Large Granular Lymphocytosis after Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study

Abstract

Introduction Large granular lymphocytosis (LGL) is observed following hematopoietic stem cell transplantation (HSCT) in 0.5-18.4% of patients. The development of LGL has been associated with and attributed to various conditions such as immune system reconstitution, CMV viremia, and graft-versus-host disease. There is literature available that suggests the development of LGL may be associated with improved outcomes, but management varies greatly because of the different theories surrounding this condition. Thus, we aimed to review a cohort of patients from our institution who developed LGL after HSCT in order to further our understanding and guide management recommendations. Methods We performed a single-center retrospective cohort analysis of patients who had a hematopoietic stem cell transplant from April 1, 2015 to June 30, 2018 and developed large granular lymphocytosis up to one year after transplantation. We collected and reviewed various clinical aspects of each patientOs transplant course and the management of large granular lymphocytosis. Results Of the 127 patients who received an allogeneic HSCT in this time period, 13 patients (10%) were diagnosed with large granular lymphocytosis. Patient demographics, transplant information, and LGL management are listed in Table 1. LGL was diagnosed between 57 and 236 days post-transplant. None of the 13 patients developed EBV viremia by PCR after transplant. 7 of 13 (54%) had CMV viremia/reactivation by PCR after transplant but before LGL diagnosis; 3 of 13 (23%) had CMV viremia by PCR after LGL diagnosis; 3 of 13 (23%) did not develop CMV viremia by PCR before or after LGL diagnosis. 4 of 13 (31%) developed chronic GVHD, and 3 of 13 (23%) developed acute GVHD. Of note, 6 of 13 (46%) had post-transplant cyclophosphamide and 2 of 13 (15%) had CD34 selected grafts; therefore, 8 of 13 (62%) had T-cell depleted transplants. All of the patients in this cohort were alive at day 100. 11 patients had a transplant greater than 1 year ago, and all of these patients were alive at the 1-year mark. Conclusions Based upon the results from this study, we cannot definitively attribute the development of LGL after allogeneic HSCT to one etiology. More importantly, all patients were alive at day 100 and 1 year regardless of the management approach, which suggests that this process may be self-limiting. Therefore, we believe a more conservative and supportive approach to management is warranted.