Human Rhinovirus Infections in Hematopoietic Cell Transplant Recipients: Risk Score for Progression to Lower Respiratory Tract Infection

Abstract

A B S T R A C T Human rhinovirus lower respiratory tract infection (LRTI) is associated with mortality after hematopoietic cell transplantation (HCT); however, risk factors for LRTI are not well characterized. We sought to develop a risk score for progression to LRTI from upper respiratory tract infection (URTI) in HCT recipients. Risk factors for LRTI within 90 days were analyzed using Cox regression among HCT recipients with rhinovirus URTI between January 2009 and March 2016. The final multivariable model included factors with a meaningful effect on the bootstrapped optimism corrected concordance statistic. Weighted score contributions based on hazard ratios were determined. Cumulative incidence curves estimated the probability of LRTI at various score cut-offs. Of 588 rhinovirus URTI events, 100 (17%) progressed to LRTI. In a final multivariable model allogeneic grafts, prior rhinovirus URTI, low lymphocyte count, low albumin, positive cytomegalovirus serostatus, recipient statin use, and steroid use 2 mg/kg/day were associated with progression to LRTI. A weighted risk score cut-off with the highest sensitivity and specificity was determined. Risk scores above this cut-off were associated with progression to LRTI (cumulative incidence 28% versus 11% below cut-off; P < .001). The weighted risk score for progression to rhinovirus LRTI can help identify and stratify patients for clinical management and for future clinical trials of therapeutics in HCT recipients.

Community-Acquired Respiratory Viruses in Transplant Patients: Diversity, Impact, Unmet Clinical Needs

“…In view of the prolonged shedding, defining predictors of HRV lower RTID and mortality, such as grading SID or ISI, are warranted to guide decisions regarding transplant deferral and/or selective treatment of allogeneic HCT patients at highest risk ( 5 ). In a recent retrospective single-center study of 588 HRV upper RTID events in 150 autologous and 438 allogeneic HCT recipients, 16 and 84 were found to progress to lower RTID, respectively ( 182 ). Following multivariate analysis, a novel weighted risk score was derived consisting of a total of 99 points, which were given at upper RTID diagnosis, including for steroid use (20 for ≥2 mg/kg bodyweight; 12 for ≥1 to <2 mg/kg), 16 for lymphocyte counts of <100/μl, 14 for allogeneic/unrelated donor, and 12 for a positive CMV recipient status.…”

Respiratory syncytial virus in hematopoietic cell transplant recipients and patients with hematologic malignancies

“…These definitions were also applied in studies on coronavirus, 32 parainfluenza virus 33 and rhinovirus. 34…”

The effect of timing on community acquired respiratory virus infection mortality during the first year after allogeneic hematopoietic stem cell transplantation: a prospective epidemiological survey

“…Several studies have looked at the effect on mortality of when CARV infection occurs after allo-HCT using heterogeneous cut-off time points, showing discrepant results [6,10,11,[14][15][16][17][18][19][20][21][22][23][24]. In fact, most of them were unable to find any association between timing and mortality [14][15][16][17][18][19][20][21][22]24]. In contrast, our detailed analysis of 3-month all-cause mortality conducted monthly during the first year revealed that most deaths occurred in recipients who developed a CARV infection within the first 6 months of transplant (see Fig.…”

“…Accordingly, some studies found that developing a CARV infection within 30 days after transplant was linked to worse outcome [6,10] whereas others did not [14][15][16][17][18]. In addition, studies using day + 100 as a cut-off time could not show significant association with outcome [19][20][21][22], while others observed worse outcome for CARV infections occurring before day + 180 [11]. Finally, while some studies found that CARVs beyond 1 year after allo-HCT showed favorable outcomes [23], others did not [14,17,24].…”