Impact of Infectious Complications Should be Considered When Choosing Chemotherapy for Elderly Acute Myeloid Leukemia Fit Patients: Results of a Large Monocentric Retrospective Study
Authors: Borlenghi Erika , Borlenghi Erika , Terrenato Irene , Oberti Margherita , Soverini Giulia , Spolzino Angelica , Cerqui Elisa , Maifredi Simone , Lovato Ester , Masina Lorenzo , Federico Francesca , Bertoli Diego , Marchesi Francesco , Rossi Giuseppe , Tucci Alessandra 
Published: December 2024

Background. In elderly acute myeloid leukemia (AML) patients (pts) the debate about the use of intensive chemotherapy (cht) as opposed to non-intensive therapy or best supportive care is a hot topic, particularly after the introduction of the new effective non-cytostatic drugs. Geriatric assessment and fitness criteria may help to determine the treatment tolerance, but it is unclear if the impact of the profound neutropenia and the related infectious toxicity caused by intensive cht is higher in elderly pts. Aims. The prognosis of infectious complications and their impact on the outcome of AML fit pts were evaluated in all consecutive newly diagnosed (ND) AML pts treated with intensive cht and in the subgroups of pts aged &gt;65 during an observation period of 8 years. Patients and Methods. Between 2016 and 2023, all ND AML pts consecutively admitted and treated with intensive cht at the Hematology Unit of the Spedali Civili of Brescia were analyzed. Incidence of bloodstream infections (BSI), pneumonia and proven/probable invasive fungal infections (p/p IFI) occurring after cht (induction, consolidation and reinduction) and their impact on outcome were evaluated. Antibacterial (levofloxacin) and antifungal (posaconazole during induction or reinduction cht, itraconazole during consolidation) prophylaxis during neutropenia was given to all the pts. Logistic regression models were conducted to estimate the risk of infectious complications and of disease relapse. Overall survival (OS) analyses were conducted with Kaplan-Meier methods and Cox regression models to study the potential impact of infectious complications on time to death. We conducted multivariate models with all variables that resulted statistically significant at univariate analysis. Results. Two-hundred and sixty-nine pts were evaluated during the observation period (M/F ratio: 144/125; median age: 61y, range 18-79). Ninety-eight (36.4%) pts were older than 65y. A secondary AML was diagnosed in 45 (16.7%) pts; its incidence was higher in older than younger pts (25/98, 25.5% vs 20/171, 11.7%; p=0.0049). Similarly, the relapse/refractoriness rate during chemotherapy was higher in older pts (60/98, 61.2% vs 63/171, 36.8%; p=0.0001). Overall, at any phase of cht treatment, 149 (55.4%) pts developed a BSI, 119 (44.2%) a pneumonia and 39 (14.5%) a p/p IFI (33 pulmonary aspergillosis, 1 pulmonary+cerebral aspergillosis, 1 paranasal sinus aspergillosis, 2 candidemia+aspergillosis, 1 fusariosis, 1 S. capitata fungemia). Pts developed BSI infections significantly less frequently during induction cht than consolidation (57/269, 21.2% vs 97/207, 46.9%; p&lt;0.0001), whereas pneumonia was more frequent during induction than consolidation (82/269, 30.5% vs 28/207, 13.5%; p&lt;0.0001). P/p IFI were slightly less frequent during consolidation than induction, although not significantly (12/207, 5.8% vs 21/269, 7.8% vs; p=0.4682). Compared to younger pts, those aged&gt;65 had a significantly higher incidence of BSI (OR=2.15, CI 1.19-3.89, p=0.012) and pneumonia (OR=1.70, CI 1.0-2.89 p=0.05) during induction cht. After a median follow-up of 24 months, 132 (49.1%) pts had died. Median OS was significantly inferior in pts developing a BSI or a p/p IFI during induction (respectively: 31 vs 60 months, p=0.05 and 47 vs 17 months, p=0.044) or a pneumonia at any phase of treatment (64 vs 26 months, p=0.0296). When we conducted bivariate logistic regression model, we found that age at diagnosis resulted significantly associated with disease relapse (OR 2.54, CI 1.51-4.27, p&lt;0.001) and, with borderline statistical significance, BSI during induction (OR 1.78, CI 0.96-3.28, p=0.066). Results from multivariate Cox regression model showed that IFI p/p (overall) (OR 1.93, CI 1.04-3.57, p=0.036) and disease relapse (OR 3.24, CI 2.21-4.74, p&lt;0.0001) were the two factors significantly associated to death. Conclusions. Infectious complications represent an unfavorable prognostic factor for AML pts, particularly p/p IFI and BSI during induction and pneumonia at any phase of treatment. Advanced age is associated to a higher incidence of infections, mainly during induction, which may impact on disease relapse and survival. Therefore, in elderly fit AML pts treated with intensive cht, proper antimicrobial prophylaxis, early diagnostic and therapeutic pathways for infectious complications should be systematically undertaken.