CMV-specific immune reconstitution following allogeneic stem cell transplantation

Abstract

Cytomegalovirus (CMV) remains a major contributor to morbidity and mortality following allogeneic haemopoietic stem cell transplant (HSCT) despite widespread use of viraemia monitoring and preemptive antiviral therapy. Uncontrolled viral replication occurs primarily in the first 100 d post transplant but this high risk period can extend to many months if immune recovery is delayed. The re-establishment of a functional population of cellular effectors is essential for control of virus replication and depends on recipient and donor serostatus, the stem cell source, degree of HLA matching and post-transplant factors such as CMV antigen exposure, presence of GVHD and ongoing use of immune suppression. A number of immune monitoring assays exist but have not yet become widely accessible for routine clinical use. Vaccination, adoptive transfer of CMV specific T cells and a number of graft engineering processes are being evaluated to enhance of CMV specific immune recovery post HSCT.

ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia

“…Importantly, these data also identified a potential donor-selection tool considering most patients have multiple haploidentical donors available [48], and the optimal donor could be selected before cell collection by measuring third-party reactivity in donor PBMCs. If only one donor is available, or third-party reactivity is limited in all donors, donor vaccination before apheresis and adoptive transfer of antivirus-specific T cells may be considered [49][50][51]. Our findings regarding the contribution of donor T cells to HSCT outcomes are also in line with donor T-cell genomic profile predicting for GvHD after HLA-matched T-cellreplete transplants and warrant further investigation [52].…”

The clinical and economic impact of cytomegalovirus infection in recipients of hematopoietic stem cell transplantation

“…However, the effect of donor seropositivity is not well defined. For example, it has been shown that the absence of CMV‐specific T cells in CMV‐naïve donors is a significant risk factor for unchecked CMV reactivation before immune reconstitution . However, several studies have observed a paradoxical increase in CMV risk with seropositive donors .…”

“…For example, it has been shown that the absence of CMV-specific T cells in CMV-naïve donors is a significant risk factor for unchecked CMV reactivation before immune reconstitution. 38 However, several studies have observed a paradoxical increase in CMV risk with seropositive donors. 17,34,39,40 In our cohort, risk ratios for CMV-I and CMV-D were higher in D−/R+ compared with D+/R+ and all other serostatuses.…”

Investigation of Cytomegalovirus, Epstein-Barr Virus and Adenovirus Infections After Hematopoietic Stem Cell Transplantation (HSCT) in Pediatric Patients

“…İlk infeksiyon sonrasında virüs lenfositlerde, monositlerde ve dendritik hücrelerde latent kalır. Allojenik HKHT alıcılarında CMV infeksiyonu asemptomatik infeksiyondan pnömoni, hepatit, gastroenterit, retinit ve ensefalite değişen çeşitli hastalıklarla ilişkilidir [1,3,4] . Yine herpesvirüs ailesinin üyesi olan Epstein-Barr virüs (EBV) popülasyonun %90'dan fazlasını infekte eden yaygın bir virüstür.…”