Improved Relapse Free Survival and Overall Survival in Patients with High Immune Reconstitution of Gamma Delta T Cells 2 Months after Allogeneic Hematopoietic Stem Cell Transplantation
Introduction: The role of T cell receptor (TCR) gd cells in allogeneic hematopoietic stem cell transplantation (HSCT) is becoming of increasing interest1,2. In contrast to conventional alloreactive TCR ab cells, TCR gd cells are believed to have anti tumor effects without causing graft versus host disease (GVHD) We conducted a single center, prospective study to assess the impact of early TCR gd cell immune reconstitution on overall survival, relapse and acute GVHD after HSCT. Methods: From October 2015 to March 2017, 108 consecutive patients transplanted for malignant diseases at the Bone Marrow Transplant Unit, Department of Hematology, Copenhagen University Hospital, Rigshospitalet, were included in the study, table 1. Fresh blood samples days 28, 56, 91, 180 and 360 after transplantation were analyzed for absolute concentrations of CD3 CD4 and CD8 positive T cells together with a multi color flow cytometry panel with staining for TCRab, TCRgd, Vd1, Vd2, CD3, CD4, CD8, HLA DR, CD196, CD45RO, CD45RA, CD16, CD56, CD314 (NKG2D) and CD337 (NKp30) for immune phenotyping. Results: After a median of 673 (386 913) days, 28 (26% patients had died from relapse (n=14) and from transplant related mortality(n=14) respectively. A total of 24 (22% patients experienced relapse during the observation time with median time to relapse of 177 (56 778) days. Acute GVHD grade 2 4 was diagnosed in 38 (35% of patients. Patients were divided into two groups by dichotomization at the median value of TCR gd cell concentrations for Kaplan Meier analyses of overall survival (OS) relapse free survival (RFS) and cumulative incidence analyses (Gray9s test for competing risks) of relapse and acute GVHD. Patients with high concentrations of TCR gd cells 56 days after transplantation had significantly higher OS and RFS compared with patients with low concentrations, p Conclusion: The results of this prospective study suggest a protective effect of early robust TCR gd cell immune reconstitution on relapse and acute GVHD resulting in increased OS after HSCT, and support further research in adoptive TCR gd cell therapy in transplant patients. Handgretinger, R. Schilbach, K. The potential role of gd T cells after allogeneic HCT for leukemia. Blood131, 1063 1072 (2018) Scheper, W. Grunder, C. Straetemans, T. Sebestyen, Z. Kuball, J. Hunting for clinical translation with innate like immune cells and their receptors. Leukemia28, 1181 1190 (2014) Disclosures No relevant conflicts of interest to declare.