Large granular lymphocytosis and its impact on long-term clinical outcomes following allo-SCT

Abstract

A total of 418 patients receiving hematopoietic SCT and surviving beyond day 100 were examined for the occurrence of large granular lymphocytes (LGLs). LGL lymphocytosis was defined as the presence of at least two of the following criteria: (1) sustained lymphocytosis above 3.0 × 10(9)/L observed in at least three consecutive determinations over a time frame of 2-3 months, (2) predominance (>30%) of LGLs in peripheral blood, (3) confirmation of monoclonality by T-cell receptor analysis using PCR 77 patients developed LGL lymphocytosis during their post-transplant course with a median onset of 312 days from transplant. The cumulative incidence at 1-, 2- and 3-years was 12.3±1.8, 20.8±2.4 and 23.6±2.7%. Patients with LGL lymphocytosis showed an OS advantage (86.2 vs 53.8%, P<0.001), lower non-relapse mortality (NRM; 3.2 vs 27.3%, P<0.001) and lower relapse incidence (9.6 vs 29.4%, P<0.001). Three clinical factors were associated with the development of LGL lymphocytosis: (1) CMV seropositive recipients (CMV-R(+)) compared with CMV seronegative recipients (CMV-R(-); P<0.001) regardless of CMV serostatus of donor; (2) CMV reactivation (P<0.001); (3) chronic GVHD (P=0.007). In conclusion, the incidence of LGL lymphocytosis following allogeneic hematopoietic SCT was detected in ~20% of recipients and is associated with favorable outcomes.