Invasive Pulmonary Aspergillosis in Acute Leukemia in the Era of New Antifungal Treatment and Prophylaxis Is Still Frequent, Even in Patients with Acute Lymphoblastic Leukemia, and Adversely Affects the Overall Treatment Outcome. Results of a 5-Year Study at a Single Institution

Abstract

Abstract Introduction. Invasive pulmonary aspergillosis (IPA) remains a major clinical issue in Acute Leukemia (AL) patients (pts) and can affect the outcome of hematological treatment. Acute Myeloid Leukemia (AML) is considered the most frequent hematological condition predisposing to IPA; however, the introduction of posaconazole prophylaxis has significantly reduced IPA during AML induction. On the other hand, incidence of IPA among Acute Lymphoblastic Leukemia (ALL) pts seems to be increasing. In order to confirm these epidemiological data and to analyze the impact of IPA on the outcome of AL, we analyzed all AML and ALL pts consecutively admitted to our Institution during a 5-year period of observation. Patients and Methods. From Jul-11 to Jun-16, all consecutive AML and ALL pts admitted to our Institution and treated with intensive chemotherapy were analyzed. IPA was diagnosed according to EORTC/MSG criteria and categorized as possible (poss) and probable/proven (p/p). Anti-mold prophylaxis (posaconazole) was always administered during induction/reinduction only in AML pts. CT scan was performed in case of persisting neutropenic fever for 3 days despite broad-spectrum antibiotic therapy. The effects of age, gender, type of AL, disease risk (ELN 2010 for AML, ESMO 2016 for ALL) and status [complete remission (CR), relapse/refractory (Rel/Refr)], IPA, allogeneic stem cell transplantation (alloSCT) on outcome were evaluated. Results. During the 5-year period, 175 AL patients were observed (136 AML/39 ALL; median age 55, range 14-74; M/F ratio 6/5). Overall, 28 (16%) IPA were diagnosed, 11 (6.3%) poss and 17 (9.7%) p/p. Frequency was similar in AML (22/136, 16.2%) and in ALL pts (6/39, 15.4%,) but p/p IPA were relatively more frequent in ALL (83%) (1 poss, and 5 p/p) than in AML (54.5%) (10 poss and 12 p/p). Considering the disease phase, IPA occurred in 8% of 175 pts during induction, in 4.4% of 159 pts during consolidation and in 13.5% of 52 pts during reinduction. The frequency of IPA, particularly p/p, observed during induction was lower in AML (10/22, 45%; 5 poss and 5 p/p) than in ALL (4/6, 67%, all p/p). More than half of the IPA observed in AML were recorded in phases different from induction (6 during consolidation and 6 during reinduction). Median time from AL diagnosis to IPA was 2.5 mo (range 0-26) in AML and 1 mo (0-6) in ALL (p=0.089). After a median follow-up of 36 mo (range 4-68), 69 pts died: 12 (17.4%) of refractory AL and concomitant IPA and 2 (2.9%) of IPA while on CR. Thirteen pts with previous IPA underwent alloSCT; 9 (69.2%, 6/8 poss and 3/5 p/p IPA) died, as compared to 24 of 65 (36.9%) pts transplanted without a history of IPA (p=0.03). AL 2-year overall survival (OS) was significantly affected by the development of IPA, with no differences between poss and p/p IPA (no IPA 71.9% vs poss IPA 36.4% or p/p IPA 33.1%; p=0.0003 and Download : Download high-res image (59KB) Download : Download full-size image Figure . Disclosures Rossi: Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees.