Total body irradiation versus busulfan based intermediate intensity conditioning for stem cell transplantation in ALL patients >45 years—a registry-based study by the Acute Leukemia Working Party of the EBMT

• Published in: Bone marrow transplantation (Basingstoke) 2023-08, Vol.58 (8), p.874-880
• Main Authors: Hirschbühl, Klaus, Labopin, Myriam, Polge, Emmanuelle, Blaise, Didier, Bourhis, Jean Henri, Socié, Gerard, Forcade, Edouard, Yakoub-Agha, Ibrahim, Labussière-Wallet, Hélène, Bethge, Wolfgang, Chevallier, Patrice, Bonnet, Sarah, Stelljes, Matthias, Spyridonidis, Alexandros, Peric, Zinaida, Brissot, Eolia, Savani, Bipin, Giebel, Sebastian, Schmid, Christoph, Ciceri, Fabio, Nagler, Arnon, Mohty, Mohamad
• Format: Article
• Language: English
• Subjects: 692/308/2171; 692/700/565/2319; Acute lymphoblastic leukemia; Allografts; Busulfan; Cell Biology; Conditioning; Fludarabine; Graft-versus-host reaction; Hematology; Hematopoietic stem cells; Internal Medicine; Irradiation; Leukemia; Life Sciences; Lymphatic leukemia; Medicine; Medicine & Public Health; Multivariate analysis; Public Health; Radiation; Remission; Risk analysis; Stem cell transplantation; Stem Cells; Survival; Toxicity; Transplantation
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-023-01966-w

Allogeneic hematopoietic cell transplantation is a potentially curative treatment in high-risk acute lymphoblastic leukemia (ALL). Conditioning regimens based on ≥12 Gray total body irradiation (TBI) represent the current standard in patients ≤45 years, whereas elderly patients frequently receive intermediate intensity conditioning (IIC) to reduce toxicity. To evaluate the role of TBI as a backbone of IIC in ALL, a retrospective, registry-based study included patients >45 years transplanted from matched donors in first complete remission, who had received either fludarabine/TBI 8 Gy (FluTBI8, n  = 262), or the most popular, irradiation-free alternative fludarabine/busulfan, comprising busulfan 6.4 mg/kg (FluBu6.4, n  = 188) or 9.6 mg/kg (FluBu9.6, n  = 51). At two years, overall survival (OS) was 68.5%, 57%, and 62.2%, leukemia-free survival (LFS) was 58%, 42.7%, and 45%, relapse incidence (RI) was 27.2%, 40%, and 30.9%, and non-relapse-mortality (NRM) was 23.1%, 20.7%, and 26.8% for patients receiving FluTBI8Gy, FluBu6.4, and FluBu9.6, respectively. In multivariate analysis, the risk of NRM, acute and chronic graft-versus-host disease was not influenced by conditioning. However, RI was higher after FluBu6.4 (hazard ratio [HR] [95% CI]: 1.85 [1.16–2.95]), and LFS was lower after both FluBu6.4 (HR: 1.56 [1.09–2.23]) and FluBu9.6 (HR: 1.63 [1.02–2.58]) as compared to FluTBI8. Although only resulting in a non-significant advantage in OS, this observation indicates a stronger anti-leukemic efficacy of TBI-based intermediate intensity conditioning.