Infections and association with different intensity of chemotherapy in children with acute myeloid leukemia

Cancer (Impact Factor: 5.2). 02/2009; 115(5):1100 - 1108. DOI: 10.1002/cncr.24107

ABSTRACT BACKGROUND:The objectives were to compare infections during different intensities of therapy in children with acute myeloid leukemia (AML).METHODS:Subjects were children enrolled in Children's Cancer Group 2891 with AML. In phase 1 (induction), patients were randomized to intensive or standard timing. In phase 2 (consolidation), those with a family donor were allocated allogeneic stem cell transplantation (SCT); the remainder were randomized to autologous SCT or chemotherapy. This report compares infections between different treatments on an intent-to-treat basis.RESULTS:During phase 1, intensive timing was associated with more bacterial (57.7% vs 39.4%; P < .001), fungal (27.4% vs 9.9%; P < .001), and viral (14.0% vs 3.9%; P < .001) infections compared with standard timing. During phase 2, chemotherapy was associated with more bacterial (56.5% vs 40.1%; P = .005), but similar fungal (9.5% vs 6.1%; P = 1.000) and viral (4.2% vs 12.9%; P = .728) infections compared with allogeneic SCT. No differences between chemotherapy and autologous SCT infections were seen. Fatal infections were more common during intensive compared with standard timing induction (5.5% vs 0.9%; P = .004). Infectious deaths were similar between chemotherapy, autologous SCT, and allogeneic SCT.CONCLUSIONS:Prevalence of infection varies depending on the intensity and type of treatment. This information sheds insight into the mechanisms behind susceptibility and outcome of infections in pediatric AML. Cancer 2009. © 2009 American Cancer Society.

  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate association of host genomic variation and risk of infections during treatment of childhood acute lymphoblastic leukaemia (ALL). We explored association of 34 000 single nucleotide polymorphisms (SNPs) related primarily to pharmacogenomics and immune function to risk of infections among 69 ALL patients on induction therapy. Forty-eight (70%) patients experienced infectious events including 23 with positive blood cultures. Infectious events and positive blood cultures associated significantly with 24 and 21 SNPs, respectively (P < 0.01). Classification and regression tree analysis demonstrated rs11033797 (OR51F1), rs2835265 (CBR1), rs28627172 (POLDIP3) and rs1129844 (CCL11) to be predictive of outcome. Among 61 patients for whom readouts were available for all four SNPs, 40 of 41 patients with the worst SNP profile experienced at least one infectious event compared to five of the remaining 20 patients (Hazard ratio 9.0, 95% CI 3.4-23.5, which was unchanged after adjustments for neutrophil counts). Pathway analysis identified variations in 'G-protein-coupled receptor (GPCR) downstream signalling', 'Bile acid and bile salt metabolism' and 'Class I MHC mediated antigen processing & presentation' to be highly predictive of infections. Our data indicate that host genomic profiling may predict the risk of infections during induction therapy. This may facilitate development of individualised supportive care.
    European Journal Of Haematology 12/2013; · 2.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. Invasive fungal infections (IFI) cause significant morbidity and mortality for children with acute myeloid leukemia (AML). Data on the comparative effectiveness of antifungal prophylaxis in this population are limited. Methods. A pediatric AML cohort was assembled from the Pediatric Health Information System database using ICD-9 codes and pharmacy data. Antifungal prophylaxis status was determined by pharmaceutical data review within 21 days of starting induction chemotherapy. Patients were followed until end of induction, death, or loss to follow-up. Cox regression analyses compared induction mortality and resources utilized between patients receiving and not receiving antifungal prophylaxis. A propensity score accounted for variation in demographic factors, location of care and severity of illness at presentation. Results. 871 AML patients were identified; the induction case fatality rate was 3.7%. In the adjusted Cox regression model, patients receiving antifungal prophylaxis (57%) had a decreased hazard for induction mortality (HR: 0.42, 95% CI: 0.19- 0.90). Children receiving prophylaxis were less frequently exposed to broad-spectrum Gram-positive (IRR: 0.87, 95% CI: 0.79-0.97) and anti-pseudomonal beta-lactam agents (HR: 0.91, 95% CI: 0.85-0.96), had fewer blood cultures (IRR: 0.78, 95% CI: 0.71-0.86) and fewer chest CT scans (IRR: 0.73, 95% CI: 0.60-0.88). Conclusions. Antifungal prophylaxis in pediatric AML patients is associated with reduced induction mortality rates and supportive care resources. Further investigation is necessary to determine whether antifungal prophylaxis should include anti-mold activity.
    Clinical Infectious Diseases 11/2013; · 9.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND Intensive chemotherapy for pediatric acute myeloid leukemia incurs the risk of infectious complications, but the benefits of antibiotic prophylaxis remain unclear.METHODS In the current study, among 103 children treated on the AML02 protocol between October 2002 and October 2008 at St. Jude Children's Research Hospital, the authors retrospectively assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia, clinically or microbiologically confirmed infections (including bacteremia), and antibiotic resistance, as well as on the results of nasal and rectal surveillance cultures. Initially, patients received no prophylaxis or oral cephalosporin (group A). The protocol was then amended to administer intravenous cefepime alone or intravenous vancomycin plus either oral cephalosporin, oral ciprofloxacin, or intravenous cefepime (group B).RESULTSThere were 334 infectious episodes. Patients in group A had a significantly greater frequency of documented infections and bacteremia (both P < .0001) (including gram-positive and gram-negative bacteremia; P = .0003 and .001, respectively) compared with patients in group B, especially viridans streptococcal bacteremia (P = .001). The incidence of febrile neutropenia without documented infection was not found to be different between the 2 groups. Five cases of bacteremia with vancomycin-resistant enterococci (VRE) occurred in group B (vs none in group A), without related mortality. Two of these cases were preceded by positive VRE rectal surveillance cultures.CONCLUSIONS Outpatient intravenous antibiotic prophylaxis is feasible in children with acute myeloid leukemia and reduces the frequency of documented infection but not of febrile neutropenia. Despite the emergence of VRE bacteremia, the benefits favor antibiotic prophylaxis. Creative approaches to shorten the duration of prophylaxis and thereby minimize resistance should be explored. Cancer 2014. © 2014 American Cancer Society.
    Cancer 03/2014; · 5.20 Impact Factor

Full-text (2 Sources)

Available from
May 20, 2014