Humoral/cellular immune discordance in stem cell donors: impact on CMV-specific immune reconstitution after related hematopoietic transplantation

Background: Cytomegalovirus (CMV) reactivation is an important cause of complications after hematopoietic stem cell transplantation (HSCT). Discrepancies between serological and cellular CMV-specific immune response have been reported.

Objective: This study evaluates the impact of lack of CMV-specific CD8+ T-cell response in seropositive donors (discordant donors) on the reconstitution of CMV-specific cell-mediated immunity (CMV-CMI) after related HSCT in seropositive recipients.

Study design: CMV-CMI was assessed in donors and recipients using the QuantiFERON-CMV assay (QF). CMV-CMI was prospectively assessed for one year in 81 CMV-seropositive HSCT recipients with haploidentical or matched related donors. A Cox proportional hazard regression analysis was performed.

Results: Of the 67 CMV-seropositive donors, 54 (80.6%) were D+QFpos. The remaining 13 CMV-seropositive donors (19.4%) had a QFneg result and were therefore discordant donors (D+QFneg). We found that patients with D+QFneg had a significantly higher risk of impaired CMV-CMI reconstitution compared to patients with D+QFpos (Log-rank, p = 0.001) or D- donors (Log-rank, p = 0.023). Additionally, the D+QFneg group had a higher incidence of single-episode reactivation than patients with D+QFpos or D- donors (69.2% vs. 44.4% and 28.6%, respectively), but a lower incidence of CMV recurrence compared to the D- group (7.7% vs 57.1%, respectively; p = 0.003). After adjusting for other relevant variables, immune discordance in donors was independently associated with an impaired CMV-CMI reconstitution compared with D+QFpos donors (adjusted hazard ratio [HR] 0.18, 95% confidence interval [CI] 0.06-0.52; p = 0.001) and D- donors (adjusted HR 0.17, 95% CI 0.05-0.59; p = 0.005).

Conclusions: Discordant donors were associated with undetectable CMV-CMI during the 12-month follow-up period using the QF assay. The incapacity of these patients to become QFpos persisted even after CMV reactivation. This might be related to the low frequency of CMV recurrence in this group. CMV-CMI assessment, in conjunction with CMV serostatus, can be of utility to better classify stem cell donors as well as the risk of impaired CMV-CMI reconstitution after HSCT.

CITA DEL ARTÍCULO Transplant Cell Ther. 2022 Oct;28(10):703.e1-703.e8. doi: 10.1016/j.jtct.2022.07.005. Epub 2022 Jul 11.