Real World Incidence and Etiology of Infectious Complications in Adults With Ph-Negative Acute Lymphoblastic Leukemia Treated With the Pediatric-Inspired GIMEMA LAL1913 Program. A Campus All Study

Abstract

Infections often complicate pediatric-inspired treatments for adult Philadelphia-negative acute lymphoblastic leukemia (Ph- ALL). Literature data on these complications are difficult to interpret due to the heterogeneity of types of infections analyzed or patients and treatment characteristics. A deeper insight on the infections occurring in the real life in uniformly treated ALL patients is lacking. This study investigated infectious complications in 240 newly diagnosed adult Ph- ALL patients treated in the real life according to the GIMEMA LAL1913 protocol by 18 Italian centers participating in the Campus ALL network. Incidence, etiology of microbiologically documented infections and invasive fungal infections (IFI) and mortality for infection were determined. Potential risk factors and the prophylactic strategies used during the first chemotherapy course (C1) were analyzed. Of 240 patients, 145 (60%) experienced at least one infectious episode, with bacterial infections being the most common (74.3%), followed by viral (13.9%), fungal (10.1%), and Pneumocystis jirovecii (1.7%) infections. The blood stream was the most involved site, pneumonia occurred in 14.6% of cases, half of which being fungal. Infections were prevalent during C1, affecting 40.5% of patients; IFI occurred in 12.5% of patients, most of them in C1. Risk factors for infections included older age (≥ 55 years and particularly > 65 years) and comorbidities only for IFI. The mortality rate for infection was 3.3%. Antibacterial, antiviral, antifungal, and anti-PJ prophylaxis were variably administered and did not associate with a significant reduced infection rate. In conclusion, the rate of infectious complications in the real life of adult Ph- ALL patients treated with a pediatric-inspired intensive regimen is high, mainly during induction and mostly bacterial, particularly in the bloodstream, with a high IFI rate. Older age, mainly over 65 years, is a risk factor for all types of infection. The antimicrobial prophylaxis was not associated to a reduced risk of infection.

Keywords: GIMEMA LAL1913; acute lymphoblastic leukemia; infections; real life.