Lynne Strasfeld
Oregon Health & Science University
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Featured researches published by Lynne Strasfeld.
Lancet Infectious Diseases | 2011
Francisco M. Marty; Per Ljungman; Genovefa A. Papanicolaou; Drew J. Winston; Roy F. Chemaly; Lynne Strasfeld; Jo Anne H. Young; Tulio E. Rodriguez; Johan Maertens; Michael Schmitt; Hermann Einsele; Augustin Ferrant; Jeffrey H. Lipton; Stephen A. Villano; Hongzi Chen; Michael Boeckh
BACKGROUND Available drugs against cytomegalovirus have adverse effects that compromise their prophylactic use in recipients of allogeneic stem-cell transplants. We assessed the safety, tolerability, and antiviral activity of oral maribavir in such patients. METHODS In this placebo-controlled, randomised, double-blind, multicentre phase 3 study, we enrolled adult patients recipient-seropositive or donor-seropositive for cytomegalovirus who had undergone allogeneic stem-cell transplantation. Patients were recruited from 90 centres in Canada, Europe, and the USA. After engraftment, patients were stratified by recipient cytomegalovirus serostatus and conditioning regimen (myeloablative or reduced-intensity) and assigned (2:1) by masked computer-generated randomisation sequence to receive maribavir 100 mg twice daily or placebo for up to 12 weeks, with weekly blood cytomegalovirus surveillance. If the virus was detected, administration of study drug was stopped and pre-emptive anticytomegalovirus treatment started. The primary endpoint was cytomegalovirus disease within 6 months of transplantation. Analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov, NCT00411645. FINDINGS Between December, 2006, and May, 2008, 681 patients were enrolled and assigned to receive maribavir (454) or placebo (227). The incidence of cytomegalovirus disease within 6 months was 20 of 454 (4%) for the maribavir group and 11 of 227 (5%) for the placebo group (OR 0.90; 95% CI 0.42-1.92). During the 100 days following transplantation, cytomegalovirus infection rates as measured by pp65 antigenaemia were lower in the maribavir group (26.4%) than in the placebo group (34.8%; OR 0.67; 0.47-0.95), but not when measured by plasma cytomegalovirus DNA PCR (27.8%vs 30.4%; OR 0·88; 0.62-1.25), nor by initiation of treatment against cytomegalovirus (30.6%vs 37.4%; OR 0.73, 0.52-1.03). Maribavir was well tolerated: most adverse events, including incident acute graft-versus-host disease and neutropenia, affected both groups equally, except for taste disturbance (15% maribavir, 6% placebo). INTERPRETATION Compared with placebo, maribavir prophylaxis did not prevent cytomegalovirus disease when started after engraftment. Cytomegalovirus disease as a primary endpoint might not be sufficient to show improvements in cytomegalovirus prevention in recipients of allogeneic stem-cell transplants in the setting of pre-emptive antiviral treatment. Clinical and virological composite endpoints should be used in future trials. FUNDING ViroPharma Incorporated.
Transplant Infectious Disease | 2010
Robin K. Avery; Francisco M. Marty; Lynne Strasfeld; I. Lee; A. Arrieta; S. Chou; W. Tatarowicz; Stephen A. Villano
R.K. Avery, F.M. Marty, L. Strasfeld, I. Lee, A. Arrieta, S. Chou, W. Tatarowicz, S. Villano. Oral maribavir for treatment of refractory or resistant cytomegalovirus infections in transplant recipients. Transpl Infect Dis 2010: 12: 489–496. All rights reserved
Infectious Disease Clinics of North America | 2010
Lynne Strasfeld; Sunwen Chou
Antiviral drug resistance is an increasing concern in immunocompromised patient populations, where ongoing viral replication and prolonged drug exposure lead to the selection of resistant strains. Rapid diagnosis of resistance can be made by associating characteristic viral mutations with resistance to various drugs as determined by phenotypic assays. Management of drug resistance includes optimization of host factors and drug delivery, selection of alternative therapies based on knowledge of mechanisms of resistance, and the development of new antivirals. This article discusses drug resistance in herpesviruses and hepatitis B.
The Journal of Infectious Diseases | 2010
Lynne Strasfeld; Ingi Lee; Walter Tatarowicz; Stephen Villano; Sunwen Chou
The experimental cytomegalovirus UL97 kinase inhibitor maribavir was used to treat 2 cases of infection in which viral mutations that conferred ganciclovir and foscarnet resistance had evolved sequentially. In one case, viral shedding was cleared without evidence of maribavir resistance in an isolate obtained after therapy. In the other case, a high-grade viremia was initially reduced 50-fold but rebounded 2 months later, coincident with the emergence of viral UL97 mutations T409M and H411Y, which confer maribavir resistance. The relatively rapid onset of maribavir resistance probably resulted from incomplete viral suppression in an immunosuppressed host with a high viral load.
Biology of Blood and Marrow Transplantation | 2011
Luis Espinosa-Aguilar; Jaime S. Green; Graeme N. Forrest; Edward D. Ball; Richard T. Maziarz; Lynne Strasfeld; Randy Taplitz
Respiratory virus infections, such as influenza A, cause significant morbidity in hematopoietic stem cell transplantation (HSCT) recipients. The clinical characteristics and impact of infection with the novel H1N1 virus in this patient population is not yet well defined, however. HSCT recipients diagnosed with proven or probable H1N1 during the 2009 pandemic were identified and charts were retrospectively reviewed with analysis of clinical descriptions, risk factors, diagnosis, treatments, and outcomes. Twenty-seven patients from two medical centers were identified. Fever and cough were the most common presenting symptoms. The incidence of influenza lower respiratory tract infection (LRTI) was 52% (14/27). Compared with patients with LRTI, those with influenza upper respiratory tract infection (URTI) were more likely to have a classic influenza-like syndrome. Compared to patients with URTI, those with LRTI were started on antiviral therapy significantly later after symptom onset (3.0 days vs 6.58 days after onset of symptoms; P = .03; 95% confidence interval [CI], 0.29-6.8). Overall influenza-related 30-day mortality was 22% (6/27), and that in patients with LRTI was 43% (6/14). Chronic steroid use (≥20 mg/day of prednisone equivalent) at the time of presentation was associated with LRTI (P = .006) and mortality (P = .003) on univariate analysis. Five cases were hospital-acquired. In this first season of the novel H1N1 pandemic, infection in HSCT often presented as an atypical severe illness with a high incidence of LRTI and high mortality.
Antimicrobial Agents and Chemotherapy | 2014
Sunwen Chou; Ronald J. Ercolani; Malaya K. Sahoo; Martina I. Lefterova; Lynne Strasfeld; Benjamin A. Pinsky
ABSTRACT 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.
Transplant Infectious Disease | 2011
J.S. Doggett; Lynne Strasfeld
J.S. Doggett, L. Strasfeld. Disseminated Mycobacterium genavense with pulmonary nodules in a kidney transplant recipient: case report and review of the literature. Transpl Infect Dis 2011: 13: 38–43. All rights reserved
Bone Marrow Transplantation | 2017
Richard T. Maziarz; Ruta Brazauskas; Min Chen; A. A. McLeod; Rodrigo Martino; John R. Wingard; Mahmoud Aljurf; Minoo Battiwalla; Christopher C. Dvorak; B. Geroge; Eva C. Guinan; Gregory A. Hale; Hillard M. Lazarus; Jeongjin Lee; Jane L. Liesveld; Muthalagu Ramanathan; Vijay Reddy; Bipin N. Savani; Franklin O. Smith; Lynne Strasfeld; R. A. Taplitz; Celalettin Ustun; Michael Boeckh; Juan Gea-Banacloche; Caroline A. Lindemans; Jeffery J. Auletta; Marcie L. Riches
Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT). However, little is known about the impact of prior IFI on survival. Patients with pre-transplant IFI (cases; n=825) were compared with controls (n=10247). A subset analysis assessed outcomes in leukemia patients pre- and post 2001. Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of AML and having received cord blood, reduced intensity conditioning, mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior PFS and overall survival (OS) for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, P<0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13% vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared with later cases. Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates. Documented pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT. However, mortality post transplant is more influenced by advanced disease status than previous IFI. Pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT.
Journal of Clinical Microbiology | 2014
Morgan Hakki; Lynne Strasfeld; John M. Townes
ABSTRACT 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.
Clinical Lymphoma, Myeloma & Leukemia | 2013
Lynne Strasfeld; Luis Espinosa-Aguilar; James Gajewski; Peter Stenzel; Agustin Pimentel; Elana Mater; Richard T. Maziarz
Clinical Practice Points Cunninghamella, a relatively infrequent cause of mucormycosis, is associated with aggressive and often fatal disseminated invasive fungal infection in hematopoietic stem cell transplant (HSCT) recipients, in particular those receiving high-dose immune suppression. Polyene-based antifungal agents, such as amphotericin B and its lipid derivatives, are first-line therapy for invasive mucormycosis. Despite currently available treatment approaches, the attributable mortality of mucormycosis remains very high. Our single-center experience suggests that infection with Cunninghamella species portends worse outcomes. The impact of prophylactic approaches (eg, with extended-spectrum azoles such as posaconazole) in preventing this infection in high-risk patients awaits further investigation.