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2124 Risk Factors Influencing Transplant Outcomes of Adults with Acute Lymphoblastic Leukemia in First Complete Remission: A Retrospective Analysis from the ALWP of the EBMT

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster I
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Biological therapies, Diseases, Therapies, Lymphoid Malignancies, Transplantation, Minimal Residual Disease
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Martina Calabrò, MD1*, Myriam Labopin, MD2,3,4*, Giorgia Battipaglia, MD1,5*, Mutlu Arat, MD6, Ibrahim Yakoub-Agha, MD, PhD7, Urpu Salmenniemi, MD8*, Jan Vydra, MD9*, Didier Blaise, MD, PhD10, Regis Peffault De Latour11*, Caroline Besley, FRCPath, PhD12*, Jean-Henri Bourhis, M.D.13, Renato Fanin, MD14*, Nicolaus Kröger, MD15*, Alessandro Rambaldi, MD16, Ben Carpenter17*, Péter Reményi, MD18*, Tobias Gedde-Dahl, MD19*, Sebastian Giebel, MD, PhD20*, Arnon Nagler, MD21, Fabio Ciceri, MD22* and Mohamad Mohty, MD PhD2,3,4

1Federico II University of Naples, Hematology Department, Naples, Italy
2Sorbonne Universités, UPMC Univ Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris, France
3EBMT Statistical Unit, Paris, France
4Hematology Department, Hôpital Saint Antoine, Service d'Hématologie Thérapie Cellulaire, Paris, France
5Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
6Hematopoietic SCT Unit, Demiroglu Bilim University Istanbul Florence Nightingale Hospital, Istanbul, Turkey
7CHU de Lille LIRIC, INSERM U995, Université de Lille, Lille, France
8Stem Cell Transplantation Unit, HUCH Comprehensive Cancer Center, Helsinki, Finland, Helsinki, Finland
9Institute of Hematology and Blood Transfusion, Prague, Czech Republic
10Département d'hématologie, Programme de transplantation et de thérapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Aix-Marseille University, Institut Paoli Calmettes, Marseille, France
11Hopital St. Louis, Department of Hematology - BMT, Paris, France
12Bristol Royal Hospital for Children, Dept. of Paediatric Oncology/BMT, Bristol, United Kingdom
13Division of Hematology, Department of Medical Oncology, Gustave Roussy, institut de cancérologie, BMT Service, Villejuif, France
14Division of Hematology and BMT, Department of Medical Area, University of Udine, Udine, Italy
15University Medical Center Eppendorf, Bone Marrow Transplantation Centre, Hamburg, Germany
16Department of Oncology-Hematology, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
17University College London Hospital, Department of Haematology, London, United Kingdom
18Dél-pesti Centrumkórház – Országos Hematológiai és Infektológiai Intézet, Dept. Haematology and Stem Cell Transplant, Budapest, Hungary
19Rikshospitalet, Clinic for Cancer Medicine, Hematology Dept., Section for Stem Cell Transplantation, Oslo University Hospital, Oslo, Norway
20Department of Bone Marrow Transplantation and Hematology-Oncology, Maria Sklodowska-Curie Cancer Center and Institute of Oncology, Gliwice, Poland
21The Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer , Tel Aviv University, Ramat Gan, Israel
22Hematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) remains a standard of care for adult patients with acute lymphoblastic leukemia (ALL) at high risk of relapse, i.e. high-risk features at time of diagnosis (ex. Philadelphia (Ph) positive ALL), or detectable minimal residual disease (MRD+). The aim of our study was to identify risk factors influencing transplant outcomes in ALL patients transplanted between 2015 and 2021.

Methods: We included adults undergoing allo-HSCT for ALL in CR1 with available data of ALL phenotype, Ph-status, and MRD pre-transplant. All donor types and stem cell sources were eligible, except cord blood. Ex-vivo T-cell depletion (TCD) represented an exclusion criterion.

Results: We identified 2349 transplanted patients including 870 from HLA-matched sibling (MSD), 1150 from unrelated (79% 10/10 and 21% 9/10 UD), and 329 from haploidentical donors (Haplo). Median age was 42.6 (range 18-76.1) years. Median follow-up was 23.5 (95% CI 21.8-24.2) months. The entire cohort was composed of 667 patients (28.4%) with Ph-negative B-ALL, 1325 (56.4%) with Ph-positive B-ALL and 357 (15.2%) with T-ALL. Median time from diagnosis to allo-HSCT was 5.8 (range 1.3-18) months. Stem cell source was peripheral blood (PB) in 85.3% of cases. Conditioning regimen was reduced-intensity (RIC) in 21% and myeloablative (MAC) in 79% of cases. Total body irradiation (TBI) was used in 65.8% of patients, mostly as a MAC (93.9%). Pre-transplant MRD+ was reported in 35.4% while in-vivo TCD was used in 51.5% of cases.

At 180 days, cumulative incidence of grade II-IV and grade III-IV acute graft-versus-host disease (aGVHD) were 29.2% (95% CI 27.3-31.1) and 10.1% (95% CI 8.9-11.4), respectively. Two-years overall and extensive chronic GVHD (cGVHD) were 34% (95% CI 31.7-36.3) and 15% (95% CI 13.2-16.8), respectively. At two years, relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS) and GVHD-free/relapse free survival (GRFS) were 22.2% (95% CI 20.3-24.2), 15.4% (95% CI 13.8-17.1), 62.3% (95% CI 60-64.6) 73.9% (95% CI 71.7-76) and 48% (95% CI 45.6-50.3), respectively.

By multivariate analysis, MSD (reference group) was associated to higher RI compared to 9/10 UD (HR 1.47, 95% CI 1.01-2.12; p<0.05) and Haplo (HR 1.64, 95% CI 1.15-2.27; p<0.01) but lower NRM and grade II-IV aGVHD compared to both 9/10 and 10/10 UD (for NRM HR 0.54, 95% CI 0.36-0.81; p<0.01 and HR 0.65, 95% CI 0.48-0.88; p<0.01; for aGVHD: HR 0.58, 95% CI 0.44-0.78; p<0.01 and HR 0.70, 95% CI 0.56-0.87; p<0.01). Compared to Ph-negative ALL (reference group), Ph-positive ALL was associated with a lower RI (HR=0.61, 95% CI 0.49-0.77; p<0.01) and higher LFS (HR=0.71, 95% CI 0.60-0.85; p<0.01), OS (HR=0.59, 95% CI 0.48-0.72; p<0.01) and GRFS (HR=0.81, 95% CI 0.70-0.94; p<0.01), while T-ALL was associated to lower NRM (HR 0.58, 95% CI 0.37-0.91: p<0.02) and cGVHD (HR 0.73, 95% CI 0.54-0.98; p<0.04). MRD+ group faced higher RI (HR=1.74, 95% CI 1.42-2.12; p<0.01), lower LFS (HR=1.41, 95% CI 1.21-1.65; p<0.01), OS (HR=1.31, 95% CI 1.08-1.58; p<0.01) and GRFS (HR=1.31, 95% CI 1.14-1.49; p<0.01). Use of TBI enabled lower RI (HR 0.78, 95% CI 0.61-0.99; p=0.04), higher LFS (HR=0.80, 95% CI 0.67-0.96; p<0.02) but higher grade II-IV aGVHD (HR 1.54, 95% CI 1.23-1.92; p<0.01) and cGVHD (HR 1.47, 95% CI 1.16-1.87; p<0.01) compared to chemotherapy. Patients receiving a RIC had a higher RI (HR=1.52, 95% CI 1.17-1.98; p<0.01) and a lower NRM (HR=0.55, 95% CI 0.39-0.77; p<0.01). In vivo TCD allowed lower risk of cGVHD (HR=0.69, 95% CI 0.55-0.85; p<0.01) and higher GRFS (HR=0.78, 95% CI 0.66-0.91; p<0.01). PB stem cells and female-donor to male-recipient were independently associated to higher risk of cGVHD. Elderly patients faced lower LFS, OS and GRFS.

Conclusions: Our study reported overall favorable outcomes in the population of recently allografted patients with ALL in CR1 (LFS> 60% et OS> 70% at 2 years). Prognostic role of pre-transplant MRD is confirmed. Results in Ph-positive ALL are not inferior compared to Ph-negative ALL, most probably due to the use of tyrosine kinase inhibitors. Whether incorporation of novel agents will change the role of allo-HSCT in Ph-positive ALL is under investigation. Use of TBI and HLA mismatches are both associated with lower RI despite a higher risk of GVHD, highlighting the importance of tailoring GVHD prophylaxis in these settings.

Disclosures: Labopin: Jazz Pharmaceuticals: Honoraria. Yakoub-Agha: Bristol Myers Squibb: Honoraria; Janssen: Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. 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. 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. Rambaldi: Pfizer: Honoraria; Astellas: Honoraria; ABBVIE: Honoraria; Jazz: Honoraria; Kite-Gilead: Honoraria; Novartis: Honoraria; Incyte: Honoraria; Roche: Honoraria; Janssen: Honoraria; Celgene-BMS: Honoraria; Amgen: Honoraria; Omeros: Honoraria. Carpenter: Novartis: Membership on an entity's Board of Directors or advisory committees; Vertex: Membership on an entity's Board of Directors or advisory committees. Ciceri: Kite Pharma: Consultancy. Mohty: Pfizer,: Honoraria; GSK: Honoraria; Oncopeptides: Honoraria; Adaptive Biotechnologies: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Jazz Pharmaceuticals: Honoraria, Research Funding; Gilead: Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

*signifies non-member of ASH