Despite effective therapies, cytomegalovirus (CMV) continues to have a significant impact on morbidity and mortality in hematopoietic cell transplant recipients. At particular risk are recipients of alternative grafts such as umbilical cord blood (UCB), haploidentical transplants (haplo), or patients conditioned with T-cell depleting regimens such as anti-thymocyte globulin (ATG). With the approval of letermovir, its impact on high-risk patients is of particular interest. To evaluate the impact of letermovir prophylaxis at our center, we performed a retrospective analysis of 114 high-risk patients who received letermovir as prophylaxis (LET PPX) between January 2018 through December 2019, including 30 UCB and 22 haplo recipients, compared with 637 historical controls with comparable risk between January 2013 and December 2019. By post-transplant day 100 (D+100), letermovir prophylaxis significantly decreased the incidence of both CMV DNAemia compared with controls (45.37% versus 74.1%; P < .001) and clinically significant CMV infection (12.04% versus 48.82%; P < .001). The impact of LET PPX was even more profound on the incidence of clinically significant CMV infection (CSI), defined as the administration of antiviral therapy as preemptive therapy for CMV DNAemia or treatment for CMV disease. CSI was significantly lower in haplo recipients on LET PPX compared with controls (13.64% versus 73.33%; P= .02) and UCB recipients on LET PPX compared with controls (3.45% versus 37.5%; P < .001). No patients on LET primary PPX developed CMV disease in any treatment group by D+100 compared with controls (0% versus 5.34%, respectively; P = .006). Patients on LET PPX had fewer hospitalizations involving initiation of anti-CMV therapy compared with controls (0.93% versus 15.23%, respectively). Our analysis of the largest cohort of patients at high risk for CMV reactivation published to date demonstrates that letermovir prophylaxis significantly reduces the number of patients who receive CMV-active antiviral therapy for either DNAemia or disease due to CMV.

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We present a young pregnant woman who developed ulceroglandular tularaemia following a bite wound from a kitten. She grew Francisella tularensis from the ulcer. While awaiting bacterial culture results and serology for Bartonella, she was treated with azithromycin, with resolution of fever and axillary tenderness. Treatment recommendations for tularemia are either gentamicin or doxycycline, both of which can be perilous to the fetus. A Centers for Disease Control and Prevention report on the macrolide susceptibility of North American isolates of this organism has been underappreciated. The unanticipated result from this patient may give another potential option for treatment of tularemia in pregnancy.

BackgroundDaratumumab is an IgG kappa monoclonal antibody (mAB) against CD38 which is expressed on myeloma cells. It has recently been approved for treatment of patients with relapsed refractory multiple myeloma. Our objective was to identify the potential infectious complications associated with daratumumab use.MethodsWe conducted a retrospective analysis of myeloma patients who received daratumumab at our institution from October 2015 to December 2016. Patients were divided into four groups based on administration regimen of daratumumab: (1) single agent with dexamethasone; (2) triple therapy with proteasome inhibitor (PI), immune-modulating drug (IMiD), mitogen-activated protein kinase (MEK) inhibitor or mAB; (3) quadruple therapy with IMiD + PI ± mAB or cyclophosphamide; (4) with high-dose chemotherapy. For each group, we evaluated the incidence of infection, neutropenia (defined as ANC <1,000), hospitalization, and 90-day survival.ResultsA total of 171 patients (63% male, 37% female) were included in the study and received a total of 343 cycles of daratumumab. Median age was 68 years. A total of 151 infections occurred in 121 of the 343 cycles (40% bacterial; 52% viral). There was a significant association between development of infection and chemotherapy regimen used (χ2 = 17, P ≤ 0.001). Patients developed neutropenia in 129 of 254 cycles (51%). There was a significant association between the development of neutropenia and chemotherapy regimen used (χ2 = 43.51, P < 0.00001). Discontinuation of chemotherapy occurred in 65 cycles (19%), mainly due to progression of disease (54%). Eighty subjects (23%) required hospitalization, infection being the main cause (51%). Ninety-day survival was 91.8%.ConclusionInfection is common among myeloma patients who receive daratumumab. Myeloma patients who receive daratumumab in conjunction with multidrug chemotherapy regimens have an increased risk of infection and neutropenia. Because daratumumab is given predominantly as outpatient therapy, a greater understanding of the potential immunomodulatory effects of daratumumab will lead to increased vigilance in identifying and treating clinically significant infections.Disclosures F. Davies, Janssen: Consultant, Speaker honorarium. G. Morgan, Janssen: Consultant and Research Contractor, Research support and Speaker honorarium.

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