Effect of Stem Cell Boost and Donor Lymphocyte Infusion on the Incidence of Graft-Versus-Host Disease at Emory University Hospital

Abstract

Introduction Allogeneic hematopoietic stem cell transplantation (SCT) is a widely used to treat refractory and relapsed hematological malignancies. Additional CD34+ selected cells, or stem cell boosts (SCB), and CD3+ T cells, or donor lymphocyte infusions (DLI) are often administered to treat poor hematopoietic graft function or relapse of the underlying malignancy, respectively, following SCT. Although the T cell dose in SCB and DLI vary by more than 3 logs, graft-versus-host disease (GVHD) can be a major cause of morbidity and mortality in patients who receive additional post-transplant donor T cells. The purpose of this study is to test the hypothesis that the incidence of GVHD after infusions of additional donor T cells is associated with the cumulative incidence of GVHD in patients who received DLI vs SCB. Methods A retrospective cohort study was conducted on consecutive patients at Emory University Hospital who received a DLI or CD34+ cell-selected SCB from January 2000 to September 2016. Excluding patients with incomplete records, 46 DLI and 15 SCB patients were analyzed for post-infusion GVHD and 2-year post-infusion survival. SPSS Statistics was used to conduct a binary logistic regression on DLI and SCB patients in order to determine significant variation in GVHD incidence per relevant covariates. Results The median doses of CD3+ T cells were 18 × 10E6 cells/kg and 0.054 × 10E6 cells/kg for DLI and SCB recipients, respectively. 73% of SCB patients received prophylactic immunosuppressive drug therapy versus 20% of DLI patients (Table 1). In spite of receiving less than 0.3% of the T cell dose of DLI recipients, SCB recipients had a 60% cumulative incidence of GVHD by 2-years of follow-up versus 37% in DLI patients (Figure 1; p=0.142). Binary regression models showed that GVHD incidence did not vary significantly with the dose of T cells and other covariates, except age in the DLI group (Tables 2 and 3). Overall survival at 2 years was 48% for DLI recipients and 87% for SCB recipients, with relapse of the underlying malignancy being the major cause of death among both DLI patients and SCB patients. Conclusions DLI patients had a lower incidence of GVHD compared to SCB patients, despite the former receiving higher median doses of T cells. Neither delivered T cell dose nor post-infusion immune-prophylaxis were significantly associated with the development of GVHD after post-transplant infusions of donor hematopoietic cells. These data suggest the hypothesis that failure of thymic selection of donor-stem cell derived T cells may contribute to GVHD following infusions of CD34-cell selected SCB.