Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT

• Published in: Bone marrow transplantation (Basingstoke) Vol. 58; no. 5; pp. 506 - 513
• Main Authors: Giebel, Sebastian, Labopin, Myriam, Socié, Gerard, Aljurf, Mahmoud, Salmenniemi, Urpu, Labussière-Wallet, Hélène, Srour, Micha, Kröger, Nicolaus, Zahrani, Mohsen Al, Lioure, Bruno, Reményi, Péter, Arat, Mutlu, Bourhis, Jean Henri, Helbig, Grzegorz, Tbakhi, Abdelghani, Forcade, Edouard, Huynh, Anne, Brissot, Eolia, Spirydonidis, Alexandros, Savani, Bipin N., Peric, Zinaida, Nagler, Arnon, Mohty, Mohamad
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2023; Nature Publishing Group
• Subjects: 692/699/1541/1990/283/2125; 692/700/565/2319; Acute Disease; Acute lymphoblastic leukemia; Adult; Allografts; Cell Biology; Conditioning; Cyclophosphamide; Cyclophosphamide - therapeutic use; Fludarabine; Graft versus host disease; Graft vs Host Disease - etiology; Graft-versus-host reaction; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic stem cells; Humans; Influenza; Internal Medicine; Irradiation; Leukemia; Leukemia, Myeloid, Acute - complications; Lymphatic leukemia; Medical prognosis; Medicine; Medicine & Public Health; Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Public Health; Radiation; Recurrence; Remission; Remission (Medicine); Retrospective Studies; Risk management; Stem cell transplantation; Stem Cells; Transplantation; Transplantation Conditioning - adverse effects; Transplantation, Homologous - adverse effects; Whole-Body Irradiation - adverse effects
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-023-01917-5

In this registry-based study we retrospectively compared outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with acute lymphoblastic leukemia (ALL) following conditioning with total body irradiation (TBI) combined with either cyclophosphamide (Cy) or fludarabine (Flu). TBI 12 Gy + Cy was used in 2105 cases while TBI 12 Gy + Flu was administered to 150 patients in first or second complete remission. In a multivariate model adjusted for other prognostic factors, TBI/Cy conditioning was associated with a reduced risk of relapse (HR = 0.69, p  = 0.049) and increased risk of grade 2–4 acute graft-versus-host disease (GVHD, HR = 1.57, p  = 0.03) without significant effect on other transplantation outcomes. In a matched-pair analysis the use of TBI/Cy as compared to TBI/Flu was associated with a significantly reduced rate of relapse (18% vs. 30% at 2 years, p  = 0.015) without significant effect on non-relapse mortality, GVHD and survival. We conclude that the use of myeloablative TBI/Cy as conditioning prior to allo-HCT for adult patients with ALL in complete remission is associated with lower risk of relapse rate compared to TBI/Flu and therefore should probably be considered a preferable regimen.