Involvement of the cerebrospinal fluid (CSF) by hematopoietic malignancies may be difficult to document by morphology alone. The diagnoses of """"""""atypical"""""""" or """"""""suspicious"""""""" is frequently used in cases with low numbers of cells or ambiguous morphology. In a study comparing morphology alone to morphology with flow cytometry, we demonstrated that flow cytometric immunophneotyping was useful in establishing a diagnosis of neoplasia in a series of patients with known lymphoma or leukemia and an initial diagnosis of """"""""atypical"""""""" or """"""""suspicious"""""""" CSF using morphologic criteria. The Flow Cytometry Unit evaluated the role of flow cytometric analysis in staging and management of patients with high grade B cell lymphomas. We assessed the cerebrospinal fluid (CSF) by flow cytometry and cytology in patients newly diagnosed with aggressive B-cell lymphomas and at risk for central nervous system (CNS) involvement. Flow cytometry identified neoplastic clones that constituted as little as 0.2% of total CSF lymphocytes. Flow cytometry detected involvement where cytology, chemistry and cell counts failed. Flow cytometric detection of disease was a negative prognostic factor and now prompts therapeutic intervention in patients on NCI protocols. As a result of the study we recommended that patients at risk for CNS involvement by aggressive B cell lymphoma undergo staging CSF evaluation by flow cytometry. Many flow cytometry laboratories report a low success rate in analysis of CSF specimens. The Flow Cytometry Unit, CCR, NCI, NIH developed special protocols for flow cytometric analysis of CSF that has led to a high success rate. The Flow Cytometry Unit participated in an international consensus conference to determine optimal methodology for flow cytometric analysis of CSF. The Flow Cytometry Unit has helped Vanderbilt University Medical Center implement our system and is currently assisting University of Pittsburgh Medical Center.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Scientific Cores Intramural Research (ZIC)
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National Cancer Institute Division of Basic Sciences
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Lionakis, Michail S; Dunleavy, Kieron; Roschewski, Mark et al. (2017) Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma. Cancer Cell 31:833-843.e5
Kreitman, Robert J; Stetler-Stevenson, Maryalice; Jaffe, Elaine S et al. (2016) Complete Remissions of Adult T-cell Leukemia with Anti-CD25 Recombinant Immunotoxin LMB-2 and Chemotherapy to Block Immunogenicity. Clin Cancer Res 22:310-8
Lee, Daniel W; Kochenderfer, James N; Stetler-Stevenson, Maryalice et al. (2015) T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 385:517-28
Kranick, Sarah M; Goncalves, Priscila H; Stetler-Stevenson, Maryalice et al. (2015) Paradoxical central nervous system immune reconstitution syndrome in acquired immunodeficiency syndrome-related primary central nervous system lymphoma. Haematologica 100:e21-4
Wilson, Wyndham H; Bromberg, Jacoline E C; Stetler-Stevenson, Maryalice et al. (2014) Detection and outcome of occult leptomeningeal disease in diffuse large B-cell lymphoma and Burkitt lymphoma. Haematologica 99:1228-35
Greig, B; Stetler-Stevenson, M; Lea, J (2013) Stabilization media increases recovery in paucicellular cerebrospinal fluid specimens submitted for flow cytometry testing. Cytometry B Clin Cytom :
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Song, Joo Y; Filie, Armando C; Venzon, David et al. (2012) Flow cytometry increases the sensitivity of detection of leukemia and lymphoma cells in bronchoalveolar lavage specimens. Cytometry B Clin Cytom 82:305-12
Herishanu, Yair; Perez-Galan, Patricia; Liu, Delong et al. (2011) The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia. Blood 117:563-74
Calvo, Katherine R; McCoy, Catharine S; Stetler-Stevenson, Maryalice (2011) Flow cytometry immunophenotyping of hematolymphoid neoplasia. Methods Mol Biol 699:295-316

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