differentiated Acute Leukemias
Nemanja Rodic, Amy Duffield, Christopher D Gocke, Kathleen H Burns, Michael J Borowitz, Milena Vuica-Ross. Johns Hopkins Medical Institute, Baltimore, MD
Background: Immunophenotype is a major determinant in the categorization of acute leukemias as myeloid, lymphoid or mixed phenotype. In a few cases, definitive assignment cannot be achieved because blasts do not show definitive evidence of differentiation. These undifferentiated leukemias (AUL) are relatively rare and are not well-characterized.
Design: 17 cases of AUL were identified in the pathology archives from 2001-2010 based on the absence of differentiation markers using WHO 2008 criteria. Flow cytometric analysis, morphology, molecular and cytogenetic studies, and outcomes data were reviewed for these AUL cases.
Results: Of 1480 acute leukemia patients admitted to our institution between July of 2001 and July of 2011, 17 cases (1.1%) met phenotypic and morphologic criteria of AUL. Cases of AUL expressed CD34 (15/16), CD38 (16/16), HLA-DR (15/16), TdT (6/7), CD117 (4/15), CD13 (5/15) and CD33 (6/16). They were negative for CD19, CD10, CD3, CD5, CD14, CD2, CD64 and CD61. Seven cases (7/17; 42%) had no prior history of malignancy or hematologic disorders and are considered primary leukemias. A prior history of treatment for malignant neoplasm (1), Hodgkin lymphoma (1), T cell leukemias (2), myelodysplastic syndrome (4) and bone marrow failures (2) was seen in the remainder of the cases (10/17; 58%), consistent with secondary leukemias. No difference between the de novo and secondary groups were observed in respect to average age at presentation (35 vs 48 years respectively, p=0.549), median survival time (12 vs 7 months, p=0.902), resistance to therapy (88 vs 71%, p=0.9) and expression of most antigens tested. CD7 was less likely to be expressed on de novo AUL than secondary leukemias (40 vs 100%, p=0.027), as were CD56 (20 vs 60%, p= 0.23) and CD33 (16 vs 50%, p=0.11). No consistent genetic lesions were identified, although de novo AUL was less likely to show a complex karyotype than the secondary leukemias with an undifferentiated phenotype (16 vs 77%, p= 0.34).
Conclusions: Acute undifferentiated leukemias represent a heterogeneous group of rare disorders with poor outcome. Correlation with clinical and cytogenetic information is recommended, as many leukemias with an undifferentiated immunophenotype were ultimately classified as secondary leukemias. Inclusion of EGIL criteria might be helpful to distinguish between these two groups.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 215, Tuesday Morning