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1.
Haematologica ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029509

RESUMO

New therapeutic strategies are needed for pediatric acute myeloid leukemia to reduce disease recurrence and treatment-related morbidity. The Children's Oncology Group Phase III AAML1031 trial tested whether the addition of bortezomib to standard chemotherapy improves survival in pediatric patients with newly diagnosed acute myeloid leukemia. AAML1031 randomized patients younger than 30 years of age with de novo acute myeloid leukemia to standard treatment with or without bortezomib. All patients received the identical chemotherapy backbone with either four intensive chemotherapy courses or three courses followed by allogeneic hematopoietic stem cell transplantation for high-risk patients. For those randomized to the intervention arm, bortezomib 1.3 mg/m2 was given on days 1, 4 and 8 of each chemotherapy course. For those randomized to the control arm, bortezomib was not administered. In total, 1097 patients were randomized to standard chemotherapy (n=542) or standard chemotherapy with bortezomib (n=555). Remission induction rate did not differ between bortezomib and control treatment arms (89% vs 91%, p=0.531). Bortezomib failed to improve three-year event-free survival (44.8+/-4.5% vs 47.0+/-4.5%, p=0.236) or overall survival (63.6+/-4.5 vs 67.2+/-4.3, p=0.356) compared with the control arm. However, bortezomib was associated with significantly more peripheral neuropathy (p=0.006), and intensive care unit admissions (p=0.025) during the first course. The addition of bortezomib to standard chemotherapy increased toxicity but did not improve survival. These data do not support the addition of bortezomib to standard chemotherapy in children with de novo acute myeloid leukemia. (NCT01371981; https://www.cancer.gov/clinicaltrials/NCT01371981).

2.
Clin Infect Dis ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32067048

RESUMO

BACKGROUND: There is no uniform guideline for post-chemotherapy vaccination of children with acute lymphoblastic leukemia (ALL). We evaluated waning immunity to 14 pneumococcal serotypes, pertussis toxin (PT), tetanus toxoid (TT) and varicella, and immunogenicity of post-chemotherapy DTaP-IPV-Hib and pneumococcal vaccination among previously vaccinated children treated for ALL. METHODS: This was a multi-center trial of children with ALL enrolled 4-12 months post-chemotherapy completion. Exclusion criteria included: infant ALL, relapsed ALL, and stem cell transplant recipients. Immunocompetent children were recruited as controls. Post-chemotherapy participants received DTaP-IPV-Hib and 13-valent pneumococcal conjugate vaccine (PCV13) concurrently, followed by 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later. Serology was measured at baseline, 2 and 12 months post-vaccination. Adverse events were captured via surveys. RESULTS: At enrollment, post-chemotherapy participants (n=74) were less likely than controls (n=78) to be age-appropriately immunized with DTaP (41% versus 89%, p<0.001) and PCV (59% versus 79%, p=0.008). Geometric mean concentrations (GMCs) to TT, PT, PCV serotypes, and varicella were lower in post-chemotherapy participants than controls after adjusting for previous vaccine doses (p<0.001). Two months post-vaccination, GMCs to TT, PT and PCV serotypes increased from baseline (p<0.001 for all antigens) and remained elevated at 12 months post-vaccination. Antibody levels to PPV23 serotypes also increased post-vaccination (p<0.001). No serious adverse events were reported. CONCLUSIONS: Children treated for ALL had lower antibody levels than controls against pneumococcal serotypes, tetanus, pertussis and varicella despite previous vaccination. Post-chemotherapy vaccination with DTaP-IPV-Hib, PCV13 and PPV23 was immunogenic and well tolerated. Children with ALL would benefit from systematic revaccination post-chemotherapy.Clinicaltrials.gov identifier: NCT02447718.

3.
Eur J Cancer Prev ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032155

RESUMO

An infectious trigger for childhood acute lymphoblastic leukemia is hypothesized and we assessed the association between the rate, type, and critical exposure period for infections and the development of acute lymphoblastic leukemia. We conducted a matched case-control study using administrative databases to evaluate the association between the rate of infections and childhood acute lymphoblastic leukemia diagnosed between the ages of 2-14 years from Ontario, Canada and we used a validated approach to measure infections. In 1600 cases of acute lymphoblastic leukemia, and 16 000 matched cancer-free controls aged 2-14 years, having >2 infections/year increased the odds of childhood acute lymphoblastic leukemia by 43% (odds ratio = 1.43, 95% confidence interval 1.13-1.81) compared to children with ≤0.25 infections/year. Having >2 respiratory infections/year increased odds of acute lymphoblastic leukemia by 28% (odds ratio =1.28, 95% confidence interval 1.05-1.57) compared to children with ≤0.25 respiratory infections/year. Having an invasive infection increased the odds of acute lymphoblastic leukemia by 72% (odds ratio =1.72, 95% confidence interval 1.31-2.26). Having an infection between the age of 1-1.5 years increased the odds of acute lymphoblastic leukemia by 20% (odds ratio = 1.20, 95% confidence interval 1.04-1.39). Having more infections increased the odds of developing childhood acute lymphoblastic leukemia and having an infection between the ages of 1-1.5 years increased the odds of childhood acute lymphoblastic leukemia.

4.
Support Care Cancer ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974769

RESUMO

PURPOSE: Prescribing guideline-recommended anti-emetics is an effective strategy to prevent CINV. However, the rate of guideline-concordant care is not well-understood. The purpose of this study was to describe the proportion of pediatric, adolescent, and young adult patients receiving HEC or MEC who received guideline-concordant antiemetic prophylaxis for acute CINV and to identify potential predictors of guideline-concordant antiemetic prophylaxis. METHODS: Using electronic health record data from 2016 through 2018, a retrospective single-institution cohort study was conducted to investigate how often patients less than 26 years of age receiving moderately or highly emetogenic chemotherapy receive guideline-concordant prophylaxis for acute CINV. Guideline-concordant care was defined according to guidelines from the Pediatric Oncology Group of Ontario for patients < 18 years and the American Society of Clinical Oncology for those ≥ 18 years. Independent variables included: sex, age, insurance status, race, ethnicity, cancer type, chemotherapy regimen, clinical setting, chemotherapy emetogenicity, and patient location. Predictors of receiving guideline-concordant care were determined using multiple logistic regression. RESULTS: Of 180 eligible patients, 65 (36.1%) received guideline-concordant care. In multivariable analysis, being treated in adult oncology setting (aOR 14.3, CI95 5.3-38.6), with a cisplatin-based regimen (aOR 3.5, CI951.4-9.0), solid tumor diagnosis (aOR 2.2, CI95 1.0-4.8), and commercial insurance (aOR 2.4, CI95 1.1-5.2) were associated with significantly higher likelihood of receiving guideline-concordant care. CONCLUSIONS: Multi-level factors were associated with receiving guideline concordant care for prevention of CINV in children, adolescents, and young adults receiving emetogenic chemotherapy. These findings can inform current efforts to optimize implementation strategies for supportive care guidelines.

5.
Pediatr Blood Cancer ; : e28170, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31975542

RESUMO

Terms used to label types of clinical recommendations and guidance are applied inconsistently and do not reflect the methods used to create each type. Here, the international Pediatric Oncology Supportive Care Guideline Network proposes a lexicon for types of recommendations and guidance documents. A lexicon describing three types of recommendations (clinical practice guideline-derived, good practice statement, and expert opinion statement) and two types of guidance documents (clinical practice guideline and expert opinion) is presented. Consistent use of this lexicon will allow pediatric oncology clinicians to readily appreciate the methods used to create clinical guidance.

6.
Med Hypotheses ; 137: 109554, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31945656

RESUMO

Leukemia is the most common childhood cancer. While infections are a frequent and potentially severe complication while on treatment, less is known about the risk for infections following therapy completion. In this article, we propose that leukemia survivors might be at increased risk of infections following therapy completion than the general population, independently of potential confounders such as age, sex and Down syndrome. This association is conceivably due to several factors. First, therapy-induced immune dysfunction of both the humoral and cellular compartments appears to last for several years following anti-cancer therapy and after hematopoietic stem cell transplantation. Second, clinical and epidemiological research has shown leukemia survivors are disproportionally affected by comorbidities related to leukemia treatment and its complications, such as diabetes and obesity, which may induce secondary immunodeficiency and infections. Last, differences in health-related behaviors between leukemia survivors and the general population (such as re-vaccination practices) may affect the baseline risk of infections. Although under-represented in the epidemiological literature as a possible late effect of childhood leukemia and its treatment, it is plausible that leukemia survivors are at increased risk of infections for several years when compared to the general population and their siblings. Further research is needed to empirically test these hypotheses.

7.
Support Care Cancer ; 28(3): 1369-1383, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31264188

RESUMO

PURPOSE: Prompt antibiotic therapy is standard of care for patients with fever and neutropenia (FN) during chemotherapy for cancer. We systematically reviewed the association between time to antibiotics (TTA) and clinical outcomes. METHODS: The search covered seven databases; confounding biases and study quality were assessed with the ROBINS-I tool. Safety (death, intensive care unit (ICU) admission, sepsis) and treatment adequacy (relapse of infection, persistence or recurrence of fever) were assessed as primary outcomes. RESULTS: Of 6296 articles identified, 13 observational studies were included. Findings regarding safety were inconsistent. Three studies controlling for triage bias showed a possible association between longer TTA and impaired safety. Meta-analysis for TTA ≤ 60 min versus > 60 min was feasible on four studies, with three studies each reporting on death (OR 0.78, 95%CI 0.16-3.69) and on ICU admission (OR 1.43, 95%CI 0.57-3.60). No study reported data on treatment adequacy. Triage bias, i.e. faster treatment of patients with worse clinical condition, was identified as a relevant confounding factor. CONCLUSION: There seems to be an association between longer TTA and impaired safety. More knowledge about TTA effects on safety are important to optimise treatment guidelines for FN. Controlling for triage and other biases is necessary to gain further evidence. TRIAL REGISTRATION: Registration: PROSPERO [http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018092948].

8.
Lancet Child Adolesc Health ; 4(2): 141-150, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31866182

RESUMO

Despite ototoxicity being a prevalent consequence of cisplatin chemotherapy, little guidance exists on interventions to prevent this permanent and progressive adverse event. To develop a clinical practice guideline for the prevention of cisplatin-induced ototoxicity in children and adolescents with cancer, we convened an international, multidisciplinary panel of experts and patient advocates to update a systematic review of randomised trials for the prevention of cisplatin-induced ototoxicity. The systematic review identified 27 eligible adult and paediatric trials that evaluated amifostine, sodium diethyldithiocarbamate or disulfiram, systemic sodium thiosulfate, intratympanic therapies, and cisplatin infusion duration. Regarding systemic sodium thiosulfate, the panel made a strong recommendation for administration in non-metastatic hepatoblastoma, a weak recommendation for administration in other non-metastatic cancers, and a weak recommendation against its routine use in metastatic cancers. Amifostine, sodium diethyldithiocarbamate, and intratympanic therapy should not be routinely used. Cisplatin infusion duration should not be altered as a means to reduce ototoxicity. Further research to determine the safety of sodium thiosulfate in patients with metastatic cancer is encouraged.

9.
Cancer ; 126(5): 949-957, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31869454

RESUMO

Adolescents and young adults (AYAs) are underrepresented in cancer clinical trials (CCTs). Limited trial enrollment slows progress in improving survival rates and prevents the collection of valuable biospecimens. A systematic literature review was conducted to assess barriers and facilitators to AYA enrollment in CCTs and to identify opportunities to improve enrollment. The PubMed MEDLINE, Web of Science, Scopus, and PsycINFO databases were searched to identify studies relevant to AYA CCT enrollment. Eligibility criteria included the qualitative and/or quantitative evaluation of barriers and facilitators to AYA enrollment. One hundred fifty-five unique publications were identified; 13 were included in the final analysis. Barriers to AYA enrollment in CCTs included a lack of existing trials applicable to the patient population, limited access to available CCTs, and a lack of physician awareness of relevant trials. Facilitators of enrollment included optimizing the research infrastructure, improving the awareness of available CCTs among providers, and enhancing communication about CCTs between providers and patients. In conclusion, the limited available research reports institution- and patient-level barriers and facilitators to AYA CCT enrollment. Because of persistent disparities in AYA enrollment, there is an urgent need to further identify the barriers and facilitators to AYA CCT enrollment to determine actionable areas for intervention.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31784465

RESUMO

OBJECTIVE: To evaluate the feasibility of a large prospective trial aimed at improving chemotherapy-induced nausea and vomiting (CINV) control in paediatric patients undergoing oral chemotherapy during acute lymphoblastic leukaemia (ALL) maintenance therapy. METHODS: English-speaking children, 4.0-17.99 years old and undergoing ALL maintenance treatment with an English-speaking guardian, were eligible to participate in this observational, serial, cross-sectional feasibility study. Data were collected from participants over one to three 7-day periods during months 2-3, 5-6 and 11-12 of ALL maintenance treatment. A future trial was considered feasible if the mean time to enrol 10 patients in each of three data collection periods was ≤1 year with ≥80% of patients returning evaluable data. CINV control was described as a secondary endpoint. RESULTS: Twenty-nine of 31 consenting patients (median age: 6.5 years, IQR: 5.1-9.2) completed the study: 10 in months 2-3, 10 in months 5-6 and 9 in months 11-12. The total time to recruit 29 patients was 1.2 years. In each of the three data collections periods, 72% of the patients provided evaluable data. Complete CINV control was reported in 6/21 (29%) evaluable study periods. CONCLUSIONS: A future trial to evaluate interventions to improve CINV control in patients with ALL undergoing oral maintenance chemotherapy as designed in this study is not feasible. An electronic data capture method and deferring patient recruitment until the mid-maintenance to late-maintenance phase should be considered in the design of a future trial.

11.
NPJ Genom Med ; 4: 30, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839986

RESUMO

Inherited bone marrow failure syndromes (IBMFSs) are genetically heterogeneous disorders with cytopenia. Many IBMFSs also feature physical malformations and an increased risk of cancer. Point mutations can be identified in about half of patients. Copy number variation (CNVs) have been reported; however, the frequency and spectrum of CNVs are unknown. Unfortunately, current genome-wide methods have major limitations since they may miss small CNVs or may have low sensitivity due to low read depths. Herein, we aimed to determine whether reanalysis of NGS panel data by normalized coverage value could identify CNVs and characterize them. To address this aim, DNA from IBMFS patients was analyzed by a NGS panel assay of known IBMFS genes. After analysis for point mutations, heterozygous and homozygous CNVs were searched by normalized read coverage ratios and specific thresholds. Of the 258 tested patients, 91 were found to have pathogenic point variants. NGS sample data from 165 patients without pathogenic point mutations were re-analyzed for CNVs; 10 patients were found to have deletions. Diamond Blackfan anemia genes most commonly exhibited heterozygous deletions, and included RPS19, RPL11, and RPL5. A diagnosis of GATA2-related disorder was made in a patient with myelodysplastic syndrome who was found to have a heterozygous GATA2 deletion. Importantly, homozygous FANCA deletion were detected in a patient who could not be previously assigned a specific syndromic diagnosis. Lastly, we identified compound heterozygousity for deletions and pathogenic point variants in RBM8A and PARN genes. All deletions were validated by orthogonal methods. We conclude that careful analysis of normalized coverage values can detect CNVs in NGS panels and should be considered as a standard practice prior to do further investigations.

12.
Clin Infect Dis ; 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31676904

RESUMO

INTRODUCTION: Bacteremia and other invasive bacterial infections are common among children with cancer receiving intensive chemotherapy and in pediatric recipients of hematopoietic stem cell transplantation (HSCT). Systemic antibacterial prophylaxis is one approach that can be used to reduce the risk of these infections. Our purpose was to develop a clinical practice guideline (CPG) for systemic antibacterial prophylaxis administration in pediatric cancer and HSCT patients. METHODS: An international and multi-disciplinary panel was convened with representation from pediatric hematology/oncology and HSCT, pediatric infectious diseases (including antibiotic stewardship), nursing, pharmacy, a patient advocate and a CPG methodologist. The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to generate recommendations based on the results of a systematic review of the literature. RESULTS: The systematic review identified 114 eligible randomized trials of antibiotic prophylaxis. The panel made a weak recommendation for systemic antibacterial prophylaxis for children receiving intensive chemotherapy for acute myeloid leukemia and relapsed acute lymphoblastic leukemia (ALL). Weak recommendations against the routine use of systemic antibacterial prophylaxis were made for children undergoing induction chemotherapy for ALL, autologous HSCT and allogeneic HSCT. A strong recommendation against its routine use was made for children whose therapy is not expected to result in prolonged severe neutropenia. If used, prophylaxis with levofloxacin was recommended during severe neutropenia. CONCLUSIONS: We present a CPG for systemic antibacterial prophylaxis administration in pediatric cancer and HSCT patients. Future research should evaluate the long-term effectiveness and adverse effects of prophylaxis.

13.
Support Care Cancer ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31707500

RESUMO

PURPOSE: Supportive care Prioritization, Assessment and Recommendations for Kids (SPARK) is a web-based application that enables symptom screening and access to clinical practice guidelines for symptom management. Objective was to determine the feasibility of a randomized trial of daily symptom screening for 5 days among children receiving cancer treatments. METHODS: We included English-speaking pediatric cancer and hematopoietic stem cell transplantation (HSCT) patients who were 8-18 years of age at enrollment and who were expected to be in the hospital or in clinic daily for five consecutive days. We randomized children to either undergo daily symptom screening with symptom reports provided to the healthcare team using the SPARK vs. standard of care. The primary endpoint was feasibility, defined as being able to enroll at least 30 participants within 1 year, and among those randomized to intervention, at least 75% completing symptom screening on at least 60% of on-study days. RESULTS: From July 2018 to November 2018, we enrolled and randomized 30 participants. The median age at enrollment was 12.5 (range 8-18) years. Among the intervention group, the median number of days Symptom Screening in Pediatrics Tool (SSPedi) was completed at least once was 5 (range 4 to 5), with one participant missing 1 day of symptom screening. Among all participants, baseline and day 5 SSPedi scores were obtained in 29/30 participants. CONCLUSION: A randomized trial of the SPARK with daily symptom screening for 5 days was feasible. It is now appropriate to proceed toward a definitive multi-center trial to test the efficacy of SPARK to improve symptom control.

14.
BMC Cancer ; 19(1): 1058, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694583

RESUMO

BACKGROUND: This report illustrates the importance of a detailed history and physical exam and careful analysis of hematologic parameters when diagnosing ITP. This case demonstrates that even with subtle deviations from typical ITP findings one must promptly reevaluate the diagnosis. This case also highlights the importance of peripheral smear review by an expert in pediatric hematopathology. CASE PRESENTATION: A previously healthy 10 year-old Asian boy presented with 2 months of easy bruising. Review of systems was negative for any constitutional symptoms. On examination, he appeared well but had numerous large ecchymoses. He had no appreciable lymphadenopathy or splenomegaly. The liver was palpable 1.5 cm below the costal margin. A complete blood count (CBC) showed: platelets = 17 × 109/L, hemoglobin = 128 g/L, white blood cell count = 5.43 × 109/L, and neutrophils = 1.63 × 109/L. A blood smear was reported as normal. Urate was 370 umol/L and lactate dehydrogenase (LDH) was 803 U/L. The child was admitted with a presumptive diagnosis of immune thrombocytopenic purpura (ITP) and treated with intravenous immunoglobulin. The following day, the blood smear was reviewed by a hematopathologist who identified blasts. A bone marrow aspiration (BMA) confirmed the diagnosis of precursor B-cell acute lymphoblastic leukemia. CONCLUSION: In children presenting with suspected ITP, leukemia should always be considered. A BMA was historically performed on all patients with presumed ITP to rule out leukemia. In 2011, the American Society of Hematology (ASH) stopped recommending routine BMA in patients suspected of having ITP. ASH advises in cases with unusual findings on history, physical examination or CBC, it is reasonable to perform a BMA. Our patient had mild hepatomegaly, which may have qualified him for a BMA. He also had an elevated LDH and urate, which are not listed as criteria for BMA by ASH but were considered atypical for ITP by the clinical team. A literature search did not reveal any primary data assessing these markers. While corticosteroids are a first line treatment in ITP, they must be reserved for when clinicians are confident that the patient does not have leukemia. Steroid administration prior to diagnosing leukemia results in delayed diagnosis and may increase the risk of complications and decrease survival.

15.
JAMA ; 322(17): 1673-1681, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31688884

RESUMO

Importance: Children, adolescents, and young adults with acute myeloid leukemia are at high risk of life-threatening invasive fungal disease with both yeasts and molds. Objective: To compare the efficacy of caspofungin vs fluconazole prophylaxis against proven or probable invasive fungal disease and invasive aspergillosis during neutropenia following acute myeloid leukemia chemotherapy. Design, Setting, and Participants: This multicenter, randomized, open-label, clinical trial enrolled patients aged 3 months to 30 years with newly diagnosed de novo, relapsed, or secondary acute myeloid leukemia being treated at 115 US and Canadian institutions (April 2011-November 2016; last follow-up June 30, 2018). Interventions: Participants were randomly assigned during the first chemotherapy cycle to prophylaxis with caspofungin (n = 257) or fluconazole (n = 260). Prophylaxis was administered during the neutropenic period following each chemotherapy cycle. Main Outcomes and Measures: The primary outcome was proven or probable invasive fungal disease as adjudicated by blinded central review. Secondary outcomes were invasive aspergillosis, empirical antifungal therapy, and overall survival. Results: The second interim efficacy analysis and an unplanned futility analysis based on 394 patients appeared to have suggested futility, so the study was closed to accrual. Among the 517 participants who were randomized (median age, 9 years [range, 0-26 years]; 44% female), 508 (98%) completed the trial. The 23 proven or probable invasive fungal disease events (6 caspofungin vs 17 fluconazole) included 14 molds, 7 yeasts, and 2 fungi not further categorized. The 5-month cumulative incidence of proven or probable invasive fungal disease was 3.1% (95% CI, 1.3%-7.0%) in the caspofungin group vs 7.2% (95% CI, 4.4%-11.8%) in the fluconazole group (overall P = .03 by log-rank test) and for cumulative incidence of proven or probable invasive aspergillosis was 0.5% (95% CI, 0.1%-3.5%) with caspofungin vs 3.1% (95% CI, 1.4%-6.9%) with fluconazole (overall P = .046 by log-rank test). No statistically significant differences in empirical antifungal therapy (71.9% caspofungin vs 69.5% fluconazole, overall P = .78 by log-rank test) or 2-year overall survival (68.8% caspofungin vs 70.8% fluconazole, overall P = .66 by log-rank test) were observed. The most common toxicities were hypokalemia (22 caspofungin vs 13 fluconazole), respiratory failure (6 caspofungin vs 9 fluconazole), and elevated alanine transaminase (4 caspofungin vs 8 fluconazole). Conclusions and Relevance: Among children, adolescents, and young adults with acute myeloid leukemia, prophylaxis with caspofungin compared with fluconazole resulted in significantly lower incidence of invasive fungal disease. The findings suggest that caspofungin may be considered for prophylaxis against invasive fungal disease, although study interpretation is limited by early termination due to an unplanned interim analysis that appeared to have suggested futility. Trial Registration: ClinicalTrials.gov Identifier: NCT01307579.


Assuntos
Antifúngicos/uso terapêutico , Caspofungina/uso terapêutico , Fluconazol/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Micoses/prevenção & controle , Adolescente , Adulto , Antifúngicos/efeitos adversos , Aspergilose/epidemiologia , Aspergilose/prevenção & controle , Caspofungina/efeitos adversos , Criança , Pré-Escolar , Término Precoce de Ensaios Clínicos , Feminino , Fluconazol/efeitos adversos , Humanos , Lactente , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/complicações , Masculino , Neutropenia/complicações , Adulto Jovem
16.
Cancer Med ; 8(15): 6634-6643, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31532076

RESUMO

BACKGROUND: Associations between body mass index (BMI), outcome, and leukemia-related factors in children with acute myeloid leukemia (AML) remain unclear. We investigated associations between pretherapeutic BMI, cytogenetic abnormalities, and outcome in a large multinational cohort of children with AML. METHODS: We included patients, age 2-17 years, diagnosed with de novo AML from the five Nordic countries (2004-2016), Hong Kong (2007-2016), the Netherlands and Belgium (2010-2016), and Canada and USA (1995-2012). BMI standard deviations score for age and sex was calculated and categorized according to the World Health Organization. Cumulative incidence functions, Kaplan-Meier estimator, Cox regression, and logistic regression were used to investigate associations. RESULTS: In total, 867 patients were included. The median age was 10 years (range 2-17 years). At diagnosis, 32 (4%) were underweight, 632 (73%) were healthy weight, 127 (15%) were overweight, and 76 (9%) were obese. There was no difference in relapse risk, treatment-related mortality or overall mortality across BMI groups. The frequency of t(8;21) and inv(16) increased with increasing BMI. For obese patients, the sex, age, and country adjusted odds ratio of having t(8;21) or inv(16) were 1.9 (95% confidence interval (CI) 1.1-3.4) and 2.8 (95% CI 1.3-5.8), respectively, compared to healthy weight patients. CONCLUSIONS: This study did not confirm previous reports of associations between overweight and increased treatment-related or overall mortality in children. Obesity was associated with a higher frequency of t(8;21) and inv(16). AML cytogenetics appear to differ by BMI status.

17.
Support Care Cancer ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31486984

RESUMO

PURPOSE: Multiple interventions have been developed aiming to reduce time to antibiotics (TTA) in patients with fever and neutropenia (FN) following chemotherapy for cancer. We evaluated their effect to reduce TTA and their impact on important clinical outcomes in a systematic review. METHODS: The search covered seven databases. Biases and quality of studies were assessed with the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. Interventions could be implemented in any setting and performed by any person included in the FN management. Absolute change of TTA was the primary outcome. Registration: PROSPERO (CRD42018092948). RESULTS: Six thousand two hundred ninety-six titles and abstracts were screened, 177 studies were retrieved and 30 studies were included. Risk of bias was moderate to serious in 28 studies and low in two studies. All but one study reported a reduction of TTA after the intervention. Various types of interventions were implemented; they most commonly aimed at professionals. Most of the studies made more than one single intervention. CONCLUSION: This review may help centers to identify their specific sources of delay and barriers to change and to define what intervention may be the best to apply. This review supports the assertion that TTA can be considered a measure of quality of care, emphasizes the importance of education and training, and describes the very different interventions which have effectively reduced TTA.

18.
J Clin Oncol ; 37(29): 2651-2660, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31393747

RESUMO

PURPOSE: Infections are a frequent complication during childhood leukemia treatment. Little is known about the infectious risk in survivors. We compared the relative rate (RR) of infections after treatment completion between pediatric leukemia survivors and the general population. METHODS: We performed a retrospective, population-based cohort study of children diagnosed with leukemia between 1992 and 2015 in Ontario, Canada, who were alive and relapse free 30 days after treatment completion (index date). Leukemia survivors were matched 5:1 with the general population by year of birth, sex, and rural status and stratified by initial treatment, including and excluding hematopoietic stem-cell transplantation (HSCT). The primary outcome was time to infections, as identified using validated diagnostic codes from administrative databases. Individuals were censored at the earliest of death, first relapse, loss to follow-up, or end of study. RESULTS: A total of 2,204 leukemia survivors were included and matched with 11,020 controls. The rate of infections was elevated after treatment completion compared with controls (RR, 1.51; 95% CI, 1.45 to 1.57) and at less than 1 year (RR, 1.77; 95% CI, 1.69 to 1.86); 1 to 4.99 years (RR, 1.66; 95% CI, 1.62 to 1.71), and 5 or more years (RR, 1.29; 95% CI, 1.22 to 1.36) from the index date. Among those whose initial treatment excluded HSCT, the rate remained elevated more than 5 years from the index date (RR, 1.29; 95% CI, 1.23 to 1.35). Infection-related death was significantly increased in leukemia survivors both among the entire cohort (hazard ratio, 149.3; 95% CI, 20.4 to 1,091.9) and among those without HSCT (hazard ratio, 92.7; 95% CI, 12.4 to 690.7). CONCLUSION: A significant association was found between a history of leukemia therapy and an increased risk of infections. Additional study is needed to establish which exposures in patients with leukemia lead to late infections.

19.
Int J Med Inform ; 130: 103940, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31450082

RESUMO

Cancer management, including supportive care, is complex and requires availability and synthesis of published and patient-specific data to make appropriate therapeutic decisions. Clinical decision support (CDS) may be an effective implementation strategy to support complex decision making although it is unclear whether it improves process outcomes, patient outcomes or both in cancer settings. We therefore conducted a systematic review to identify CDS that have been used to support therapeutic decision making in clinical cancer settings. Outcomes of interest included the effect of CDS on the process, such as clinician's decision making and effect on patient outcomes. Ten studies met inclusion criteria, with variability in the study design, setting, and intervention. Of the nine studies that measured process outcomes, five demonstrated significant improvement; and of the six that measured patient outcomes, four demonstrated significant improvement. All included studies utilized CDS that were informed by clinical practice guidelines. In conclusion, CDS to guide cancer therapeutic decision making is an understudied but promising area. Further research is needed.


Assuntos
Tomada de Decisões , Sistemas de Apoio a Decisões Clínicas/estatística & dados numéricos , Neoplasias/terapia , Humanos
20.
BMJ Open ; 7(1): [10], Aug. 28, 2019.
Artigo em Inglês | BIGG | ID: biblio-1010328

RESUMO

To develop an evidence-based clinical practice guideline for the prevention of oral mucositis in children (0-18 years) receiving treatment for cancer or undergoing haematopoietic stem cell transplantation (HSCT). The Mucositis Prevention Guideline Development Group was interdisciplinary and included internationally recognised experts in paediatric mucositis. For the evidence review, we included randomised controlled trials (RCTs) conducted in either children or adults evaluating the following interventions selected according to prespecified criteria: cryotherapy, low level light therapy (LLLT) and keratinocyte growth factor (KGF). We also examined RCTs of any intervention conducted in children. For all systematic reviews, we synthesised the occurrence of severe oral mucositis. The Grades of Recommendation, Assessment, Development and Evaluation approach was used to describe quality of evidence and strength of recommendations. We suggest cryotherapy or LLLT may be offered to cooperative children receiving chemotherapy or HSCT conditioning with regimens associated with a high rate of mucositis. We also suggest KGF may be offered to children receiving HSCT conditioning with regimens associated with a high rate of severe mucositis. However, KGF use merits caution as there is a lack of efficacy and toxicity data in children, and a lack of long-term follow-up data in paediatric cancers. No other interventions were recommended for oral mucositis prevention in children. All three specific interventions evaluated in this clinical practice guideline were associated with a weak recommendation for use. There may be important organisational and cost barriers to the adoption of LLLT and KGF. Considerations for implementation and key research gaps are highlighted.


Assuntos
Humanos , Pré-Escolar , Criança , Adolescente , Fototerapia/métodos , Estomatite/prevenção & controle , Doenças Faríngeas/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Mucosite , Neoplasias/terapia
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