Infections after Transplantation of Bone Marrow or Peripheral Blood Stem Cells from Unrelated Donors.

Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft-versus-host disease are the 2 major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (Blood and Marrow Transplant Clinical Trials Network [BMT CTN] 0201) of transplantation of bone marrow (BM) versus peripheral blood stem cells (PBSC) from unrelated donors showed no significant differences in 2-year survival between these graft sources. In an effort to provide data regarding whether BM or PBSC could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2 years after transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201 of 249 (81%) of the evaluable patients had received a BM graft and 183 of 250 (73%) had received a PBSC graft. Of 1347 infection episodes, 373 were severe and 123 were life-threatening and/or fatal; 710 (53%) of these episodes occurred on the BM arm and 637 (47%) on the PBSC arm, resulting in a 2-year cumulative incidence 84.7% (95% confidence interval [CI], 79.6 to 89.8) for BM versus 79.7% (95% CI, 73.9 to 85.5) for PBSC, P = .013. The majority of these episodes, 810 (60%), were due to bacteria, with a 2-year cumulative incidence of 72.1% and 62.9% in BM versus PBSC recipients, respectively (P = .003). The cumulative incidence of bloodstream bacterial infections during the first 100 days was 44.8% (95% CI, 38.5 to 51.1) for BM versus 35.0% (95% CI, 28.9 to 41.1) for PBSC (P = .027). The total infection density (number of infection events/100 patient days at risk) was .67 for BM and .60 for PBSC. The overall infection density for bacterial infections was .4 in both arms; for viral infections, it was .2 in both arms; and for fungal/parasitic infections, it was .04 and .05 for BM and PBSC, respectively. The cumulative incidence of infection before engraftment was 47.9% (95% CI, 41.5 to 53.9) for BM versus 32.8% (95% CI, 27.1 to 38.7) for PBSC (P = .002), possibly related to quicker neutrophil engraftment using PBSC. Infections remain frequent after unrelated donor hematopoietic cell transplantation, particularly after BM grafts.

Improved detection of emerging drug-resistant mutant cytomegalovirus subpopulations by deep sequencing.

In immunosuppressed hosts, the development of multidrug resistance complicates the treatment of cytomegalovirus (CMV) infection. Improved genotypic detection of impending drug resistance may follow from recent technical advances. A severely T-cell-depleted patient with chronic lymphocytic leukemia developed CMV pneumonia and high plasma viral loads that were poorly responsive to antiviral therapy. Serial plasma specimens were analyzed for mutant viral populations by conventional and high-throughput deep-sequencing methods. Uncharacterized mutations were phenotyped for drug resistance using recombinant viruses. Conventional genotyping detected viruses with the UL97 kinase substitution C607Y after ganciclovir treatment, a transient subpopulation of UL54 polymerase L773V mutants first detected 8 weeks after foscarnet was started, and a subpopulation of a mutant with deletion of UL54 codons 981 and 982 2 months after the addition of cidofovir. Deep sequencing of the same serial specimens revealed the same UL54 mutants sooner, along with a more complex evolution of known and newly recognized mutant subpopulations missed by conventional sequencing. The UL54 exonuclease substitutions D413N, K513R, and C539G were newly shown to confer ganciclovir-cidofovir resistance, while L773V was shown to confer foscarnet resistance and add to the ganciclovir resistance conferred by UL97 C607Y. Increased sequencing depth provided a more timely and detailed diagnosis of mutant viral subpopulations that evolved with changing anti-CMV therapy.

Predictive value of testing nasopharyngeal samples for respiratory viruses in the setting of lower respiratory tract disease.

To determine the predictive value of nasopharyngeal (NP) sample testing for respiratory viruses (RVs) in suspected lower respiratory tract disease, 72 paired NP and bronchoalveolar lavage (BAL) fluid specimen sets, mostly from transplant recipients or patients with hematologic malignancies, were analyzed. Overall, 31.3% of the specimens tested positive for an RV. In 19 sets (26.4%), the NP and BAL fluid specimens were both positive for an RV; in 3 sets (4.2%), the NP specimens were positive but the BAL fluid specimens were negative; and in 3 other sets, the NP specimens were negative but the BAL fluid specimens were positive. The positive and negative predictive values of the NP specimens were 86.4% and 94%, respectively.

Impact of a Clostridioides Difficile Testing Computerized Clinical Decision Support Tool on an Adult Stem Cell Transplantation and Hematologic Malignancies Unit.

Clostridioides difficile infection rates are higher in hospitalized hematopoietic stem cell transplantation (HSCT) recipients and patients with hematologic malignancy (HM) compared with the general population. This is related both to extensive exposure to antibiotics as well as to frequent and often prolonged hospitalization. In this population, with numerous potential causes of diarrhea, a subset of C difficile detected is presumed to represent colonization rather than clinical infection. The use of decision support tools to guide ordering in hospitalized patients has been reported to decrease both C difficile testing and detection rates. Following implementation of a computerized decision support tool on our HSCT/HM unit, we observed a >2-fold decrease in C difficile testing volume and National Healthcare Safety Network-defined laboratory identifications of C difficile. Furthermore, the rate of oral vancomycin use, as well as the incidence of vancomycin-resistant enterococci colonization and bloodstream infection, decreased in the postintervention period.