Evaluation of treatment-related mortality among paediatric cancer deaths: a population based analysis.

BACKGROUND: Objectives were to describe the proportion of deaths due to treatment-related mortality (TRM) and to identify risk factors and probable causes of TRM among paediatric cancer deaths in a population-based cohort. METHODS: We included children with cancer ⩽18 years diagnosed and treated in Ontario who died between January 2003 and December 2012. Deaths were identified using a provincial registry, the Pediatric Oncology Group of Ontario Networked Information System. Probable causes of TRM were described. RESULTS: Among the 964 deaths identified, 821 were included. The median age at diagnosis was 6.6 years (range 0-18.8) and 51.8% had at least one relapse. Of the deaths examined, TRM occurred in 217/821 (26.4%) while 604/821 (73.6%) were due to progressive cancer. Deaths from TRM did not change over time. Using multiple regression, younger age, leukaemia diagnosis and absence of relapse were independently positively associated with TRM. The most common probable causes of TRM were respiratory, infection and haemorrhage. CONCLUSIONS: TRM was responsible for 26.4% of deaths in paediatric cancer. Underlying diagnosis, younger age and absence of relapse were associated with TRM and causes of TRM differed by diagnosis group. Future work should evaluate TRM rate and risk factors among newly diagnosed cancer patients.

Invasive Rothia infections in children with acute myeloid leukemia: A report from the Canadian infections in AML research group.

Rothia spp. (previously termed Stomatococcus) are normal flora that can cause invasive infections in immunocompromised hosts. The objective of this study was to describe infection characteristics and outcomes of Rothia spp. infections in a large cohort of children with newly diagnosed acute myeloid leukemia (AML). This retrospective chart review is a subanalysis of a larger study in which the aim was to identify factors associated with infection in pediatric patients with AML. Only sterile site infections occurring during chemotherapy were included. Among 578 children with AML, 17 (2.9%) children with at least 1 Rothia spp. infection were identified. All children were neutropenic at the time of infection. Eight (47%) had antecedent colitis or mucositis. Of the 17 infections, 16 were bacteremia and 1 was meningitis. Sepsis occurred in 4 patients, and 1 patient died due to infection. Rothia spp. infections are rare in pediatric AML but can cause significant morbidity and mortality. Future studies should describe trends in incidence and resistance patterns over time.

Impact of registration on clinical trials on infection risk in pediatric acute myeloid leukemia.

Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy-four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01-1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08-1.98; p = 0.015). Registration on trials was not associated with Gram-negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML.

Leukapheresis and low-dose chemotherapy do not reduce early mortality in acute myeloid leukemia hyperleukocytosis: a systematic review and meta-analysis.

The role of leukapheresis and low-dose chemotherapy is unclear in decreasing early mortality in acute myeloid leukemia (AML) patients with hyperleukocytosis. This systematic review was conducted to describe early mortality (deaths during first induction) in patients with AML with an initial white blood count≥100×10(9)L(-1) stratified by the approach to leukapheresis and hydroxyurea/low-dose chemotherapy. Twenty-one studies were included. Weighted mean early deaths rate (20 studies, 1354 patients) was 20.1% (95% confidence interval 15.0-25.1). Neither leukapheresis strategy (p=0.67) nor hydroxyurea/low-dose chemotherapy (p=0.23) influenced the early death rate. Early mortality related to hyperleukocytosis in AML is not influenced by universal or selected use of leukapheresis or hydroxyurea/low-dose chemotherapy.

Second Bacteremia During Antibiotic Treatment in Children With Acute Myeloid Leukemia: A Report From the Canadian Infections in Acute Myeloid Leukemia Research Group.

BACKGROUND: The risk of second bacteremia during antibiotic treatment for initial bacteremia is unknown in high-risk populations. Our objectives were to describe the prevalence of second bacteremia during treatment and identify risk factors in children with acute myeloid leukemia (AML). METHODS: We conducted a retrospective, population-based cohort study that included children and adolescents with de novo, non-M3 AML who were diagnosed and treated between January 1, 1995 and December 31, 2004 at 15 Canadian centers. Patients were monitored for bacteremia during chemotherapy until completion of treatment, hematopoietic stem cell transplantation, relapse, refractory disease, or death. RESULTS: There were 290 episodes of bacteremia occurring in 185 (54.3%) of 341 children. Eighteen (6.2%) had a second bacteremia while receiving antibiotic treatment. Two episodes of second bacteremia were complicated by sepsis; there were no infection-related deaths. Eleven episodes (61.1%) had either an initial Gram-positive and subsequent Gram-negative bacteremia or initial Gram-negative followed by Gram-positive bacteremia. Days receiving corticosteroids (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.07-1.12; P < .0001), cumulative dose of corticosteroids (OR, 1.04; 95% CI, 1.00-1.08; P = .035), and days of neutropenia from start of course to initial bacteremia (OR, 1.07; 95% CI, 1.02-1.12; P = .007) were significantly associated with second bacteremia. CONCLUSIONS: In pediatric AML, 6% of patients will experience a second bacteremia during antibiotic treatment; duration of corticosteroid exposure and neutropenia are risk factors. These patients remain at high risk for second bacteremia after identification of the initial bacteremia and warrant continued broad-spectrum treatment during profound neutropenia.

Predictors and outcomes of viridans group streptococcal infections in pediatric acute myeloid leukemia: from the Canadian infections in AML research group.

BACKGROUND: Viridans group streptococci (VGS) cause significant morbidity in children treated for acute myeloid leukemia (AML). Our goals were to determine the occurrence and impact of these infections in children treated for AML and to understand the factors that increase the risk of VGS infections and viridans streptococcal shock syndrome (VSSS) in this population. METHODS: We conducted a retrospective, population-based cohort study that included children ≤18 years of age with de novo AML treated at 15 Canadian centers. We evaluated factors related to VGS infection and VSSS. RESULTS: Among 341 children with AML, VGS occurred in 78 (22.9%) children over the entire course of therapy and 16 had recurrent episodes. VGS infection occurred in 97 of 1277 courses of chemotherapy (7.6%). VSSS occurred in 19.6% of these episodes and included 11 patients who required intensive care services with 2 VGS infections resulting in death. In multiple regression analysis, factors independently related to VGS included treatment on a Medical Research Council-based protocol (odds ratio (OR) 2.87, 95% confidence interval (CI) 1.53-5.39; P = 0.001), cytarabine dose per gram/m² (OR 1.04, 95% CI 1.01-1.07; P = 0.002) and prolonged neutropenia (OR 1.58, 95% CI: 0.97-2.56; P = 0.06). None of the evaluated factors were predictive of VSSS. CONCLUSIONS: VGS infections occur in 7.6% of chemotherapy courses and remain an important cause of morbidity and even mortality in children being treated for AML. Interventions to reduce VGS need to be identified.

Infections in children with down syndrome and acute myeloid leukemia: a report from the Canadian infections in AML research group.

BACKGROUND: Children with Down syndrome (DS) are at high risk of infectious toxicity when treated with acute lymphoblastic leukemia chemotherapy protocols optimized in children without DS. Our objective was to determine if children with DS and acute myeloid leukemia (AML) have a different risk of infection when treated with chemotherapy protocols developed for children with DS compared to AML treatment protocols developed for children without DS. METHODS: We conducted a retrospective, population-based cohort study that included DS children ≤ 18 years of age with de novo, non-M3 AML diagnosed between January 1995 and December 2004, and treated at 15 Canadian centers. Patients were monitored for infection from initiation of AML treatment until recovery from the last cycle of chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse, persistent disease or death (whichever occurred first). Trained research associates abstracted all information from each site. RESULTS: There were 31 children with DS included; median age was 1.7 (range 0.1-11.1) years. Eleven were treated according to a DS-specific protocol while 20 were treated with non-DS specific protocols. A total of 157 courses of chemotherapy were delivered. Microbiologically documented sterile site infection occurred in 11.9% and 14.3% of DS-specific and non-DS specific AML treatment courses respectively. Sepsis was rare and there were no infection-related deaths. In multiple regression, treatment with a DS-specific protocol was independently associated with a reduction in microbiologically documented sterile site infection (adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.42-0.99; P = 0.044), and clinically documented infection (adjusted OR 0.36, 95% CI 0.14-0.91; P = 0.031) but not bacteremia (adjusted OR 0.73, 95% CI 0.44-1.22; P = 0.231). CONCLUSIONS: Our study suggests that children with DS do not experience excessive infectious toxicity during treatment for AML compared to children without DS. Incorporation of DS-specific AML treatment protocols is associated with a more favorable infection profile for children with DS-AML.

Incidence, risk factors, and outcomes of enteritis, typhlitis, and colitis in children with acute leukemia.

This retrospective chart review describes pediatric patients with acute lymphoblastic leukemia or acute myeloid leukemia diagnosed between January 1999 and January 2008, who were identified with enteritis, typhlitis, or colitis. Among the acute leukemia patients, 33/449 (7.3%) with acute lymphoblastic leukemia and 13/89 (14.6%) with acute myeloid leukemia experienced 51 episodes of enteritis (n=8), typhlitis (n=15), colitis (n=19), or enterocolitis (n=9). Twenty-five (49%) patients were exposed to corticosteroids within 14 days of the episode and 35 (68.6%) had fever and neutropenia concurrent with the episode. Forty-eight (94%) patients were treated with complete bowel rest and broad-spectrum antibiotics. However, 3 patients received no therapy and had uneventful courses. Complications included sepsis in 7/51 (13.7%) and intestinal obstruction in 3/51 (5.9%). One child required surgery for abscess drainage and 2 children died of causes unrelated to their colitis. Enteritis, typhlitis, or colitis occurred in 8.6% of children treated for leukemia. The optimal management approach is uncertain.

Clostridium difficile infection in pediatric acute myeloid leukemia: from the Canadian Infections in Acute Myeloid Leukemia Research Group.

BACKGROUND: The prevalence and severity of Clostridium difficile infection (CDI) has increased over time in adult patients, but little is known about CDI in pediatric cancer. The primary objectives were to describe the incidence and characteristics of CDI in children with de novo acute myeloid leukemia (AML). The secondary objective was to describe factors associated with CDI. METHOD: We performed a multicenter, retrospective cohort study of children with de novo AML and evaluated CDI. Recurrence, sepsis and infection-related death were examined. Factors associated with CDI were also evaluated. RESULTS: Forty-three CDI occurred in 37 of 341 (10.9%) patients during 42 of 1277 (3.3%) courses of chemotherapy. There were 6 children with multiple episodes of CDI. Three infections were associated with sepsis, and no children died of CDI. Only 2 children had an associated enterocolitis. Both days of broad-spectrum antibiotics (odds ratio 1.03, 95% confidence interval: 1.01 to 1.06; P = 0.003) and at least 1 microbiologically documented sterile site infection (odds ratio 10.81, 95% confidence interval: 5.88 to 19.89; P < 0.0001) were independently associated with CDI. CONCLUSIONS: CDI occurred in 11% of children receiving intensive chemotherapy for AML, and outcomes were not severe. CDI is not a prominent issue in pediatric AML in terms of prevalence, incidence or associated outcomes.

Infections in pediatric acute promyelocytic leukemia: from the Canadian infections in acute myeloid leukemia research group.

BACKGROUND: It is not known whether children with acute promyelocytic leukemia (APL) have an infection risk similar to non- APL acute myeloid leukemia. The objective was to describe infectious risk in children with newly diagnosed APL and to describe factors associated with these infections. METHODS: We conducted a retrospective, population-based cohort study that included children ≤ 18 years of age with de novo APL treated at 15 Canadian centers. Thirty-three children with APL were included; 78.8% were treated with APL -specific protocols. RESULTS: Bacterial sterile site infection occurred in 12 (36.4%) and fungal sterile site infection occurred in 2 (6.1%) children. Of the 127 chemotherapy courses, 101 (79.5%) were classified as intensive and among these, the proportion in which a sterile site microbiologically documented infection occurred was 14/101 (13.9%). There was one infection-related death. CONCLUSIONS: One third of children with APL experienced at least one sterile site bacterial infection throughout treatment and 14% of intensive chemotherapy courses were associated with a microbiologically documented sterile site infection. Infection rates in pediatric APL may be lower compared to non- APL acute myeloid leukemia although these children may still benefit from aggressive supportive care during intensive chemotherapy.

Infectious events prior to chemotherapy initiation in children with acute myeloid leukemia.

BACKGROUND: The primary objective was to describe infectious complications in children with acute myeloid leukemia from presentation to the healthcare system to initiation of chemotherapy and to describe how these infections differ depending on neutropenia. METHODS: We conducted a retrospective, population-based cohort study that included children and adolescents with acute myeloid leukemia diagnosed and treated at 15 Canadian centers. We evaluated infections that occurred between presentation to the healthcare system (for symptoms that led to the diagnosis of acute myeloid leukemia) until initiation of chemotherapy. RESULTS: Among 328 children, 92 (28.0%) were neutropenic at presentation. Eleven (3.4%) had sterile-site microbiologically documented infection and four had bacteremia (only one Gram negative). Infection rate was not influenced by neutropenia. No child died from an infectious cause prior to chemotherapy initiation. CONCLUSION: It may be reasonable to withhold empiric antibiotics in febrile non-neutropenic children with newly diagnosed acute myeloid leukemia until initiation of chemotherapy as long as they appear well without a clinical focus of infection. Future work could examine biomarkers or a clinical score to identify children presenting with leukemia and fever who are more likely to have an invasive infection.

The GRADE approach is reproducible in assessing the quality of evidence of quantitative evidence syntheses.

OBJECTIVE: We evaluated the inter-rater reliability (IRR) of assessing the quality of evidence (QoE) using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. STUDY DESIGN AND SETTING: On completing two training exercises, participants worked independently as individual raters to assess the QoE of 16 outcomes. After recording their initial impression using a global rating, raters graded the QoE following the GRADE approach. Subsequently, randomly paired raters submitted a consensus rating. RESULTS: The IRR without using the GRADE approach for two individual raters was 0.31 (95% confidence interval [95% CI] = 0.21-0.42) among Health Research Methodology students (n = 10) and 0.27 (95% CI = 0.19-0.37) among the GRADE working group members (n = 15). The corresponding IRR of the GRADE approach in assessing the QoE was significantly higher, that is, 0.66 (95% CI = 0.56-0.75) and 0.72 (95% CI = 0.61-0.79), respectively. The IRR further increased for three (0.80 [95% CI = 0.73-0.86] and 0.74 [95% CI = 0.65-0.81]) or four raters (0.84 [95% CI = 0.78-0.89] and 0.79 [95% CI = 0.71-0.85]). The IRR did not improve when QoE was assessed through a consensus rating. CONCLUSION: Our findings suggest that trained individuals using the GRADE approach improves reliability in comparison to intuitive judgments about the QoE and that two individual raters can reliably assess the QoE using the GRADE system.

Psychometric properties of instruments used to measure fatigue in children and adolescents with cancer: a systematic review.

CONTEXT: Despite the recognized distressing symptom of fatigue in children with cancer, little information is available to assist in the selection of an instrument to be used to measure fatigue. OBJECTIVES: The objectives of this study were to 1) describe the instruments that have been used to measure cancer-related fatigue in children and adolescents and 2) summarize the psychometric properties of the most commonly used instruments used to measure fatigue in children and adolescents with cancer. METHODS: Five major electronic databases were systematically searched for studies using a fatigue measurement scale in a population of children or adolescents with cancer. Fatigue scales used in those studies were included in the review. RESULTS: From a total of 1753 articles, 25 were included. We identified two main fatigue measurement instruments used in a pediatric oncology population: 1) the Fatigue Scale-Child/Fatigue Scale-Adolescent and the proxy report versions for parents and staff and 2) the PedsQL™ Multidimensional Fatigue Scale. These two scales show similar attributes with reasonably good internal consistency and responsiveness. CONCLUSION: Either the Fatigue Scale or PedsQL Multidimensional Fatigue Scale can be incorporated into clinical research. Future research should focus on identifying specific fatigue measures more suited to different purposes such as comparative trials or identification of high-risk groups.

Attitudes toward infection prophylaxis in pediatric oncology: a qualitative approach.

BACKGROUND: The risks and benefits of infection prophylaxis are uncertain in children with cancer and thus, preferences should be considered in decision making. The purpose of this report was to describe the attitudes of parents, children and healthcare professionals to infection prophylaxis in pediatric oncology. METHODS: THE STUDY WAS COMPLETED IN THREE PHASES: 1) An initial qualitative pilot to identify the main attributes influencing the decision to use infection prophylaxis, which were then incorporated into a discrete choice experiment; 2) A think aloud during the discrete choice experiment in which preferences for infection prophylaxis were elicited quantitatively; and 3) In-depth follow up interviews. Interviews were recorded verbatim and analyzed using an iterative, thematic analysis. Final themes were selected using a consensus approach. RESULTS: A total of 35 parents, 22 children and 28 healthcare professionals participated. All three groups suggested that the most important factor influencing their decision making was the effect of prophylaxis on reducing the chance of death. Themes of importance to the three groups included antimicrobial resistance, side effects of medications, the financial impact of outpatient prophylaxis and the route and schedule of administration. CONCLUSION: Effect of prophylaxis on risk of death was a key factor in decision making. Other identified factors were antimicrobial resistance, side effects of medication, financial impact and administration details. Better understanding of factors driving decision making for infection prophylaxis will help facilitate future implementation of prophylactic regiments.

Discrete choice experiment to evaluate factors that influence preferences for antibiotic prophylaxis in pediatric oncology.

BACKGROUND: Bacterial and fungal infections in pediatric oncology patients cause morbidity and mortality. The clinical utility of antimicrobial prophylaxis in children is uncertain and the personal utility of these agents is disputed. Objectives were to use a discrete choice experiment to: (1) describe the importance of attributes to parents and healthcare providers when deciding between use and non-use of antibacterial and antifungal prophylaxis; and (2) estimate willingness-to-pay for prophylactic strategies. METHODS: Attributes were chances of infection, death and side effects, route of administration and cost of pharmacotherapy. Respondents were randomized to a discrete choice experiment outlining hypothetical treatment options to prevent antibacterial or antifungal infections. Each respondent was presented 16 choice tasks and was asked to choose between two unlabeled treatment options and an opt-out alternative (no prophylaxis). RESULTS: 102 parents and 60 healthcare providers participated. For the antibacterial discrete choice experiment, frequency of administration was significantly associated with utility for parents but not for healthcare providers. Increasing chances of infection, death, side effects and cost were all significantly associated with decreased utility for parents and healthcare providers in both the antibacterial and antifungal discrete choice experiment. Parental willingness-to-pay was higher than healthcare providers for both strategies. CONCLUSION: Chances of infection, death, side effects and costs were all significantly associated with utility. Parents have higher willingness-to-pay for these strategies compared with healthcare providers. This knowledge can help to develop prophylaxis programs.

Association between corticosteroids and infection, sepsis, and infectious death in pediatric acute myeloid leukemia (AML): results from the Canadian infections in AML research group.

BACKGROUND: Infection continues to be a major problem for children with acute myeloid leukemia (AML). Objectives were to identify factors associated with infection, sepsis, and infectious deaths in children with newly diagnosed AML. METHODS: We conducted a retrospective, population-based cohort study that included children ≤ 18 years of age with de novo, non-M3 AML diagnosed between January 1995 and December 2004, treated at 15 Canadian centers. Patients were monitored for infection from initiation of AML treatment until recovery from the last cycle of chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse, persistent disease, or death (whichever occurred first). Consistent trained research associates abstracted all information from each site. RESULTS: 341 patients were included. Median age was 7.1 years (interquartile range [IQR], 2.0-13.5) and 29 (8.5%) had Down syndrome. In sum, 26 (7.6%) experienced death as a first event. There were 1277 courses of chemotherapy administered in which sterile site microbiologically documented infection occurred in 313 courses (24.5%). Sepsis and infectious death occurred in 97 (7.6%) and 16 (1.3%) courses, respectively. The median days of corticosteroid administration was 2 per course (IQR, 0-6). In multiple regression analysis, duration of corticosteroid exposure was significantly associated with more microbiologically documented sterile site infection, bacteremia, fungal infection, and sepsis. The only factor significantly associated with infectious death was days of corticosteroid exposure (odds ratio, 1.05; 95% confidence interval, 1.02-1.08; P = .001). CONCLUSIONS: In pediatric AML, infection, sepsis, and infectious death were associated with duration of corticosteroid exposure. Corticosteroids should be avoided when possible for this population.

A systematic review of symptom assessment scales in children with cancer.

BACKGROUND: The objective was to describe symptom assessment scales that have been used in children with cancer. METHODS: We conducted electronic searches of OVID Medline and EMBASE in order to identify all symptom assessment scales that have been used in pediatric cancer. Two reviewers abstracted information from each identified study. Data collected included study demographics and information related to the instrument and children enrolled. We also collected information about the purpose of instrument administration and whether treatment was altered as a result of this information. RESULTS: Fourteen studies were identified which evaluated eight different symptom assessment scales. Eight studies used child self-report and all studies included children on active treatment for cancer although 4 studies also included children following completion of treatment. The most common purpose of instrument administration was to measure the prevalence of symptom burden (n = 8). None of the 14 studies used the scale to screen for symptoms and none changed patient management on the basis of identified symptoms. CONCLUSIONS: We failed to identify any symptom assessment scales that were used as a symptom screening tool. There is a need to develop such a tool for use in children with cancer.

Low socioeconomic status is associated with prolonged times to assessment and treatment, sepsis and infectious death in pediatric fever in El Salvador.

BACKGROUND: Infection remains the most common cause of death from toxicity in children with cancer in low- and middle-income countries. Rapid administration of antibiotics when fever develops can prevent progression to sepsis and shock, and serves as an important indicator of the quality of care in children with acute lymphoblastic leukemia and acute myeloid leukemia. We analyzed factors associated with (1) Longer times from fever onset to hospital presentation/antibiotic treatment and (2) Sepsis and infection-related mortality. METHOD: This prospective cohort study included children aged 0-16 years with newly diagnosed acute leukemia treated at Benjamin Bloom Hospital, San Salvador. We interviewed parents/caregivers within one month of diagnosis and at the onset of each new febrile episode. Times from initial fever to first antibiotic administration and occurrence of sepsis and infection-related mortality were documented. FINDINGS: Of 251 children enrolled, 215 had acute lymphoblastic leukemia (85.7%). Among 269 outpatient febrile episodes, median times from fever to deciding to seek medical care was 10.0 hours (interquartile range [IQR] 5.0-20.0), and from decision to seek care to first hospital visit was 1.8 hours (IQR 1.0-3.0). Forty-seven (17.5%) patients developed sepsis and 7 (2.6%) died of infection. Maternal illiteracy was associated with longer time from fever to decision to seek care (P = 0.029) and sepsis (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.09-8.63; P = 0.034). More infectious deaths occurred in those with longer travel time to hospital (OR 1.36, 95% CI 1.03-1.81; P = 0.031) and in families with an annual household income

Utility of peripheral blood cultures in patients with cancer and suspected blood stream infections: a systematic review.

PURPOSE: The utility of peripheral blood cultures in patients with cancer and/or hematopoietic stem cell transplantation (HSCT) recipients with central venous lines (CVL) and suspected blood stream infection (BSI) is controversial. Our main objective was to describe the proportion of bacteremia detected only by the peripheral blood (PB) culture in order to define its role in the evaluation of patients in this setting. METHODS: We performed electronic searches of OVID Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for studies of adults or children with cancer and/or HSCT that evaluated concurrent PB and CVL cultures and reported sufficient data to permit calculation of the primary outcome. The proportion of bacteremia identified by site of sample was used as the effect measure. The review was registered in PROSPERO: CRD42011001610. RESULTS: From 149 reviewed articles, 7 were included in the meta-analysis. In a total number of 10,370 paired blood cultures, bacteremia was detected in 17 %. Thirteen percent of BSI were only identified by PB, while 28 % of infections were only identified by CVL. CONCLUSIONS: PB cultures identified many episodes of bacteremia not detected in the CVL culture. This finding suggests that PB culture should be considered in the evaluation of patients with cancer and/or HSCT with suspected BSI.

Pandemic (H1N1) 2009 influenza in Canadian pediatric cancer and hematopoietic stem cell transplant patients.

BACKGROUND: The impact of pandemic H1N1 influenza (pH1N1) virus in pediatric cancer is uncertain. The objectives of this study were to characterize the clinical course of pH1N1 and identify factors associated with severe outcomes. METHODS: We conducted a Canadian multicenter retrospective review of children with cancer and stem cell transplant (SCT) recipients who were diagnosed with laboratory-confirmed pH1N1 infection between May 1, 2009 and January 31, 2010. RESULTS: We identified 100 (19 in wave 1 and 81 in wave 2) cases of pH1N1 infection. Median age was 8.7 years. 71% had a hematologic malignancy, and 20% received SCT. Median duration of fever and illness was 2 and 12.5 days, respectively. 51 (51.5%) were hospitalized for a median of 5 days, with no deaths and only 1 requiring admission to the intensive care unit. Radiologically confirmed pneumonia was diagnosed in 10 (10%). Interruption of chemotherapy or conditioning occurred in 43 patients. In multivariable analyses, age <5 years (relative to ≥ 10 years) and neutropenia were associated with hospitalization while neutropenia was associated with pneumonia. Despite oseltamivir use in 89%, viral shedding was prolonged (median, 46 days) and often persisted after symptom resolution. However, an extended treatment course (>5 days) correlated with shortened duration of viral shedding (P=0.041). CONCLUSIONS: pH1N1 infection in pediatric cancer and SCT patients infrequently caused complications but commonly interrupted cancer treatment. Persistent shedding of virus after illness resolution was common. Further research is needed to verify this finding as it could have implications for treatment guidelines and infection control practices.