Infection-Related Mortality in Adults and Children Undergoing Allogeneic Hematopoietic Cell Transplantation: An Australian Registry Report

Infection-related mortality (IRM) is the most common non-relapse-related cause of death reported after allogeneic hematopoietic cell transplantation (HCT). Information on the incidence and timing of specific infective organisms and the risk factors for IRM is essential to developing prevention strategies. This report provides the first account of IRM in adults and children undergoing HCT in Australia. Between 2013 and 2018, 2705 adult and 689 pediatric first HCTs were identified from the Australasian Bone Marrow Transplant Recipient Registry database, associated with 1075 (39.7%) total overall deaths in adults and 134 (19.4%) in children. Demographics and causes of death, including infectious etiology and causative organisms, were extracted from the database for adults and children for analysis. At day +100 and 1 year post-HCT, IRM was the leading cause of early post-HCT mortality in adults, accounting for 6.2% and 9.8%, respectively; in children, IRM was the leading cause of post-HCT mortality at day +100 at 2.5% and the second highest cause of post-HCT mortality at 1 year post-HCT at 4.9%, following relapse at 5.8%. In adults, older age, transplantation not in a first complete remission (non-CR1), the use of antithymocyte globulin (ATG) or alemtuzumab, donor-positive/recipient- negative cytomegalovirus (CMV) serostatus, and acute graft-versus-host disease were significant risk factors for IRM. However, in children, age >5 years, acute lymphocytic leukemia as the primary disease, and mismatched unrelated or haploidentical donor source were predictive of IRM. Of the deaths in which an infectious etiology was reported in adults (52.4%), 49.3% were attributed to bacteria, 25.3% to fungus, 21.7% to viruses, and 3.6% to post-transplantation lymphoproliferative disorder (PTLD). The most common organisms were Pseudomonas spp, Enterococcus spp, Candida spp, Aspergillus spp, and CMV. In children where an infectious etiology was reported (64%), 13% were attributed to bacteria, 26% to fungus, 45% to viruses, and 16% to PTLD. This report highlights that IRM was the leading cause of death early post-HCT in Australia. Strategies to reduce IRM, such as individualized pre-transplantation infection risk assessment, rapid diagnostics, and prevention management strategies should be explored to determine whether these outcomes can be improved. In addition, improving the completeness and accuracy of reported data, particularly for infectious pathogens, could assist in directing management strategies to reduce IRM in HCT. (C) 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Automated summary

Infection-related mortality (IRM) is the most common non-relapse-related cause of death after allogeneic hematopoietic cell transplantation (HCT). This report provides the first account of IRM in Australia, highlighting the importance of understanding specific infective organisms and risk factors for developing prevention strategies. The study identified key risk factors for IRM in adults and children undergoing HCT, emphasizing the need for personalized infection risk assessment and prevention strategies to reduce IRM.