CT-634 Cytomegalovirus Reactivation Following Allogeneic Hematopoietic Stem Cell Transplantation and Its Association With Donor Virus-Specific Cellular Immunity

Abstract

Introduction The monitoring of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) is known to be useful in predicting CMV reactivation (CMV-R) risk in patients undergoing allogeneic stem cell transplantation (allo-SCT). However, there is lack of data on the impact of pretransplant donor CMI on CMV-R in allo-SCT recipients. We conducted this study to examine the CMV-R profile following allo-SCT in a tertiary care cancer center in India. We also assessed the impact of donor CMI on CMV-R severity. Methods This was a prospective, observational study conducted on consecutive allo-SCT recipients from our transplant unit. Baseline demographic data and transplant outcomes were recorded. CMV PCR monitoring was done as per guidelines. CMI was computed at baseline in a subset of 19 donors. CMI was assessed by flow cytometric analysis of cytokines produced after stimulation of subject peripheral blood mononuclear cells with pp65 antigen. The clinical predictors of CMV-R duration were identified using stepwise forward multivariable linear regression. The association of donor CMI with CMV reactivation duration (DOR) and peak titers were examined using univariable linear regression, and adjustment was done for clinical characteristics identified as predictors using multivariable regression. Results Fifty-one patients were recruited including 27 haploidentical and 24-matched sibling donor transplants. The mean age of the cohort was 22 years. The incidence of CMV-R after transplant was 74.5% with mean DOR of 21.6 days. Only antithymocyte globulin receipt (regression coefficient [RC], 15.07 [3.71-26.44]; P=0.010) and acute GVHD occurrence (RC, 11.70 [0.71-22.70]; P=0.037) were associated with prolonged DOR. Higher donor age was associated with higher peak CMV titers (RC, 1292.80 [35.09-2550.51]; P=0.044). Higher proportions of donor CD4+ T cells expressing IL-2 were associated with shorter DORs (RC, –6.33 [–12.18 to –0.48); P=0.035) and with lower peak titers (RC, –31002.64 [–60863.88 to –1141.40; P=0.043). The association remained significant after adjusting for clinical characteristics. Conclusions The CMV infection incidence following allo-SCT is similar in the Indian setting as that reported world over. This is the first study showing that strong donor cellular immune responses to CMV are independently associated with shorter CMV DORs and lower peak titers in recipients. Pretransplant assessment of CMV-specific cellular immunity may aid in refining donor selection for allo-SCT.