Impact of CMV PCR Blips in Recipients of Solid Organ and Hematopoietic Stem Cell Transplantation

Background: Viral blips reflecting polymerase chain reaction (PCR) artefacts or transient low-level replication are well described in the human immunodeficiency virus setting. However, the epidemiology of such blips in transplant recipients screened for cytomegalovirus (CMV) with PCR remains uncertain and was investigated in a cohort of solid organ and hematopoietic stem cell recipients. // Methods: Eligible recipients had known donor/recipient CMV IgG serostatus, and 3 CMV PCRs ≥. The CMV PCR triplicates (3 consecutive CMV PCRs) were defined; the first CMV PCR was always negative, and the time between the second and third samples was 7 days ≤. A positive second but negative third sample represented a blip. Odds ratio (OR) for factors associated with a triplicate being a blip was estimated by binomial regression adjusted for repeated measurements. Whether blips affected the hazard ratio (HR) for subsequent CMV infection was determined with a Cox model. // Results: 851 recipients generated 3883 CMV PCR triplicates. The OR of a triplicate representing a blip decreased with increasing viral load of the second sample (vs 273 IU/mL; >273-910 IU/mL: odds ratio [OR], 0.2; 95% confidence interval [CI], 0.1-0.5; >910 IU/mL: OR, 0.08; 95% CI, 0.02-0.2; P ≤ 0.0002) and increased with intermediary-/low-risk serostatus (vs high risk) (OR, 2.8; 95% CI, 1.2-5.5; P = 0.01). Cumulative exposure to DNAemia in the CMV blips greater than 910 IU/mL indicated increased HR of subsequent CMV infection (HR, 4.6; 95% CI, 1.2-17.2; P = 0.02). // Conclusions: Cytomegalovirus blips are frequent; particularly when the viral load of the first positive PCR is < 910 IU/mL, and serostatus risk is intermediary/low. Accumulating blips suggest intermittent low-level replication. If blips are suspected, confirmation of ongoing replication before initiation of treatment is prudent

Classification of death causes after transplantation (CLASS):Evaluation of methodology and initial results

Correct classification of death causes is an important component of transplant trials.We aimed to develop and validate a system to classify causes of death in hematopoietic stem cell (HSCT) and solid organ (SOT) transplant recipients.Case record forms (CRF) of fatal cases were completed, including investigator-designated cause of death. Deaths occurring in 2010 to 2013 were used for derivation; and were validated by deaths occurring in 2013 to 2015. Underlying cause of death (referred to as recorded underlying cause) was determined through a central adjudication process involving 2 external reviewers, and subsequently compared with the Danish National Death Cause Registry.Three hundred eighty-eight recipients died 2010 to 2015 (196 [51%] SOT and 192 [49%] HSCT). The main recorded underlying causes of death among SOT and HSCT were classified as cancer (20%, 48%), graft rejection/failure/graft-versus-host-disease (35%, 28%), and infections (20%, 11%). Kappa between the investigator-designated and the recorded underlying cause of death was 0.74 (95% CI 0.69-0.80) in derivation and comparable in the validation cohort. Death causes were concordant with the Danish National Death Cause Registry in 37.2% (95% CI 31.5-42.9) and 38.4% (95% CI 28.8-48.0) in the derivation and validation cohorts, respectively.We developed and validated a method to systematically and reliably classify the underlying cause of death among transplant recipients. There was a high degree of discordance between this classification and that in the Danish National Death Cause Registry