Infectious Episodes in children with Acute Myeloid Leukemia in Argentina. Results of GATLA 18 AML Guideline trial

Introduction

Infections are a leading cause for morbidity and mortality in pediatric acute myeloid leukemia (AML). In developing countries infections are a major concern, especially in Argentina where infection outcomes have not been addressed according to trustful data.

This is the first comprehensive study where we intended to characterize infectious complications in children treated according to the latest GATLA- AML-18 guideline. Only complete data was analyzed,

Objective

to describe incidence and characteristics of infectious complications and infectious deaths in children treated according to current GATLA guideline. To create a frame to design treatment and prophylaxis strategies.

Patients and Methods

121 patients were enrolled from 25 centers in Argentina during 2018 to July 2024.

Mean age was 7 y.o (r-0.2-17) (Female 44.6%)

Risk groups according to cytogenetics characteristics were: standard-risk 28%, high-risk 20%; very high-risk 48%; N/A 4%

Infectious episodes were considered as fever of unknown origin, microbiologically documented or as clinically documented infection. Fever was considered as a temperature of 38°C maintained for an hour, or once determination of 38.3°C; neutropenia was considered with an absolute neutrophil count (ANC) <500/μl.

Diagnostic of infections episodes were performed according to standardized definitions.

Empirical antibiotics was administered according to the local guidelines. Antibiotic prophylaxis was not standardized in all centers but it was recommended that all patients received wide spectrum antibiotics during the first hour of fever.

Results

A total of 91(75.2%) patients experienced 232 infectious episodes (IE) along either on the double induction, consolidation or intensification phases. 90.1% of patients had an ANC <500/μl, no difference among risk groups was found. (P= 0.9)

Fever without identifiable source occurred in 109 IE (48%), clinically and microbiologically documented infections in 26(11%) and 95 (41%), respectively. IE were equally distributed among risk groups (pNS).

Among the 95 microbiologically documented infections, 52 episodes of bacteremia occurred (54.7%), Gram-positive (30%) and Gram-negative (61%), and fungal isolates (9%). In 4 cases, more than one pathogen was isolated. Klebseilla sp and E coli sp were the most common pathogen isolated, 20% and 17.5% respectively

Other sites of infection were central lines (15.8%), lungs (8.5%), skin (3.2%), upper respiratory tract (5.3%), urinary tract (6.3%) and enteral infections (2.1%)

Invasive fungal infections were diagnosed in a total of 13 patients (12%). Specifically, Candida spp (6 pts), Aspergillus (3 pts) and Fusarium ((1pt), 3 patients had probable fungal infections.

Overall, 8/121 (6.6%) patients died as consequence of infection, 6 patients during double induction phase, -2 patients with sepsis to Klebsiella blee ,1 with Streptococcus mitis, 1 Staphylococcus aureus methicillin-resistant, 1 Pseudomona Aeuriginosa, 1 negative cultures. After consolidation2 patients 1 died with Klebsiella sepsis, and another with negative cultures

Conclusion

Mortality infection rates are high. Gram-negative and fungal infections are prevalent in this sample. This characterization of infections will allow to tailor and development of a better prophylaxis and treatment strategies based on real data.