Jacques Azzi

Parainfluenza virus infections in hematopoietic cell transplant recipients and hematologic malignancy patients: A systematic review

Parainfluenza viral infections are increasingly recognized as common causes of morbidity and mortality in cancer patients, particularly in hematopoietic cell transplant (HCT) recipients and hematologic malignancy (HM) patients because of their immunocompromised status and susceptibility to lower respiratory tract infections. Advances in diagnostic methods, including polymerase chain reaction, have led to increased identification and awareness of these infections. Lack of consensus on clinically significant endpoints and the small number of patients affected in each cancer institution every year make it difficult to assess the efficacy of new or available antiviral drugs. In this systematic review, we summarized data from all published studies on parainfluenza virus infections in HM patients and HCT recipients, focusing on incidence, risk factors, long-term outcomes, mortality, prevention, and management with available or new investigational agents. Vaccines against these viruses are lacking; thus, infection control measures remain the mainstay for preventing nosocomial spread. A multi-institutional collaborative effort is recommended to standardize and validate clinical endpoints for PIV infections, which will be essential for determining efficacy of future vaccine and antiviral therapies.

Infection With Novel Respiratory Syncytial Virus Genotype Ontario (ON1) in Adult Hematopoietic Cell Transplant Recipients, Texas, 2011–2013

BACKGROUND Respiratory syncytial virus (RSV) can cause severe respiratory disease in adult hematopoietic cell transplant (HCT) recipients. RSV subgroups A and B have evolved into multiple genotypes. We report on a recently described RSV genotype (ON1) in a cohort of adult HCT recipients in Texas. METHODS Twenty adult HCT recipients were enrolled as a part of an efficacy trial of ribavirin therapy. RSV identification and genotyping was performed using molecular techniques. RSV-specific neutralizing antibody (NAb) responses were measured. RESULTS ON1 genotype was detected in 3 of 6 patients in the 2011-2012 season and in 8 of 14 patients in 2012-2013 season. Other genotypes detected were NA1 and BA. NAb levels were low at enrollment. Eight of 9 patients who cleared the RSV infection within 2 weeks mounted a ≥4-fold NAb response, compared with 2 of 8 who shed the virus for >2 weeks. The clinical course of those infected with ON1 was comparable to the course for individuals infected with other genotypes. CONCLUSION This is the first report of RSV ON1 genotype in the United States, and ON1 genotype was dominant genotype in adult HCT recipients. Interestingly, faster viral clearance was associated with a ≥4-fold NAb response, likely indicating a reconstituted immune system.

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.

Human metapneumovirus infections in hematopoietic cell transplant recipients and hematologic malignancy patients: A systematic review.

Over the past decade, reported incidence of human metapneumovirus (hMPV) has increased owing to the use of molecular assays for diagnosis of respiratory viral infections in cancer patients. The seasonality of these infections, differences in sampling strategies across institutions, and small sample size of published studies make it difficult to appreciate the true incidence and impact of hMPV infections. In this systematic review, we summarized the published data on hMPV infections in hematopoietic cell transplant recipients and patients with hematologic malignancy, focusing on incidence, hMPV-associated lower respiratory tract infection (LRTI), mortality, prevention, and management with ribavirin and/or intravenous immunoglobulins. Although the incidence of hMPV infections and hMPV-associated LRTI in this patient population is similar to respiratory syncytial virus or parainfluenza virus and despite lack of directed antiviral therapy, the mortality rate remains low unless patients develop LRTI. In the absence of vaccine to prevent hMPV, infection control measures are recommended to reduce its burden in cancer patients.

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).

Risk factors for mortality after respiratory syncytial virus lower respiratory tract infection in adults with hematologic malignancies

Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with high mortality in patients with hematologic malignancies (HM). We sought to determine whether allogeneic hematopoietic cell transplant (allo‐HCT) recipients would be at higher risk for 60‐day mortality.

Leukopenia and lack of ribavirin predict poor outcomes in patients with haematological malignancies and respiratory syncytial virus infection

Objectives Respiratory syncytial virus (RSV) infection causes morbidity and mortality in cancer patients. However, studies describing this infection in patients with haematological malignancies are scarce. We sought to evaluate the clinical impact of RSV infection on this patient population. Methods We reviewed the records of patients with haematological malignancies and RSV infections cared for at our institution between January 2000 and March 2013. Results Of the 181 patients, 71 (39%) had AML, ALL or myelodysplastic syndrome, 12 (7%) had CML or CLL, 4 (2%) had Hodgkin lymphoma, 35 (19%) had non-Hodgkin lymphoma and 59 (33%) had multiple myeloma. Most patients [117 (65%)] presented with an upper respiratory tract infection (URTI) and 15 (13%) had a subsequent lower respiratory tract infection (LRTI). The overall LRTI rate was 44% and the 90 day mortality rate was 15%. Multivariable regression analysis showed that having both neutropenia and lymphocytopenia (adjusted OR = 7.17, 95% CI = 1.94-26.53, P < 0.01) and not receiving ribavirin-based therapy during RSV URTI (adjusted OR = 0.03; 95% CI = 0.01-0.11, P < 0.001) were independent risk factors for LRTI. Having both neutropenia and lymphocytopenia at RSV diagnosis was also a risk factor for death at 90 days after RSV diagnosis (adjusted OR = 4.32, 95% CI = 1.24-15.0, P = 0.021). Conclusions Patients with haematological malignancies and RSV infections, especially those with immunodeficiency, may be at risk of LRTI and death; treatment with ribavirin during RSV URTI may prevent these outcomes.

Mixed Mycobacterium Avium-Intracellulare and Serratia Marcescens Cellulitis of the Breast in an HIV-Negative Patient with Breast Cancer: A Case Report

Mycobacterium avium-intracellulare (MAI) causes pulmonary infection in patients with chronic lung diseases or severe T-cell deficiency. Cutaneous manifestations caused by MAI are rare and the few cases reported describe mostly patients with hematologic malignancies who were treated with highly immunosuppressive agents. Herein, we report a case of a breast cancer survivor who developed chronic breast cellulitis due to MAI, following localized breast cancer treatment.

1120The Impact of Influenza Vaccination in Patients with Cancer on Subsequent Disease during the 2013-2014 Influenza Season

Background. Patients with cancer may experience higher morbidity and mortality from influenza infection. Influenza vaccination is universally used for prevention; however, effectiveness in patients with cancer may be suboptimal but its impact on severity of illness is yet to be determined. Methods. A phone survey for cancer patients with laboratory confirmed influenza (LCI) was carried out during the influenza season 2013-2014 to determine impact on clinical outcomes including hospitalization, intensive care unit stay and death. Results. A total of 105 out 139 adults with LCI participated in the phone survey at a rate of 77%. A total of 47 (45%) were vaccinated and 58 (55%) were not and their baseline characteristics were similar. Median age was 57 years old (21 88) while 61% were male and 59% were Caucasians. Most common underlying conditions were hematopoietic cell transplant (51%), solid tumors (19%) and leukemia (14%). On multivariable analysis, patients who progressed to pneumonia were more likely to be neutropenic, were older, had delay in diagnosis from symptoms onset, and did not receive oseltamivir at upper respiratory tract infection stage (all p < 0.05). Vaccination status had no significant impact on progression to pneumonia or mortality. Conclusion. In our cohort, almost half of the patients who had influenza were vaccinated. Interestingly, influenza vaccination during the current season did not have an impact on the severity of illness including incidence of pneumonia, hospitalization or mortality rates in our cancer patients. Although not determined in this study, vaccination may have protected our cancer patients from acquiring influenza. Disclosures. All authors: No reported disclosures.