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4986 A Multi-Center Retrospective Analysis of Outcomes Post Allogeneic Stem Cell Transplantation in AML Patients with TET2 Mutations: A Study on Behalf of the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster III
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, AML, Biological therapies, Clinical Research, Diseases, Therapies, registries, Myeloid Malignancies, Transplantation
Monday, December 11, 2023, 6:00 PM-8:00 PM

Lin Li1*, Yishan Ye, MD2*, Jacques-Emmanuel Galimard3*, Myriam Labopin4*, Depei Wu, M.D.5, Jia Chen, M.D.6*, Nicolaus Kröger, MD7*, Jakob Passweg Sr.8*, Urpu Salmenniemi9*, Maija Itäla-remes, MD, PhD10*, Xavier Poiré, MD, PhD11*, Matthias Eder12*, Johan Maertens13*, David Burns, MD, PhD14*, Henrik Sengeloev15*, Gitte Olesen, MD, PhD16*, Didier Blaise, MD, PhD17, Jürgen Finke, MD18, Alain Gadisseur, MD, PhD19*, Ali Bazarbachi, MD, PhD20, Eolia Brissot3,21*, Arnon Nagler22*, Yi Luo23, Jimin Shi24*, Fabio Ciceri25*, Mohamad Mohty, MD, PhD26,27, He Huang24* and Norbert Claude Gorin Sr.3,28

1The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
2Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Paris, France
3EBMT Paris Office, Hôpital Saint Antoine, Paris, France
4EBMT Statistical Unit, Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France
5The First Affiliated Hospital of Soochow University, SUZHOU, China
6National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
7University Medical Center Hamburg, Hamburg, Germany
8University Hospital | Basel, Basel, Switzerland
9Dept of Hematology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland
10Department of Clinical Haematology and Stem Cell Transplant Unit, University Hospital Turku, Turku, Finland
11Section of hematology, Institut Roi Albert II, Cliniques Universitaires St-Luc, Brussels, Belgium
12Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
13University Hospital Gasthuisberg, Leuven, Belgium
14University Hospital Birmingham NHS Trust, Stoke, United Kingdom
15Rigshospitalet, Copenhagen, Denmark
16Aarhus University Hospital, Aarhus, Denmark
17Program of Transplant and cellular immunotherapy, Department of Hematology, Institut Paoli Calmettes, Marseille, France
18University of Freiburg, Dept. of Medicine-Hematology, Oncology, Freiburg, Germany
19Antwerp University Hospital, Edegem, Belgium
20American University of Beirut Dept. of Medicine, Beirut, Lebanon
21Sorbonne Université Service d' Hématologie Clinique et Thérapie Cellulaire, Hospital Saint-Antoine, Centre de Recherche Saint-Antoine (CRSA), Paris, France
22Hematology Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel
23The First Affiliated Hospital, Zhejiang Unibersity School of Medicine, Hangzhou, China
24Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
25Unit of Hematology and Stem Cell Transplantation, Ospedale San Raffaele, University Vita-Salute San Raffaele, Milan, Italy
26Department of Hematology and Cell Therapy, EBMT Paris study office, Saint Antoine Hospital, Paris, France
27Hematology Department, Hôpital Saint Antoine, Service d'Hématologie et Thérapie Cellulaire, Paris, France
28Department of Hematology and Cell therapy, Hospital Saint-Antoine, Sorbonne University, Paris, France


Mutations in TET2 present in about 15% of adult AML are reported in some limited series as an adverse prognostic factor for overall survival. However the impact of allogeneic hematopoietic cell transplantation (allo-HCT) for the treatment of these patients remains unclear. We addressed this issue in a EBMT global multi-center registry-based study.

Patients and Methods

644 adult AML patients with TET2 mutations receiving first non ex-vivo depleted allo-HCT from 2013-2022 in 127 centers were analyzed. All patients achieved first complete remission (CR1) before allo-HCT.


The median age of the 644 AML patients was 59.4 (range, 18.1-86.3) years. 556 patients (86.3%) had de novo, and 88 (13.7%) had secondary AML, respectively. 367 (57.2%) patients were male. The median interval from diagnosis to allo-HCT was 4.9 (IQR, 3.8-6.2) months. Patients were categorized into favorable -(N=23, 3.9%), intermediate-(N=475, 79.8%) and adverse (N=97, 16.3%) risk categories according to cytogenetic characteristics. Conditioning regimen was myeloablative (MAC) in 46.7% of patients. 149 patients (23.1%) received a matched-sibling donor, 176 (27.3%) a haploidentical donor (Haplo), 268 (41.6%) a 10/10 unrelated donor (UD) and 51 (7.9%) a 9/10 UD allo-HCT, respectively.

For the entire cohort, with a median follow-up of 1.9 years, the 30-day cumulative incidence of engraftment was 97.6%. The 100-day cumulative incidence of grade II-IV aGVHD was 22.9% and the 2-year cumulative incidence of extensive cGVHD was 13.7%. In addition, the 2-year relapse incidence and NRM were 23.2% and 12.8%, respectively. Finally, the 2-year OS, LFS and GRFS were 69.8%, 63.9% and 49.8%, respectively.

In multivariable analyses, a donor type 9/10 UD was associated with a higher RI (HR=2.33, 95% CI 1.21-4.48; p=0.01), a lower LFS (HR=2.20, 95% CI 1.31-3.70; p<0.01) and OS (HR=2.29, 95% CI 1.33-3.96; p<0.01) as compared to MSD as reference. Compared to MSD, 10/10 UD and Haplo had similar outcomes. The adverse-cytogenetic group was associated with higher RI (HR=1.85, 95% CI 1.19-2.86; p<0.01), and higher incidence of grade II-IV acute GVHD (HR=1.74, 95% CI 1.14-2.64; p=0.01) as compared to other groups combined as reference. Compared to de novo AML (reference), secondary AML was associated with lower LFS (HR=1.49, 95% CI 1.03-2.15; p<0.05) and OS (HR=1.68, 95% CI 1.15-2.45; p<0.01). When age increased, patients faced higher RI (HR for 10y increment=1.24, 95% CI 1.01-1.53; p<0.05) and extensive chronic GVHD (HR=1.34, 95% CI 1.02-1.77; p<0.05), which translated into higher NRM (HR=1.66, 95% CI 1.23-2.24; p<0.01), lower LFS (HR=1.36, 95% CI 1.14-1.62; p<0.01) and OS (HR=1.60, 95% CI 1.31-1.96; p<0.01). Later year of transplantation was associated with lower incidence of II-IV acute GVHD (HR for 2y increment=0.76, 95% CI 0.63-0.92; p<0.01), chronic GVHD (HR=0.67, 95% CI 0.54-0.83; p<0.01) and extensive chronic GVHD (HR=0.72, 95% CI 0.52-0.99; p<0.05). Female to male, patient CMV status and interval between diagnosis and HCT did not affect significantly the transplant outcomes in multivariable analysis.


No significant difference was observed in outcomes of AML patients with TET2 mutations following MSD, HAPLO and 10/10 UD allo-HCTs, while 9/10 UD was associated with higher relapse incidence and lower survival outcomes. Higher patient age, secondary AML and adverse cytogenetics predicted worse transplant outcomes. GVHD prevention improved with time for these patients.

Disclosures: Salmenniemi: Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Immedia Pharma AB: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Viatris: Consultancy. Finke: Riemser: Honoraria, Research Funding, Speakers Bureau; Gilead Sciences: Current holder of stock options in a privately-held company; AbbVie: Current holder of stock options in a privately-held company; Roche: Current holder of stock options in a privately-held company; Neovii: Honoraria, Research Funding, Speakers Bureau; Medac: Honoraria, Research Funding. Ciceri: ExCellThera: Other: Scientific Advisory Board . Mohty: JAZZ PHARMACEUTICALS: Honoraria, Research Funding.

*signifies non-member of ASH