Single nucleotide polymorphism in IL1B is associated with infection risk in paediatric acute myeloid leukaemia.

We evaluated single nucleotide polymorphisms (SNPs) associated with infection risk in children with newly diagnosed acute myeloid leukaemia (AML). We conducted a multicentre, prospective cohort study that included children aged ≤18 years with de novo AML. DNA was isolated from blood lymphocytes or buccal swabs, and candidate gene SNP analysis was conducted. Primary outcome was the occurrence of microbiologically documented sterile site infection during chemotherapy. Secondary outcomes were Gram-positive and -negative infections, viridans group streptococcal infection and proven/probable invasive fungal infection. Interpretation was guided by consistency in risk alleles and microbiologic agent with previous literature. Over the study period 254 children and adolescents with AML were enrolled. Overall, 190 (74.8%) had at least one sterile site microbiologically documented infection. Among the 172 with inferred European ancestry and DNA available, nine significant associations were observed; two were consistent with previous literature. Allele A at IL1B (rs16944) was associated with decreased microbiologically documented infection, and allele G at IL10 (rs1800896) was associated with increased risk of Gram-positive infection. We identified SNPs associated with infection risk in paediatric AML. Genotype may provide insight into mechanisms of infection risk that could be used for supportive-care novel treatments.

Invasive fungal infections in paediatric acute myeloid leukaemia.

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in paediatric acute myeloid leukaemia (AML). This study describes risk factors for IFI and IFI-related sepsis in this population. We conducted a population-based, retrospective cohort study of children with AML in Canada. IFIs during chemotherapy and prior to haematopoietic stem cell transplantation, relapse, persistent disease or death were identified. Risk factors for proven or probable IFI were examined. Among courses complicated by IFI, risk factors for sepsis were also evaluated. There were 341 children with AML included of which 41 (12.0%) experienced 46 different episodes of IFI. Candida species accounted for 23 (50.0%) of IFIs and Aspergillus spp. accounted for 14 (30.4%). Days of broad-spectrum antibiotics, days of corticosteroids and neutropenia at start of the course were independently associated with IFI. Only days of fever were independently associated with IFI-related sepsis. Invasive fungal infections occurred in 12.0% of paediatric AML patients. Risk factors for IFI and IFI-related sepsis were identified. This knowledge may help to consider targeted strategies.

Adolescents with acute lymphoblastic leukemia treated at pediatric versus adult hospitals.

BACKGROUND: The objective was to compare 5-year overall survival (OS) between adolescent and young adult (AYA) patients (age 15-19) with acute lymphoblastic leukemia (ALL) treated at a pediatric versus an adult center. PATIENTS AND METHODS: This was a population-based analysis using administrative data of Ontario ALL AYA patients diagnosed between 1986-2009. We calculated predicted survival proportions (PSPs) and 95% confidence intervals (CI). We also surveyed sites to determine whether pediatric or adult-based protocols were used in each period. RESULTS: Overall, 290 patients between 15-19 years of age were diagnosed with ALL during the study period; 144 patients (49.7%) were treated at an adult center. When adjusted for gender, age, income quintile and time period, AYA patients treated at a pediatric center did not have a significantly different PSP (0.65, 95% CI: 0.56-0.75) in comparison to those treated at an adult center (0.62, 95% CI 0.52-0.73; P = 0.87). Most AYA patients treated at adult centers received pediatric protocols in the recent periods. CONCLUSIONS: Using population-based data, AYA ALL patients had similar outcomes whether treated at a pediatric or an adult center. Early introduction of aggressive treatment protocols in adult centers may have negated differences in outcomes among AYA patients by site of care.

Mould-active compared with fluconazole prophylaxis to prevent invasive fungal diseases in cancer patients receiving chemotherapy or haematopoietic stem-cell transplantation: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Objectives were to compare systemic mould-active vs fluconazole prophylaxis in cancer patients receiving chemotherapy or haematopoietic stem cell transplantation (HSCT). METHODS: We searched OVID MEDLINE and the Cochrane Central Register of Controlled Trials (1948-August 2011) and EMBASE (1980-August 2011). Randomised controlled trials of mould-active vs fluconazole prophylaxis in cancer or HSCT patients were included. Primary outcome was proven/probable invasive fungal infections (IFI). Analysis was completed by computing relative risks (RRs) using a random-effects model and Mantel-Haenszel method. RESULTS: From 984 reviewed articles, 20 were included in this review. Mould-active compared with fluconazole prophylaxis significantly reduced the number of proven/probable IFI (RR 0.71, 95% CI 0.52 to 0.98; P=0.03). Mould-active prophylaxis also decreased the risk of invasive aspergillosis (IA; RR 0.53, 95% confidence interval (CI) 0.37-0.75; P=0.0004) and IFI-related mortality (RR 0.67, 95% CI 0.47-0.96; P=0.03) but is also associated with an increased risk of adverse events (AEs) leading to antifungal discontinuation (RR 1.95, 95% CI 1.24-3.07; P=0.004). There was no decrease in overall mortality (RR 1.0; 95% CI 0.88-1.13; P=0.96). CONCLUSION: Mould-active compared with fluconazole prophylaxis significantly reduces proven/probable IFI, IA, and IFI-related mortality in cancer patients receiving chemotherapy or HSCT, but increases AE and does not affect overall mortality. (PROSPERO Registration: CRD420111174).

Health-related quality of life anticipated with different management strategies for febrile neutropenia in adult cancer patients.

PURPOSE: To describe anticipated health-related quality of life (HRQL) for different hypothetical strategies of febrile neutropenia (FN) management in adult cancer patients. METHODS: Seventy-eight adult cancer patients were enrolled. Our study considered four different hypothetical treatment strategies for FN: (1) entire inpatient management with intravenous (IV) antibiotics; (2) oral treatment at home after an initial observation in hospital with IV antibiotics; (3) entire outpatient management with IV antibiotics; and (4) entire outpatient management with oral antibiotics. Initially, patients were asked to rank the different treatment strategies for FN based on their personal preference. Subsequently, HRQL was rated using visual analog scale (VAS), time trade-off (TTO), and willingness-to-pay (WTP). RESULTS: Seventy-five percent of all respondents preferred an outpatient strategy for FN (36% oral, 21% intravenous, 18% early discharge). Further, outpatient strategies were associated with higher mean VAS scores (possible range 0-10) (oral: 6.1 (standard deviation (SD) 3.1); intravenous: 6.2 (SD 2.2); early discharge: 5.7 (SD 2.1)) as compared to inpatient care (5.3 (SD 2.9)). On the aggregate level, patients were willing to give up between 9 and 10 weeks of their life (TTO; corresponding to <1% of remaining life expectancy) and to pay between $255 and $327 Canadian dollars (WTP) to avoid treatment in hospital. CONCLUSIONS: Our study indicates that the majority of adult cancer patients would prefer an outpatient strategy for FN. However, patients' preferences vary substantially at the individual level. Implementation of outpatient strategies into routine clinical practice should consider this variability.

Health-related quality of life anticipated with different management strategies for paediatric febrile neutropaenia.

BACKGROUND: To describe (1) anticipated health-related quality of life during different strategies for febrile neutropaenia (FN) management and (2) attributes of those preferring inpatient management. METHODS: Respondents were parents of children 0-18 years and children 12-18 years receiving cancer treatment. Anticipated health-related quality of life was elicited for four different FN management strategies: entire inpatient, early discharge, outpatient oral and outpatient intravenous (i.v.) therapy. Tools used to measure health-related quality of life were visual analogue scale (VAS), willingness to pay and time trade off. RESULTS: A total of 155 parents and 43 children participated. For parents, median VAS scores were highest for early discharge (5.9, interquartile range 4.4-7.2) and outpatient i.v. (5.9, interquartile range 4.4-7.3). For children, median scores were highest for early discharge (6.1, interquartile range 4.6-7.2). In contrast, the most commonly preferred strategy for parents and children was inpatient in 55.0% and 37.2%, respectively. Higher current child health-related quality of life was associated with a stronger preference for outpatient management. CONCLUSION: Early discharge and outpatient i.v. management are associated with higher anticipated health-related quality of life, although the most commonly preferred strategy was inpatient care. This data may help with determining more cost-effective strategies for paediatric FN.

Dexamethasone versus prednisone for induction therapy in childhood acute lymphoblastic leukemia: a systematic review and meta-analysis.

This systematic review and meta-analysis compared the efficacy and toxicity of dexamethasone (DEX) versus prednisone (PRED) for induction therapy in childhood acute lymphoblastic leukemia (ALL). We searched biomedical literature databases and conference proceedings for randomized controlled trials comparing DEX and PRED during induction therapy for childhood ALL. A total of eight studies were eligible for inclusion in this meta-analysis. DEX, in comparison with PRED, reduced events (that is, death from any cause, refractory or relapsed leukemia, or second malignancy; risk ratio (RR) 0.80; 95% confidence interval (CI), 0.68-0.94) and central nervous system relapse (RR 0.53; 95% CI, 0.44-0.65), but did not alter bone marrow relapse (RR 0.90; 95% CI, 0.69-1.18) or overall mortality (RR 0.91; 95% CI, 0.76-1.09). Patients receiving DEX had a higher risk of mortality during induction (RR 2.31; 95% CI, 1.46-3.66), neuro-psychiatric adverse events (RR 4.55; 95% CI, 2.45-8.46) and myopathy (RR 7.05; 95% CI, 3.00-16.58). There was no statistically significant difference in the risk of osteonecrosis, sepsis, fungal infection, diabetes or pancreatitis. DEX in induction therapy for children with ALL is more efficacious than PRED. However, DEX is also associated with more toxicity, and currently it remains unclear whether short-term superiority of DEX will also result in better overall survival.

Outpatient management of cancer patients with febrile neutropenia: a systematic review and meta-analysis.

BACKGROUND: In some centers, outpatient management for cancer patients with low-risk febrile neutropenia (FN) has been implemented into routine clinical practice. Our objective was to evaluate the current level of evidence before supporting widespread adoption of outpatient management for this population. METHODS: We systematically reviewed randomized controlled trials evaluating efficacy and safety of outpatient management of FN. RESULTS: From 1448 reviewed articles, 14 studies were included for meta-analysis. (i) Inpatient versus outpatient setting (6 studies) was not significantly associated with treatment failure [risk ratio 0.81; 95% confidence interval (CI) 0.55-1.19; P = 0.28]. Death occurred in 13 of 742 FN episodes with no difference between the two groups (risk ratio 1.11; 95% CI 0.41-3.05; P = 0.83). (ii) Outpatient oral versus outpatient parenteral antibiotics (8 studies) were similarly efficacious with no association between route of drug administration and treatment failure (risk ratio 0.93; 95% CI 0.65-1.32; P = 0.67). No death occurred in 857 FN episodes. CONCLUSION: Based on the current literature, outpatient treatment of FN is a safe and efficacious alternative to inpatient management. Variation between studies in terms of time to discharge, choice of antibiotic class, and age of study population may limit the interpretation of the data.