Antifungal prophylaxis in pediatric hematology/oncology: New choices & new data
Division of Pediatric Blood & Marrow Transplant, Department of Pediatrics, University of California San Francisco, San Francisco, California 94143-1278, USA. Pediatric Blood & Cancer
(Impact Factor: 2.39).
07/2012; 59(1):21-6. DOI: 10.1002/pbc.23415
A severe complication of the treatment of pediatric cancers is the development of an invasive fungal infection (IFI). The data to support antifungal prophylaxis in pediatric oncology patients derive primarily from adult patients, and thus the optimal agent to utilize is not clear. Fluconazole has been a standard option, but agents with antimold activity are now available, each with limitations. Pediatric dosing for voriconazole and posaconazole is uncertain and multiple drug interactions exist. The echinocandins are well-tolerated, but only available in intravenous form. Ultimately, studies demonstrating biologic risk factors for the development of IFI may lead to personalized prophylactic strategies.
Available from: David B Dix
- "Even with this large infectious burden, there is great variability in supportive care strategies used for pediatric AML across institutions . Clinical trials are currently being conducted to address these uncertainties [3,4]. However, there are some common themes; most North American centers do not use routine anti-bacterial prophylaxis (other than for Pneumocystis jirovecii) and most use fluconazole as antifungal prophylaxis . "
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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.
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.
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.
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.
BMC Cancer 06/2013; 13(1):276. DOI:10.1186/1471-2407-13-276 · 3.36 Impact Factor
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ABSTRACT: Invasive opportunistic fungal infections are important causes of morbidity and mortality in children and adolescents with cancer or haematopoietic stem cell transplantation (HSCT). Difficulties in establishing the diagnosis continue to delay antifungal therapy, and this has been shown to adversely impact on survival. Apart from ongoing attempts to improve early recognition, effective chemoprophylaxis of invasive fungal infections remains a goal of high priority in populations with disease-related incidence rates of 10% or higher. These include patients with acute myeloid leukaemia, high-risk acute lymphoblastic leukaemias, recurrent leukaemias and those following allogeneic HSCT. Incidence rates in other paediatric cancer entities, including autologous HSCT, are considerably lower and do not justify the general implementation of antifungal prophylaxis. The difficulties in obtaining a timely diagnosis, the consequences of infectious morbidity on delaying anticancer treatment, and mortality rates >20% and >50% for invasive yeast and mould infections, respectively, provide a clear rationale for antifungal prophylaxis in high-risk populations. However, while antifungal prophylaxis has become part of infectious disease supportive care algorithms in most paediatric leukaemia and allogeneic transplantation programmes, antifungal prophylaxis remains a topic of controversy, with no clear consensus amongst different centres and groups. This is largely based on the limited paediatric data, with only a small number of meaningful studies, and on the fact that the scientific evidence for the benefit of antifungal prophylaxis has been generated exclusively by prospective, randomized, clinical phase III trials conducted in adults with comparable, but not similar conditions. In this article, we briefly review the epidemiology of invasive fungal infections in children and adolescents with cancer and following HSCT; delineate regulatory principles of paediatric drug development with relevant examples for their successful implementation with new antifungal compounds; provide information on the pharmacology and paediatric development of current antifungal compounds; discuss for each compound the evidence for effectiveness as primary or secondary antifungal prophylaxis in adults and the pertinent data published in paediatric patients; and conclude by providing practical options for prophylaxis in children and adolescents with haematological malignancies and following allogeneic HSCT.
Drugs 03/2012; 72(5):685-704. DOI:10.2165/11599810-000000000-00000 · 4.34 Impact Factor
Available from: bloodjournal.org
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ABSTRACT: Acute myeloid leukemia is a heterogeneous disease that accounts for approximately 20% of acute leukemias in children and adolescents. Despite the lack of targeted therapy for most subtypes and a dearth of new agents, survival rates have reached approximately 60% for children treated on clinical trials in developed countries. Most of the advances have been accomplished by better risk classification, the implementation of excellent supportive care measures, adaptation of therapy on the basis of each patient's response to therapy, and improvements in allogeneic hematopoietic stem cell transplantation. However, it is unlikely that further gains can be made through these measures alone. In this regard, high-resolution, genome-wide analyses have led to greater understanding of the pathogenesis of this disease and the identification of molecular abnormalities that are potential targets of new therapies. The development of molecularly targeted agents, some of which are already in clinical trials, holds great promise for the future.
Blood 05/2012; 119(25):5980-8. DOI:10.1182/blood-2012-02-392506 · 10.45 Impact Factor
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