Dataset Information

Donor NKG2C Copy Number: An Independent Predictor for CMV Reactivation After Double Cord Blood Transplantation.

ABSTRACT: Cytomegalovirus (CMV) remains a major cause of morbidity following allogeneic hematopoietic stem cell transplant. Natural killer cells expressing NKG2C have been shown to play a role in the immune surveillance of human CMV. We studied NKG2C copy number in the donor graft and the risk of CMV reactivation after double umbilical cord blood transplantation (DUCBT) in 100 CMV seropositive DUCBT recipients and their corresponding cord blood (CB) grafts (n = 200). In the setting of DUCBT, the combined graft may contain 0-4 functional copies of NKG2C gene. Sixteen patients received a combined graft with 1 or 2 NKG2C copies and 84 patients were recipients of a combined graft with 3 or 4 NKG2C copies. The 6-month cumulative incidence of CMV reactivation for the two groups was 93.7 and 58.4%, respectively (p = 0.0003). In multivariate analysis, low NKG2C copies in the graft was an independent predictor of CMV reactivation (HR = 2.72, CI = 1.59-4.64; p < 0.0001). Our study points to an important role for donor NKG2C for protection against CMV reactivation after DUCBT. These novel findings may help identify patients at a higher risk of CMV reactivation after DUCBT. Donor NKG2C genotype may be used as a potential criterion in the algorithm for graft selection for DUCBT.

SUBMITTER: Cao K

PROVIDER: S-EPMC6206267 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Donor NKG2C Copy Number: An Independent Predictor for CMV Reactivation After Double Cord Blood Transplantation.

Cao Kai K Marin David D Sekine Takuye T Rondon Gabriela G Zhao Weicheng W Smith Nathaniel T NT Daher May M Wang Qing Q Li Li L Saliba Rima M RM Pingali Ravi R Popat Uday U Hosing Chitra C Olson Amanda A Oran Betul B Basar Rafet R Mehta Rohtesh S RS Champlin Richard R Shpall Elizabeth J EJ Rezvani Katayoun K

Frontiers in immunology 20181023

Cytomegalovirus (CMV) remains a major cause of morbidity following allogeneic hematopoietic stem cell transplant. Natural killer cells expressing NKG2C have been shown to play a role in the immune surveillance of human CMV. We studied NKG2C copy number in the donor graft and the risk of CMV reactivation after double umbilical cord blood transplantation (DUCBT) in 100 CMV seropositive DUCBT recipients and their corresponding cord blood (CB) grafts (n = 200). In the setting of ...[more]

PMID: 30405633

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Project description:RATIONALE:In the United States, an algorithm known as the "match-run" creates an ordered ranking of potential recipients for available lung allografts. A potential recipient's match-run position, or "sequence number," is available to the transplant center when contacted with a lung offer. Lung offers with higher sequence numbers may be interpreted as a crowd-sourced evaluation of poor organ quality, though the association between the sequence number at which a lung is accepted and its recipient's post-transplant outcomes is unclear. OBJECTIVES:We sought to evaluate the primary reasons provided when a lung offer was refused by a transplant center, transplant center and donor/organ factors associated with a higher sequence number at acceptance, and the association of the sequence number at acceptance with post-transplant mortality and graft failure. METHODS:Match-run outcomes for lung offers that occurred in the United States from May 2007 through June 2014 were merged with recipient follow-up data through December 2017. Associations between the sequence number at the time of acceptance and selected transplant center and donor characteristics were estimated using multivariable logistic and multinomial regression models. The associations between the final sequence number and recipient survival and graft survival were estimated using multivariable time-to-event models. RESULTS:Of 10,981 lung offer acceptances, nearly 70% were accepted by one of the top 10 ranked candidates. Higher median annual center volume and potential indicators of organ quality (e.g., abnormal chest radiograph or bronchoscopy) were associated with a higher sequence number at acceptance. There was weak evidence for a small positive relationship between the sequence number at acceptance and both mortality and graft failure. For example, the unadjusted and adjusted hazard ratios for death associated with the log-sequence number at acceptance were 1.019 (95% confidence interval, 1.001-1.038) and 1.011 (95% confidence interval, 0.989-1.033), respectively. On the absolute scale, using the multivariable model, a 10-fold increase in the sequence number translated into a 0.8% absolute decline in the predicted 5-year survival. CONCLUSIONS:Acceptance of a donor lung offer at a later point in the match-run was associated with measurable indicators of organ quality, but not with clinically meaningful differences in post-transplant mortality or graft failure.

Dataset Information

Donor NKG2C Copy Number: An Independent Predictor for CMV Reactivation After Double Cord Blood Transplantation.

Publications

Donor NKG2C Copy Number: An Independent Predictor for CMV Reactivation After Double Cord Blood Transplantation.

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