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Interleukin-1 Receptor Antagonist Gene Polymorphism Increases Susceptibility to Septic Shock in Children With Acute Lymphoblastic Leukemia

Zapata-Tarrés, Marta MD, MSc*; Arredondo-García, Jose Luis MD; Rivera-Luna, Roberto MD; Klünder-Klünder, Miguel MSc§; Mancilla-Ramírez, Javier MD, PhD; Sánchez-Urbina, Rocío MD, PhD; Vázquez-Cruz, Margarita Yolanda ClinCh; Juárez-Villegas, Luis Enrique MD*; Palomo-Colli, Miguel Angel MD, MSc*

Pediatric Infectious Disease Journal: February 2013 - Volume 32 - Issue 2 - p 136–139
doi: 10.1097/INF.0b013e31827566dd
Immunology Reports

Background: Interleukin-1 receptor antagonist polymorphism (ILRN) 2 (ILRN*2) has been associated with a poor outcome in septic patients because of an elevated production of anti-inflammatory cytokines. In >70% of patients, morbidity and mortality in childhood acute lymphoblastic leukemia is caused by infections. The aim of this study was to determine the association between this polymorphism and the frequency of septic shock from the time of diagnosis until completion of treatment.

Methods: This cohort study was conducted in 57 consecutive children with acute lymphoblastic leukemia. At the end of follow-up, children were stratified according to their IL1RN polymorphism (ILRN*1/ILRN*2), evaluating the impact of genotype on the severity of febrile neutropenic events during their treatment.

Results: Overall survival was 80% at 55 months after treatment. The average number of febrile neutropenic events in this cohort was 2.82 per patient. Genotype distribution was 50.9% for homozygote IL-1RN*1, 38.6% for heterozygote ILRN*1/ILRN*2 and 10.5% for homozygote IL-1RN*2. The risk of presenting septic shock for homozygote IL1RN*2/IL1RN*2 and heterozygote ILRN*1/ILRN*2 patients was significantly greater (odds ratio, 45; P = 0.001) adjusted for age, gender, risk of leukemia and presence of pathogenic bacteria. Genotype IL-1RN*2 is associated with the risk of development of septic shock in children with acute lymphoblastic leukemia. Further research in larger population-based studies is needed to replicate these findings.

Conclusions: This information would allow us to identify more predictive factors in this group of acute lymphoblastic leukemia patients in whom this information is lacking to establish an earlier and more aggressive approach.

From the *Division of Pediatric Oncology, Hospital Infantil de Mexico Federico Gomez; Divisions of Clinical Research, Pediatric Hem-Oncology, Instituto Nacional de Pediatria; §Community Health Research, Hospital Infantil de Mexico Federico Gomez; Instituto Nacional de Perinatología; and Laboratory Research on Development Biology and Experimental Teratogenesis, Hospital Infantil de México Federico Gómez, Mexico City, Mexico.

Accepted for publication September 20, 2012.

This project was performed under the auspices of the Federal Fund program (2009) from the Ministry of Health, México. The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: José Luis Arredondo García, MD, Division of Clinical Research, Instituto Nacional de Pediatría, Av. Insurgentes Sur 3700, Col. Coyoacan Cuicuilco, Mexico City, Mexico. E-mail: joselag@gmail.com.

© 2013 Lippincott Williams & Wilkins, Inc.