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3525 Trends in Allogeneic Stem Cell Transplantation for Good Risk Acute Myelogenous Leukemia in First Complete Remission: A Longitudinal Study of > 15 Years from the ALWP/EBMT

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster II
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Arnon Nagler, MD1, Myriam Labopin2*, Urpu Salmenniemi3*, Depei Wu4, Didier Blaise, MD, PhD5, Alessandro Rambaldi, M.D.6, Péter Reményi, MD7*, Edouard Forcade, MD, PhD8*, Regis Peffault De Latour9*, Patrice Chevallier, MD10, Peter von dem Borne Sr.11*, David Burns, MD, PhD12*, Christoph Schmid, MD13*, Johan Maertens, MD, PhD14*, Nicolaus Kröger, MD15*, Gesine Bug, MD16*, Mahmoud Aljurf, MD17*, Jan Vydra, MD18*, Kazimierz Halaburda19*, Fabio Ciceri, MD20* and Mohamad Mohty, MD, PhD21,22

1Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel
2EBMT Statistical Unit, Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France
3Dept of Hematology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland
4The First Affiliated Hospital of Soochow University, Suzhou, China
5Program of Transplant and cellular immunotherapy, Department of Hematology, Institut Paoli Calmettes, Marseille, France
6Department of Oncology and Hematology, University of Milan and Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
7Department of Hematology and Stem Cell Transplantation, South-Pest Central Hospital, Budapest, Hungary
8Service d'Hématologie Clinique et Thérapie Cellulaire, CHU Bordeaux, F-33000, Bordeaux, France
9Hôpital Saint-Louis,, Paris, France
10CHU De NANTES, Nantes Cedex 1, France
11Leiden University Medical Center, Leiden, Netherlands
12University Hospital Birmingham NHS Trust, Stoke, United Kingdom
13Klinikum Augsburg, Augsburg, Ghana
14Department of Hematology, University Hospitals Leuven, Leuven, Belgium
15University Hospital Eppendorf, Bone Marrow Transplantation Centre, Hamburg, Germany
16Klinik fuer Innere Medzin III, Ulm, Germany
17Dept of Hematology, Stem Cell Transplantation and Cellular Therapy , KFSHRC, Riyadh, Saudi Arabia
18Institute of Hematology and Blood Transfusion, Prague 10, CZE
19Institute of Hematology and Transfusion Medicine, Warsaw, POL
20IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy
21Saint-Antoine Hospital, Sorbonne University, Paris, France
22Hôpital Saint Antoine, Paris, FRA


Favorable acute myelogenous leukemia (AML) includes AML with t (8:21), inv (16), and those with NPM1 without FLT3-ITD, without adverse cytogenetics (ELN 2022). The incidence of relapse (RI) in favorable-risk AML with chemotherapy is 35%-40%. Although RI is ~20% lower with allogeneic transplantation (HSCT), transplantation is usually not indicated in favorable risk AML at first complete remission (CR1) due to transplant-related mortality. However, in recent years, HSCTs have been associated with significantly lower non relapse mortality (NRM) and better outcomes.

Methods: Our aim was to assess outcomes of HSCT in favorable risk AML (t (8:21), inv (16), and NPM1mutFLT3WT) in CR1, comparing 3 time periods: 2005-2009, 2010-2014, and 2015-2021. Statistical tests included a multivariate analysis (MVA) adjusting for potential confounding factors performed using a Cox proportional-hazards regression model for main outcomes.

Results: 1850 patients (pts) were included, 526 with t (8:21), 625 with inv (16), and 699 with NPM1mutFLT3WT (normal karyotype). 222 pts were transplanted in 2005-2009, 392 in 2010-2014, and 1236 in 2015-2021. As the follow-up period differed, being 103.1 (IQR, 92.1-114.0), 78.3 (IQR, 69.4-86.3), and 32.0 (IQR, 29.5-34.5) months, respectively (p<0.0001), all survival events were censored at 3 y. Pts undergoing HSCT in 2015-2021 were older, with a median age of 50.9 (range 18.2-76.4) vs 40.4 (range 18.3-67.7) and 42.4 (range 18.4-71) y, in those transplanted in 2005-2009 and 2010-2014, respectively (p<0.0001). More pts >50 y of age were transplanted in the latest period with 52.7% vs the 2 earlier periods 27.9% and 32.1% (p<0.0001) and figures for >60 y were 25.4% vs 8.1% and 11% (p<0.0001), respectively. In 2005-2009 the most frequent diagnosis was t (8:21) at 44.6%, while in 2015-2021, it was NPM1mutFLT3WT at 45.6% (p<0001). In 2005-2009, the most frequent donors were matched siblings (MSD) (63.1%), while in 2015-2021 they were unrelated (UD) (50.7%). Haploidentical (haplo) transplants increased from 5.9% to 14.5% (p<0.0001). Bone marrow grafts decreased from 24.8% to 13.2%, while peripheral blood (PB) grafts increased from 75.2% to 86.8% (p<0.0001). Conditioning was myeloablative in 69.8%, 64.8%, and 60.2% and was reduced intensity in 30.2%, 35.2%, and 39.8% in pts transplanted in 2005-2009, 2010-2014, and 2015-2021 (p=0.014). Graft-versus-host disease (GVHD) prophylaxis with in vivo T cell depletion or post-transplant cyclophosphamide (PTCy) was more frequent in 2015-2021 compared to the other two periods (p<0.0001).

Day 60 engraftment (ANC >0.5 x 109/L) was 98.2 % vs 98.4% vs 98.5% (p=0.17). Day 180 incidence of acute (a) GVHD grade II-IV was 18.2%, 21.1%, and 21.6%; grade III-IV was 5.1%, 5.7%, and 7.3% while the incidence of 3-y chronic (c) GVHD was 49.3%, 50.4% and 39.2%.

On MVA the incidence of total cGVHD was reduced in HSCTs performed >2015 compared to those performed in 2005-2009, hazard ratio (HR) =0.74 (95% CI 0.56-0.99, p=0.046) and GVHD-free, relapse-free survival (GRFS) improved for pts transplanted from 2010-2014 vs those transplanted in 2005-2009, HR=0.74 (95% CI 0.56-0.98, p=0.037) (Figure 1). All other HSCT outcome parameters including NRM, RI, leukemia-free survival (LFS), and overall survival (OS) did not differ (Figure 1) with no improvement >2015 compared to 2010-2014 (Figure-1 A). LFS, OS, and GRFS were superior in pts with t (8:21) with HR=1.32 (95% CI 1.03-1.68, p=0.026), HR=1.38 (95% CI 1.04-1.83, p=0.027) and HR=01.25 (95% CI 1.02-1.53, p=0.035), respectively. Other poor prognostic factors were older pt age (by 10 y) for NRM and OS; 10/10 and 9/10 UD vs MSD for aGVHD II-IV (9/10 also for III-IV aGVHD) and haplo vs MSD for NRM, OS, aGVHD II-IV, and total cGVHD. The combination of female donor to male pt was a poor prognostic factor for NRM, OS, GRFS, and cGVHD. In vivo, T cell depletion was a positive prognostic factor for GRFS and reduced incidence of aGVHD and cGVHD. PTCy was associated with a lower incidence of cGVHD and PB grafts with an increased risk of total cGVHD.

Conclusions: In this retrospective analysis of HSCT in pts with favorable risk AML in CR1, transplanted over 16 years, we observed an increased number of transplants in pts >60y, from UD and haplo with PB grafts and in vivo T cell depletion or PTCy as GVHD prophylaxis. Most importantly, 3-y GRFS improved >2010 and total cGVHD reduced >2015, while other HSCT outcome parameters have not changed.

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. Rambaldi: Roche: Honoraria, Other: support for attending meetings & participation on a safety advisory board; Kite-Gilead: Honoraria, Other: support for attending meetings & participation on a safety advisory board; Incyte: Honoraria, Other: Support for attending meetings & participation on a safety advisory board; Janssen: Honoraria, Other: Support for attending meetings & participation on a data safety monitoring board; Jazz: Honoraria, Other: support for attending meetings & participation on a data safety monitoring board; Astellas: Honoraria, Other: support for attending meetings & safety monitoring board; Pfizer: Honoraria, Other: Support for attending meetings & safety monitoring board; Amgen: Honoraria, Other: Support for attending meetings & data safety monitoring; Novartis: Honoraria, Other: Support for attending meetings & data safety monitoring; Abbvie: Honoraria; Omeros: Honoraria, Other: support for attending meetings & participation on a safety advisory board. Forcade: Alexion: Other: Travel support, Speakers Bureau; Novartis: Consultancy, Other: Travel support, Speakers Bureau; Astellas: Speakers Bureau; Gilead Sciences: Other: Travel support, Speakers Bureau; MSD: Other: Travel support; Sanofi: Speakers Bureau; GSK: Speakers Bureau. Peffault De Latour: Jazz Pharmaceuticals: Honoraria. Chevallier: Mallinckrodt Pharmaceuticals: Honoraria; Sanofi: Honoraria; Incyte: Honoraria, Research Funding; Takeda: Honoraria; Immedica Pharma: Honoraria; Servier: Honoraria. Schmid: Jazz: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; MSD: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Abbvie: Research Funding; Roche: Honoraria. Kröger: Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Neovii Biotech: Honoraria, Research Funding; MSD: Honoraria; Jazz: Honoraria; Kite/Gilead: Honoraria; Pfizer: Honoraria; BMS: Honoraria, Research Funding; Takeda: Consultancy; Sanofi: Honoraria. Bug: Jazz: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria. Mohty: JAZZ PHARMACEUTICALS: Honoraria, Research Funding.

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