Infectious complications in children with acute myeloid leukemia: decreased mortality in multicenter trial AML-BFM 2004

Abstract

Infections are an important cause for morbidity and mortality in pediatric acute myeloid leukemia (AML). We therefore characterized infectious complications in children treated according to the trial AML-BFM 2004. Patients with Down syndrome were excluded from the analysis. Data were gathered from the medical records in the hospital where the patients were treated. A total of 405 patients (203 girls; median age 8.4 years) experienced 1326 infections. Fever without identifiable source occurred in 56.1% of the patients and clinically and microbiologically documented infections in 17.5% and 32.4% of the patients, respectively. In all, 240 Gram-positive (112 viridans group streptococci) and 90 Gram-negative isolates were recovered from the bloodstream. Invasive fungal infection was diagnosed in 3% of the patients. Three children each died of Gram-negative bacteremia and invasive aspergillosis, respectively. As compared with the results of AML-BFM 93 with lower dose intensity, infection-related morbidity was slightly higher in AML-BFM 2004 (3.3. versus 2.8 infections per patient), whereas infection-related mortality significantly decreased (1.5% versus 5.4% P=0.003). Specific anti-infective recommendations included in the treatment protocol, regular training courses for pediatric hematologists and increasing experience may be the reason for reduced infection-related mortality in children with AML. Further studies are needed to decrease infection-related morbidity.

Antibiotic prophylaxis with teicoplanin on alternate days reduces rate of viridans sepsis and febrile neutropenia in pediatric patients with acute myeloid leukemia

“…Retrospective data from study AML-BFM 93 indeed demonstrated a significantly higher VGS sepsis rate following high-dose cytarabine cycles whereas in a recent NOPHO-AML study and in the AML-BFM 2004 study, no significant difference of VGS sepsis rate was observed between lower-dose and high-dose courses [4, 9, 22]. In our study, rate of VGS sepsis was comparably high following intermediate-dose and high-dose cycles (9.3 and 7.4 %) while no VGS sepsis occurred after induction cycles with low-dose cytarabine.…”

“…According to data from study AML-BFM 93 and 2004, VGS was isolated in more than 20 and 30 % of cases with neutropenic bacteremia, respectively. While incidence of VGS sepsis was significantly higher after chemotherapy cycles containing high-dose cytarabine in protocol AML-BFM 93, this difference was not obvious in the 2004 study [4, 9]. Infection with VGS bears substantial risk for viridans streptococcal shock syndrome with a reported mortality rate of up to 100 % [10].…”

Lack of Effectiveness of Neutropenic Diet and Social Restrictions as Anti-Infective Measures in Children With Acute Myeloid Leukemia: An Analysis of the AML-BFM 2004 Trial

“…Infections were defined as clinical signs and symptoms of infection associated with the institution of antibiotics, the isolation of a pathogen, or an identifiable site of infection by physical examination or imaging study. 2,9 Infectious episodes were categorized as fever of unknown origin (FUO) or as clinically or microbiologically documented infection. Fever was defined as having a temperature above 38.5°C once or 38°C to 38.5°C twice within a 4-hour interval.…”

“…Fever was defined as having a temperature above 38.5°C once or 38°C to 38.5°C twice within a 4-hour interval. 2,9 Bacteremia was defined as fever with a positive blood culture for bacteria. If the bloodstream isolate was a potential skin contaminant (eg, coagulase-negative Staphylococcus), the presence of an intravascular catheter was required for the diagnosis of a bloodstream infection.…”

“…8 Data regarding infectious complications of a total of 466 patients were gathered in the hospital where the patient had been treated, and part of this analysis has been reported recently. 9 In 2010, we performed an international survey in 27 countries on restricting social contacts, pets at home, and food for children with AML. 10 The survey demonstrated a wide variation in recommendations regarding nonpharmacologic anti-infective measures between different institutions, countries, and continents.…”