Incidence of Invasive Aspergillosis in Allogeneic Stem Cell Transplantation Patients: An Italian Prospectic Multicenter Study.
Authors: Mordini Nicola , Bruno Benedetto , Busca Alessandro , Sorasio Roberto , Boccadoro Mario , Gallo Eugenio , Gallamini Andrea , Mattei Daniele 
Published: October 2019

Abstract
Between January 2003 and June 2004, every consecutive patient admitted for HSCT in three institutions was monitored for circulating galactomannan (GM) with Platelia Aspergillus assay (Bio-Rad) twice weekly from admittance until day 100, and then once weekly until day 365. Following fever occurence or GM optical density index increase (+ve cut-off value was >0.7), screening with weekly chest HR CT scan was started. Diagnosis of IA was made according to the EORTC/MSG criteria. 74 patients were analyzed, and 100 entered by now in the present study. Clinical characteristics of the patients are reported in table 1. We observed 10 cases of probable IA and 2 cases of possible IA. IA occurred before day 40 in 3 patients (median, day 13 after HSCT), between day 40 and day 180 in 8 cases (median, day 109 after HSCT), and after day 180 in 1 patient. Among the probable IA group of patients, 7/10 had GVHD, 6/10 were given steroids, and 3/10 had fever. Two consecutive positive GM test results were observed in the sera of 6/10 patients, GM was detected in BAL only in 3/10 cases and 1 patient had GM detected only in a SNC fluid. Chest CT scan was diagnostic in 8/10 cases, and in another patient CNS RMN scan shown lesions consistent with IA. All patients were lymphopenic at the time of IA diagnosis with an absolute count <450 mm^3, and only 1 patient was neutropenic. 3/10 patients had CMV reactivation during the IA episode and 4/10 had CMV reactivation in the 100 days following IA diagnosis. Cumulative incidence of IA after day 60 was 8,1%, overall incidence of IA was 16.2%, and probability of developing IA reached 24% at 1year after HSCT. Cumulative incidence of IA in the RIC group was 12.3%.6/12 patients died of IA, with a median survival of 24 days (range 1–83). IA accounted for 37.5% (6/16) of all deaths and for 55% of non-relapse deaths. 1-year survival in the IA group was 22% and 80% in non-IA group. Bimodal incidence distribution of IA after HSCT was confirmed, 25% of IA cases were diagnosed early (< day 40) after HSCT, 67% were diagnosed between day 40 and day 180, and an additional 8% developed after day 180. We confirm the role of GVHD and lymphopenia as important risk factors during the late post-transplantation periods. The relatively high incidence of IA could be a consequence of the increase of IA in recent years and of diagnostic improvement (GM+HR CT scan). We recommend the use of serial screening for GM after day 100 in patients lymphopenic or with GVHD. We need new diagnostic and therapeutic strategies for HSCT patients as IA accounts still for an unacceptable high portion of non-relapse deaths.
Clinical characteristics of patients
Patients 71 Disease Multiple myeloma 27 (38%) Myelodisplastic syndrome 8 (11.3%) Acute myeloid leukemia 9 (12.7%) Chronic myeloid leukemia 6 (8.5%) Hodgkin’s disease 5 (7%) Non Hodgkin’s lymphoma 8 (11.3%) Acute lymphoblastic leukemia 4 (5.6%) Chronic lymphatic leukemia 2 (2.8%) Aplastic anemia 1 (1.4%) Renal cell carcinoma 1 (1.4%) Mean age years (range) 48.8% (20–70) HSCT 74* HLA id RIC 52 (70.3%) MUD RIC 5 (6.8%) HLA id conventional 10 (13.5%) Syngeneic conventional 1 (1.3%) MUD conventional 5 (6.8%) MUD conventional UCB 1 (1.3%) Stem cell source PBSC 64 (86.5%) BM 9 (12.2%) UCB 1 (1.3%) Follow up days Median 214 Min 48 Max 595 GVHD Acute 53/74 (71%) Chronic 36/51 (70%) Chronic extensive 14/36 (39%) *Second transplant 3 patients