ISSN 1866-8836
Клеточная терапия и трансплантация

PI-07. Epidemiology of infectious complications in patients with acute graft-versus-host disease

Aleksander A. Siniaev, Marina O. Popova, Yuliya A. Rogacheva, Oleg V. Goloshchapov, Anna A. Spiridonova, Sergey N. Bondarenko, Ivan S. Moiseev, Alexander D. Kulagin

RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University, St. Petersburg, Russia

Contact: Dr. Marina O. Popova, e-mail: marina.popova.spb@gmail.com

doi 10.18620/ctt-1866-8836-2020-9-3-1-152

Summary

Introduction

Patients with acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) are at high risk of infectious complications [1, 2]. However, the number of published studies on the epidemiology of infections in GVHD is limited [3, 4]. The objective of our work was to study epidemiology of infections in patients with acute GVHD.

Patients and methods

A single-center retrospective study included 65 adult patients with acute GVHD after allo-HSCT performed from 2014 to 2017. Their clinical characteristics are outlined in Table 1. Antimicrobial prophylaxis for the patients with acute GVHD was performed according to the EBMT Guidelines. Analysis of infectious complications proceeded within one year from the onset of acute GVHD, and was censored by the date of chronic GVHD onset, or by relapse of underlying disease. The median time for acute GVHD onset was 39 days (16-114) following allo-HSCT. The median follow-up time was 22.2 months (6 days – 63.8 months).

Table 1. Clinical characteristics of the patients with acute GVHD and infectious conditions

Siniaev-tab01.jpg

Results

Infectious complications developed in 86% of the patients with acute GVHD. Incidence of bacterial infections (BI) was 27.7% (n=18). The median time of the BI onset was 35 days (0-276). The following main pathogens were detected: Klebsiella pneumoniae (41%), Pseudomonas aeruginosa (23%), Streptococcus viridians group (12%), with different primary location, i.e., lungs (41%), bloodstream infections (23.5%), colitis (17.6 %). The significant risk factors were as follows: 3-4 grade acute GVHD (p=0.004), usage of ATG for GVHD prophylaxis (p=0.0001), grade 4 neutropenia (p=0.001), and grade 4 lymphopenia (p=0.007), as well as lacking response to first line immunosuppressive therapy for 28 days (p=0.0001). The incidence of viral infections (VI) was 66.2% (n=43). The median onset time for viral infections was 17 days (0 to 88). Detectable viral agents were represented by cytomegalovirus (64% of cases), BK/JC polyomaviruses (20%), Epstein-Barr virus (9%). Specific clinical symptoms associated with viral infections were observed in 51% of the patients, e.g., affecting gastrointestinal tract (50%), cystitis (45%). CMV-positive status of donor-recipient pair before HSCT was the main risk factor (p=0.025). Incidence of invasive fungal disease (IFD) was 6.2% (n=4), and pulmonary aspergillosis was diagnosed in all cases. The median time of IFD onset was 11 days (3-38). Grade 4 neutropenia (p=0.0001) and grade 4 lymphopenia (p=0.004) were major risk factors for IFD The 2-year overall survival (OS) from the onset of acute GVHD was 61.5%. Grade 3-4 acute GVHD (p=0.02) and sepsis (p=0.0001) were associated with significantly decreased OS rate.

Conclusion

Infectious complications developed in 86% of patients with acute GVHD. Viral infections showed highest incidence, followed by bacterial infections, and invasive fungal disease was tedected in 6.2% of the cases. Grade 4 neutropenia and lymphopenia proved to be the main risk factors for bacterial infections and invasive fungal disease. Higher risk for viral infections was connected with CMV status of the donor-recipient pair. Viral infections and invasive fungal disease did not influence overall 2-year survival rates of the patients with acute GVHD. Among infectious complications, sepsis is the main cause of mortality in the patients with acute GVHD.

References

1. Sahin U, Toprak SK, Atilla PA, Atilla E, Demirer T. An overview of infectious complications after allogeneic hematopoietic stem cell transplantation. J Infect Chemother. 2016; 22(8):505-514.
2. Kolb H-J, Weber D, Pinto Simões B, Holler E. Infection and GVHD. Cell Ther Transplant. 2018; 7(1): 8-17.
3. Abedin S, McKenna E, Chhabra S, Pasquini M, Shah NN, Jerkins J, Baim A, Runaas L, Longo W, Drobyski W, Hari PN, Hamadani M. Efficacy, Toxicity, and Infectious Complications in Ruxolitinib-Treated Patients with Corticosteroid-Refractory Graft-versus-Host Disease after Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2019; 25(8):1689-1694.
4. Miller HK, Braun TM, Stillwell T, et al. Infectious Risk after Allogeneic Hematopoietic Cell Transplantation Complicated by Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2017;23(3):522-528.

Keywords

Allogeneic hematopoietic stem cell transplantation, infectious complications, acute graft-versus-host disease, bacteria, fungi, viruses.


Volume 9, Number 3
09/30/2020

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doi 10.18620/ctt-1866-8836-2020-9-3-1-152

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