Year: 2011
Type: article
Study design: Observational Study
Abstract: Umbilical cord blood grafts are increasingly used as a source of hematopoietic stem cells for patients with high-risk hematologic diseases. Despite appropriate CD34+ cell numbers after transplantation, immune recovery remains delayed and insufficient, and infection-related morbidity remains a leading cause of mortality in this patient group. The purpose of this study was to (i) evaluate the tempo of functional T cell immune reconstitution after cord blood transplant (CBT) using the IFNg ELIspot to measure the frequency of T cells reactive against common viruses including EBV, CMV, adenovirus (Adv), BK virus, influenza, and Respiratory syncytial virus (RSV), as well as Staphylococcal enterotoxin B from Staphylococcus aureus (Staph) at sequential timepoints pre- and post transplant, and (ii) to delineate the types of infections in the post-CBT period and how frequently they occur. To assess immune reconstitution we prospectively isolated PBMCs from 52 CBT recipients before and then at monthly intervals after transplant. We assessed immune function by co-culturing the cells with Staph as well as pepmixes (15mer peptide libraries) spanning the viral antigens pp65 and IE1 (CMV), LMP1, LMP2, EBNA1, EBNA3a, EBNA3b, EBNA3c, BZLF1 (EBV), hexon and penton (Adv), VP1 and large T (BK virus), MP1 and NP1 (Influenza), and N and F (RSV). We were consistently able to detect T cell reactivity to Staph (median 395.5 spot forming cells (SFC)/2x105, range 23-845.5) pre-transplant, but evidence of immune recovery was delayed until at least 6 months post-CBT with an average of 86 SFC/2x105, which increased to normal (pre-transplant levels) by approx. 9 months post-transplant. Recovery of virus-specific T cells, exemplified by CMV-specific immune reconstitution, was even more delayed with recovery to detectable levels (ave. 89 SFC/2 x105 cells) at the 9 month time point. In a small subset of patients viral reactivation appeared to accelerate recovery of T cells reactive against the infecting virus with a subsequent decrease in viral load suggesting that the reconstituting cells had direct anti-viral activity in vivo. We also retrospectively evaluated the incidence of viral, bacterial, and fungal infections after CBT in the same patient cohort. Approximately 30 of the patients that received a CBT died within two years of transplant with 18 of these patients succumbing to infection. The statistical analysis and conclusions are in progress and will be presented.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2024212964