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ARTICLE
Decrease of lethal infectious complications in the context of
causes of death (COD) after hematopoietic cell transplantation:
COD-2 and COD-1 study of the Infectious Diseases Working
Party EBMT
Jan Styczynski
1
✉, Gloria Tridello
2,3
, Linda Koster
3
, Nina Knelange
3
, Lotus Wendel
3
, Anja van Biezen
3
, Steffie van der Werf
3
,
Malgorzata Mikulska
4
, Lidia Gil
5
, Catherine Cordonnier
6
, Per Ljungman
7
, Diana Averbuch
8
, Simone Cesaro
2
,
Helen Baldomero
9
, Christian Chabannon
10
, Selim Corbacioglu
11
, Harry Dolstra
12
, Bertram Glass
13
, Raffaella Greco
14
,
Nicolaus Kröger
15
, Régis Peffault de Latour
16
, Mohamad Mohty
17
, Benedicte Neven
18
, Zinaida Peric
19
, John A. Snowden
20
,
Anna Sureda
21
, Ibrahim Yakoub-Agha
22
and Rafael de la Camara
23
© The Author(s), under exclusive licence to Springer Nature Limited 2023
We previously analyzed trends in incidence and factors associated with lethal complications in ALL/AML/CML patients (causes of
deaths; COD-1 study). The objective of this study was the analysis of incidence and specific causes of death after HCT, with focus on
infectious deaths in two time periods, 1980–2001 (cohort-1) and 2002–2015 (cohort-2). All patients with HCT for lymphoma, plasma
cell disorders, chronic leukemia (except CML), myelodysplastic/myeloproliferative disorders, registered in the EBMT-ProMISe-
database were included (n=232,618) (COD-2 study). Results were compared to those in the ALL/AML/CML COD-1 study. Mortality
from bacterial, viral, fungal, and parasitic infections decreased in very early, early and intermediate phases. In the late phase,
mortality from bacterial infections increased, while mortality from fungal, viral, or unknown infectious etiology did not change. This
pattern was similar for allo- and auto-HCT in COD-1 and COD-2 studies, with a distinct and constant lower incidence of all types of
infections at all phases, after auto-HCT. In conclusion, infections were the main cause of death before day +100, followed by
relapse. Mortality from infectious deaths significantly decreased, except late phase. Post-transplant mortality has significantly
decreased in all phases, from all causes after auto-HCT; it has decreased in all phases after allo-HCT except late phase.
Bone Marrow Transplantation (2023) 58:881–892; https://doi.org/10.1038/s41409-023-01998-2
INTRODUCTION
Improvement in outcome of hematopoietic cell transplantation
(HCT) is a key factor in this field of medicine. Outcome of HCT is
most often presented as overall survival (OS), disease-free survival
(DFS), event-free survival (EFS), relapse-free survival (RFS) or graft-
versus-host disease (GVHD)-free, relapse-free survival (GRFS) and is
determined by a variety of factors. OS is dependent mainly on two
factors: relapse-related mortality and treatment-related mortality
(TRM). Main causes of TRM include GVHD (after allogeneic HCT
only), infections, toxicity, and other/unknown causes. In the
Infectious Diseases Working Party (IDWP) of the European Society
for Blood and Marrow Transplantation (EBMT) study on causes of
Received: 20 December 2022 Revised: 15 April 2023 Accepted: 19 April 2023
Published online: 6 May 2023
1
Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, Torun, Bydgoszcz, Poland.
2
Pediatric Hematology Oncology,
Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
3
EBMT Leiden Study Unit, Leiden, The Netherlands.
4
Division of Infectious Diseases,
University of Genoa (DISSAL) and Ospedale Policlinico San Martino, Genoa, Italy.
5
Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical
Sciences, Poznan, Poland.
6
Hôpital Henri Mondor, Assistance Publique-Hopitaux de Paris (AP-HP) and Paris-Est-Créteil University, Creteil, France.
7
Deptartment of Cellular Therapy
and Allogeneic Stem Cell Transplantation, Karolinska Comprehensive Cancer Center, Karolinska University Hospital Huddinge, Department of Medicine Huddinge, Karolinska
Institutet, Stockholm, Sweden.
8
Faculty of Medicine, Hebrew University of Jerusalem, Pediatric Infectious Diseases, Hadassah Medical Center, Jerusalem, Israel.
9
EBMT Activity
Survey Office, Hematology, Department of Medicine, University Hospital, Basel, Switzerland.
10
Institut Paoli Calmettes Comprehensive Cancer Center and Inserm CBT-1409,
Centre d’Investigations Cliniques en Biothérapies, Marseille, France.
11
Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg,
Regensburg, Germany.
12
Laboratory of Hematology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
13
Klinik für
Hämatologie und Stammzelltransplantation, HELIOS Klinikum Berlin-Buch, Berlin, Germany.
14
Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific
Institute, Vita-Salute San Raffaele University, Milan, Italy.
15
Department of Stem Cell Transplantation, University Hospital Eppendorf, Hamburg, Germany.
16
BMT Unit, Department
of Hematology, Hospital St. Louis, Paris, France.
17
Department of Hematology, Hospital Saint Antoine, Sorbonne University, INSERM UMRs938, Paris, France.
18
Pediatric Immune-
Hematology Unit, Necker Children Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
19
School of Medicine, University of Zagreb, University Hospital Center Zagreb,
Zagreb, Croatia.
20
Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
21
Clinical Hematology Department, Institut Català d’Oncologia-
Hospitalet, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), University of Barcelona, Barcelona, Spain.
22
CHU de Lille, Université de Lille, INSERM U1286, Infinite, Lille,
France.
23
Hematology Department, Hospital de la Princesa, Madrid, Spain. ✉email: jstyczynski@cm.umk.pl
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