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

Abstract Abstract 2241 Poster Board II-218 Introduction: 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. Patients and Methods: 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). Results: 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. T-LGL expansion TCR-GR Positive TCR-GR Negative/Not done No. of patients 14 10 Type of transplantation Unrelated 6 ; Related 8 Unrelated 7 ; Related 3 Pre-transplantation diagnosis AML 3 AML 4 NHL 5 NHL 2 CLL 2 ALL 2 ALL 3 CML 1 MM 1 MM 1 GVHD Prophylaxis TAC/CELL 11 TAC/CELL 9 CSA 1 ATG/TAC/SIRO 1 ATG/ TAC/ SIRO 2 CMV status D-/R+ 8 D-/R+ 3 D+/R+ 6 D+/R+ 6 D+/R- 1 CMV viremia by PCR Positive 13; Negative 1 Positive 7; Negative 3 GVHD Present 14; Absent 0 Present 10; Absent 0 Median lymphocyte count at diagnosis (cells per mm3) 3900 (range 1600-16,800) 4000 (range 3100-8600) Median time to diagnosis (Days post HSCT) 188 (range 69-1280) 575 (range 154-1454) AML- Acute myeloid leukemia; NHL- Non-Hodgkin's lymphoma; CLL- Chronic lymphocytic leukemia; ALL- Acute lymphocytic leukemia; MM- Multiple myeloma TAC- Tacrolimus; CELL- Mycophenolate mofetil; CSA- Cyclosporine; ATG- Anti-thymocyte globulin; Siro- Sirolimus Disclosures: Lum: Transtarget Corporation: Founder