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Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study.

ABSTRACT: Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.

SUBMITTER: Willasch AM

PROVIDER: S-EPMC8376634 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study.

Willasch Andre Manfred AM Peters Christina C Sedláček Petr P Dalle Jean-Hugues JH Kitra-Roussou Vassiliki V Yesilipek Akif A Wachowiak Jacek J Lankester Arjan A Prete Arcangelo A Hamidieh Amir Ali AA Ifversen Marianne M Buechner Jochen J Kriván Gergely G Hamladji Rose-Marie RM Diaz-de-Heredia Cristina C Skorobogatova Elena E Michel Gérard G Locatelli Franco F Bertaina Alice A Veys Paul P Dupont Sophie S Or Reuven R Güngör Tayfun T Aleinikova Olga O Sufliarska Sabina S Sundin Mikael M Rascon Jelena J Kaare Ain A Nemet Damir D Fagioli Franca F Klingebiel Thomas Erich TE Styczynski Jan J Bierings Marc M Nagy Kálmán K Abecasis Manuel M Afanasyev Boris B Ansari Marc M Vettenranta Kim K Alseraihy Amal A Chybicka Alicja A Robinson Stephen S Bertrand Yves Y Kupesiz Alphan A Ghavamzadeh Ardeshir A Campos Antonio A Pichler Herbert H Dalissier Arnaud A Labopin Myriam M Corbacioglu Selim S Balduzzi Adriana A Galimard Jacques-Emmanuel JE Bader Peter P

Bone marrow transplantation 20200317 8

Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) ...[more]

PMID: 32203263

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Project description:BackgroundAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended for patients with KMT2A-rearranged (KMT2A-r) leukemia whereas relapse remains high. We aimed to determine whether intensified conditioning containing decitabine (Dec) could reduce relapse compared with standard myeloablative conditioning in adult patients with KMT2A-r leukemia.MethodsWe performed a multicenter retrospective study at seven institutions in China. Eligible patients were aged 14 years or older at transplantation, had a diagnosis of KMT2A-r leukemia, and underwent the first allo-HSCT. Standard myeloablative conditioning regimens (standard group) included BuCy (busulfan 3.2 mg/kg/day on days -7 to -4; cyclophosphamide 60 mg/kg/day on days -3 to -2) and TBI-Cy (total body irradiation 4.5 Gy/day on days -5 to -4; Cy 60 mg/kg/day on days -3 to -2). Intensified conditioning regimens containing Dec (intensified group) consisted of Dec-BuCy (Dec 20 mg/m2/day on days -14 to -10; the same dose of BuCy) and Dec-TBI-Cy (Dec 20 mg/m2/day on days -10 to -6; the same dose of TBI-Cy).ResultsBetween April 2009 and December 2019, 218 patients were included in this study, of whom 105 were in the intensified group and 113 were in the standard group. The 3-year cumulative incidence of relapse was 17.6% and 34.5%, overall survival was 71.3% and 61.0%, disease-free survival was 70.1% and 56.0%, and non-relapse mortality was 12.3% and 9.5% in the intensified and standard groups, respectively (P = 0.001; P = 0.034; P = 0.005; P = 0.629). Subgroup analysis showed that the relapse rate of intensified conditioning was lower than that of standard conditioning in multiple subgroups, including different leukemia types, disease status at transplantation, high-risk cytogenetics and Bu-based regimens. There was no difference in regimen-related toxicity, engraftment, or graft-versus-host disease between the intensified and standard groups.ConclusionsThese results suggest that intensified conditioning containing Dec might be a better strategy than standard myeloablative conditioning for adult patients with KMT2A-r leukemia undergoing allo-HSCT.

Dataset Information

Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study.

Publications

Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study.

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