Clonal T-Cell Large Granular Lymphocytic Proliferations of Donor Origin in Peripheral Blood Stem Cell Transplant (PBSCT) Recipients: A Case Series
LK Habib, BC Gehrs, G Bentley, J Uberti, M Palutke. Detroit Medical Center/Wayne State University, Detroit, MI; Oklahoma University Medical Center, Oklahoma City, OK
Background: Clonal T-cell large granular lymphocyte (T-LGL) expansions have been described following allogeneic bone marrow and solid organ transplants. Clonal and oligoclonal expansions of T-LGLs post bone marrow transplant have been theorized to represent a response to immune stimuli from alloantigens and/or viral infections such as CMV. In the last 2 years we observed an increase in T-LGL expansions among PBSCT recipients at our institution with at least 26 cases to date; of these, 18 have proven to be clonal.
Design: From January 2007 we carefully reviewed blood and bone marrow morphology, clinical, flow cytometric and molecular data in 10 patients with clonal proliferations of CD3, CD8 and CD57 positive LGL cells. Clonality was assessed by Southern blot and PCR for TCR-GR. One patient's blood was sent for quantitative CMV T-cell immune competence testing to Mayo Clinic.
Results: There were 8 males and 2 females with a median age of 60. Diagnoses included 3 CLL/SLL, 2 DLBCL, 1 follicular lymphoma, 1 MDS, 2 AML and one precursor B-ALL. Either or both members of 9 of 10 donor-recipient pairs had CMV-positive status and 8 of 10 recipients had documented post-transplant CMV viremia. All had graft-versus-host-disease. T-LGL expansion was noted from 56 to 1,280 days post-transplant (median 172). T-LGLs in blood ranged from 28% to 70% of total lymphocytes with concurrent bone marrow histology ranging from small to prominent lymphoid aggregates occupying up to 90% of marrow space. Peripheral blood lymphocytes in one patient reached 29,900/μm. All clonal T-LGL proliferations were of donor origin. At last follow-up of the 18 patients with clonal T-LGL there were only 2 relapses and all were free of CMV viremia. Lymphocyte counts for 7 of 9 patients had decreased, and none were being treated for their T-LGL proliferations. CMV competence testing was inconclusive for the one patient so tested.
Conclusions: Our data do not contradict a theory of viral infection driven expansion of T-LGLs. Long-term follow-up of these patients as well as comparison to those with polyclonal T-LGL proliferations are in progress. Further testing of the specificity of the T-LGLs to a variety of antigens, including CMV, is essential.
Monday, March 22, 2010 1:00 PM
Poster Session II # 150, Monday Afternoon