Immunologic tolerance after allogeneic hematopoietic cell transplantation (HCT) is operationally defined by complete discontinuation of immune suppression (IS) and the absence of subsequent graft vs. host disease (GVHD). Acute and chronic GVHD, the sentinel manifestations of immunologic injury driven by donor immune cells, result in morbidity and death, and often develop or reoccur after IS discontinuation. Current scientific understanding of tolerance after HCT is limited, and there are no validated clinical or biologic determinants of immune tolerance after HCT. Therefore, current clinical practice of IS discontinuation is empiric, markedly heterogeneous and complicated by GVHD following IS discontinuation. Comprehensive analysis of IS discontinuation after HCT and subsequent risk for GVHD is needed to advance the field. We propose a robust secondary analysis of existing data (total n=827) from two major Blood and Marrow Transplant Clinical Trials Network (CTN) randomized trials (CTN 0201 and 0402) to address this need. Analysis of these data is ideal, as coverage of relevant patient, transplantation, and GVHD variables, as well as long-term follow up data on IS discontinuation and subsequent GVHD is complete. We will employ multi-state modeling to address our research questions, as this technique can accommodate the multiple health states after HCT relevant to this analysis, estimate the probability for each health state a serial time points after HCT, and model the effect of relevant covariates on the outcomes of IS discontinuation and GVHD following IS discontinuation. Our planned analyses will (1) examine which patient, transplant, and GVHD variables are associated with successful IS discontinuation, and (2) determine the incidence of GVHD following IS discontinuation, and investigate predictors of GVHD development after IS discontinuation.
Success after bone marrow transplant includes cure of cancer, freedom from transplant-related complications including a syndrome called graft vs. host disease (GVHD), and the ability to safely discontinue transplant immune suppressive medications. One major challenge in the field is inability to determine when patients can safely stop immune suppressive therapy, and whether they will experience GVHD afterward. Our study will examine existing data from two large national studies to determine when patients come off immune suppressive therapy, identify what factors are relevant to reaching that goal, and determine which patients will subsequently suffer GVHD.
