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2876 Higher Efficacy of TBI + Cyclophosphamide Than TBI + Fludarabine As Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia: An Analysis By the Acute Leukemia Working Party of the EBMT

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster II
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Biological, Adults, Non-Biological, Clinical Research, Chemotherapy, Clinically Relevant, Diseases, Therapies, Registries, Lymphoid Malignancies, Radiation Therapy, Study Population, Transplantation, Clinical Practice (e.g. Guidelines, Health Outcomes and Services, and Survivorship, Value; etc.)
Sunday, December 12, 2021, 6:00 PM-8:00 PM

Sebastian Giebel, MD, PhD1*, Myriam Labopin2*, Gerard Socie, M.D.3, Mahmoud Aljurf4, Urpu Salmenniemi, MD5*, Ibrahim Yakoub-Agha6, Nicolaus Kröger, MD7*, Mohsen Alzahrani, MD8*, Bruno Lioure9*, Péter Reményi, MD10*, Mutlu Arat, MD11*, Jean-Henri Bourhis, MD12*, Grzegorz Helbig, MD PhD13*, Abdelghani Tbakhi, MD14*, Edouard Forcade, MD, PhD15*, Helene Labussiere-Wallet, MD16*, Anne Huynh17*, Eolia Brissot, MD, PhD18*, Alexandros Spyridonidis19*, Bipin Savani, MD20, Zinaida Perić, MD PhD21*, Arnon Nagler, M.D.22 and Mohamad Mohty, MD, PhD23

1Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
2Department of Clinical Hematology and Cellular Therapy, Saint Antoine Hospital, Assistance Publique - Hôpitaux de Paris, Sorbonne Université, Paris, France
3APHP, Hématologie-Transplantation Hôpital St Louis, Université de Paris and INSERM UMR 976, Paris, France
4Oncology, Section of Adult Haematolgy/BMT, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
5Stem Cell Transplantation Unit, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland
6Centre Hospitalier Universitaire de Lille LIRIC, INSERM U1286, Université de Lille, Lille, France
7Department of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany
8Division of Adult Hematology and SCT, Department of Oncology, King Abdul-Aziz Medical City, Riyadh, Saudi Arabia
9Department of Hematology, University Hospital of Strasbourg Institut De Canc, Strasbourg, FRA
10St. István and St. Laszlo Hospital, Budapest, Hungary
11Florence Nightingale Sisli Hospital, Hematopoietic SCT Unit, Istanbul, Turkey
12Département d’Hématologie, Institut Gustave Roussy, Villejuif, France
13Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland
14Department of Cell Therapy and Applied Genomics, King Hussein Cancer Center, Amman, Jordan
15Service d'Hématologie Clinique et Thérapie Cellulaire, CHU Bordeaux, F-33000, Bordeaux, France, CHU Bordeaux, Hospital Haut-Leveque, Pessac, FRA
16Hematology department 1 G, Centre Hospitalier Lyon Sud, Pierre Benite, France
17Département d’Hématologie, CHU-Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France
18Department of Clinical Hematology and Cellular Therapy, Hopital Saint Antoine, Paris, France
19BMT Unit, University Hospital of Patras, PATRA, Greece
20Department of Medicine, Division of Hematology-Oncology, Vanderbilt University Medical Center, Houston, TX
21Department of Hematology, University of Zagreb School of Medicine, Zagreb, HRV
22Division of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Israel
23Department of Clinical Hematology and Cellular Therapy, Saint Antoine Hospital, Paris, France

BACKGROUND: Allogeneic hematopoietic cell transplantation (allo-HCT) is a standard of care for adults with high-risk acute lymphoblastic leukemia (ALL) in first or subsequent complete remission (CR). Myeloablative total body irradiation (TBI) combined with cyclophosphamide (Cy) is the most frequently used conditioning regimen. In order to reduce toxicity Cy may be replaced by fludarabine (Flu). The goal of this registry-based, retrospective study was to compare outcomes of allo-HCT following TBI/Cy vs. TBI/Flu conditioning.

PATIENTS AND METHODS: Included in the analysis were 2255 patients aged 18-65 years, treated with allo-HCT from either a matched sibling (43%) or unrelated (57%) donor in CR1 (83%) or CR2 (17%), between the years 2010-2020. Patients with Ph(-) B-ALL, Ph(+) B-ALL, and T-ALL were represented in equal proportions. TBI 12Gy + Cy was used in 2105 cases while TBI 12Gy + Flu was administered to 150 patients. Patients treated with TBI/Flu were significantly older (median 35 years vs. 33 years, p=0.006), with poorer Karnofsky performance score (<90, 27% vs. 20%, p=0.03), more frequently transplanted from unrelated donors (71% vs. 57%, p=0.0007) with less frequently use of bone marrow as a source of stem cells (5% vs. 21%, p<0.0001), and in more recent year (median 2018 vs. 2015, p<0.0001).

RESULTS: Engraftment rate was 99% for both TBI/Cy and TBI/Flu patients. In a univariate analysis the use of TBI/Cy as compared to TBI/Flu was associated with a tendency to reduced incidence of relapse (24% vs. 29% at 2 years, p=0.1), increased incidence of grade 2-4 acute graft versus host disease (GVHD, 35.5% vs. 28%, p=0.08) and improved leukemia-free survival (LFS, 62% vs. 57%, p=0.18). The rates and causes of non-relapse mortality (NRM) did not differ significantly between the two conditioning groups. In a multivariate model adjusted for other prognostic factors, TBI/Cy conditioning was associated with reduced risk of relapse (HR=0.69, p=0.049) and increased risk of grade 2-4 acute GVHD (HR=1.57, p=0.03) without significant effect on other transplantation outcomes.

An additional analysis was performed with TBI/Cy treated patients (n=132) matched strictly to those treated with TBI/Flu (n=132) in terms of disease subtype, disease status and donor type with the nearest neighbor for patient age, patient and donor sex, in vivo T-cell depletion, Karnofsky score and source of stem cells; the use of TBI/Cy as compared to TBI/Flu was associated with significantly reduced rate of relapse (18% vs. 30% at 2 years, p=0.015) and a tendency to an improved LFS (65% vs. 59%, p=0.07) and overall survival (OS, 73% vs. 68%, p=0.16) without effect on NRM and GVHD.

CONCLUSIONS: The use of myeloablative TBI/CY as conditioning prior to allo-HCT for adult patients with ALL in CR1 or CR2 is associated with stronger anti-leukemic effect leading to significantly lower relapse rate compared to TBI/Flu and therefore should be likely considered a preferable regimen.

Disclosures: Giebel: Janssen: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Labopin: Jazz Pharmaceuticals: Honoraria. Socie: Alexion: Research Funding. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Kröger: Novartis: Research Funding; Riemser: Honoraria, Research Funding; Sanofi: Honoraria; Neovii: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Gilead/Kite: Honoraria; Celgene: Honoraria, Research Funding; AOP Pharma: Honoraria. Forcade: Novartis: Consultancy, Other: Travel Support, Speakers Bureau; Gilead: Other: Travel Support, Speakers Bureau; Jazz: Other: Travel Support, Speakers Bureau; MSD: Other: Travel Support. Huynh: Jazz Pharmaceuticals: Honoraria. Spyridonidis: Menarini: Current Employment. Perić: therakos: Honoraria; servier: Honoraria; MSD: Honoraria; Astellas: Honoraria; NOVARTIS: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria. Mohty: Pfizer: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Astellas: Honoraria; Gilead: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria; Bristol Myers Squibb: Honoraria; Takeda: Honoraria; Sanofi: Honoraria, Research Funding; Adaptive Biotechnologies: Honoraria.

*signifies non-member of ASH