Incidental, Immunophenotypically Aberrant Cytotoxic T-Cell Clones in Patients with Other Hematologic Malignancies
AM Harrington, H Olteanu, SH Kroft. Medical College of Wisconsin, Milwaukee, WI
Background: Clonal or oligoclonal expansions of immunophenotypically normal CD8(+) T-cells are well described in viral infections, autoimmune disorders, aging, and malignancy. Also, large granular lymphocytic leukemia (LGLL) has been reported in association with other malignancies, although criteria for LGLL diagnosis in this setting are unclear. Recent studies emphasized the presence of immunophenotypic (IP) aberrancy in all LGLLs. We describe our experience with incidental clonal, immunophenotypically aberrant CD8(+) T cell populations in patients with other hematologic malignancies.
Design: Cytotoxic T-cell populations were found in 6 pts during 4-color FC of blood (PB) or bone marrow (BM) for hematolymphoid malignancy. Populations were detected with one of the following routine tubes: CD7/CD4/CD8/CD3 or CD5/CD8/CD3/CD4; additional studies were then obtained to further characterize IP features. IP aberrancies were defined relative to normal CD8(+) T-cells in each sample. Vbeta analysis was performed on PB samples in all cases, with specific gating on the aberrant population.
Results: Distinct, abnormal T-cell populations were initially found in BM (4) or PB(2) of 4 females and 2 males, ages 63-88 yrs, with CLL (2), AML (2), or non-CML myeloproliferative neoplasms (2). There were 1-9 FC studies per pt, 3 pts with 3-9 studies over 11-34 mos. Populations were all CD3(+)/CD8(+)/CD4(-)/CD57(+) and demonstrated 2-4 aberrancies in T-cell antigens: dim or bright CD3 (1 each), dim (5) or negative (1) CD5, dim or bright CD7 (1 each), and dim (3) or bright (2) CD8. Two were CD16 (partial dim+) and 4 were CD56 (partial dim to +). Each showed Vbeta restriction. Clones were found at diagnosis of the 1° malignancy in 5/6 pts, with the last developing 6 yrs after CLL diagnosis. Clones accounted for 1.5-8.9% of events at the time of detection, with absolute PB clone counts ranging from 55-439/μL (median 181.5). All pts with multiple studies had persistence of both their 1° disease and the abnormal clone on each analysis, with essentially stable clone size.
Conclusions: The abnormal cytotoxic T-cell populations in this series are distinct from published data in that they were detected incidentally, based on distinctly aberrant IPs, in routine FC studies for evaluation of other hematologic malignancies. While clonal, they did not satisfy numeric criteria for LGLL. Presumed to originate as an immune response to the 1° neoplasia, their relationship to LGLL is uncertain. Notably, the populations were stable in size over 1-3 years in 3 patients.
Monday, March 22, 2010 1:00 PM
Poster Session II # 151, Monday Afternoon