Prolonged Febrile Neutropenia in the Pediatric Patient with Cancer

2012 ◽  
pp. 565-569
Author(s):  
Andrew Y. Koh
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Pediatric Patients ◽  
Fungal Infections ◽  
Hematologic Malignancy ◽  
Infectious Complications ◽  
Great Promise ◽  
High Risk Patients ◽  
Patients With Cancer ◽  
Risk Patients

Overview: Infectious diseases continue to be major causes of morbidity and mortality in pediatric patients with cancer. Yet not all pediatric patients with cancer with fever and neutropenia are at equal risk for substantial morbidity or mortality from infection. Patients at highest risk for developing infectious complications are those with severe and prolonged neutropenia, substantial medical comorbidity, and hematologic malignancy, or recipients of stem-cell transplantation. These “high-risk” patients also have concomitant host immune deficits as well: severe mucositis, lymphopenia, hypogammaglobulinemia, and gut microbial dysbiosis. Because bacterial and fungal infections are the most common infectious complications, continuation of empirical antibacterial antibiotics that were initiated at the onset of febrile neutropenia and prompt initiation of empirical antifungal therapy in the setting of prolonged fever and neutropenia continue to be the standard of care. In high-risk patients, antibiotic therapy should be maintained until neutrophil counts have recovered. Adjunctive therapies have been shown to be ineffective (e.g., colony-stimulating factors) or necessitate further study (e.g., granulocyte infusions or keratinocyte growth factor treatment to heal mucositis). Prophylactic use of antibacterial and antifungal antibiotics in high-risk patients has shown promise but the fear of inducing antimicrobial-resistant strains remains a deterrent. Finally, the novel concepts of manipulating the host gut microbiota and/or augmenting GI mucosal immunity to prevent invasive bacterial and fungal infections in pediatric patients with cancer offers great promise, but more definitive studies need to be performed.

scholarly journals A questionnaire survey on evaluation for penetration and compliance of the Japanese Guideline on Febrile Neutropenia among hematology-oncology physicians and surgeons

2021 ◽  
Author(s):  
Nobu Akiyama ◽  
Takuho Okamura ◽  
Minoru Yoshida ◽  
Shun-ichi Kimura ◽  
Shingo Yano ◽  
...  
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Supportive Care ◽  
Questionnaire Survey ◽  
Primary Treatment ◽  
Beta Lactam ◽  
Clinical Practices ◽  
High Risk Patients ◽  
Mascc Score ◽  
Risk Patients

Abstract Purpose The Japanese Society of Medical Oncology published a guideline (GL) on febrile neutropenia (FN) in 2017. The study’s purpose is to reveal how widely GL penetrated among physicians and surgeons providing chemotherapy. Methods A questionnaire survey was conducted with SurveyMonkey™ for members of the Japanese Association of Supportive Care in Cancer and relevant academic organizations. Each question had four options (always do, do in more than half of patients, do in less than half, do not at all) and a free description form. Responses were analyzed with statistical text-analytics. Result A total of 800 responses were retrieved. Major respondents were experts with more than 10-year experience, physicians 54%, and surgeons 46%. Eighty-seven percent of respondents knew and used GL. Forty-eight percent assessed FN with Multinational Association of Supportive Care in Cancer (MASCC) score “always” or “more than half.” Eighty-one percent chose beta-lactam monotherapy as primary treatment in high-risk patients. Seventy-seven percent did oral antibacterial therapy in low-risk patients ambulatorily. Seventy-eight percent administered primary prophylactic G-CSF (ppG-CSF) in FN frequency ≥ 20% regimen. Fifty-nine percent did ppG-CSF for high-risk patients in FN frequency 10–20% regimen. Ninety-seven percent did not use ppG-CSF in FN frequency < 10% regimen. The medians of complete and complete plus partial compliance rates were 46.4% (range 7.0–92.8) and 77.8% (range 35.4–98.7). The complete compliance rates were less than 30% in seven recommendations, including the MASCC score assessment. Conclusion GL is estimated to be widely utilized, but some recommendations were not followed, presumably due to a mismatch with actual clinical practices in Japan.

scholarly journals 1701. Differences in Diagnostic Performance of β-d-Glucan Testing in Patients with Varying Degrees of Susceptibility to Invasive Fungal Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S623-S623
Author(s):  
Eliel Nham ◽  
Si-Ho Kim ◽  
Hyunjoo Lee ◽  
Jae-Hoon Ko ◽  
Kyungmin Huh ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Diagnostic Performance ◽  
Fungal Infections ◽  
Pneumocystis Pneumonia ◽  
Host Factors ◽  
European Organization ◽  
High Risk Patients ◽  
Risk Patients ◽  
Group A

Abstract Background Usefulness of β-d-glucan (BDG) testing in high-risk patients for invasive fungal infection (IFI) diagnosis has been well demonstrated. However, data on its usefulness in patients without risk factors are limited. We evaluated differences in the diagnostic performance of BDG testing in patients with varying degrees of susceptibility to IFI. Methods From April 2017 to May 2018, all consecutive patients (≥18year-old) who were performed BDG testing (Beijing Gold Mountainriver Tech) were enrolled. Patients were classified into three groups: Group A for patients with host factors defined by 2008 European Organization for Research and Treatment of Cancer-Mycoses Study Group diagnostic (EORTC-MSG) criteria, Group B for patients with malignancy receiving recent chemotherapy within 1 month without host factors, and Group C for others. Cases of proven and probable IFI defined by EORTC-MSG criteria, Pneumocystis pneumonia and all fungemia were considered as true IFIs. Sensitivity, specificity, positive and negative predictive value (PPV and NPV) were calculated with a cut-off value for positivity ≥80 pg/mL. Results Among 473 eligible patients, 190, 142, and 141 patients were classified into group A, B, and C, respectively. Rates of true IFI were significantly different in each group (57/190, 19/142, and 10/141 in each group, P < 0.001). Sensitivities were 0.83, 0.68, and 0.70 and specificities were 0.62, 0.59, and 0.63 in group A, B, and C, respectively. PPVs were considerably different among three groups (PPV for 0.48, 0.20, and 0.12; NPV for 0.89, 0.92 and 0.97 in each group, respectively). Conclusion The BDG test is a useful assay for IFI diagnosis; however, the clinical interpretation should be different by patient risks. Whereas BDG testing could be considered as a tool for predicting IFI in high-risk patients, it only could be a tool for excluding IFI in patient without risk factors. Disclosures All authors: No reported disclosures.

Is Antifungal Prophylaxis Useful In Stem Cell Transplantation (SCT) During Hospitalization?.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4541-4541
Author(s):  
Giuseppe Irrera ◽  
Messina Giuseppe ◽  
Giuseppe Console ◽  
Massimo Martino ◽  
Cuzzola Maria ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Mucosal Damage ◽  
Invasive Disease ◽  
Secondary Prophylaxis ◽  
Antifungal Prophylaxis ◽  
Antifungal Drugs ◽  
High Risk Patients ◽  
Risk Patients

Abstract Abstract 4541 Introduction: Limited data demonstrate to what extent preventing fungal exposures is effective in preventing infection and disease. Further studies are needed to determine the optimal duration of fluconazole prophylaxis in allogeneic recipients to prevent invasive disease with fluconazole-susceptible Candida species during neutropenia. Oral, nonabsorbable antifungal drugs might reduce superficial colonization and control local mucosal candidiasis, but have not been demonstrated to reduce invasive candidiasis. Anti-fungal prophylaxis is recommended in a subpopulation of autologous recipients with underlying hematologic malignancies with prolonged neutropenia and mucosal damage. Methods: This is a retrospective study of 1007 SCT performed in our center between 1992 and 2009 in 809 consecutive patients, irrespective of diagnosis. HEPA filter and environmental monitoring (air, water, surfaces) are attributes of our transplant center. Results: The main characteristics of the patients are reported in Table 1. Systemic prophylaxis was used according to the guidelines (Table 2): fluconazole in the nineties, then itraconazole and from 2004 was either abolished or substituted with non-adsorbable prophylaxis in transplants with standard risk. Secondary prophylaxis was prescribed for high risk patients (with infectious fungal history, suggestive iconography, positive fungal biomarker). In 17 years our Center has never been colonized by mould. Only 3 probable aspergillosis infections and 4 proven fungal infections (fusarium, mucor and 2 aspergillosis) were diagnosed, all in allogeneic patients (2 haplotipical, 1 singenic, 1 sibiling, 1 MUD and 2 mismatched), resulting in death in all cases. No infection was documented in autologous setting, while the infection rate in allogenic setting was 3.6% with an incidence rate of 1.1 infection per 10000 transplants/year. These results are significantly lower than published reports. Conclusion: Systemic antifungal prophylaxis should not be performed in autologous SCT patients. The abuse of systemic prophylaxis targeting yeasts has influenced the change of epidemiology in the transplant setting with prevalence of mould infections. The identification of high risk patients is useful to select patients for systemic antifungal or secondary prophylaxis to reducing overtreatment, incidence of resistant strains and costs. Disclosures: No relevant conflicts of interest to declare.

Shifting paradigms in the management of pediatric differentiated thyroid cancer from static to dynamic risk stratification: a step forward toward precision medicine

2019 ◽  
Vol 58 (03) ◽  
pp. 249-257
Author(s):  
Sadegh Ebrahim Ajdari ◽  
Babak Shafiei ◽  
Motahareh Motazedian ◽  
Mohsen Qutbi ◽  
Paridokht Esmaeilzadeh ◽  
...  
Keyword(s):  
High Risk ◽  
Pediatric Patients ◽  
Initial Therapy ◽  
High Risk Patients ◽  
Dynamic Risk ◽  
Radioiodine Ablation ◽  
Risk Patients ◽  
Structural Disease ◽  
Response Group

Abstract Introduction This study aimed to assess the usefulness of a risk-adopted management system known as dynamic risk stratification (DRS) in comparison with the American (ATA) and European Thyroid Associations’ (ETA) risk classifications in the management of pediatric patients with differentiated thyroid cancer (DTC). Materials and Methods The current study included 50 pediatric patients with DTC who were treated with total or near total thyroidectomy and radioiodine ablation whose risk assessment was initially defined according to the ATA and ETA guidelines. During the two years after initial treatment, patients were reclassified according to their DRS. Results The study showed that the ability of the DRS system to predict the final outcome was superior to that of the ATA and ETA guidelines. The observed variance in predicting final outcome was 2.3 % for ETA, 14.8 % for ATA, and 83.4 % for DRS. In intermediate/high-risk patients, according to the ATA/ETA guidelines, an excellent response to initial therapy resulted in a noteworthy reduction (about 40 %) for detection of structural disease at the time of final follow-up. The risk of structural disease at the time of final follow-up was significantly higher in the structural incomplete response group (HR = 23.34, P = 0.00) and biochemical incomplete response group (HR = 13.83, P = 0.03) than in the excellent response group. Conclusion The data documented the significance of re-stratifying pediatric patients with DTC on the basis of the findings obtained at the time of or after their initial therapy (total thyroidectomy and radioiodine ablation), predominantly in the intermediate/high-risk patients. In addition, DRS helped to better modulate the later follow-up, excluding a large number of intermediate/high risk patients from needless intensive workups, allowing personalization of follow-up management.

scholarly journals Phase 1b Study of New Posaconazole Tablet for Prevention of Invasive Fungal Infections in High-Risk Patients with Neutropenia

2014 ◽  
Vol 58 (10) ◽  
pp. 5758-5765 ◽  
Author(s):  
Rafael F. Duarte ◽  
Javier López-Jiménez ◽  
Oliver A. Cornely ◽  
Michel Laverdiere ◽  
David Helfgott ◽  
...  
Keyword(s):  
High Risk ◽  
Fungal Infections ◽  
Average Concentration ◽  
Myelogenous Leukemia ◽  
Time Curve ◽  
Once Daily ◽  
High Risk Patients ◽  
Exposure Target ◽  
Risk Patients ◽  
Neutropenic Patients

ABSTRACTPosaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of ≥500 ng/ml and ≤2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n= 20) and 300 mg posaconazole once daily (n= 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ≤28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered atClinicalTrials.govunder registration no. NCT01777763.)

Mortality, length of hospitalization, and costs associated with invasive fungal infections in high-risk patients

2009 ◽  
Vol 66 (19) ◽  
pp. 1711-1717 ◽  
Author(s):  
Joseph Menzin ◽  
Juliana L. Meyers ◽  
Mark Friedman ◽  
John R. Perfect ◽  
Amelia A. Langston ◽  
...  
Keyword(s):  
High Risk ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
High Risk Patients ◽  
Risk Patients ◽  
Length Of Hospitalization

scholarly journals Evaluation of Posaconazole Serum Concentrations from Delayed-Release Tablets in Patients at High Risk for Fungal Infections

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Alan Chin ◽  
Steven A. Pergam ◽  
David N. Fredricks ◽  
Andrew N. Hoofnagle ◽  
Kelsey K. Baker ◽  
...  
Keyword(s):  
High Risk ◽  
Fungal Infections ◽  
Medical Condition ◽  
Solid Organ Transplantation ◽  
Serum Levels ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
High Risk Patients ◽  
Delayed Release ◽  
Risk Patients

ABSTRACT The purpose of our study was to determine the frequency of patients who achieved a therapeutic drug level after receiving posaconazole (PCZ) delayed-release tablets (DRT) for prophylaxis or treatment of invasive fungal infections (IFIs) and to examine the effect of demographic traits and treatment characteristics on PCZ serum levels. A retrospective single-center study was conducted on high-risk inpatients at the University of Washington Medical Center (UWMC) that had received PCZ and obtained PCZ serum levels for either treatment or prophylaxis between 1 August 2014 and 31 August 2015. High-risk patients were defined as those undergoing chemotherapy for a primary hematologic malignancy and those undergoing hematopoietic cell transplantation (HCT) or solid organ transplantation. Serum trough concentrations of ≥700 μg/liter and ≥1,000 μg/liter were considered appropriate for prophylaxis and treatment, respectively. The most frequent underlying medical condition was a hematological malignancy (43/53, 81%). Twenty-six of 53 patients (49%) received PCZ for prophylaxis; the rest received PCZ for treatment. A total of 37/53 (70%) patients had PCZ serum levels of ≥700 μg/liter regardless of indication, including 22/26 (85%) that received PCZ for prophylaxis. Of the patients that received PCZ for treatment, only 12/27 (44%) had PCZ serum levels of ≥1,000 μg/liter. The odds of having therapeutic PCZ serum levels were not statistically different in patients with a weight of ≥90 kg, a diarrhea grade of ≥2, a mucositis grade of ≥2, or poor dietary intake. However, the odds of having therapeutic PCZ serum levels was 5.85 times higher in patients without graft-versus-host disease (GVHD) treatment than in those with GVHD treatment. Four patients on prophylaxis (15%) developed breakthrough IFIs, one of which had a subtherapeutic level. We concluded that the use of PCZ DRT provided adequate concentrations in only 70% of our patients and that recommended dosing may lead to insufficient levels in patients treated for IFIs. Lower concentrations noted among high-risk patients with GVHD suggest a need for prospective studies evaluating therapeutic drug monitoring and/or dose adjustments among these patients.

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