Bacterial and Fungal Co-Infections in Patients with COVID-19 Related Pneumonia: A Retrospective Cohort Study

Background: The study analyzed risk factors for bacterial and fungal coinfection in patients with COVID-19 and the impact on mortality. Methods: This is a single-center retrospective study conducted on 387 patients with confirmed COVID-19 pneumonia admitted to an Italian Tertiarycare hospital, between 21 February 2020 and 31 May 2020. Bacterial/fungal coinfection was determined by the presence of characteristic clinical features and positive culture results. Multivariable logistic regression was used to analyze risk factors for the development of bacterial/fungal co-infection after adjusting for demographic characteristics and comorbidities. Thirty-day survival of the patients with or without co-infections was analyzed by Kaplan- Meier method. Results: In 53/387 (13.7%) patients with COVID-19 pneumonia, 67 episodes of bacterial/fungal co-infection occurred (14 presented >1 episode). Pneumonia was the most frequent co-infection (47.7%), followed by BSI (34.3%) and UTI (11.9%). S. aureus was responsible for 24 episodes (35.8%), E. coli for 7 (10.4%), P. aerugionsa and Enterococcus spp. for 5 episodes each (7.4%). Five (7.4%) pulmonary aspergillosis, 3 (4.4%) pneumocystosis and 5 (7.4%) invasive candidiasis were observed. Multivariable analysis showed a higher risk of infection in patients with an age >65 years (csHR 2.680; 95% CI: 1.254-5.727; p=0.054), with cancer (csHR 5.243; 95% CI: 1.173-23.423; p=0.030), with a LOS >10 days (csHR 12.507; 95% CI: 2.659 - 58.830; p=0.001), early (within 48h) admitted in ICU (csHR 11.766; 95% CI: 4.353-31.804; p<0.001), and with a SOFA score >5 (csHR 3.397; 95% CI: 1.091-10.581; p=0.035). Estimated cumulative risk of developing at least 1 bacterial/fungal co-infection episode was of 15% and 27% after 15 and 30 days from admission, respectively. Kaplan-Meier estimated a higher cumulative probability of death in patients with bacterial/fungal co-infection (log-rank=0.031). Thirty-day mortality rate of patients with pneumonia was 38.7%, higher than those with BSI (30.4%). Conclusions: Bacterial and fungal infections are a serious complication affecting the survival of patients with COVID-19- related pneumonia. Some issues need to be investigated, such as the best empirical antibiotic therapy and the need for possible antifungal prophylaxis.

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Bacterial and Fungal Co-Infections in Patients with COVID-19 Related Pneumonia: A Retrospective Cohort Study

10.21203/rs.3.rs-576997/v1 ◽

2021 ◽

Author(s):

Andrea Bedini ◽

Marianna Menozzi ◽

Gianluca Cuomo ◽

Erica Franceschini ◽

Gabriella Orlando ◽

...

Keyword(s):

Risk Factors ◽

Fungal Infections ◽

Tertiary Care ◽

Multivariable Analysis ◽

Cumulative Risk ◽

Antifungal Prophylaxis ◽

Cumulative Probability ◽

Care Hospital ◽

Kaplan Meier ◽

The Impact

Abstract Background: The study analysed risk factors for bacterial and fungal co-infection in patients with COVID-19 and the impact on mortality.Methods: This is a single-center retrospective study conducted on 387 patients with confirmed COVID-19 pneumonia admitted to an Italian Tertiary-care hospital, between 21 February 2020 and 31 May 2020. Bacterial/fungal coinfection was determined by the presence of characteristic clinical features and positive culture results. Multivariable logistic regression was used to analyze risk factors for the development of bacterial/fungal co-infection after adjusting for demographic characteristics and comorbidities. Thirty-day survival of the patients with or without co-infections was analysed by Kaplan-Meier method.Results: In 53/387 (13.7%) patients with COVID-19 pneumonia, 67 episodes of bacterial/fungal co-infection occurred (14 presented >1 episode). Pneumonia was the most frequent co-infection (47.7%), followed by BSI (34.3%) and UTI (11.9%). S. aureus was responsible for 24 episodes (35.8%), E. coli for 7 (10.4%), P. aerugionsa and Enterococcus spp. for 5 episodes each (7.4%). Five (7.4%) pulmonary aspergillosis, 3 (4.4%) pneumocystosis and 5 (7.4%) invasive candidiases were observed. Multivariable analysis showed a higher risk of infection in patients with an age>65 years (csHR 2.680; 95%CI: 1.254 - 5.727; p=0.054), with cancer (csHR 5.243; 95%CI: 1.173-23.423; p=0.030), with a LOS>10 days (csHR 12.507; 95%CI: 2.659 – 58.830; p=0.001), early (within 48h) admitted in ICU (csHR 11.766; 95% CI: 4.353-31.804; p<0.001), and with a SOFA score>5 (csHR 3.397; 95% CI: 1.091 - 10.581; p=0.035). Estimated cumulative risk of developing at least 1 bacterial/fungal co-infection episode was of 15% and 27% after 15 and 30 days from admission, respectively. Kaplan-Meier estimated a higher cumulative probability of death in patients with bacterial/fungal co-infection (log-rank=0.031). Thirty-day mortality rate of patients with pneumonia was 38.7%, higher than those with BSI (30.4%).Conclusions: Bacterial and fungal infections are a serious complication affecting the survival of patients with COVID-19-related pneumonia. Some issues need to be investigated, such as the best empirical antibiotic therapy and the need for possible antifungal prophylaxis.

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Incidence and Risk Factors for Breakthrough Invasive Mold Infections in Acute Myeloid Leukemia Patients Receiving Remission Induction Chemotherapy

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz176 ◽

2019 ◽

Vol 6 (5) ◽

Cited By ~ 5

Author(s):

Heena P Patel ◽

Anthony J Perissinotti ◽

Twisha S Patel ◽

Dale L Bixby ◽

Vincent D Marshall ◽

...

Keyword(s):

Risk Factors ◽

Acute Myeloid Leukemia ◽

Induction Chemotherapy ◽

Myeloid Leukemia ◽

Fungal Infections ◽

Multivariable Analysis ◽

Antifungal Prophylaxis ◽

Remission Induction ◽

Invasive Mold Infections ◽

Acute Myeloid

Abstract Background Despite fungal prophylaxis, invasive mold infections (IMIs) are a significant cause of morbidity and mortality in patients with acute myeloid leukemia (AML) receiving remission induction chemotherapy. The choice of antifungal prophylaxis agent remains controversial, especially in the era of novel targeted therapies. We conducted a retrospective case–control study to determine the incidence of fungal infections and to identify risk factors associated with IMI. Methods Adult patients with AML receiving anti-Aspergillus prophylaxis were included to determine the incidence of IMI per 1000 prophylaxis-days. Patients without and with IMI were matched 2:1 based on the day of IMI diagnosis, and multivariable models using logistic regression were constructed to identify risk factors for IMI. Results Of the 162 included patients, 28 patients had a possible (n = 22), probable, or proven (n = 6) diagnosis of IMI. The incidence of proven or probable IMI per 1000 prophylaxis-days was not statistically different between anti-Aspergillus azoles and micafungin (1.6 vs 5.4, P = .11). The duration of prophylaxis with each agent did not predict IMI occurrence on regression analysis. Older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.004–1.081; P = .03) and relapsed/refractory AML diagnosis (OR, 4.44; 95% CI, 1.56–12.64; P = .003) were associated with IMI on multivariable analysis. Conclusions In cases that preclude use of anti-Aspergillus azoles for prophylaxis, micafungin 100 mg once daily may be considered; however, in older patients and those with relapsed/refractory disease, diligent monitoring for IMI is required, irrespective of the agent used for antifungal prophylaxis.

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Higher Infused Cell Dose Is Associated with a Decreased Risk of Invasive Fungal Infections After Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood.v120.21.4134.4134 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4134-4134

Author(s):

Aazim Kamal Omer ◽

Panayiotis D Ziakas ◽

Theodora Anagnostou ◽

Themistoklis Kourkoumpetis ◽

Steven L. McAfee ◽

...

Keyword(s):

Risk Factors ◽

Fungal Infections ◽

Multivariable Analysis ◽

Antifungal Prophylaxis ◽

Invasive Fungal Infections ◽

Candida Spp ◽

Hematopoietic Stem ◽

Allogeneic Hct ◽

Cell Dose ◽

Donor Type

Abstract Abstract 4134 Invasive fungal infections/disease (IFI/IFD) are a major cause of morbidity and mortality after hematopoietic stem cell transplants (HCT), but their incidence and risk factors are not well defined. We performed a retrospective review of 270 consecutive adults (152 M/118 F), median age 53 (18–75) years, with hematologic malignancy receiving allogeneic HCT at Massachusetts General Hospital between 2000 to 2010 to determine the incidence, risk factors and outcomes of patients that developed IFD. All patients received antifungal prophylaxis from the start of conditioning until Day +100; 90% received fluconazole 400 mg daily. We defined IFD using the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, defining proven cases as evidence of fungal elements in a sterile tissue, and probable as presence of fungal elements in non sterile tissue or positive Galactomannan antigen or β-D-Glucan test in patients with clinical features suggestive of IFI. Diagnoses were Acute Myeloid Leukemia (34%), Non Hodgkin's Lymphoma (24%), Myelodysplastic syndrome (15%), Acute Lymphoblastic Leukemia (8%), Chronic Lymphocytic Leukemia (5%), Myeloproliferative disorders, Hodgkin Lymphoma and Multiple Myeloma (4% each), and others (2%). 15% had a prior autologous transplant. Conditioning included reduced intensity (64%) or myeloablative (36%) regimens. Donor source was fully HLA matched (MRD) in 60%, matched unrelated (MUD) in 20%, Haploidentical in 12% and Cord Blood in 8%. 41% received ATG based aGVHD prophylaxis vs non ATG based in 59%. 11% were diabetic, while 6% had a history of IFD prior to transplant. 55% received systemic steroids for GVHD and 34% received TPN during transplant course. Median follow up was 28 (1.0–141.0) months. 49 distinct episodes of IFI were observed in 40 subjects (15%). Aspergillus spp (47%) was most frequently encountered, followed by Candida spp (43%). Mucor was isolated in 1 case. Among the Candida spp, the majority (52%) were non albicans- Candida glabrata (8) vs 1 each of Candida krusei, Candida tropicalis and Candida parapsilosis. Most frequently infected site was the lungs (69%), followed by the blood stream and paranasal sinuses (14% each), and GI tract (4%). Spleen (hepatosplenic candidiasis), kidneys and brain were affected in 1 patient each. In 6%, involvement of both the lungs and sinuses was observed. The estimated probability of early IFD (within 100 days post transplant) was 7%. Patients and transplant factors, including age, diagnosis, prior autologous transplant, type of conditioning regimen, type of aGVHD prophylaxis, donor type, CD34+ cell dose infused, history of diabetes or prior IFD, systemic use of steroids for GVHD and TPN administration, were examined to determine risk factors for developing IFD. In multivariable analysis, haploidentical donor transplants (HR 3.48, 95% CI 1.35–8.99, p=0.01) and the development of Grade III and IV aGVHD (HR 3.32, 95% CI 1.23–9.01, p=0.02) were risk factors for the development of IFD. Conversely, higher CD34+ cell dose infused was associated with a lower risk of IFD (HR 0.80, 95% CI 0.68–0.94, p=0.01, per 1×10⋀6 cells/kg increase). The overall mortality (OM) of patients with IFD was 41%. A higher non-relapse mortality (NRM) was observed for patients with IFD as compared to patients without IFD, 55% vs 18% (HR 3.76, 95% CI 2.03–6.97, p<0.001). In multivariable analysis, accounting for CD34+ cell count, donor type and Grade III-IV aGVHD, the effect of IFI on NRM remained significant (HR 3.32, 95% CI 1.65–6.67, p=0.001). Patients with IFD had lower overall survival (OS), 16 months as opposed to 50 months for patients without IFD. In summary, 1) The risk of IFD after allogeneic HCT was 15%; 2) Patients with IFD have a high mortality after allogeneic HCT; 3) Haploidentical donor type and development of Grades III-IV GVHD are risk factors for IFD; 4) A higher CD34+ cell dose may be protective against IFD; 5) Prior IFD did not predict for higher risk of IFD or higher mortality, suggesting these patients should not be excluded from allogeneic HCT. Further studies looking at alternate aGVHD prophylaxis regimens, strategies to increase cell dose infused and better antifungal prophylaxis for these high risk patients are needed to lessen this potentially life threatening complication. Disclosures: Mylonakis: T2 Biosystems: Research Funding; Astellas inc : Research Funding.

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The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

Acta Haematologica ◽

10.1159/000514920 ◽

2021 ◽

pp. 1-9

Author(s):

Leonard Naymagon ◽

Douglas Tremblay ◽

John Mascarenhas

Keyword(s):

Hemophagocytic Lymphohistiocytosis ◽

Proportional Hazards ◽

Multivariable Analysis ◽

Cox Proportional Hazards ◽

Rank Test ◽

Kaplan Meier ◽

Hazard Ratios ◽

Significant Difference ◽

The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

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Abstract T P136: Potential Contributors to the Declining Impact of Stroke Risk Factors with Age: Implications for Stroke Epidemiology in the Elderly

Stroke ◽

10.1161/str.45.suppl_1.tp136 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

George Howard ◽

Mary Cushman ◽

Maciej Banach ◽

Brett M Kissela ◽

David C Goff ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Stroke Risk ◽

Multivariable Analysis ◽

The Elderly ◽

Stroke Risk Factors ◽

Age Related ◽

Increased Risk ◽

The Impact ◽

Age Related Changes

Purpose: The importance of stroke research in the elderly is increasing as America is “graying.” For most risk factors for most diseases (including stroke), the magnitude of association with incident events decreases at older ages. Potential changes in the impact of risk factors could be a “true” effect, or could be due to methodological issues such as age-related changes in residual confounding. Methods: REGARDS followed 27,748 stroke-free participants age 45 and over for an average of 5.3 years, during which 715 incident strokes occurred. The association of the “Framingham” risk factors (hypertension [HTN], diabetes, smoking, AFib, LVH and heart disease) with incident stroke risk was assessed in age strata of 45-64 (Young), 65-74 (Middle), and 75+ (Old). For those with and without an “index” risk factor (e.g., HTN), the average number of “other” risk factors was calculated. Results: With the exception of AFib, there was a monotonic decrease in the magnitude of the impact across the age strata, with HTN, diabetes, smoking and LVH even becoming non-significant in the elderly (Figure 1). However, for most factors, the increasing prevalence of other risk factors with age impacts primarily those with the index risk factor absent (Figure 2, example HTN as the “index” risk factor). Discussion: The impact of stroke risk factors substantially declined at older ages. However, this decrease is partially attributable to increases in the prevalence of other risk factors among those without the index risk factor, as there was little change in the prevalence of other risk factors in those with the index risk factor. Hence, the impact of the index risk factor is attenuated by increased risk in the comparison group. If this phenomenon is active with latent risk factors, estimates from multivariable analysis will also decrease with age. A deeper understanding of age-related changes in the impact of risk factors is needed.

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The Risk of Seizure Recurrence After a First Unprovoked Afebrile Seizure in Childhood: An Extended Follow-up

PEDIATRICS ◽

10.1542/peds.98.2.216 ◽

1996 ◽

Vol 98 (2) ◽

pp. 216-225 ◽

Cited By ~ 2

Author(s):

Shlomo Shinnar ◽

Anne T. Berg ◽

Solomon L. Moshe ◽

Christine O'Dell ◽

Marta Alemany ◽

...

Keyword(s):

Risk Factors ◽

Age Of Onset ◽

Multivariable Analysis ◽

Cumulative Risk ◽

Febrile Seizures ◽

Recurrence Risk ◽

Early Recurrence ◽

Seizure Recurrence ◽

Unprovoked Seizure ◽

History Of

Objective. To assess the long-term recurrence risks after a first unprovoked seizure in childhood. Methods. In a prospective study, 407 children who presented with a first unprovoked seizure were then followed for a mean of 6.3 years from the time of first seizure. Results. One hundred seventy-one children (42%) experienced subsequent seizures. The cumulative risk of seizure recurrence was 29%,37%,42%, and 44% at 1,2,5, and 8 years, respectively. The median time to recurrence was 5.7 months, with 53% of recurrences occurring within 6 months, 69% within 1 year, and 88% within 2 years. Only 5 recurrences (3%) occurred after 5 years. On multivariable analysis, risk factors for seizure recurrence included a remote symptomatic etiology, an abnormal electroencephalogram (EEG), a seizure occurring while asleep, a history of prior febrile seizures, and Todd's paresis. In cryptogenic cases, the risk factors were an abnormal EEG and an initial seizure during sleep. In remote symptomatic cases, risk factors were a history of prior febrile seizures and age of onset younger than 3 years. Risk factors for late recurrences (after 2 years) were etiology, an abnormal EEG, and prior febrile seizures in the overall group and an abnormal EEG in the cryptogenic group. These are similar to the risk factors for early recurrence. Conclusions. The majority of children with a first unprovoked seizure will not have recurrences. Children with cryptogenic first seizures and a normal EEG whose initial seizure occurs while awake have a particularly favorable prognosis, with a 5-year recurrence risk of only 21%. Late recurrences do occur but are uncommon.

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Isavuconazole Is as Effective as and Better Tolerated Than Voriconazole for Antifungal Prophylaxis in Lung Transplant Recipients

Clinical Infectious Diseases ◽

10.1093/cid/ciaa652 ◽

2020 ◽

Cited By ~ 4

Author(s):

Palash Samanta ◽

Cornelius J Clancy ◽

Rachel V Marini ◽

Ryan M Rivosecchi ◽

Erin K McCreary ◽

...

Keyword(s):

Risk Factors ◽

Lung Transplantation ◽

Lung Transplant ◽

Fungal Infections ◽

Oral Intake ◽

Antifungal Prophylaxis ◽

Red Blood Cell Transfusion ◽

Transplant Recipients ◽

Independent Risk Factors ◽

Lung Transplant Recipients

Abstract Background Invasive fungal infections (IFIs) are common following lung transplantation. Isavuconazole is unstudied as prophylaxis in organ transplant recipients. We compared effectiveness and tolerability of isavuconazole and voriconazole prophylaxis in lung transplant recipients. Methods A single-center, retrospective study of patients who received isavuconazole (September 2015–February 2018) or voriconazole (September 2013–September 2015) for antifungal prophylaxis. IFIs were defined by EORTC/MSG criteria. Results Patients received isavuconazole (n = 144) or voriconazole (n = 156) for median 3.4 and 3.1 months, respectively. Adjunctive inhaled amphotericin B (iAmB) was administered to 100% and 41% of patients in the respective groups. At 1 year, 8% of patients receiving isavuconazole or voriconazole developed IFIs. For both groups, 70% and 30% of IFIs were caused by molds and yeasts, respectively, and breakthrough IFI (bIFI) rate was 3%. Outcomes did not significantly differ for patients receiving or not receiving iAmB. Independent risk factors for bIFI and breakthrough invasive mold infection (bIMI) were mold-positive respiratory culture and red blood cell transfusion >7 units at transplant. Bronchial necrosis >2 cm from anastomosis and basiliximab induction were also independent risk factors for bIMI. Isavuconazole and voriconazole were discontinued prematurely due to adverse events in 11% and 36% of patients, respectively (P = .0001). Most common causes of voriconazole and isavuconazole discontinuation were hepatotoxicity and lack of oral intake, respectively. Patients receiving ≥90 days prophylaxis had fewer IFIs at 1 year (3% vs 9%, P = .02). IFIs were associated with increased mortality (P = .0001) and longer hospitalizations (P = .0005). Conclusions Isavuconazole was effective and well tolerated as antifungal prophylaxis following lung transplantation.

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Complete Remissions (CRs) with Azacitidine Regimens Compared to Crs with 7+3 Induction Chemotherapy and the Effect on Overall Survival

Blood ◽

10.1182/blood.v128.22.1613.1613 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1613-1613 ◽

Cited By ~ 2

Author(s):

Megan Othus ◽

Mikkael A Sekeres ◽

Sucha Nand ◽

Guillermo Garcia-Manero ◽

Frederick R. Appelbaum ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Research Funding ◽

Cox Regression ◽

Intensive Therapy ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Curative Intent ◽

Kaplan Meier ◽

The Impact

Abstract Background: CR and CR with incomplete count recovery (CRi) are associated with prolonged overall survival (OS) for acute myeloid leukemia (AML) patients (pts) treated with curative-intent, induction therapy. For AML pts treated with azacitidine (AZA), response (CR, partial response, marrow CR, or hematologic improvement) is also associated with prolonged OS. We evaluate whether patients given AZA for myelodysplastic syndromes (MDS) or AML had longer OS if they achieved CR. We also compare the effect size of CR on OS between AZA regimens and 7+3. Patients and Methods: We analyzed four SWOG studies: S1117 (n=277) was a randomized Phase II study comparing AZA to AZA+lenalidomide or AZA+vorinostat for higher-risk MDS and CMML pts (median age 70 years, range 28-93); S0703 (n=133) treated AML pts not eligible for curative-intent therapy with AZA+mylotarg (median age 73 years, range 60-88). We analyzed the 7+3 arms of S0106 (n=301 were randomized to 7+3, median age 48 years, range 18-60) and S1203 (n=261 were randomized to 7+3, median age 48 years, range 19-60). CR was defined per 2003 International Working Group criteria. In S1117 CR was assessed every 16 weeks and patients remained on therapy until disease progression. In S0703, S0106, and S1203 CR was assessed following 1-2 induction cycles; patients not achieving CR (S0106) or CRi (S0703 and S1203) were removed from protocol treatment. OS was measured from date of study registration. To avoid survival by response bias, we performed landmark analyses of OS. We present results based on the study-specific landmark date that 75% of pts who eventually achieved a CR had done so (S1117 144 days, S0703 42 days, S0106 44 days, S1203 34 days). Pts who did not achieve CR by this date were analyzed with pts who never achieved CR. Pts who died or were lost to follow-up before this date were excluded from analyses. As a sensitivity analysis we also analyzed based on the 90% date; results were not materially different. Log-rank tests were used to compare survival curves and Cox regression models were used for multivariable modeling including baseline prognostic factors age, sex, performance status, white blood cell count, platelet count, marrow blast percentage, de novo disease (versus antecedent MDS or therapy-related disease), study arm (for S1117 only), and cytogenetic risk (IPSS criteria for S1117, SWOG criteria for S0703, S0106, and S1203). The following analysis considers morphologic CR only. S0106 treated CR with incomplete count recover (CRi) pts as treatment failures (S0703 and S1203 did not) and CRi was not defined for S1117. Hematologic improvement was only defined for S1117 patients. Results: In univariate analysis, CR was significantly associated with prolonged survival among MDS pts treated with azactidine on S1117 (HR=0.55, p=0.017), confirming the results seen in AML pts treated with azacitidine (and mylotarg, S0703, HR=0.60, p=0.054) and 7+3 (S0106 HR=0.44, p<0.001; S1203 HR=0.32, p<0.0001) (Figure 1). For each study this relationship remained significant in multivariable analysis controlling for baseline prognostic factors (S1117 HR=0.25, p<0.001; S0703 HR=0.64, p=0.049; S0106 HR=0.45, p<0.001; S1203 HR=0.41, p<0.001). There was no evidence that the impact of CR varied across the four cohorts (interaction p-value = 0.76). In the full cohort, the effect of CR was associated with a HR of 0.45 (Table 1). Conclusion: Adjusting for pt characteristics, achievement of morphologic CR was associated with a 60% improvement in OS, on average, compared to that seen in pts who don't achieve a CR, regardless of whether pts were treated with 7+3 or AZA containing regimens, and suggesting that value CR is similar of whether pts receive more or less "intensive" therapy for these high grade neoplasms. Support: NIH/NCI grants CA180888 and CA180819 Acknowledgment: The authors wish to gratefully acknowledge the important contributions of the late Dr. Stephen H. Petersdorf to SWOG and to study S0106. Figure 1 Kaplan-Meier plots of landmark survival by response. Figure 1. Kaplan-Meier plots of landmark survival by response. Table 1 Multivariable analysis, N=878 Table 1. Multivariable analysis, N=878 Disclosures Othus: Glycomimetics: Consultancy; Celgene: Consultancy. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees. Erba:Millennium Pharmaceuticals, Inc.: Research Funding; Amgen: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Agios: Research Funding; Gylcomimetics: Other: DSMB; Juno: Research Funding; Daiichi Sankyo: Consultancy; Sunesis: Consultancy; Pfizer: Consultancy; Ariad: Consultancy; Jannsen: Consultancy, Research Funding; Incyte: Consultancy, DSMB, Speakers Bureau; Celator: Research Funding; Astellas: Research Funding; Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau.

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The relationship between pathologic nodal disease and residual tumor viability (RV) in patients with locoregionally advanced (LRA) adenocarcinoma (ACA) of the esophagus and gastroesophageal junction (E/GEJ) receiving induction chemotherapy, surgery, and postoperative chemoradiotherapy (CRT).

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.165 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 165-165

Author(s):

Michael J. McNamara ◽

Lisa A. Rybicki ◽

Cristina P. Rodriguez ◽

Gregory M.M. Videtic ◽

Kevin L. Stephans ◽

...

Keyword(s):

Induction Chemotherapy ◽

Clinical Stage ◽

Gastroesophageal Junction ◽

Multivariable Analysis ◽

Residual Tumor ◽

Nodal Disease ◽

Curative Intent ◽

Kaplan Meier ◽

Poor Outcomes ◽

The Impact

165 Background: A complete pathologic response to induction CRT has been identified as a favorable prognostic factor for patients with LRA ACA of the E/GEJ. Less is known, however, about the impact of pathologic regression after induction chemotherapy. Methods: Between 2/08 and 1/12, 60 evaluable patients with ACA of the E/GEJ enrolled in a phase II trial of induction chemotherapy, surgery, and post-operative CRT. Eligibility required a clinical stage of T3 or N1 or M1a (AJCC 6th). Induction chemotherapy with epirubicin 50mg/m2 d1, oxaliplatin 130mg/m2 d1, and fluorouracil 200mg/m2/day continuous infusion for 3 weeks, was given every 21 days for 3 courses and was followed by surgical resection. Adjuvant CRT consisted of 50-55Gy @ 1.8-2.0 Gy/d and 2 courses of cisplatin (20mg/m2/d) and fluorouracil (1000mg/m2/d) over 4 days during weeks 1 and 4 of radiotherapy. RV was defined as the amount of remaining tumor in relation to acellular mucin pools and scarring. Results: Of the 60 evaluable patients, 54 completed induction therapy and underwent curative intent surgery. The Kaplan-Meier (KM) projected 3 year OS for patients with pathologic N0 (n=20), N1 (n=12), N2 (n=13), and N3 (n=9) disease is 73%, 57%, 35%, and 0% respectively (p<0.001). The KM projected 3 year OS of patients with low (0-25%, n=19), intermediate (26-75%, n=26), and high (>75%, n=9) RV was 67%, 42%, and 17% respectively (p=0.004). On multivariable analysis, both the pN descriptor and RV were independently prognostic for OS. In patients with less nodal dissemination (N0/N1), RV was prognostic for OS [3yr OS 85% (0-25% viable) v 51% (>25% viable), p=0.028]. Outcomes were poor, however, for patients with advanced nodal disease (N2/N3) regardless of RV [3yr OS 20% (0-25% viable) v 21% (>25% viable), p=0.55]. Conclusions: RV and the pN descriptor after induction chemotherapy are independent pathologic prognostic factors for OS in patients with LRA ACA of the E/GEJ. Patients with extensive nodal disease, however, have poor outcomes irrespective of viability. Clinical trial information: NCT00601705.

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Anti-mold prophylaxis may reduce the risk of invasive fusariosis in hematologic patients with superficial skin lesions with positive culture forFusarium

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00636-16 ◽

2016 ◽

pp. AAC.00636-16 ◽

Cited By ~ 1

Author(s):

Andrea G. Varon ◽

Simone A. Nouér ◽

Gloria Barreiros ◽

Beatriz Moritz Trope ◽

Tiyomi Akiti ◽

...

Keyword(s):

High Risk ◽

Hematopoietic Cell Transplantation ◽

Positive Culture ◽

Primary Prophylaxis ◽

Skin Lesions ◽

Antifungal Prophylaxis ◽

Fungal Culture ◽

Superficial Skin ◽

The Difference ◽

The Impact

Hematologic patients with superficial skin lesions on admission growingFusariumspp. are at high risk to develop invasive fusariosis during neutropenia. We evaluated the impact of primary prophylaxis with a mold-active azole in preventing the occurrence of invasive fusariosis in these patients. From August 2008 to December 2014, patients with acute leukemia, aplastic anemia, or recipients of hematopoietic cell transplantation were screened on admission with dermatologic examination and direct exam and fungal culture of superficial skin lesions. Until November 2009, no intervention was made. Beginning in December 2009, patients with baseline skin lesions with direct exam and/or culture suggestive of the presence ofFusariumspp. received prophylaxis with voriconazole or posaconazole. Skin lesions in the extremities (mostly onychomycosis and interdigital intertrigo) were present on admission in 88 of 239 episodes (36.8%); 44 had hyaline septate hyphae on direct exam, and 11 grewFusariumspp. Anti-mold prophylaxis was given in 20 episodes (voriconazole in 17 and posaconazole in 3). Invasive fusariosis was diagnosed in 14 episodes (5.8%). Among patients with baseline skin lesions with positive culture forFusariumspp., 4 of 5 without anti-mold prophylaxis developed invasive fusariosis vs. none of 6 with anti-mold prophylaxis (p=0.01, 95% confidence interval for the difference between proportions 22% - 96%). Primary antifungal prophylaxis with an anti-mold azole may prevent the occurrence of invasive fusariosis in high-risk hematologic patients with superficial skin lesions on admission growingFusariumspp.

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