Allogeneic hematopoietic stem cell transplantation (HCT) is a curative therapy for hematological malignancies. Two major allo-immune reactions take place in the recipient after HCT: the beneficial graft versus leukemia (GvL) wherein the donor immune cells identify and eradicate the leukemic cells of the recipient and the graft versus host (GvH) where the donor immune cells react against the normal cells of the host causing a debilitating illness called graft versus host disease (GvHD). The primary objective of this doctoral research was to distinguish between GvH and GvL allo-immune reactions by meticulously profiling the immune recovery at multiple time points post-HCT. Immune reconstitution in both adult and pediatric HCT recipients was evaluated at the transcriptomic level via gene expression profiling of 579 immunity-related genes using NanoString technology and at the cellular level through flow cytometric analysis of cell subset counts. Peripheral blood mononuclear cells from HCT recipients were analyzed at Day14, Day28, Day56, and Day84 posttransplant. An immune signature characterized by higher counts of T cells and overexpressed T cell-related genes, was identified in patients who developed acute GvHD grades 2-4 as early as Day14 posttransplant. The gene expression signature showing overexpressed T cell related genes especially CD161 expressing cytotoxic T cells was validated in an independent validation cohort. T cell counts and related transcriptomes were notably higher in cytomegalovirus (CMV) seropositive donor and recipient (D+R+) patients compared to other serostatus groups. The recovery pattern was similar in both adult and pediatric patients. The influence of CMV D+R+ on T cell reconstitution was not significant at early time points (Day 28) but became evident at 2 and 3 months post-transplant. Signatures indicating a lack of GvL response were observed at 3 months (Day 84) post-transplant characterized by downregulated expression of CD8 Tcell genes, including TIGIT and EOMES in patients at high risk of relapse. While this study succeeded in partially differentiating GvH and GvL allo-immune reactions through temporal and differential T cell gene expression profiling, further comprehensive transcriptomic analysis in larger cohorts is essential for a complete understanding of the separation between GvH and GvL.