Admission Clinical and Laboratory Factors Associated With Death in Children With Cancer During a Febrile Neutropenic Episode

Santolaya, Marı́a Elena; Álvarez, Ana María Arias; Avilés, Carmen L; Becker, Ana; Mosso, Claudio; O’Ryan, Miguel; Payá, Ernesto; Salgado, Carmen; Silva, Pamela; Topelberg, Santiago; Tordecilla, Juan; Varas, Mónica; Villarroel, Milena; Viviani, Tamara; Zubieta, Marcela

doi:10.1097/inf.0b013e318124aa44

Cited by 63 publications

(53 citation statements)

References 21 publications

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“…This case illustrates that, by definition, risk-prediction rules are not perfect [9,18]. Since secondary deteriorations are well-known in children with FN [24,37,38], close follow-up is essential after step-down to outpatient management.…”

Section: Discussionmentioning

confidence: 93%

First‐day step‐down to oral outpatient treatment versus continued standard treatment in children with cancer and low‐risk fever in neutropenia. A randomized controlled trial within the multicenter SPOG 2003 FN study

Brack

Bodmer

Simon

et al. 2012

Pediatric Blood & Cancer

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BackgroundThe standard treatment of fever in chemotherapy‐induced neutropenia (FN) includes emergency hospitalization and empirical intravenous antimicrobial therapy. This study determined if first‐day step‐down to oral outpatient treatment is not inferior to continued standard regarding safety and efficacy in children with low‐risk FN.ProcedureIn a randomized controlled non‐blinded multicenter study, pediatric patients with FN after non‐myeloablative chemotherapy were reassessed after 8–22 hours of inpatient intravenous antimicrobial therapy. Low‐risk patients were randomized to first‐day step‐down to experimental (outpatient, oral amoxicillin plus ciprofloxacin) versus continued standard treatment. Exact non‐inferiority tests were used for safety (no serious medical complication; non‐inferiority margin of difference, 3.5%) and efficacy (resolution of infection without recurrence, no modification of antimicrobial therapy, no adverse event; 10%).ResultsIn 93 (26%) of 355 potentially eligible FN episodes low‐risk criteria were fulfilled, and 62 were randomized, 28 to experimental (1 lost to follow‐up) and 34 to standard treatment. In intention‐to‐treat analyses, non‐inferiority was not proven for safety [27 of 27 (100%) vs. 33 of 34 (97%; 1 death) episodes; 95% upper confidence border, 6.7%; P = 0.11], but non‐inferiority was proven for efficacy [23 of 27 (85%) vs. 26 of 34 (76%) episodes; 95% upper confidence border, 9.4%; P = 0.045]. Per‐protocol analyses confirmed these results.ConclusionsIn children with low‐risk FN, the efficacy of first‐day step‐down to oral antimicrobial therapy with amoxicillin and ciprofloxacin in an outpatient setting was non‐inferior to continued hospitalization and intravenous antimicrobial therapy. The safety of this procedure, however, was not assessable with sufficient power. Pediatr Blood Cancer 2012;59:423–430. © 2012 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 93%

First‐day step‐down to oral outpatient treatment versus continued standard treatment in children with cancer and low‐risk fever in neutropenia. A randomized controlled trial within the multicenter SPOG 2003 FN study

Brack

Bodmer

Simon

et al. 2012

Pediatric Blood & Cancer

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“…Documented mortality associated with paediatric febrile neutropenia is 2% [2]. The potential for early diagnosis of bacteraemia through serum biomarkers has been the subject to extensive research [3].…”

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confidence: 99%

The role of CRP, PCT, IL-6 and presepsin in early diagnosis of bacterial infectious complications in paediatric haemato-oncological patients

Plesko¹,

Suvada²,

Makohusová³

et al. 2016

neo

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Bacterial infection is the most common complication in paediatric oncological patients during cancer treatment. A suitable tool for early prediction of unfavourable course of infection is still needed. We performed a prospective longitudinal observational study to evaluate of the role of serum biomarkers (C-reactive protein, procalcitonin, interleukin-6, presepsin) in the early diagnosis of bacteraemia (gram-negative versus gram-positive) in patients with haematological malignancies. We observed 69 febrile episodes in 33 patients (17 male, 16 female; 1.5-18.9 years, mean 7.31 years, median 5 years). Within this sample, there were 22 cases of positive blood cultures, 16 cases of sepsis, 38 cases of fever with no signs or symptoms of sepsis, and two deaths from infectious complications. All markers tested had good negative predictive value (73% -93%). CRP was characterized by good specificity for registration bacteraemia (96%, 95% CI: 85% -99%), but other results were inconclusive. We identified comparably balanced sensitivity (64% -81%) and specificity (61% -88%) for interleukin-6 and procalcitonin, and we proved their quality to predict positive blood culture and clinical signs of sepsis as well. Patients with gram-negative bacteraemia had significantly elevated levels of PCT and IL-6 in comparison with a group of patients with gram-positive bacteraemia (p = 0.04 for PCT and p = 0.005 for IL-6). Presepsin was characterized by poor specificity (27%, 95% CI: 15% -43%) and positive predictive value (24%, 95% CI: 12 -39%) for predicting bacteraemia, and by better sensitivity (84%, 95% CI: 55% -98%) and specificity (58%, 95% CI: 42% -73%) for predicting clinical signs of sepsis. Key words: C-reactive protein, procalcitonin, interleukin-6, presepsin, fever, sepsisBacterial infection is the most common treatment-related complication in patients with haematological malignancies [1]. Documented mortality associated with paediatric febrile neutropenia is 2% [2]. The potential for early diagnosis of bacteraemia through serum biomarkers has been the subject to extensive research [3]. In 2012 Phillips et al published large meta-analysis of 25 studies exploring 14 different biomarkers in 3,585 episodes of febrile neutropenia. CRP, PCT and IL-6 were subject to quantitative meta-analysis. The bivariate estimates of diagnostic precision of these biomarkers and outcomes were done. Data were available for meta-analysis for CRP for microbiologically or clinically documented infection (results: cut off > 50mg/dl, sensitivity 65%, specificity 73%), for PCT assessing microbiologically or clinically documented infection (results: cut off > 0.2 mg/ml, sensitivity 96%, specificity 85%), for IL-6 reporting microbiologically or clinically documented infection (results: cut off > 235 pg/ml, sensitivity 68%, specificity 94%), and gram-negative bacteraemia (results: cut off > 1000 pg/ml, sensitivity 78%, specificity 96%). Huge inconsistencies and heterogeneity in the studies included in this review were the most important limiting factors [...

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“…Although severe neutropenia (ANC <500 cells/ mm 3 ) has been linked to poor outcomes in febrile cancer patients, 9 our study demonstrated that, in immunocompromised children with a CVC and fever, the presence or absence of severe neutropenia at presentation did not predict the likelihood of bacteremia. These results are in concordance with a report by Schwartz et al, who observed no significant difference in the incidence of bacteremia between neutropenic and non-neutropenic pediatric cancer patients with CVCs (27.6% and 29.1%, respectively).…”

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confidence: 61%

Emesis predicts bacteremia in immunocompromised children with central venous catheters and fever

Richardson

Grewal²,

Visintainer

2009

Cancer

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BACKGROUND:The objective of this study was to determine whether vomiting at presentation of a febrile illness in immunocompromised children with central venous catheters (CVCs) predicts bacteremia.METHODS:A chart review was conducted of children who were admitted to the hospital with a diagnosis of cancer or aplastic anemia, fever, and a CVC. Data were collected on the presence or absence of vomiting, catheter type, presence or absence of severe neutropenia, C‐reactive protein (Crp) value, and culture results.RESULTS:There were 143 admissions for fever among 48 children. Among 35 admissions with emesis, 19 included bacteremia; whereas, among 107 admissions without emesis, 19 included bacteremia (P < .001). There was a 5‐fold greater risk of bacteremia in children with children without vomiting (odds ratio, 5.50; 95% confidence interval, 2.20‐13.67). Gram‐negative organisms were more likely to be associated with vomiting than Gram‐positive organisms (P = .008). Children with severe neutropenia did not have a significantly higher rate of bacteremia than children who had neutrophil counts >500 cells/mm3. Other factors that were associated with higher rates of bacteremia were underlying diagnosis and catheter type.CONCLUSIONS:Immunocompromised children with a CVC and a fever who presented with vomiting were more likely to have bacteremia than similar children who presented without vomiting. Gram‐negative organisms were more likely to be associated with emesis than Gram‐positive organisms. The absence of severe neutropenia was not associated with a decreased likelihood of bacteremia. These findings may be useful in identifying children who are at high risk for bacteremia and in determining initial, empiric therapy. Cancer 2009. © 2009 American Cancer Society.

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Admission Clinical and Laboratory Factors Associated With Death in Children With Cancer During a Febrile Neutropenic Episode

Abstract: We identified early clinical and laboratory findings significantly associated with death occurring at a later stage. Routine evaluation of these variables may prove to be useful in the early identification of children with a high-risk FN episode at risk for death.

Cited by 63 publications

References 21 publications

First‐day step‐down to oral outpatient treatment versus continued standard treatment in children with cancer and low‐risk fever in neutropenia. A randomized controlled trial within the multicenter SPOG 2003 FN study

First‐day step‐down to oral outpatient treatment versus continued standard treatment in children with cancer and low‐risk fever in neutropenia. A randomized controlled trial within the multicenter SPOG 2003 FN study

The role of CRP, PCT, IL-6 and presepsin in early diagnosis of bacterial infectious complications in paediatric haemato-oncological patients

Emesis predicts bacteremia in immunocompromised children with central venous catheters and fever

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