Human Metapneumovirus Infections Following Hematopoietic Cell Transplantation: Factors Associated With Disease Progression

Abstract

Background: Human metapneumovirus (HMPV) is a newly identified pulmonary pathogen that can cause fatal lower respiratory tract disease (LRD) in hematopoietic cell transplantation (HCT) recipients. Little is known about progression rates from upper respiratory tract infection (URI) to LRD and risk factors associated with progression.

Methods: A total of 118 HCT recipients receiving transplantation between 2004 and 2014 who had HMPV detected in nasopharyngeal, bronchoalveolar lavage, or lung biopsy samples by real-time reverse transcription polymerase chain reaction were retrospectively analyzed.

Results: More than 90% of the cases were identified between December and May. Among the 118 HCT patients, 88 and 30 had URI alone and LRD, respectively. Among 30 patients with LRD, 17 patients progressed from URI to LRD after a median of 7 days (range, 2-63 days). The probability of progression to LRD within 40 days after URI was 16%. In Cox regression analysis, steroid use ≥1 mg/kg prior to URI diagnosis (hazard ratio [HR], 5.10; P = .004), low lymphocyte count (HR, 3.43; P = .011), and early onset of HMPV infection after HCT (before day 30 after HCT; HR, 3.54; P = .013) were associated with higher progression to LRD. The median viral load in nasal wash samples was 1.1 × 10(6) copies/mL (range, 3.3 × 10(2)-1.7 × 10(9)) with no correlation between the viral load and progression.

Conclusions: Progression from URI to LRD occurred in up to 60% of HCT recipients with risk factors such as systemic corticosteroid use or low lymphocyte counts. Further studies are needed to define the role of viral load in the pathogenesis of progressive disease.

Keywords: hematopoietic cell transplantation; human metapneumovirus; lower respiratory tract disease; progression.

Figure 1.

Monthly distribution of human metapneumovirus (HMPV) infection. A, Number of cases with HMPV infection by month, July 2008–June 2014, at our transplantation center. B, Number of cases with HMPV infection by month, July 2008–June 2014, diagnosed by the University of Washington (UW) reference laboratory, which tests samples from both Seattle and regional hospitals and healthcare providers. C, Number of cases with HMPV infection by year, January 2009–June 2014, at our center. *Number of cases in 2014 was obtained between January and June. D, Number of cases with HMPV infection by year, January 2009–June 2014, diagnosed by the UW reference laboratory. *Number of cases in 2014 was obtained between January and June. Abbreviations: HCT, hematopoietic cell transplantation; LRD, lower respiratory tract disease; URI, upper respiratory tract infection.

Figure 2.

Probability of progression to lower respiratory tract disease (LRD) after human metapneumovirus (HMPV) upper respiratory tract infection (URI) diagnosis.

Figure 3.

Incidence of progression to lower respiratory tract disease (LRD) after diagnosis of human metapneumovirus (HMPV) upper respiratory tract infection (URI). A, Cumulative incidence of progression to LRD by days between hematopoietic cell transplantation (HCT) and diagnosis of URI (global P = .01, log-rank test). B, Cumulative incidence of progression to LRD by lymphocyte count (global P = .0007). C, Cumulative incidence of progression to LRD by steroid dose before diagnosis of URI (global P = .006).