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Background: Ex vivo T-cell depletion (TCD) by CD34+ selection has been used successfully for graft-versus-host disease prevention alleviating the need for additional pharmacologic immunosuppressants. TCD has been associated with higher rates of viral infections and cytomegalovirus (CMV) disease in particular compared to conventional (CONV) HCT. Modern methods of TCD achieve up to 5 log reduction of T-cells. At MSK, TCD HCT recipients (R) are routinely monitored for CMV, adenovirus (ADV), Epstein-Barr virus (EBV), and human herpes virus 6 (HHV6) in the blood by quantitative polymerase chain reaction (qPCR) assays. We report the incidence of viremia and end organ disease (EOD) by these viruses in TCD HCT recipients. Methods: Retrospective review of adults with acute leukemia (AL) and myelodysplastic syndrome (MDS) patients (pts) who received TCD HCT at MSK from June 2010 -December 2014. TCD was performed by the FDA approved CliniMACS CD34+ reagent system (Miltenyi Biotec, Gladbach, Germany). CMV was monitored at least weekly from day 14-100 and at least every 14 days until day 180. EBV was monitored through day 180. Monitoring for CMV and EBV was performed by the Clinical Microbiology Laboratory at MSK using Roche analyte specific reagents, and since March 2013, the Cobas Ampliprep/Cobas Taqman (CAP/CTM) CMV qPCR in plasma. Monitoring for ADV/HHV6 was performed by Viracor-IBT laboratories (Lenexa, KS). Preemptive treatment for CMV was started for ≥2 consecutive PCR >500copies/ml in whole blood or >300 IU/ml in plasma. Treatment of ADV/HHV6 viremia was at clinician's discretion. EBV post-transplant lymphoproliferative disorder (PTLD) was treated with rituximab as primary therapy. During the study, 11 pts were enrolled in CMV prevention trials of brincidofovir (BCV), and 5 pts received BCV for treatment of ADV. EOD was scored by standard criteria. Follow up was through June 2015. The cumulative incidence (CI) was estimated for viremia at 180 days and EOD at 365 days for CMV, ADV, HHV6, and EBV. Kaplan-Meier method and log-rank test were used to compare CI between groups. P Results: Of239 pts (median age 56.3 years, range 19.6-73.3), 161 (67%) pts had AL and 78 (33%) pts had MDS. Donors were matched-related 76 (32%), matched unrelated 116 (48%), or mismatched (related or unrelated) 47(20%); CMV R+ 148 (62%) or R- 91 (38%). CMV infection had the earliest onset post HCT at a median of 28 days (d) (IQR: 25-33), followed by HHV6 33d (25-52), ADV 71d (44-89), and EBV 85d (58-107). 188 (79%) pts had ≥1 dsDNA viral infection with 182 (76%) pts experiencing infection prior to d100. The CIs of viremia were: CMV 42% (68% in R+ vs 0% in R-, P Conclusions: 1) Viremias by dsDNA viruses occurred frequently and early post TCD HCT: 189 (79%) pts had at least 1 dsDNA viral infection, with onset of first infection before d100 in 183 (77%) pts. Around 58% of pts with CMV had coinfections with additional dsDNA virus(es). 2) Two thirds (67%) of CMV R+ and 41% of total pts received CMV antiviral treatment. 3) Overall, 18% of patients developed end organ disease by dsDNA viruses. 4) Viremias were managed effectively with intense monitoring and antiviral treatment, and rates of EOD were comparable to those of CONV HCT. Our data highlights the need for effective strategies to reduce the total burden of dsDNA viruses after TCD HCT. Figure 1. CIs of dsDNA viremia. Figure 1. CIs of dsDNA viremia. Figure 2. dsDNA viral co-infections Figure 2. dsDNA viral co-infections Figure 3. Coinfections among pts with CMV viremia Figure 3. Coinfections among pts with CMV viremia Disclosures Perales: Merck: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Giralt:TAKEDA: Consultancy, Honoraria, Research Funding; JAZZ: Consultancy, Honoraria, Research Funding, Speakers Bureau; AMGEN: Consultancy, Research Funding; SANOFI: Consultancy, Honoraria, Research Funding; CELGENE: Consultancy, Honoraria, Research Funding.

Background: Streptococcus pneumoniae is a major cause of sepsis, pneumonia and meningitis leading to significant morbidity and mortality. Invasive pneumococcal disease (IPD) and mortality rates in cancer patients (pts) are higher than in the general population. Since the introduction of routine childhood immunization with the 7-valent pneumococcal conjugate vaccine (PREVNAR) in 2000, the overall rate of invasive pneumococcal disease (IPD) decreased in adults in the US. The impact of PREVNAR on rates of IPD in cancer pts is not well studied. Methods: Retrospective review of pts treated at Memorial Sloan-Kettering Cancer Center from 1991-2012. Unique patient visits per year were obtained from the hospital database. Prevalence was calculated as number of cases per 1000 patient-visits per year. Pts with positive culture(s) for S. pneumoniae were identified from microbiology records. Serotype data is available through 2001. IPD was defined as a positive S. pneumoniae culture from a sterile site such as blood, CSF, or pleural fluid culture. Pneumococcal pneumonia was defined as a positive S. pneumoniae culture from thelower respiratory tract or a positive upper respiratory culture with either radiographic evidence for pneumonia and/or ICD-9 code "pneumococcal pneumonia" or "pneumonia" associated with the positive culture for S. pneumoniae. Colonization was defined as positive culture for S. pneumoniae without IPD or pneumonia. We compared prevalence between "early" (prior to PREVNAR, 1992-2001) and "late" (2002-2012) periods, in those with diagnoses of solid tumors and hematologic malignancies, and between ages ≤21 and >21 years. Pneumococcal vaccination rates were calculated as the number of patients who received any pneumococcal vaccine divided by the number of patient-visits per year. Results: The mean number of patient-visits per year was 46,394 and 96,954, for the early and late period, respectively. Of 1,033 patients with ≥1 culture positive for S. pneumoniae during the study, 329 (32%) had IPD, 394 (38%) had pneumococcal pneumonia and 310 (30%) had colonization. S. pneumoniae type 6 accounted for 39 (22%) isolates where serotype data was available. The annual prevalence of IPD, pneumonia and colonization gradually declined over the course of the study (Figure 1). Compared to the early period, the prevalence of IPD, pneumonia and colonization were lower in the late period (Table 1). The highest prevalence of IPD was observed in pts ≤21 years of age (2.8 and 1.3 for early and late periods, respectively). The prevalence of IPD in pts with hematologic malignancies was 5-fold higher than pts with solid tumors in the early period (1.8 vs 0.39 respectively; P Conclusions: 1) Over a 20 year period we observed a decline in the prevalence of IPD, pneumococcal pneumonia and colonization in cancer patients at a tertiary cancer center in NYC. 2) The prevalence of IPD, pneumococcal pneumonia and colonization was significantly lower (P Table 1. Prevalence for IPD, Pneumonia and Colonization by Period Prevalence Period IPD PNA Colonization 1992-2001 0.36 0.48 0.48 2002-2012 0.16 0.16 0.08 Prevalence ratio (Early/Late) 2.25 3.0 6.0 95% CI 2.0-2.7 2.6-3.4 4.8-7.7 P value Figure 1. Annual prevalence of IPD, pneumonia and colonization Figure 1. Annual prevalence of IPD, pneumonia and colonization Disclosures Kaltsas: Pfizer: Research Funding.

Background: Hematopoietic cell transplant (HCT) patients are at risk for serious infections by Herpes simplex1/2 (HSV) and Varicella zoster(VZV). Current guidelines recommend prophylaxis (PPX) with acyclovir (ACV) during the peri-transplant period and continuing throughout the period of immunosuppression. Brincidofovir (BCV, CMX001) is a broad-spectrum nucleotide analog with in vitro activity against double stranded DNA (dsDNA) viruses including HSV and VZV. BCV is in Phase 3 development for the prevention of cytomegalovirus (CMV) infection post-HCT. At present, there is no clinical data to support the efficacy of BCV PPX for HSV/VZV post-HCT. At Memorial Sloan-Kettering Cancer Center (MSK) from 2010 to June 2015, approximately 70 alloHCT recipients were treated with BCV for various indications. We examined rates of breakthrough HSV and VZV infections during administration of BCV. Methods: Retrospective review of alloHCT patients (pts) treated for ≥14 days with BCV, on protocols or emergency investigational new drug application (EIND) at MSK. Administration of concomitant (CON) ACV for HSV PPX during BCV treatment was at clinician discretion. CMX001-350 was an expanded access study of BCV for treatment of subjects with dsDNA viruses and limited or no therapeutic options. CMX001-202 was a placebo-controlled study of BCV as preemption of adenovirus (ADV) post-HCT. CMX001-304 is a currently ongoing open label study of BCV for preemption of ADV disease. After June 2011, all pts received BCV 200mg total weekly dose [100mg twice weekly (BIW) or 200mg weekly (QW)] for adult/adolescent pts and 4mg/kg total weekly dose (2mg/kg BIW or 4mg/kg QW) for pediatric pts. Patients enrolled on CMX-304 through June 16, 2015 are included in this analysis. Based on CON ACV PPX during BCV treatment, 3 patient groups were identified: 1) No CON ACV PPX (group A); 2) Partial CON ACV PPX (group B); and 3) CON ACV PPX (group 3). Diagnosis of HSV or VZV infection was based on viral culture or PCR and clinical symptoms. Data was extracted from medical, pharmacy, and microbiology records. Results: Of 55 alloHCT pts who received BCV ≥14 days, 27 (49%) were treated on CMX001-350, 1 (2%) on CMX001-202, 12 (22%) on CMX001-304 and 15 (27%) under EIND. The median age was 53 years (range, 3-69). Thirty nine (71%) pts received T-cell depleted allografts, 9 (16%) cord blood, and 7 (13%) conventional allografts. BCV started a median of 85 days [Interquartile range (IQR), 59.5-209.5] post-HCT. The primary indication for BCV was: ACV resistant HSV in 2 (4%) pts, disseminated VZV in 1 (2%) pts, CMV in 28 (51%) pts, ADV in 21 (38%) pts and other dsDNA viruses (BK polyoma virus, Human herpesvirus 6, John Cunningham virus) in 3 (5%) pts. Thirty one (56%) pts received BCV 100mg BIW. Among 35 pts in group A, duration of BCV was a median of 39 days (IQR, 29.5-78). One pt in group A received concomitant anti-CMV antivirals for 12 days. Among 13 pts in group B, the median duration of BCV monotherapy was 23 days (IQR, 13-40). Two pts in group B had brief concomitant exposure to anti-CMV antivirals. Among 7 patients in group C, the median duration of BCV treatment was 71 days (IQR, 40-132) (Table 1). Two pts developed HSV infections during BCV treatment. For one pt, the primary indication for BCV was ACV resistant HSV. The pt initially responded to BCV with resolution of oral lesions. During his treatment with BCV, he had intermittent oral ulcers and oral cultures positive for HSV. The second pt developed breakthrough HSV infection during interruption of BCV for severe diarrhea related to graft versus-host disease. There were no breakthrough VZV infections. For one pt, the primary indication for BCV was disseminated VZV. The pt had complete resolution of VZV and no further VZV reactivation during BCV treatment. Conclusions: 1) During 2,806 patient-days of BCV monotherapy in highly immunosuppressed HCT pts, there were no VZV infections and only 2 breakthrough HSV infections. 2) BCV treatment interruptions and impaired gastrointestinal absorption likely explain the breakthrough HSV infections. 3) Our retrospective analysis in this heterogeneous cohort of sick alloHCT recipients supports that BCV administration at doses currently studied for CMV prevention is likely effective for prophylaxis of HSV/VZV in HCT. Disclosures Off Label Use: Brincidofovir (CMX001) for the efficacy of prophylaxis for Herpes simples 1/2 and Varicella zoster..