Infections and Febrile Neutropenia in Pediatric Acute Lymphoblastic Leukemia Patients from South India: Microbial Profile and Outcome Analysis

Introduction

Overall survival from both disease and treatment related complications is lower in developing countries compared to developed nations in pediatric, adolescent and young adult (AYA) patients with Acute Lymphoblastic Leukemia (ALL). Infections and febrile neutropenia are leading causes of treatment related morbidity and mortality in pediatric and AYA patients in developing countries. Socio-economic and cultural factors continue to play a big role in treatment decision process. We surveyed the accessibility to health care, microbial profile, infection related mortality and overall survival in leukemic patients admitted with fever to a multi-specialty center in South India.

Methods

All patients < 31 years of age diagnosed with ALL treated per Berlin-Frankfurt-Muenster (BFM) 95 protocol, consecutively admitted for fever from 2005 to 2014, were retrospectively analyzed.

Results

Of the 288 Pediatric and AYA patients diagnosed with cancer, 82 patients had newly diagnosed ALL. 14 patients (17%) with ALL were lost to follow-up, transferred care to another center or abandoned treatment. Of the evaluable 68 patients, 25 febrile neutropenic episodes occurred in 20 patients, requiring hospitalization. Majority of febrile patients (66.6%) had microbiologically documented infections (MDI). Of the MDI, 71% were gram-negative organisms. Only 2 patients had central venous device (Mediport) insitu at the time of admission. Among the hospitalized patients, the incidence of febrile neutropenic episodes during the induction phase was 60%, however, 20% occurred during the maintenance phase of therapy. At the time of admission to the hospital the absolute neutrophil count was < 1000/mm³ in all patients. Blood stream infections (BSI) comprised the majority of MDI (36%) followed by urine tract infections (20%) and oral mucosal infections (16%). Commonly isolated bacterium was E. Coli followed by Pseudomonas Aeroginosa and Klebsiella Pneumoniae. The first line antibiotic regimen in these patients at the time of hospitalization consisted of Cefaperazone - Sulbactam. Endemic infections like Tuberculosis, Dengue and Leptospirosis were not seen in this cohort of patients. Infection related mortality resulted in 13.2% of the overall mortality in patients with newly diagnosed ALL. The overall survival for Pediatric and AYA patients with ALL was 62%. Most of the patients (80%) were able to reach the emergency room within 2 hours of diagnosis of febrile episode and all of these patients belonged to higher socio-economic strata.

Conclusion

Great progress has been made in the treatment of pediatric cancer in India. However, economic, social and cultural factors continue to dictate treatment options for this condition in remote parts of the country. Compared to developed nations, high infection related mortality and treatment attrition serve as the biggest obstacles to improving overall survival.