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.

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.

Cost effectiveness of outpatient treatment for febrile neutropaenia in adult cancer patients.

BACKGROUND: There is uncertainty whether low-risk episodes of febrile neutropaenia (FN) in adult cancer patients are best managed in the in- or outpatient setting. METHODS: A Monte Carlo cost-utility model was created to compare four treatment strategies for low-risk FN: (1) treatment in hospital with intravenous antibiotics (HospIV); (2) early discharge after 48 h in-patient observation, followed by oral outpatient treatment (EarlyDC); (3) outpatient management with IV antibiotics (HomeIV); and (4) outpatient management with oral antibiotics (HomePO). The model used a health-care payer perspective and a time horizon of one FN episode. Outcome measures were quality-adjusted FN episodes (QAFNE), costs (Canadian dollars) and incremental cost-effectiveness ratios (ICER). Parameter uncertainty was assessed with probabilistic sensitivity analyses. RESULTS: HomePO was cost saving ($3470 vs $4183), but less effective (0.65 QAFNE vs 0.72 QAFNE) than HomeIV. The corresponding ICER was $10,186 per QAFNE. Both EarlyDC ($6115; 0.66 QAFNE) and HospIV ($13,557; 0.62 QAFNE) were dominated strategies. At a willingness-to-pay (WTP) threshold of $4,000 per QAFNE, HomePO and HomeIV were cost effective in 54 and 38% of simulations, respectively. INTERPRETATION: For adult cancer patients with an episode of low-risk FN, treatment in hospital is more expensive and less effective than outpatient strategies.

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.

The impact of cyclosporin A on acute graft-versus-host disease after allogeneic bone marrow transplantation in children and adolescents with acute lymphoblastic leukemia.

Experimental and clinical data demonstrate an antileukemia effect of acute graft-versus-host disease (aGVHD). In all, 58 pediatric patients with acute lymphoblastic leukemia (ALL) who had received an allogeneic bone marrow transplant (BMT) at our institution were retrospectively analyzed for a correlation between the development of aGVHD and leukemic relapse. Probability of relapse after 5 (3) years was 13% (7%) in patients developing grade II-IV aGVHD vs 30% in patients with grade 0 or I aGVHD. There was a trend for a difference of the point estimates at 3 years, but no overall significance because of an unusual late relapse. Moreover, we analyzed the impact of cyclosporin A (CsA) on aGVHD in a subgroup of 22 children who had received a matched sibling donor (MSD) BMT. An increased dose of CsA within the first 2 weeks after BMT led to decreased occurrence and severity of aGVHD (P=0.035). The cumulative CsA dose appeared to have more impact than the average CsA whole-blood levels within the first 2 weeks and than the CsA dose given from day 15 to 40. In this subgroup, no life-threatening aGVHD or death from aGVHD occurred. In all cases (6/22), leukemic relapse was the cause of death. We therefore suggest that there is a relation between dose of CsA and relapse rate in childhood ALL transplanted from a MSD.

Prenatal origin of separate evolution of leukemia in identical twins.

Several studies involving identical twins with concordant leukemia and retrospective scrutiny of archived neonatal blood spots have shown that the TEL-AML1 fusion gene in childhood acute lymphoblastic leukemia (ALL) frequently arises before birth. A prenatal origin of childhood leukemia was further supported by the detection of clonotypic immunoglobulin gene rearrangements on neonatal blood spots of children with various other subtypes of ALL. However, no comprehensive study is available linking these clonotypic events. We describe a pair of 5-year-old monozygotic twins with concordant TEL-AML1-positive ALL. Separate leukemic clones were identified in the diagnostic samples since distinct IGH and IGK-Kde gene rearrangements could be detected. Additional differences characterizing the leukemic clones included an aberration of the second, nonrearranged TEL allele observed in one twin only. Interestingly, both the identical TEL-AML1 fusion sequence and distinct immunoglobulin gene rearrangements were identified on the neonatal blood spots indicating that separate preleukemic clones evolved already before birth. Finally, we compared the reported twins with an additional 31 children with ALL by using the microarray technology. Gene expression profiling provided evidence that leukemia in twins harbours the same subtype-typical feature as TEL-AML1-positive leukemia in singletons suggesting that the leukemogenesis model might also be applicable generally.

Preliminary experience with the angiotensin II receptor antagonist irbesartan in chronic kidney disease.

UNLABELLED: Blocking the formation of angiotensin II with converting enzyme inhibitors is an established intervention for kidney disease. The advent of antagonists of the angiotensin II receptor has increased the options for inhibiting the renin-angiotensin-aldosterone system. In adults, angiotensin II antagonists have antihypertensive and antiproteinuric effects similar to those of converting enzyme inhibitors and an adverse effect profile similar to that of placebo. In children, no information is available on angiotensin II antagonists. A total of 20 children (aged 4 to 17 years) with chronic kidney disease received the angiotensin II antagonist irbesartan given once daily. They had hypertension (n = 11), overt proteinuria (n = 3), or both (n = 6). At last follow-up, 2 to 17 months after starting irbesartan (median dosage: 3.3 mg/kg body weight daily), arterial pressure was significantly reduced: the systolic value by 16 [6-22] and the diastolic value by 11 [4-22] mmHg (median and interquartile range). In nine patients with proteinuria, the urinary albumin/creatinine ratio significantly decreased by 145 [105-209] mg/mmol. The frequency of reported adverse events was similar before and with irbesartan. CONCLUSION: In children with chronic kidney disease the effects of the angiotensin II antagonist irbesartan on arterial pressure and proteinuria mimic those observed with the converting enzyme inhibitors. The effectiveness of a single daily dose and the paucity of side-effects suggest that angiotensin II antagonists expand therapeutic options for inhibiting the renin-angiotensin-aldosterone system in children.