T-Cell Large Granular Lymphocyte (T-LGL) Expansion Post Adult Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) – ‘A Prognostic Indicator for Improved Overall Survival’.

T-LGL has the phenotype characteristics of a post-thymus mature T cell. Expansion of T-LGL has been reported to occur in association with viral infections, autoimmune diseases, lymphoproliferative malignancy and HSCT. The clinical significance of finding T-LGL expansion post HSCT is unclear. We recently reviewed the incidence of T-LGL expansion in patients who underwent allogeneic HSCT in our institution. We specifically asked whether T-LGL expansion was associated with increased viral infections, stable chimerism, graft-versus-host disease (GvHD), recurrence of primary disease, and overall survival.

A retrospective analysis was done on all adult patients who underwent allogeneic HSCT at the Karmanos Cancer Institute between January 1, 2004 to June 30, 2009. In patients with persistent lymphocytosis (>3000 cells/mm³) post HSCT, expansion of T-LGL phenotype was identified by flow cytometry (CD2, CD3, CD5, CD7, CD8 and CD57 positive) and clonality was confirmed by T cell receptor beta and/or gamma gene rearrangement (TCR-GR) using southern blot analysis and polymerase chain reaction (PCR).

A total of 547 patients underwent allogeneic HSCT during the study period. We identified T-LGL expansion in 24 patients with persistent lymphocytosis using flow cytometry. Median age of patients with T-LGL expansion was 50 years (range 24-68 years). Median time to diagnosis was 275 days post HSCT (range 69-1454 days) and median duration of follow-up was 811 days (range 85-1701 days). All 24 patients achieved full donor chimerism post transplantation by STR analysis. Fourteen out of 24 patients with T-LGL expansion had positive TCR-GR, in 2 patients TCR-GR was not done and the remainder was negative. Twenty out of 24 patients had cytomegalovirus (CMV) viremia confirmed by PCR before the onset of T-LGL expansion; the remainder had no CMV viremia. In all patients with T-LGL expansion there was no subsequent recurrence of CMV viremia or infection. All 24 patients had documented graft versus host disease (GvHD). In the group with T-LGL expansion only 2 patients relapsed with primary disease and only one patient died (due to a cardiac event). The cumulative incidence of T-LGL expansion was 4.4% at the end of the study period. Conclusion: To our knowledge, this is the largest reported series of T-LGL expansion post allogeneic HSCT. T-LGL expansion was associated with an interesting sequence of CMV viremia preceding T-LGL expansion and subsequent lack of recurrence of CMV viremia or infection. We also observed a very low number of relapse of primary disease or death in patients with T-LGL expansion. One hypothesis is that T-LGL expansion may be a result of specific stimulation with CMV antigens post allogeneic HSCT. An alternate hypothesis is that T-LGL expansion is a surrogate marker for accelerated immune reconstitution. At present, it is also unclear if T-LGL expansion is a marker of ‘graft-versus-leukemia' effect with respect to relapse of primary disease warranting further research.

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