Disseminated Histoplasmosis in a Patient with Myelofibrosis on Ruxolitinib: A Case Report and Review of the Literature on Ruxolitinib-Associated Invasive Fungal Infections.

Ruxolitinib, a selective inhibitor of Janus kinases, is a standard treatment for intermediate/high-risk myelofibrosis (MF) but is associated with a predisposition to opportunistic infections, especially herpes zoster. However, the incidence and characteristics of invasive fungal infections (IFIs) in these patients remain uncertain. In this report, we present the case of a 59-year-old woman with MF who developed disseminated histoplasmosis after seven months of ruxolitinib use. The patient clinically improved after ten weeks of combined amphotericin B and azole therapy, and ruxolitinib was discontinued. Later, the patient received fedratinib, a relatively JAK2-selective inhibitor, without relapse of histoplasmosis. We also reviewed the literature on published cases of proven IFIs in patients with MF who received ruxolitinib. Including ours, we identified 28 such cases, most commonly due to Cryptococcus species (46%). IFIs were most commonly disseminated (39%), followed by localized lung (21%) infections. Although uncommon, a high index of suspicion for opportunistic IFIs is needed in patients receiving JAK inhibitors. Furthermore, the paucity of data regarding the optimal management of IFIs in patients treated with JAK inhibitors underscore the need for well-designed studies to evaluate the epidemiology, pathobiology, early diagnosis, and multimodal therapy of IFIs in patients with hematological malignancies receiving targeted therapies.

Mortality in recipients of allogeneic haematopoietic cell transplantation in the era of cytomegalovirus primary prophylaxis: a single-centre retrospective experience.

OBJECTIVES: Allogeneic haematopoietic cell transplant (allo-HCT) recipients who are cytomegalovirus (CMV)-seronegative have better post-transplant outcomes than CMV-seropositive recipients. Letermovir (LTV) is approved for CMV primary prophylaxis in adults who are CMV-seropositive after allo-HCT, and its use is associated with improved long-term post-transplant outcomes. We analysed whether LTV has affected the relationship between CMV serostatus and post-transplant outcomes. METHODS: We conducted a retrospective single-centre cohort study of allo-HCT recipients, stratified according to donor (D) and recipient (R). CMV serostatus and the use of LTV: D-/R-, R+/LTV-, and R+/LTV+. Outcomes measured were all-cause and non-relapse mortality, clinically significant CMV infection, graft-versus-host disease, and relapse up to week 48 after allo-HCT. The D-/R- group served as the reference for comparisons in univariate, competing risk regression, and cumulative incidence functions. RESULTS: The analysis included 1071 consecutive allo-HCT recipients: 131 D-/R-, 557 R+/LTV-, and 383 R+/LTV+. All-cause mortality by day 100 was 6.1% for the D-/R- group, compared with 14.0% (p 0.024) and 7.8% (p 0.7) for the R+/LTV- and R+/LTV + groups, respectively. Non-relapse mortality by day 100 was 11.0%, 6.8% and 3.8% for R+/LTV-, R+/LTV+, and D-/R- groups, respectively, without significant difference. When including relapse as a competing event, the hazard ratio for non-relapse mortality was 1.83 (95% CI: 1.12-2.99, p 0.017) for R+/LTV- compared with D-/R- and 1.05 (95% CI 0.62-1.77, p 0.85) for R+/LTV + compared with D-/R-. DISCUSSION: CMV primary prophylaxis with LTV abrogated the mortality gap based on CMV serostatus, a protective effect that persisted after discontinuation of primary prophylaxis.

Impact of Baseline and Week 2 and Week 4 Posttransplant CMV Cell-Mediated Immunity on Risk of CMV Infections and Mortality in Recipients of Allogeneic Hematopoietic Cell Transplant.

Background: Cytomegalovirus (CMV) infection is a common opportunistic infection after allogeneic hematopoietic cell transplant (alloHCT). We explored whether a change in CMV cell-mediated immunity during the first month after transplant predicts the risk of development of CMV infection and all-cause mortality. Methods: This follow-up analysis is based on data from the REACT study, a multicenter prospective observational study of recipients of alloHCT who were CMV-seropositive. Production of interferon γ following ex vivo stimulation with CMV antigens IE1 (immediate early 1) and pp65 (phosphoprotein 65) was assessed by CMV ELISPOT assay at baseline and 2 and 4 weeks after transplant. Clinically significant CMV infection (CS-CMVi) was defined as CMV viremia and/or disease necessitating antiviral therapy. We evaluated the impact of CMV CMI changes on the risk of CS-CMVi and post transplant mortality. Results: The analysis included 226 recipients of alloHCT with CMV cell-mediated immunity data at baseline and 2 and/or 4 weeks after transplant. CS-CMVi occurred in 64 patients (28%). On Cox regression analyses, independent predictors of CS-CMVi included a negative Δ change from baseline to week 2 of pp65 spot counts (hazard ratio, 3.65 [95% CI, 1.65-8.04]; P = .001) to week 4 of IE1 spot counts (hazard ratio, 2.79 [95% CI, 1.46-5.35]; P = .002), anti-thymocyte globulin conditioning regimen, type of transplant, female sex, and corticosteroid use. Kaplan-Meir analysis showed a significant association of a negative IE1 change from baseline to week 4 and increased all-cause mortality after transplant (log rank test = 0.041). Conclusions: A decrease in CMV-specific T-cell responses during the first month after transplant may predict CS-CMVi and is associated with all-cause mortality in recipients of alloHCT.

Refractory and Resistant Cytomegalovirus After Hematopoietic Cell Transplant in the Letermovir Primary Prophylaxis Era.

BACKGROUND: Cytomegalovirus (CMV) reactivation is one of the most common infectious complications after allogeneic hematopoietic cell transplant (HCT) and may result in significant morbidity and mortality. Primary prophylaxis with letermovir demonstrated a reduction in clinically significant CMV infections (CS-CMVi) in clinical trials of CMV-seropositive HCT recipients. This study aims at exploring the effect of primary letermovir prophylaxis in this population on the incidence and outcomes of refractory or resistant CMV infections. METHODS: This is a single-center, retrospective cohort study of 537 consecutive CMV-seropositive allogeneic HCT recipients cared for between March 2016 and October 2018. Baseline demographics, HCT characteristics, CMV infections, treatment, and mortality data were collected from the electronic medical record. CMV outcomes were defined according to the recently standardized definitions for clinical trials. Characteristics and outcomes were assessed according to receipt of primary letermovir prophylaxis. RESULTS: Of 537 patients identified, 123 received letermovir for primary prophylaxis during the first 100 days after HCT; 414 did not. In a multivariate analysis, primary prophylaxis with letermovir was associated with reductions in CS-CMVi (hazard ratio [HR] 0.26; 95% confidence interval [CI], 0.16-0.41), CMV end-organ disease (HR 0.23; 95% CI, 0.10-0.52), refractory or resistant CMV infection (HR 0.15; 95% CI, 0.04-0.52), and nonrelapse mortality at week 48 (HR 0.55; 95% CI, 0.32-0.93). There was neither resistant CMV nor CMV-related mortality in the primary letermovir prophylaxis group. CONCLUSIONS: Primary letermovir prophylaxis effectively prevents refractory or resistant CMV infections and decreases nonrelapse mortality at week 48, as well as CS-CMVi and CMV disease after allogeneic HCT.

Surveillance and identification of clusters of healthcare workers with coronavirus disease 2019 (COVID-19): Multidimensional interventions at a comprehensive cancer center.

BACKGROUND: Cases of novel coronavirus disease 2019 (COVID-19) were first reported in Wuhan, China, in December 2019. In this report, we describe 3 clusters of COVID-19 infections among healthcare workers (HCWs), not associated with patient exposure, and the interventions undertaken to halt ongoing exposure and transmission at our cancer center. METHODS: A cluster of cases was defined as 2 or more cases of severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-positive COVID-19 among HCWs who work in the same unit area at the same time. Cases were identified by real-time reverse transcription polymerase chain reaction testing. Contact tracing, facility observations, and infection prevention assessments were performed to investigate the 3 clusters between March 1 and April 30, 2020, with subsequent implementation of containment strategies. RESULTS: The initial cluster involved HCWs from an ancillary services unit, with contacts traced back to a gathering in a break room in which 1 employee was symptomatic, although not yet diagnosed with COVID-19, with subsequent transmission to 7 employees. The second cluster involved 4 employees and was community related. The third cluster involved only 2 employees with possible transmission while working in the same office at the same time. A step-up approach was implemented to control the spread of infection among employees, including universal masking, enhanced cleaning, increase awareness, and surveillance testing. No nosocomial transmission to patients transpired. CONCLUSIONS: To our knowledge, this is the first report of a hospital-based cluster of COVID-19 infections among HCWs in a cancer hospital describing our steps to mitigate further transmission.

Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in Transplant Recipients: A Phase 2, Randomized Clinical Trial.

Background: Triplex vaccine was developed to enhance cytomegalovirus (CMV)-specific T cells and prevent CMV reactivation early after hematopoietic stem cell transplant (HCT). Objective: To determine the safety and efficacy of Triplex. Design: First-in-patient, phase 2 trial. (ClinicalTrials.gov: NCT02506933). Setting: 3 U.S. HCT centers. Participants: 102 CMV-seropositive HCT recipients at high risk for CMV reactivation. Intervention: Intramuscular injections of Triplex or placebo were given on days 28 and 56 after HCT. Triplex is a recombinant attenuated poxvirus (modified vaccinia Ankara) expressing immunodominant CMV antigens. Measurements: The primary outcomes were CMV events (CMV DNA level ≥1250 IU/mL, CMV viremia requiring antiviral treatment, or end-organ disease), nonrelapse mortality, and severe (grade 3 or 4) graft-versus-host disease (GVHD), all evaluated through 100 days after HCT, and grade 3 or 4 adverse events (AEs) within 2 weeks after vaccination that were probably or definitely attributable to injection. Results: A total of 102 patients (51 per group) received the first vaccination, and 91 (89.2%) received both vaccinations (46 Triplex and 45 placebo). Reactivation of CMV occurred in 5 Triplex (9.8%) and 10 placebo (19.6%) recipients (hazard ratio, 0.46 [95% CI, 0.16 to 1.4]; P = 0.075). No Triplex recipient died of nonrelapse causes during the first 100 days or had serious AEs, and no grade 3 or 4 AEs related to vaccination were observed within 2 weeks after vaccination. Incidence of severe acute GVHD after injection was similar between groups (hazard ratio, 1.1 [CI, 0.53 to 2.4]; P = 0.23). Levels of long-lasting, pp65-specific T cells with effector memory phenotype were significantly higher in Triplex than placebo recipients. Limitation: The lower-than-expected incidence of CMV events in the placebo group reduced the power of the trial. Conclusion: No vaccine-associated safety concerns were identified. Triplex elicited and amplified CMV-specific immune responses, and fewer Triplex-vaccinated patients had CMV viremia. Primary Funding Source: National Cancer Institute and Helocyte.

Active Mycobacterium tuberculosis infection at a comprehensive cancer center, 2006-2014.

BACKGROUND: Morbidity and mortality from Mycobacterium tuberculosis (Mtb) infection remain significant in cancer patients. We evaluated clinical characteristics, management, and outcomes in patients with active Mtb infection at our institution who had cancer or suspicion of cancer. METHODS: We retrospectively examined medical records of all patients with laboratory-confirmed active Mtb infection diagnosed between 2006 and 2014. RESULTS: A total of 52 patients with laboratory-confirmed active Mtb infection were identified during the study period, resulting in an average rate of 6 new cases per year. Thirty-two (62%) patients had underlying cancer, while 20 (38%) patients did not have cancer but were referred to the institution because of suspicion of underlying malignancy. Among patients with cancer, 18 (56%) had solid tumors; 8 (25%) had active hematologic malignancies; and 6 (19%) had undergone hematopoietic-cell transplantation (HCT). Patients with and without cancer were overall similar with the exception of median age (61 years in cancer patients compared to 53 years in noncancer patients). Pulmonary disease was identified in 32 (62%) patients, extrapulmonary disease in 10 (19%) patients, and disseminated disease in 10 (19%) patients. Chemotherapy was delayed in 53% of patients who were to receive such treatment. Eleven patients (all of whom had cancer) died; 3 of these deaths were attributable to Mtb infection. CONCLUSIONS: Although not common, tuberculosis remains an important infection in patients with cancer. Approximately one-third of patients were referred to our institution for suspicion of cancer but were ultimately diagnosed with active Mtb infection rather than malignancy.

Update on infection control practices in cancer hospitals.

Therapies in oncology have evolved rapidly over the last years. At the same pace, supportive care for patients receiving cancer therapy has also evolved, allowing patients to safely receive the newest advances in treatment in both an inpatient and outpatient basis. The recognition of the role of infection control and prevention (ICP) in the outcomes of patients living with cancer has been such that it is now a requirement for hospitals and involves multidisciplinary groups. Some unique aspects of ICP for patients with cancer that have gained momentum over the past few decades include catheter-related infections, multidrug-resistant organisms, community-acquired viral infections, and the impact of the health care environment on the horizontal transmission of organisms. Furthermore, as the potential for infections to cross international borders has increased, alertness for outbreaks or new infections that occur outside the area have become constant. As the future approaches, ICP in immunocompromised hosts will continue to integrate emerging disciplines, such as antibiotic stewardship and the microbiome, and new techniques for environmental cleaning and for controlling the spread of infections, such as whole-genome sequencing. CA Cancer J Clin 2018;000:000-000. © 2018 American Cancer Society.

Delay of alternative antiviral therapy and poor outcomes of acyclovir-resistant herpes simplex virus infections in recipients of allogeneic stem cell transplant - a retrospective study.

Acyclovir is commonly used to prevent and treat herpes simplex virus (HSV) reactivation after hematopoietic cell transplant (HCT), and only few reports have been published on acyclovir-resistant HSV in HCT recipients. We reviewed the medical records of patients with a microbiologic diagnosis of acyclovir-resistant HSV by plaque reduction test who received an HCT from 2002 through 2014. A total of 4 028 HCTs were performed during the study period, and 18 of the recipients met the diagnostic criteria for acyclovir-resistant HSV. All cases had undergone allogeneic HCTs. Most patients were in the pre-engraftment period or on systemic corticosteroid therapy for graft-versus-host disease (GVHD). The median time between diagnosis and susceptibility testing was 15 days, and antiviral therapy was changed at a median of 27 days. Patients required prolonged therapy (~80 days), and many had serious complications including renal failure and hospitalization. In conclusion, acyclovir-resistant HSV infection is more likely during the period of profound deficit in T-cell-mediated immunity and is associated with significant morbidities. Higher doses of acyclovir prophylaxis might be needed for patients with history of HSV during pre-engraftment or GVHD treatment. In patients who do not respond or progress after 1 week of acyclovir therapy, testing for drug-resistant HSV, and early switch to an alternative antiviral should be considered.

Low Rate of Cervical Cancer Screening among Women with Hematologic Malignancies after Stem Cell Transplant.

Annual cervical cancer screening with Papanicolaou (Pap) and human papillomavirus (HPV) testing after stem cell transplant (SCT) is recommended, but the uptake is unknown. We aimed to determine the prevalence and predictors of cervical cancer screening in patients with hematologic malignancies. We searched MarketScan Commercial Claims database for women who underwent allogeneic or autologous SCT. The primary outcome was cervical cancer screening, defined as procedures or abnormal results for HPV and/or Pap testing according administrative codes within 2 years after SCT. A multivariable logistic regression model was fitted with cancer type, SCT year, age, geographic area, insurance plan, comorbidity, and presence of graft-versus-host disease (GVHD).The study included 1484 patients; 1048 patients (70.6%) had autologous and 436 (29.4%) allogeneic SCT. Mean age was 52.5 years. Overall, 660 patients (44.5%) had screening within 2 years after SCT, 214 (49.1%) with allogeneic SCT and 446 (42.6%) with autologous SCT (P = .02). In the allogeneic SCT group, patients with GVHD had a lower rate of screening than patients without GVHD (42.5% versus 55.4%, P < .01), and GVHD was associated with lower odds of screening (odds ratio, .50; 95% confidence interval, .32 to .79). In the autologous SCT group, patients with comorbid medical conditions had a lower rate of screening than patients without comorbidity (36.0% versus 45.7%, P < .01). In both allogeneic and autologous SCT groups older patients had lower odds of screening. Cervical cancer screening rates after SCT are low, particularly in patients with GVHD, who are at significant risk of second malignancies. Future work is needed to develop strategies to increase uptake.

False-positive HIV nucleic acid amplification testing during CAR T-cell therapy.

Advancements in immunotherapy have opened a new era in oncology, to include genetic modification of human T-cells to express a chimeric antigen receptor (CAR) that enables targeted tumor recognition (Kochenderfer et al., 2015; Lee et al., 2015; Maus and Levine 2016; Rosenberg et al., 2008). Herein, we report a false-positive HIV testing in a patient who had undergone CAR T-cell therapy created with a lentiviral vector.

Rhodococcus Infection in Solid Organ and Hematopoietic Stem Cell Transplant Recipients1.

We conducted a case-control study of 18 US transplant recipients with Rhodococcus infection and 36 matched controls. The predominant types of infection were pneumonia and bacteremia. Diabetes mellitus and recent opportunistic infection were independently associated with disease. Outcomes were generally favorable except for 1 relapse and 1 death.

Burden of human metapneumovirus infections in patients with cancer: Risk factors and outcomes.

BACKGROUND: Human metapneumovirus (hMPV) causes upper and lower respiratory tract infections (URIs and LRIs, respectively) in healthy and immunocompromised patients; however, its clinical burden in patients with cancer remains unknown. METHODS: In a retrospective study of all laboratory-confirmed hMPV infections treated at the authors' institution between April 2012 and May 2015, clinical characteristics, risk factors for progression to an LRI, treatment, and outcomes in patients with cancer were determined. RESULTS: In total, 181 hMPV infections were identified in 90 patients (50%) with hematologic malignancies (HMs), in 57 (31%) hematopoietic cell transplantation (HCT) recipients, and in 34 patients (19%) with solid tumors. Most patients (92%) had a community-acquired infection and presented with URIs (67%), and 43% developed LRIs (59 presented with LRIs and 19 progressed from a URI to an LRI). On multivariable analysis, an underlying HM (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.12-8.64; P = .029), nosocomial infection (aOR, 26.9; 95% CI, 2.79-259.75; P = .004), and hypoxia (oxygen saturation [SpO2], ≤ 92%) at presentation (aOR, 9.61; 95% CI, 1.98-46.57; P = .005) were identified as independent factors associated with LRI. All-cause mortality at 30 days from hMPV diagnosis was low (4%), and patients with LRIs had a 10% mortality rate at day 30 from diagnosis; whereas patients with URIs had a 0% mortality rate. CONCLUSIONS: hMPV infections in patients with cancer may cause significant morbidity, especially for those with underlying HM who may develop an LRI. Despite high morbidity and the lack of directed antiviral therapy for hMPV infections, mortality at day 30 from this infection remained low in this studied population. Cancer 2017;123:2329-2337. © 2017 American Cancer Society.

Antiviral therapy for respiratory viral infections in immunocompromised patients.

INTRODUCTION: Respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, coronavirus, human metapneumovirus, and rhinovirus) represent the most common causes of respiratory viral infections in immunocompromised patients. Also, these infections may be more severe in immunocompromised patients than in the general population. Early diagnosis and treatment of viral infections continue to be of paramount importance in immunocompromised patients; because once viral replication and invasive infections are evident, prognosis can be grave. Areas covered: The purpose of this review is to provide an overview of the main antiviral agents used for the treatment of respiratory viral infections in immunocompromised patients and review of the new agents in the pipeline. Expert commentary: Over the past decade, important diagnostic advances, specifically, the use of rapid molecular testing has helped close the gap between clinical scenarios and pathogen identification and enhanced early diagnosis of viral infections and understanding of the role of prolonged shedding and viral loads. Advancements in novel antiviral therapeutics with high resistance thresholds and effective immunization for preventable infections in immunocompromised patients are needed.

Brincidofovir (CMX-001) for refractory and resistant CMV and HSV infections in immunocompromised cancer patients: A single-center experience.

BACKGROUND: The emergence of resistance to available antiviral drugs may cause higher Cytomegalovirus (CMV)-associated morbidity and mortality in hematopoietic cell transplant (HCT) recipients. Few novel antiviral drugs are being developed with potential effect against refractory or resistant CMV infections. Brincidofovir, an oral nucleotide analog and prodrug of cidofovir, has shown in vitro activity against CMV. METHODS: We reviewed data of 4 cancer patients with resistant CMV or herpes simplex virus (HSV) infections and were treated with brincidofovir under emergency IND application. RESULTS: Three out of the 4 patients with resistant CMV or HSV infections responded to brincidofovir. Brincidofovir achieved virological response in 2 patients with confirmed UL97 mutation (ganciclovir-resistant CMV infection), but failed to control CMV when a specific UL54 mutation was present (conferring resistance to foscarnet and cidofovir), as seen with patient 3. Furthermore, brincidofovir was effective for treatment of acyclovir resistant HSV infection, as described in patient 4 which is in alignment with the high in vitro potency of brincidofovir (about 100-fold more than acyclovir) for inhibition of HSV replication. Only one patient had brincidofovir-related diarrhea without any evidence of concurrent gastrointestinal GVHD. CONCLUSION: Without the nephrotoxicity of cidofovir, brincidofovir could be an effective alternative for CMV-resistant and HSV-resistant infections. Combination therapy of brincidofovir with other antiviral agent, at a conventional or a lower dose, could be considered to potentiate efficacy and minimize side effects of the approved antiviral agents.

Association Between Hepatitis C Virus and Head and Neck Cancers.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with hepatocellular carcinoma and non-Hodgkin's lymphoma. In 2009, MD Anderson established the first US clinic for treating HCV-infected cancer patients, where we observed an unexpectedly large number of patients with head and neck cancers (HNCs). We sought to determine whether HCV is associated with HNCs. METHODS: In this case-control study, medical records of cancer patients tested for HCV antibodies at our center from 2004 through 2014 were identified. Case subjects had new-onset primary oropharyngeal or nonoropharyngeal (oral cavity, nasopharynx, hypopharynx, or larynx) HNCs. Control subjects had smoking-associated (lung, esophagus, or urinary bladder) cancers. Biopsy reports of oropharyngeal cancers tested for human papillomavirus (HPV) were reviewed. Patients with lymphoma were excluded. Multivariable logistic regression models were constructed. All statistical tests were two-sided. RESULTS: Of 34 545 cancer patients tested for HCV antibodies, 409 case subjects (164 oropharyngeal and 245 nonoropharyngeal) and 694 control subjects (378 lung, 168 esophagus, and 148 urinary bladder) were studied. The prevalence of HCV seropositivity was higher in oropharyngeal cancer patients (14.0%, 95% confidence interval [CI] = 8.7% to 19.4%, vs 6.5%, 95% CI = 4.6% to 8.3%), particularly HPV-positive oropharyngeal cancer patients (16.9%, 95% CI = 8.7% to 24.9%, vs 6.5%, 95% CI = 4.6% to 8.3%), and nonoropharyngeal HNC patients (20.0%, 95% CI = 14.9% to 25.0%, vs 6.5%, 95% CI = 4.6% to 8.3%) than in control subjects. Adjusted models showed a statistically significant association of HCV seropositivity with nonoropharyngeal (except nasopharyngeal) HNCs (odds ratio [OR] = 2.85, 95% CI = 1.38 to 5.88) and HPV-positive oropharyngeal cancers (OR = 2.97, 95% CI = 1.31 to 6.76). CONCLUSIONS: HCV is associated with nonoropharyngeal (except nasopharyngeal) and HPV-positive oropharyngeal HNCs. Further studies are required to explore the possible interaction between HCV and HPV, and the association between HCV and other HPV-related malignancies.

Utility of the Enzyme-Linked Immunospot Interferon-γ-Release Assay to Predict the Risk of Cytomegalovirus Infection in Hematopoietic Cell Transplant Recipients.

The ability to distinguish allogeneic hematopoietic cell transplant (allo-HCT) recipients at risk for cytomegalovirus (CMV) reactivation from those who are not is central for optimal CMV management strategies. Interferon γ (IFN-γ) produced by CMV-challenged T cells may serve as an immune marker differentiating these 2 populations. We prospectively monitored 63 CMV-seropositive allo-HCT recipients with a CMV-specific enzyme-linked immunospot (ELISPOT) assay and for CMV infection from the period before transplantation to day 100 after transplantation. Assay results above certain thresholds (50 spots per 250 000 cells for immediate early 1 or 100 spots per 250 000 cells for phosphoprotein 65) identified patients who were protected against CMV infection as long as they had no graft-versus-host disease and/or were not receiving systemic corticosteroids. Based on the multivariable Cox proportional hazards regression model, the only significant factor for preventing CMV reactivation was a CMV-specific ELISPOT response above the determined thresholds (adjusted hazard ratio, 0.21; 95% confidence interval, .05-.97; P = .046). Use of this assay as an additional tool for managing allo-HCT recipients at risk for CMV reactivation needs further validation in future studies. Application of this new approach may reduce the duration and intensity of CMV monitoring and the duration of prophylaxis or treatment with antiviral agents in those who have achieved CMV-specific immune reconstitution.

Outcomes of Influenza Infections in Hematopoietic Cell Transplant Recipients: Application of an Immunodeficiency Scoring Index.

Hematopoietic cell transplant (HCT) recipients have lower immune response to influenza vaccination and are susceptible to lower respiratory tract infection (LRI) and death. We determined clinical characteristics and outcomes of laboratory-confirmed influenza, including 2014/H3N2 infection, in 146 HCT recipients. An immunodeficiency scoring index (ISI) was applied to identify patients at high risk for LRI and death. Thirty-three patients (23%) developed LRI and 7 (5%) died within 30 days of diagnosis. Most patients received antiviral therapy (83%); however, only 18% received it within 48 hours of symptom onset. The incidence of LRI was significantly higher in the ISI high-risk group than it was in the low-risk group (P < .001). Receiving early antiviral therapy was associated with a substantial reduction in LRI for all ISI risk groups with the greatest risk reduction observed in the high-risk group. When compared with previous seasons, no significant differences in patient outcomes were observed during the 2014/H3N2 season; however, antiviral therapy was more promptly initiated in the latter season. The ISI that was originally developed for respiratory syncytial virus may help identify HCT recipients at risk for progression to LRI and mortality after influenza infection. These patients should be monitored more closely. Early initiation of antiviral therapy for influenza in HCT recipients, regardless of the ISI risk group, may improve morbidity as well as mortality.

Influenza vaccination in patients with cancer: factors associated with vaccination practices for patients and their household members.

Presented in part: IDWeek 2014; Philadelphia, PA; October 8-12, 2014 (Poster 1120).