scholarly journals Real-World Experience of Voriconazole Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients: A Single-Center Study

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S76-S77 ◽  
Author(s):  
Shuk-Ying Chan ◽  
Dionysios Neofytos ◽  
Rachel M Hughes ◽  
Yao-Ting Huang ◽  
Miguel-Angel Perales ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Ex Vivo ◽  
Normal Liver ◽  
Antifungal Prophylaxis ◽  
Standards Of Care ◽  
Cell Transplant ◽  
Research Support ◽  
Hematopoietic Cell Transplant ◽  
Significant Difference ◽  
Research Grant

Abstract Background High rates of discontinuation of voriconazole (VCZ) antifungal prophylaxis (AFP) due to toxicities have been reported from single centers in allogeneic hematopoietic (allo-HCT) recipients. We sought to describe (i) adherence to AFP guidelines and (ii) reasons for premature VCZ discontinuation (D/C). Methods Retrospective review of 215 adult allo-HCT recipients from September 1, 2014–December 31, 2015 at our center. Per standards of care (SOC), patients received micafungin from Day 2 post-allo-HCT, then switched to VCZ by D7 unless contraindicated, and remained on AFP until cessation of immunosuppression or D100 for high-risk patients. AFP modification, D/C and treatment emergent adverse events (TEAE) regardless of causality were captured through D100. Standard definitions were used for invasive fungal infections (IFI). Results Of 215 patients, 42 had contraindications to VCZ at baseline. Of 173 patients included in the analysis, 65 (37.6%) received ex vivo T-cell depleted (TCD) peripheral blood (PB), 15% cord and 47.4% conventional PB or marrow allografts. All TCD recipients received myeloablative conditioning (MA) and all cord recipients received reduced intensity conditioning (RIC). For conventional transplant, 65.9 and 26.8% of the patients received RIC and MA, respectively. One hundred and sixty-eight (97%) patients had normal liver function tests (LFT) at VCZ initiation. One hundred and twenty-nine (74.6%) patients started VCZ by D7 and 95% started by D15. Median duration of VCZ AFP was 68D (IQR 22–91). Abnormal LFTs was the most frequently encountered TEAE (42/58, 72%), followed by neurologic/visual TEAE (11/58, 19%) leading to VCZ D/C. Median time to VCZ D/C due to neurologic/visual TEAE (4D, IQR 4–9) was significantly shorter than abnormal LFTs (25D, IQR 16–42) (P < 0.05). Eight (5%) breakthrough proven/probable IFIs were observed by D180, without significant difference based on transplant types or AFP duration. Duration and reasons for VCZ D/C were shown in Table 1 by HCT type. Conclusion 75% of the patients started VCZ per SOC and 95% by D15. Most TEAE leading to VCZ D/C were abnormal LFTs in all HCT types, and most commonly in cord HCT. 3) Neurologic/visual TEAE were similar across types. Rates of IFI were 3–4% in CONV and TCD and 12% in UCB. Disclosures Y. T. Huang, Merck & Co.: Grant Investigator, Research grant. M. A. Perales, Merck: Consultant, Grant Investigator and Investigator, Consulting fee and Research grant. Astella: Consultant, Grant Investigator and Investigator, Consulting fee and Research grant. G. Papanicolaou, Astellas Pharma: Consultant and Grant Investigator, Consulting fee, Research grant and Research support. Merck &Co: DSC member and Investigator, Consulting fee, Research grant and Research support

scholarly journals 736. The Use of Bacteriophages to Inhibit Different Strains of Vancomycin-Resistant or Susceptible Enterococci

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S329-S330
Author(s):  
Lynn El Haddad ◽  
Cynthia P Harb ◽  
Mark Stibich ◽  
Roy F Chemaly ◽  
Roy F Chemaly
Keyword(s):  
Good Alternative ◽  
Rapid Onset ◽  
Advisory Board ◽  
Cell Transplant ◽  
Research Support ◽  
Hematopoietic Cell Transplant ◽  
Normal Microbiota ◽  
Vancomycin Resistant ◽  
Research Grant

Abstract Background Vancomycin-resistant Enterococci (VRE) is a well-known infectious complication among immunocompromised patients, especially hematopoietic cell transplant (HCT) recipients. VRE colonization of the gastrointestinal tract could be associated with VRE bacteremia and worse outcomes in HCT recipients. The use of systemic antibiotics to eradicate VRE colonization is highly discouraged because of the lack of efficacy, the rapid onset of antibiotic resistance, and the disruption of the normal microbiota. Bacteriophages (phages) may constitute a good alternative to antibiotics to eliminate specific pathogens without disrupting the patient’s normal microbiota. Methods Sewage samples were collected from the City of Houston for phages isolation. Samples were centrifuged, filtered and exposed to several targeted VRE host strains. After several amplification, the final filtrate was titrated and checked for the presence of VRE-specific phages. Isolated phages were observed under electron microscopy and were tested against multiple VRE strains isolated from different sources including patients’ stool samples, patients’ room environment, sewage samples, clinical isolates of daptomycin-resistant VRE strains or vancomycin-susceptible Enterococcus faecium (VSEF) and Enterococcus faecalis (VSEf) strains. Results Four VRE-specific phages were isolated from sewage samples (MDA1, MDA2, MDA3, and MDA4). All phages belong to the Caudovirales order. Phage MDA1 belongs to the Podoviridae family, phage MDA2 is a Siphoviridae, whereas MDA3 and MDA4 belong to the Myoviridae family (Figure 1A). All phages were lytic and were able to inhibit at least four VRE strains and only MDA1 had activity against VSEF and MDA4 against VSEf. The efficacy of these lytic phages complemented one another as the combination of these four phages inhibited all different VRE strains (Figure 1B). Conclusion Our results highlight the feasibility and the potential success of these phages in inhibiting VRE in vitro. These VRE-specific phage cocktails may be used in future studies to reduce VRE colonization and subsequent infections in HCT recipients. Disclosures Roy F. Chemaly, MD, MPH, FACP, FIDSA, Chimerix: Advisory Board, Research Grant; Clinigen: Advisory Board; Merck: Advisory Board, Consultant, Grant/Research Support, Research Grant, Speaker’s Bureau; Oxford immunotec: Consultant, Grant/Research Support; Shire: Research Grant, Speaker’s Bureau; Viracor: Grant/Research Support.

scholarly journals 1291. Safety of Isavuconazole Compared with Voriconazole as Primary Antifungal Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S660-S661
Author(s):  
Yael Bogler ◽  
Anat Stern ◽  
Yiqi Su ◽  
Yeon Joo Lee ◽  
Susan K Seo ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Panel Member ◽  
Antifungal Prophylaxis ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Review Panel ◽  
Material Support ◽  
End Of Treatment ◽  
All Cause Mortality ◽  
Research Grant

Abstract Background Voriconazole (VCZ) is used as mold active primary antifungal prophylaxis (AFP) after allogenic hematopoietic cell transplant (HCT) but is frequently discontinued due to adverse events (AE), variable pharmacokinetics and drug-drug interactions. Limited data exists on the safety of Isavuconazole (ICZ) as AFP in HCT patients (pts). The study objectives were to compare 1) rates of AFP premature discontinuation (d/c), 2) changes in transaminases values from start to end of treatment (EOT) and 3) rates of invasive fungal infections (IFI) and all-cause mortality by Day (D) +180 post HCT between VCZ and ICZ AFP. Methods This is a matched cohort analysis of 95 pts enrolled in a clinical trial of ICZ AFP from 7/1/2017-10/31/2018 (ICZ-cohort) and 210 pts who received VCZ AFP standard of care between 9/1/2014-12/31/2015 at MSKCC (VCZ-cohort). The cohorts were matched using propensity scores (Table 1). AFP was administered for 75-100 days per institutional guidelines. Premature d/c of AFP was defined as d/c for IFI or AE by D +100 post HCT or interruption of >14 days for any reason. The cumulative incidence function and log rank test were used to compare groups. Mean transaminase values were compared using paired T-tests. Table 1. Baseline characteristics Results The median (Interquartile range) duration of AFP was 94 (87-100) days and 76 (23-94) days in ICZ and VCZ cohorts respectively (p< 0.0001). Premature d/c occurred in 14/95 (14.7%) of ICZ and 92/210 (43.8%) of VCZ cohorts (p< 0.0001) (Figure 1). The most common cause for AFP d/c was hepatotoxicity: ICZ-cohort: 5/95 (5.26%) vs VCZ-cohort: 48/210 (22.8%). Transaminases at EOT and up to 14 days were increased in VCZ but not ICZ cohort (Figure 2). IFI occurred in 3.15% (3/95) in ICZ-cohort and 2.85% (6/210) in VCZ-cohort (p=0.88) (Figure 3). In ICZ-cohort IFI included 3 Candida bloodstream infections (BSI) occurring on ICZ AFP. In VCZ-cohort IFI included one Candida BSI after VCZ d/c, and 5 probable mold infections; 3/5 with serum galactomannan > 0.5 and 2 with beta-D-glucan > 80. IFI occurred on VCZ in 1 pt and after VCZ premature d/c in 5 pts. All-cause mortality was 6.31% (6/95) in ICZ-cohort and 2.85% (6/210) in VCZ-cohort (p=0.089). Figure 1. Cumulative incidence of premature discontinuation of AFP by D+100 Figure 2. Transaminases at baseline,end of treatment (EOT), EOT +7 days and EOT +14 days in ICZ- and VCZ cohorts Figure 3. Cumulative incidence of IFI by day +180 Conclusion There was less premature discontinuation and hepatotoxicity with ICZ AFP, but no increase in IFI or death compared to VCZ AFP in allogeneic HCT pts. Disclosures Yeon Joo Lee, MD, MPH, Ansun BioPharma (Scientific Research Study Investigator)Astellas Pharma (Scientific Research Study Investigator) Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Dionysios Neofytos, MD, Basilea (Advisor or Review Panel member)Gilead (Advisor or Review Panel member)MSD (Advisor or Review Panel member, Research Grant or Support)Pfizer (Advisor or Review Panel member, Research Grant or Support) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

scholarly journals Reasons for voriconazole prophylaxis discontinuation in allogeneic hematopoietic cell transplant recipients: A real-life paradigm

2020 ◽  
Vol 58 (8) ◽  
pp. 1029-1036 ◽  
Author(s):  
Shuk Ying Chan ◽  
Rachel M Hughes ◽  
Kimberly Woo ◽  
Miguel-Angel Perales ◽  
Dionysios Neofytos ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Real Life ◽  
Antifungal Prophylaxis ◽  
Hematopoietic Cell ◽  
P Value ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Cell Transplant ◽  
Early Discontinuation ◽  
Allogeneic Hematopoietic Cell Transplant

Abstract We sought to describe the clinical experience of voriconazole as primary antifungal prophylaxis (AFP) in allogeneic hematopoietic cell transplant recipients (allo-HCTr). This was a single-center retrospective study of adult allo-HCTr (1 January 2014 to 31 December 2016) who received ≥two doses of voriconazole-AFP. Voriconazole-AFP was started on day +7 post-HCT and continued at least through day +60 post-HCT, or longer as clinically indicated. We reviewed the rate, reasons, and risk factors of voriconazole-AFP discontinuation until day-100 post-HCT. A total of 327 patients were included. Voriconazole-AFP was continued for a median of 69 days (mean: 57.9; range 1, 100): for a median of 90 days (mean :84; range 2, 100) in 180/327 (55%) in the standard-of-care (SOC) group and 20 days (mean :25.6 ; range 1, 89; P-value < .001) in 147/327 (45%) patients in the early-discontinuation-group. Early-voriconazole-AFP discontinuation was due to adverse events, drug interactions, insurance coverage, and other reasons in 101/147 (68.7%), 27 (18.4%), 13 (8.8%), and 6 (4.1%) patients, respectively. Early-voriconazole-AFP discontinuation occurred in 73/327 (22.3%) patients due to hepatotoxicity. Important predictors for early-voriconazole-AFP discontinuation included: graft-versus-host disease grade ≥2 (odds ratio [OR]: 1.9, P-value: .02), alanine-aminotransferase ≥75 IU/ml on voriconazole-administration day-14 (OR: 5.6, P-value: .02) and total bilirubin ≥1.3 mg/dl on voriconazole-administration day-7 (OR: 3.0, P-value: .03). There were 13 proven/probable invasive fungal infections by day-180 post-HCT (8/147, 5.4%, and 5/180, 2.8% in the early-discontinuation and SOC-groups, respectively; log-rank:0.13). By day-180 post HCT, 23/147 (15.6%) and 14/180 (7.8%) patients in the early-discontinuation and SOC-groups had died, respectively (log-rank:0.03). Voriconazole-AFP was discontinued in up to 45% of allo-HCTr. Hepatotoxicity during the first 2 weeks post-HCT is a significant predictor of early-voriconazole-AFP discontinuation.

scholarly journals Antifungal Resistance and Predictors of Response in Patients with Hematologic Malignancy

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S85-S85
Author(s):  
Shiuan (Shannon) Wey ◽  
Jane Kriengkauykiat ◽  
Ayla Chan ◽  
Bernard Tegtmeier ◽  
James Ito ◽  
...  
Keyword(s):  
Treatment Response ◽  
Amphotericin B ◽  
Hematologic Malignancy ◽  
Antifungal Susceptibility ◽  
Hematologic Malignancies ◽  
Antifungal Prophylaxis ◽  
Cell Transplant ◽  
Research Support ◽  
Hematopoietic Cell Transplant ◽  
The Past

Abstract Background Invasive aspergillosis (IA) causes significant morbidity and mortality in patients with hematologic malignancies (HM). Azole resistance has emerged as a therapeutic challenge in managing IA. The aim of this study was to investigate Aspergillus susceptibility to antifungals over the past decade among HM patients, and correlate susceptibility to clinical outcomes. Methods All Aspergillusisolates banked from 2002 to 2014 isolated from HM patients with probable/proven IA were tested for antifungal susceptibility. Patients with hematopoietic cell transplant, duplicate and non-viable isolates were excluded. Data were collected on demographics and clinical factors that could affect the treatment response, antifungal susceptibility (MICs/MECs), and treatment response at 14, 30, and 90 days. Results Forty patients were identified. MICs for amphotericin B slightly increased over the past decade (R = 0.32, P = 0.09), but were stable for voriconazole (R = −0.08, P = 0.61). The MIC50 during the first 3 years (2002–2004) and last 3 years (2012–2014) for amphotericin B were 0.5 and 1 mg/l, and for voriconazole 0.5 and 1. Mean age 56 years, 48% male, 82% had active HM and 45% had received chemotherapy within 14 days of IA. 50% were neutropenic and 30% had circulating blasts. Forty percent were on antifungal prophylaxis. Seventy-five percent of isolates were A. fumigatus. Fourteen responded to treatment (TR) and 26 were non-responders (NTR), and they did not differ in baseline characteristics. However, neutropenia (14% TR vs. 58%, NTR, P < 0.017) and circulating blasts (0% TR vs. 35% NTR, P < 0.02) at 14 days differed. The MIC50 for voriconazole was 0.5 mg/l in both groups, and for amphotericin B was 0.25 in TR vs. 1 mg/l in NTR. Fourteen-day response correlated with 90-day response (R = 0.74, P < 0.01) which validated the use of 14-day response for clinical outcome. All responders on amphotericin B at 14, 30, and 90 days had isolates with MIC < 1, whereas no apparent MIC-response correlation was found for voriconazole. Conclusion Although not statistically significant, a trend of increasing Aspergillus amphotericin B MICs was observed over the past decade. Neutropenia and persistent disease correlated with treatment failure. Clinical response was not affected by the azole or polyene MICs. Disclosures J. Ito, Astellas: Speaker’s Bureau, Speaker honorarium. S. Dadwal, Merck: Investigator, Research support. GlaxoSmithKline: Investigator, Research support. Ansun Biopharma: Investigator, Research support. Oxford Immunotec: Investigator, Research support. Gilead Sciences: Investigator, Research support

Approaches to the Management of Invasive Fungal Infections in Hematologic Malignancy and Hematopoietic Cell Transplantation

2009 ◽  
Vol 27 (20) ◽  
pp. 3398-3409 ◽  
Author(s):  
Mauricette Michallet ◽  
James I. Ito
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Fungal Infections ◽  
Hematologic Malignancy ◽  
Treatment Strategies ◽  
Underlying Disease ◽  
Antifungal Prophylaxis ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Increased Risk

Patients with hematologic malignancy and hematopoietic cell transplant (HCT) recipients are at increased risk for invasive fungal infection (IFI) as a result of immunosuppression or organ damage stemming from their underlying disease, its treatment, or both. Such IFIs can cause significant morbidity and mortality, and the diagnosis and treatment of infected patients frequently are clinically challenging. This article discusses the epidemiology and risk factors for IFI in patients with hematologic malignancy and HCT recipients. The pros and cons of available antifungal agents are discussed, and evolving treatment strategies and recent prophylaxis guidelines from various professional organizations are reviewed. Finally, recommendations are offered for antifungal prophylaxis according to risk group.

scholarly journals 986. Evaluation of Moderate-to-Severe Influenza Disease in Children 6 Months to 8 Years of Age in Colorado

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S291-S292
Author(s):  
Suchitra Rao ◽  
Molly Lamb ◽  
Angela Moss ◽  
Emad Yanni ◽  
Rafik Bekkat-Berkani ◽  
...  
Keyword(s):  
Risk Difference ◽  
Antimicrobial Use ◽  
Clinical Endpoint ◽  
Research Support ◽  
Mild Disease ◽  
Significant Difference ◽  
Ed Visits ◽  
Emergency Room Care ◽  
Negative Controls ◽  
Research Grant

Abstract Background A clinical endpoint of moderate-to-severe (M/S) influenza has been proposed in children, defined as fever >39°C, otitis media, lower respiratory tract infection, or serious extrapulmonary manifestations. This definition has not been evaluated against clinically relevant outcomes like hospitalization, emergency room care, antimicrobial use, and child/parental absenteeism. Methods We conducted a prospective observational study of children aged 6 months–8 years with influenza at the Children’s Hospital Colorado Emergency Department (ED) and its affiliates during two influenza seasons (2016–2017 and 2017–2018). Children with influenza-like-illness (ILI) were enrolled and tested for influenza by polymerase chain reaction (PCR). Parents of influenza cases and matched influenza-negative controls were contacted 2 weeks later for follow-up. The primary outcome was hospitalization for M/S influenza vs. mild influenza. Secondary outcomes included recurrent ED visits, antimicrobial use, child/parental absenteeism. Interim analyses were conducted using SAS v9.4. Results Among the 1,480 enrolled children with ILI, 410 (28%) tested positive for influenza by PCR. The median age of influenza cases was 4.0 years (IQR 2.2–6.1), and 20% were considered high-risk for influenza complications. Of influenza cases, 284 (69%) met the definition for M/S influenza. Among M/S influenza subjects, 8.4% were hospitalized, compared with 1.6% with mild influenza (risk difference (RD) 6.9%; 95% CI: 3.0–10.8, P < 0.01). Subjects with M/S influenza were more likely to receive antibiotics (RD 12.0%, 95% CI: 3.4–20.6, P < 0.01) with a trend to higher antiviral use (RD 6.9%, 95% CI: −0.7–14.5, P = 0.09). There was no significant difference for recurrent ED visits nor child/parental absenteeism. After adjusting for comorbidities, age, and influenza strain, the relative risk (RR) of hospitalization or recurrent ED visits was higher among those with M/S influenza vs. mild influenza (RR 2.18, 95% CI: 1.02–4.64, P = 0.04). Conclusion Children with M/S influenza have a higher risk of hospitalization compared with mild disease. This proposed definition is a useful clinical endpoint to study the public health and clinical impact of influenza interventions in children. Disclosures S. Rao, GSK: Investigator, Research grant. E. Yanni, GSK: Employee, Salary. R. Bekkat-Berkani, GSK: Employee, Salary. A. Schuind, GSK: Employee, Salary. B. Innis, GSK: Employee, Salary. R. Mistry, GSK: Investigator, Research support. E. J. Asturias, GSK: Investigator, Research grant and Research support.

scholarly journals Adenovirus Viral Kinetics and Mortality in Ex Vivo T Cell-Depleted Hematopoietic Cell Transplant Recipients With Adenovirus Infection From a Single Center

2020 ◽  
Vol 222 (7) ◽  
pp. 1180-1187
Author(s):  
Yeon Joo Lee ◽  
Jiaqi Fang ◽  
Phaedon D Zavras ◽  
Susan E Prockop ◽  
Farid Boulad ◽  
...  
Keyword(s):  
T Cell ◽  
Ex Vivo ◽  
Area Under The Curve ◽  
Absolute Lymphocyte Count ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Viral Kinetics ◽  
Cox Models ◽  
Viral Loads

Abstract Background We report on predictors of adenovirus (ADV) viremia and correlation of ADV viral kinetics with mortality in ex vivo T-cell depleted (TCD) hematopoietic cell transplant (HCT). Methods T cell-depleted HCT recipients from January 1, 2012 through September 30, 2018 were prospectively monitored for ADV in the plasma through Day (D) +100 posttransplant or for 16 weeks after the onset of ADV viremia. Adenovirus viremia was defined as ≥2 consecutive viral loads (VLs) ≥1000 copies/mL through D +100. Time-averaged area under the curve (AAUC) or peak ADV VL through 16 weeks after onset of ADV viremia were explored as predictors of mortality in Cox models. Results Of 586 patients (adult 81.7%), 51 (8.7%) developed ADV viremia by D +100. Age <18 years, recipient cytomegalovirus seropositivity, absolute lymphocyte count <300 cells/µL at D +30, and acute graft-versus-host disease were predictors of ADV viremia in multivariate models. Fifteen (29%) patients with ADV viremia died by D +180; 8 of 15 (53%) died from ADV. Peak ADV VL (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.52–3.33) and increasing AAUC (HR, 2.95; 95% CI, 1.83–4.75) correlated with mortality at D +180. Conclusions In TCD HCT, peak ADV VL and ADV AAUC correlated with mortality at D +180. Our data support the potential utility of ADV viral kinetics as endpoints in clinical trials of ADV therapies.

scholarly journals Primary or Secondary Prophylaxis with Voriconazole Compared with Posaconazole for Prevention of Invasive Fungal Infections After Hematopoietic Stem Cell Transplantation

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S75-S75
Author(s):  
Jeffrey W Jansen ◽  
Anupam Pande ◽  
Rizwan Romee ◽  
Steven J Lawrence ◽  
William Powderly
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Hematopoietic Stem ◽  
Research Grant

Abstract Background Invasive fungal infections (IFI) remain a serious complication in hematopoietic stem cell transplantation (HSCT) patients and are associated with increased costs, morbidity, and mortality. Posaconazole (PCZ) and voriconazole (VCZ) are frequently utilized as antifungal prophylaxis in this population. To date, no direct comparison between PCZ and VCZ exists for the prevention of IFI in adult HSCT patients. Methods A retrospective cohort analysis of HSCT patients aged ≥18 years who received ≥28 continuous days of primary (PPPx) or secondary (SPPx) antifungal prophylaxis with either VCZ or PCZ between February 26, 2003 and September 30, 2015 at Barnes-Jewish Hospital was conducted. Patients who received PPPx or SPPx with both VCZ and PCZ were analyzed following intention to treat of the initial agent received. Patients who received both PPPx and SPPx were included once for both PPPx and SPPx. The primary outcome of interest was development of possible, probable, or proven IFI as defined by EORTC/MSG guidelines. In the SPPx patients, development of IFI was confirmed as a distinct event from primary IFI based on manual chart review and radiographic evidence. Results Overall, there were 472 patients included; 402 in the VCZ group and 70 in the PCZ group. At baseline, patients in the PCZ group had more graft vs. host disease (GVHD) prior to prophylaxis (27.1% vs. 16.7%, P = 0.04) and were more likely to be on SPPx (60% vs. 41%, P < 0.01). There were 22 and 1 IFI events in the VCZ and PCZ groups, respectively, which corresponded to a crude incidence rate of 0.345 and 0.077 per 1000 person-days of prophylaxis. Figure 1 displays the Cox proportional hazard model which was completed in the backwards stepwise method accounting for gender, transplant type, GVHD prior to prophylaxis, disease remission, and PPPx or SPPX. The hazard ratio for development of IFI while on prophylaxis between VCZ and PCZ was 5.22 (95% CI: 0.69–39.4; P = 0.11) after controlling for PPPx or SPPx. Conclusion There was not a significant difference between rates of IFI in HSCT patients who received antifungal prophylaxis with VCZ compared with PCZ. Our data trends towards favoring PCZ but is limited by low rates of IFI. Larger, prospective analyses are necessary to confirm our findings. Disclosures W. Powderly, Merck: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Gilead: Scientific Advisor, Consulting fee. Astellas: Grant Investigator, Research grant

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