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Br J Haematol. 2019 Oct 14. doi: 10.1111/bjh.16185. [Epub ahead of print]

Graft-versus-host disease and graft-versus-leukaemia effects in secondary acute myeloid leukaemia: a retrospective, multicentre registry analysis from the Acute Leukaemia Working Party of the EBMT.

Author information

1
Laboratory of Haematology, GIGA-I3, University of Liege, Liege, Belgium.
2
EBMT Paris Office, Hospital Saint Antoine, Paris, France.
3
AP-HP, Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, Paris, France.
4
Service d'Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, Université Pierre & Marie Curie and INSERM UMRs U938, Paris, France.
5
Vanderbilt University Medical Center, Nashville, TN, USA.
6
Division of Haematology & Oncology, University Hospital Leipzig, Leipzig, Germany.
7
Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
8
Department of Haematological Medicine, GKT School of Medicine, London, UK.
9
Bone Marrow Transplantation Centre, University Hospital Eppendorf, Hamburg, Germany.
10
Department of Bone Marrow Transplantation, West German Cancer Center, University Hospital of Essen, Essen, Germany.
11
Department of Haematology - BMT, Hopital St. Louis, Paris, France.
12
Stem Cell Transplantation Unit, HUCH Comprehensive Cancer Centre, Helsinki, Finland.
13
Medizinische Klinik und Poliklinik I, Universitaetsklinikum TU Dresden, Dresden, Germany.
14
Division of Haematology and Bone Marrow Transplantation, The Chaim Sheba Medical Centre, Tel-Hashomer, Ramat-Gan, Israel.

Abstract

We assessed the susceptibility of secondary acute myeloid leukaemia (sAML) to graft-versus-leukaemia effects. Data from 2414 sAML patients in first (n = 2194) or second (n = 220) complete remission were included. They were given grafts from human leucocyte antigen (HLA)-matched sibling (MSD, n = 1085), 10/10 unrelated donor (MUD, n = 1066) or 9/10 mismatched unrelated donor (MMUD, n = 263). The 100-day incidence of grade II-IV acute graft-versus-host disease (GVHD) was 25% while 2-year incidence of chronic GVHD was 38%. Relapse rates declined steadily by duration of follow-up and were significantly lower in patients with chronic GVHD (P < 0·001). Limited (hazard ratio [HR] = 0·66, P < 0·001) and extensive (HR = 0·52, P < 0·001) chronic GVHD were associated with a lower incidence of relapse. Each grade III-IV acute (HR = 7·04, P < 0·001) as well as limited (HR = 1·42, P = 0·03) and extensive (HR = 3·97, P < 0·001) chronic GVHD were associated with higher non-relapse mortality (NRM). This translated to better overall survival (OS; HR = 0·61, P < 0·001) in patients with limited chronic GVHD. In contrast, grade III-IV acute and extensive chronic GVHD were associated with worse OS (HR = 3·16, P < 0·001 and HR = 1·21, P = 0·03, respectively). Further, in comparison to HLA-identical sibling recipients, MUD recipients had a lower risk of relapse (HR = 0·82, P = 0·03) but higher NRM (HR = 1·38, P = 0·004). In conclusion, these data demonstrate that sAML is susceptible to graft-versus-leukaemia effects.

KEYWORDS:

GVHD; graft-versus-leukaemia effects; reduced intensity conditioning; secondary AML

PMID:
31612473
DOI:
10.1111/bjh.16185

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