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3443 Artificial Intelligence Methods to Estimate Overall Mortality and Non-Relapse Mortality Following Allogeneic Hematopoietic Cell Transplantation in the Modern Era: An EBMT Transplant Complications Working Party Study

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster II
Hematology Disease Topics & Pathways:
Research, Lymphoid Leukemias, ALL, Hodgkin lymphoma, Acute Myeloid Malignancies, AML, MDS, Clinical Practice (Health Services and Quality), Lymphomas, non-Hodgkin lymphoma, MPN, Clinical Research, health outcomes research, Plasma Cell Disorders, Chronic Myeloid Malignancies, Diseases, Lymphoid Malignancies, Myeloid Malignancies
Sunday, December 11, 2022, 6:00 PM-8:00 PM

Blanca Rius Sansalvador1*, Alberto Mussetti2,3*, Victor Moreno4*, Christophe Peczynski5*, Emmanuelle Polge6*, Nicolaus Kröger, MD7*, Didier Blaise, MD, PhD8,9, Regis Peffault De Latour10,11*, Alexander D. Kulagin, MD, PhD12*, Ashrafsadat Mousavi13*, Matthias Stelljes, MD14*, Rose-Marie Hamladji, MD, PhD15*, Martin Bornhäuser, MD16*, Urpu Salmenniemi, MD17*, Henrik Sengeloev18*, Edouard Forcade, MD, PhD19, Uwe Platzbecker, MD20, Péter Reményi, MD21*, Emanuele Angelucci, MD22, Patrice Chevallier, MD23, Ibrahim Yakoub-Agha, MD, PhD24, Charles Craddock25, Fabio Ciceri, MD26*, Thomas Schroeder27*, Mahmoud Aljurf, MD28, Ivan Moiseev, MD29, Olaf Penack, MD30*, Helene Schoemans, MD31*, Mohamad Mohty, MD PhD32, Bertram Glass, MD33*, Anna Sureda34, Grzegorz W Basak, MD, PhD35* and Zinaida Peric, MD, PhD36*

1IDIBELL, Barcelona, Spain
2Department of Hematology, Hospital Duran i Reynals, Instituto Catalán de Oncología, L'Hospitalet De Llobregat, Barcelona, Spain
3Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet De Llobregat, Barcelona, Spain
4Catalan Institute of Oncology, Hospitalet, ESP
5EBMT Paris study office; Department of Haematology,, Saint Antoine Hospital; INSERM UMR 938, Sorbonne University, Paris, France
6EBMT Global Committee and Acute Leukemia Working Party, Hopital Saint-Antoine APHP and Sorbonne University, Paris, France
7University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation, Hamburg, Germany
8Hematology Department, Institut Paoli-Calmettes, Marseille, France
9Département d'hématologie, Programme de transplantation et de thérapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Aix-Marseille University, Institut Paoli Calmettes, Marseille, France
10French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Paris, France
11Assistance Publique–Hôpitaux de Paris, Saint-Louis Hospital, Université Paris Cité, Paris, France
12RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russian Federation
13Shariati Hospital ,Hematology-Oncology and BMT Research, Tehran, Iran (Islamic Republic of)
14University Hospital of Muenster, Muenster, Germany
15Centre Pierre et Marie Curie, Alger, Algeria
16Department of Internal Medicine I, University Hospital Dresden, Dresden, Germany
17Stem Cell Transplantation Unit, HUCH Comprehensive Cancer Center, Helsinki, Finland, Helsinki, Finland
18Rigshospitalet, Copenhagen, Denmark
19Service d'Hématologie Clinique et Thérapie Cellulaire, CHU Bordeaux, Hôpital Haut-Leveque, Bordeaux, France
20Medical Clinical and Policlinic 1, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany
21Dél-pesti Centrumkórház – Országos Hematológiai és Infektológiai Intézet, Dept. Haematology and Stem Cell Transplant, Budapest, Hungary
22Department of Hematology II, Ospedale San Martino, Genoa, Italy
23Hematology Department, Nantes University Hospital, Nantes, France
24Centre Hospitalier Universitaire de Lille LIRIC, INSERM U1286, Université de Lille, LILLE, France
25Department of Haematology, University Hospital Birmingham NHS Trust, Queen Elizabeth Medical Centre, Birmingham, ENG, United Kingdom
26Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
27Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Medical Faculty, Düsseldorf, Germany
28Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
29RM Gorbacheva Research Institute, Pavlov University, Saint-Petersburg, Russia
30Department of Hematology, Oncology and Tumorimmunology (Campus Virchow-Klinikum), Charite University Berlin, Berlin, Germany
31Department of Hematology, University Hospitals Leuven and KU Leuven, Leuven, Belgium
32EBMT Paris study office / CEREST-TC, Paris, France, Department of Hematology, Saint Antoine Hospital, Paris, France, INSERM UMR 938, Sorbonne University, Paris, France
33Department of Hematology, HELIOS Klinikum Berlin-Buch, Berlin, Germany
34Institut Català d'Oncologia, Hospital Duran i Reynals. Institut d’Investigació Biomèdica de Bellvitge (IDIBELL). Universitat de Barcelona, Barcelona, Spain
35Department of Hematology, Transplantation, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
36University Hospital Centre Zagreb, Zagreb, Croatia

Introduction
Allogeneic hematopoietic cell transplantation (alloHCT) is a life-saving procedures for many hematological diseases. However, its toxicity counterbalances its curative potential. Several prognostic scores have been created in the last two decades. Most scores derive from small sized and monocentric cohorts of patients. Also, contemporary patients and alternative donors are usually excluded from these scores.

Methods
We selected patients from the EBMT registry with the following characteristics: age > 18 years old; allogeneic hematopoietic cell transplantation (alloHCT) performed between 2010 and 2019; hematological disease diagnosis (AML/ALL; MDS/MPN; NHL/HL; plasma cell dyscrasias); any disease status at transplant; use of HLA-matched (familiar or unrelated) or haploidentical donor; myeloablative or RIC/NMA conditioning regimen; peripheral blood or bone marrow graft source. The primary objective was to create a prognostic score able to predict overall mortality (OM) at +2 years. The secondary objective was to predict non-relapse mortality (NRM) at 2 years. To create a newer prognostic score, we explored the following statistic and machine-learning techniques: step-wise logistic regression, support vector machine with linear and radial kernels, random forest, gradient boosting, elasticnet. We also tested simple fully connected neural network. The score included all the pre-transplant variables with a well-known prognostic role in terms of NRM related to disease (disease type) patient (age, gender, Karnofsky score, body mass index, presence of significant comorbidities, CMV status) transplant (time from diagnosis to transplant, donor type, GVHD prophylaxis, conditioning intensity, graft type) and transplant center characteristics (JACIE accreditation, > 20 alloHCT/year). OM model development was made on 70% of the data set, optimized on 15% and validated on the 15% of remaining data. Models with the best accuracy were selected to build the prognostic score.

Results
A total of 48984 patients were included into the analysis (Table 1). Median follow-up time for survivors was 38.4 months. Overall mortality and NRM at +2 years were 39.5% (95% CI=39.0-40.0%) and 19.0% (95% CI=18.5-19.5%), respectively. The 5 models predicted 2-year OM and NRM with similar AUC values. Best models were, for OM, gradient boosting (XGBoost) with AUC=0.64 (95% CI 0.630-0.655) and for NRM, elasticnet with AUC=0.58 (0.566-0.594). Neural networks had slightly higher performance for NRM but has limitations regarding the explicability of results. Same results were observed also when performing the analysis with the haploidentical cohort (n=5.934, AUC 0.66 for OM and 0.57 for NRM). In the final prognostic score including all the variables, gradient boosting was used to predict OM and elasticnet to predict NRM. The score was able to furnish a personalized prediction for each patient with continuous values. Patients with the lowest score had a 2-year OM and NRM of 22.2% and 8.7%, respectively. Patients with the highest score had a 2-year OM and NRM of 81.2% and 87.1%, respectively. A visual representation of the score prediction distribution was made on the validation cohort grouping the potential results into 4 groups (figure 1).

Conclusion
Our score showed to be useful in improving risk stratification of OM and NRM in the current era, including haploidentical transplants and post-transplant cyclophosphamide GVHD prophylaxis which were not included in previous scores. However, a generally poor accuracy despite the robust methodology confirms previous observations highlighting that the results of a prognostic score itself should not be used to exclude patients from a life-saving procedure. In such high-risk cases, more comprehensive evaluations (e.g. geriatric scores), biological scores (e.g. EASIX scores) and the overall patient’s clinical phenotype should be evaluated to establish the actual transplantation risk and help in this difficult therapeutic choice

Disclosures: Mussetti: GILEAD: Research Funding; BMS: Consultancy; TAKEDA: Honoraria; JAZZ PHARMACEUTICALS: Consultancy. Kröger: Takeda: Consultancy, Honoraria; Sanofi: Honoraria; Kite: Honoraria; Neovii: Honoraria, Research Funding; Riemser: Research Funding; DKMS: Research Funding; Amgen: Honoraria; BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Jazz: Honoraria. Peffault De Latour: Samsung: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; MSD: Consultancy, Honoraria; Keocyte: Consultancy, Honoraria; Jazz: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Sobi: Consultancy, Honoraria. Forcade: MSD: Other: Travel Support; Gilead: Other: Travel Support, Speakers Bureau; Jazz: Other: Travel Support, Speakers Bureau; Novartis: Speakers Bureau; GSK: Speakers Bureau; Sanofi: Other: Travel Support. Platzbecker: Takeda: Honoraria; Silence Therapeutics: Honoraria; Novartis: Honoraria; Jazz: Honoraria; Abbvie: Honoraria; BMS/Celgene: Honoraria; Janssen: Honoraria; Geron: Honoraria. Angelucci: Vifopr: Honoraria, Other: Data monitoring committee; Sanofi: Speakers Bureau; Vertex: Honoraria, Other: Data monitoring committee; Roche: Consultancy; Gilead: Consultancy; Glaxo: Consultancy; Bluebird Bio: Consultancy; Celgene: Honoraria, Other: Data monitoring committee; Novartis: Honoraria; Menarini/Stemline: Consultancy. Chevallier: Incyte: Research Funding; Takeda: Honoraria; Pfizer: Research Funding; Abbvie: Honoraria; Jazz Pharmaceuticals: Honoraria. Yakoub-Agha: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Janssen: Honoraria; Bristol Myers Squibb: Honoraria. Craddock: Novartis: Consultancy; Abbvie: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; JAZZ: Consultancy, Research Funding; Daiichi-Sankyo: Consultancy. Ciceri: Kite Pharma: Consultancy. Schroeder: Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Moiseev: Janssen: Honoraria; Jazz: Honoraria; Takeda: Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Penack: Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Equillium Bio: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees; Priothera: Membership on an entity's Board of Directors or advisory committees, Research Funding; Shionogi: Membership on an entity's Board of Directors or advisory committees; SOBI: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Therakos: Honoraria; Pfizer: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Schoemans: Incyte, Janssen, Novartis , Jazz Pharmaceuticals, Takeda: Other: Personal Fees; Belgian Hematological Society (BHS): Other: Fees paid to institution; Novartis and the BHS (Belgian Hematological Society): Research Funding; serEBMT, EUPATI (the European Patient academy): Other: serves regularly as a volunteer for EBMT and occasionally for EUPATI (the European Patient academy). Mohty: Adaptive Biotechnologies: Honoraria; Astellas: Honoraria; Pfizer,: Honoraria; GSK: Honoraria; Novartis: Honoraria; Oncopeptides: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Jazz Pharmaceuticals: Honoraria, Research Funding; Celgene: Honoraria; Bristol Myers Squibb: Honoraria; Gilead: Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Glass: Gilead: Consultancy; Novartis: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Sureda: ROCHE: Consultancy, Honoraria; JANSSEN: Consultancy, Honoraria; BMS: Consultancy, Honoraria; NOVARTIS: Consultancy, Honoraria; MSD: Honoraria; TAKEDA: Consultancy, Honoraria, Speakers Bureau; SANOFI: Consultancy, Honoraria; GILEAD: Consultancy. Basak: Gilead: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Saventic Health: Consultancy, Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Human Biome Institute: Consultancy, Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria.

*signifies non-member of ASH