Cytomegalovirus Viral Load and Virus-Specific Immune Reconstitution after Peripheral Blood Stem Cell versus Bone Marrow Transplantation

Abstract

Peripheral blood stem cell (PBSC) products contain more T cells and monocytes when compared to bone marrow (BM), leading to fewer bacterial and fungal infections. CMV viral load and disease as well as CMV-specific immune reconstitution were compared in patients enrolled in a randomized trial comparing PSBC and BM transplantation. There was a higher rate of CMV infection and disease during the first 100 days after transplantation among PBSC recipients (any antigenemia/DNAemia: PBSC, 63% vs. BM, 42%, P=0.04; CMV disease: PBSC, 17% vs. BM, 4%, P=0.03). By two years, CMV disease rates were similar. The early increase in CMV events correlated temporarily with lower CMV-specific CD4+ T helper and CD8+ cytotoxic T lymphocyte function at 30 days after transplantation in PBSC recipients. By 3 months after transplantation and thereafter, CMV-specific immune responses were similar between BM and PBSC recipients. In conclusion, higher CMV infection and disease rates occurred in PBSC transplant recipients early after transplantation. These differences may be due to a transient delay in CMV specific immune reconstitution following PBSC transplantation.

Outcomes of acute leukemia patients transplanted with naive T cell–depleted stem cell grafts

“…T cell numbers recovered much earlier after T N -depleted HCT relative to patients that received TCD HCT (33), and EBV reactivation and post-HCT lymphoproliferative disease (PTLD), which occur in 18% and 2% of TCD HCT recipients, respectively (7,33), were not observed at all after T N -depleted HCT, consistent with transfer of protective EBV-specific immunity. CMV reactivation is common after allogeneic HCT, independent of whether T cells are depleted or not, and the frequency of viral reactivation among patients at risk in the T N -depleted cohort (73%) and T cell-replete control group (87%) is similar to that reported in the literature for T cell-replete grafts (53,54). Current practice dictates preemptive treatment of CMV reactivation at low levels of viremia after HCT, and progression to CMV disease is consequently now rare in HLA-matched HCT, precluding assessment of whether a particular HCT approach would change the natural history of CMV reactivation (55).…”

Impact of viral reactivations in the era of pre-emptive antiviral drug therapy following allogeneic haematopoietic SCT in paediatric recipients

“…CMV viraemia was frequent in children receiving PBSC as a stem cell source, possibly reflecting delayed CMV-specific immune-reconstitution following PBSC Viral reactivation in haematopoietic SCT P Hiwarkar et al grafts. 15 As recently reported, significant EBV viraemia was observed frequently in reduced intensity conditioned transplant reflecting the profound immunosuppression and incomplete ablation of recipient B-cells in this setting. 16 These high-risk groups of patients were more likely to develop blood viraemia and were at risk of virus-related organ disease and mortality.…”

Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study

“…Our studies showed that CD19.CARVSTs can be detected at low levels in the PB for up to 12 weeks, but because of the length of time that had elapsed after allogeneic HSCT before these patients received CD19.CAR-VSTs (3 months to 13 years), only 3 patients had viral reactivations that allowed us to assess the influence of viral-directed native TCR specificity on the persistence and numbers of CD19.CAR-VSTs. At such a late time after HSCT, endogenous immune reconstitution with VSTs has usually occurred 25,26,34 and may dominate the antiviral response, reducing the likelihood that CD19.CAR-VSTs receive activation and expansion signals through their native TCRs.…”