Analysis of Risk Factors Determining Incidence and Outcome of Infections in Children and Adults after Hematopoietic Cell Transplantation
Authors: Styczynski Jan , Czyzewski Krzysztof , Giebel Sebastian , Fraczkiewicz Jowita , Salamonowicz Malgorzata , Zajac-Spychala Olga , Zaucha-Prazmo Agnieszka , Drozd-Sokolowska Joanna , Waszczuk-Gajda Anna , Dybko Jaroslaw , Joanna Manko , Wysocki Mariusz , Kowalczyk Jerzy , Wachowiak Jacek , Gozdzik Jolanta , Basak Grzegorz W , Kalwak Krzysztof , Adamska Monika , Hus Marek , Piekarska Agnieszka , Sadowska-Klasa Alicja , Mensah-Glanowska Patrycja , Kyrcz-Krzemien Slawomira , Biernat Monika , Wierzbowska Agnieszka , Rzepecki Piotr , Tomaszewska Agnieszka , Halaburda Kazimierz , Gil Lidia 
Published: October 2019

Abstract
BACKGROUND: Recent EBMT analysis showed that infections are responsible for 21% of deaths after allo-HCT and 11% after auto-HCT. However, the risk, types and outcome of infections vary between age groups. The aim of the study is the direct comparison of risk factors of incidence and outcome of infections in children and adults.
PATIENTS AND METHODS: We analyzed risk factors for the incidence and outcome of bacterial, fungal, and viral infections in 650 children and 3200 adults who received HCT between 2012-2015. The risk factors were determined by multivariable logistic regression analysis.
RESULTS: A total number of 395/650 (60.8%) children and 1122/3200 (35.0%) adults were diagnosed for microbiologically confirmed infection, including 345/499 (69.1%) and 679/1070 (63.5%), respectively after allo-HCT, and 50/151 (33.1%) and 443/2130 (20.8%) respectively, after auto-HCT. At 2 years after HCT, the incidences of microbiologically documented bacterial infection were 36.0% and 27.6%, (p<0.001) for children and adults, respectively. Incidences of proven/probable invasive fungal disease (IFD) were 8.4% and 3.7% (p<0.001), respectively; and incidences of viral infection were 38.3%, and 13.5% (p<0.001), respectively. Overall, 31/650 (4.8%) children and 206/3200 adults (6.4%) have died after these infections. The distribution of deaths was different in children (35.5% bacterial, 48.4% fungal, 16.1% viral) and adults (61.7% bacterial, 24.7% fungal, 13.6% viral). BACTERIAL INFECTIONS: In multivariable analysis, the risk of infections was higher after allo-HCT (HR=1.8; p<0.001). In allo-HCT patients, the risk was higher in children (HR=2.1; p<0.001), in patients with acute leukemia (HR=1.6; p<0.001), matched unrelated (MUD) vs matched family-donor (MFD) HCT (HR=1.6; p<0.001), mismatched unrelated (MMUD) vs MFD HCT (HR=2.0; p<0.001), myeloablative vs reduced-intensity conditioning (RIC) (HR=1.3; p<0.001), delayed (>21d) hematological recovery (HR=3.3; p<0.001), acute GVHD before infection (HR=1.7; p<0.001), and chronic GVHD before infection (HR=1.4; p=0.014). In auto-HCT patients, the risk was higher in children (HR=1.7; p<0.001), and in patients with delayed hematological recovery (HR=2.8; p<0.001). In patients with multiple myeloma (MM) the risk was decreased (HR=0.7; p=0.005). FUNGAL INFECTIONS: The risk of proven/probable IFD was higher after allo-HCT (HR=5.4; p<0.001). In allo-HCT patients, the risk was higher in children (HR=3.9; p<0.001), in patients with acute leukemia (HR=3.8; p<0.001), MUD vs MFD HCT (HR=1.5; p=0.013), MMUD vs MFD HCT (HR=2.5; p<0.001), delayed hematological recovery (HR=3.3; p<0.001), acute GVHD before infection (HR=1.5; p=0.021), and chronic GVHD before infection (HR=2.2; p<0.001). In auto-HCT patients, the risk was higher in children (HR=1.8; p=0.025). Patients with MM were at decreased risk of IFD (HR=0.6; p=0.005). VIRAL INFECTIONS: In multivariable analysis, the risk of infections was higher after allo-HCT (HR=6.1; p<0.001). In allo-HCT patients, the risk was higher in children (HR=1.3; p=0.010), in patients with acute leukemia (HR=1.7; p<0.001), MUD vs MFD HCT (HR=2.0; p<0.001), MMUD vs MFD HCT (HR=3.3; p<0.001), myeloablative vs RIC (HR=1.8; p=0.050), acute GVHD before infection (HR=1.5; p<0.001) and chronic GVHD before infection (HR=2.7; p=0.014). Among auto-HCT patients, diagnosis of MM brought decreased risk of viral infections (HR=0.5; p<0.001). DEATH FROM INFECTION: In allo-HCT patients, adults (HR=3.3; p<0.001), recipients of MMUD-HCT (HR=3.8; p<0.001), patients with acute leukemia (HR=1.5; p=0.023), chronic GVHD before infection (HR=3.6; p=0.014), CMV reactivation (HR=1.4; p=0.038) and with duration of infection treatment >21 days (HR=1.4; p=0.038) were associated with increased risk of death from infection. Among patients with bacterial infections, the risk was higher in G- infections (HR=1.6; p=0.031). Among auto-HCT patients, no child died of infection. In adults, the risk of death was higher if duration of treatment of infection was >21 days (HR=1.7; p<0.001). In patients with MM the risk was decreased (HR=0.4; p<0.001).
CONCLUSIONS: The profile of infections and related deaths varies between children and adults. MMUD transplants, diagnosis of acute leukemia, chronic GVHD, CMV reactivation and prolonged infection are relative risk factors for death from infection after HCT.

Disclosures
Kalwak: Sanofi: Other: travel grants; medac: Other: travel grants.