Kalwak Krzysztof, Moser Laura M, Pötschger Ulrike, Bader Peter, Kleinschmidt Katharina, Meisel Roland, Dalle Jean-Hugues, Yesilipek Akif, Balduzzi Adriana, Krivan Gergely, Goussetis Evgenios, Staciuk Raquel, Sedlacek Petr, Pichler Herbert, Svec Peter, Gabriel Melissa, Güngör Tayfun, Bilic Ernest, Buechner Jochen, Renard Marleen, Vettenranta Kim, Ifversen Marianne, Diaz-de-Heredia Cristina, Stein Jerry, Toporski Jacek, Bierings Marc, Peters Christina, Ansari Marc, Locatelli Franco
Department of Pediatric Hematology, Oncology, and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.
Division for Stem Cell Transplantation and Immunology, Department of Pediatrics, Goethe University Frankfurt, University Hospital, Frankfurt, Germany.
Blood Adv. 2025 Feb 25;9(4):741-751. doi: 10.1182/bloodadvances.2024014548.
The superiority of total body irradiation (TBI)-based vs chemotherapy conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukemia (ALL) has been established in the international, prospective phase-3 FORUM study, randomizing 417 patients aged 4-18 years in complete remission (CR), who received allo-HSCT from HLA-matched sibling or unrelated donors. Because of the unavailability of TBI in some regions and to accommodate individual contraindications, this study reports the prespecified comparison of outcomes of patients receiving busulfan (BU)- or treosulfan (TREO)-based regimens from 2013 to 2018. Overall, 180 and 128 patients received BU/thiotepa (THIO)/fludarabine (FLU) or TREO/THIO/FLU, respectively. Data were analyzed as of February 2023, with a median follow-up of 4.2 years (range, 0.3-9.1). 3-year overall survival was 0.71 (BU, 95% confidence interval [0.64-0.77]) and 0.72 (TREO, [0.63-0.79]) and 3-year event-free survival was 0.60 (BU, [0.53-0.67]) and 0.55 (TREO, [0.46-0.63]). The 3-year cumulative incidence of relapse (BU, 0.31 [0.25-0.38]; TREO, 0.36 [0.27-0.44]); and nonrelapse mortality (BU, 0.08 [0.05-0.13]; TREO, 0.09 [0.05-0.15]) were comparable. One case of fatal veno-occlusive disease occurred in each group. No significant differences in acute and chronic graft-versus-host disease (GVHD) or 3-year GVHD-free and relapse-free survival (BU, 0.48 [0.41-0.55]; TREO, 0.45 [0.37-0.54]) were recorded. Outcomes for patients in first and second CR were similar irrespective of the regimen. In conclusion, BU/THIO/FLU or TREO/THIO/FLU regimens can be an alternative to TBI for patients with ALL aged >4 years with contraindications or lack of access to TBI. This trial was registered at www.ClinicalTrials.gov as #NCT01949129.
在国际前瞻性3期FORUM研究中，已证实对于急性淋巴细胞白血病（ALL）患儿，基于全身照射（TBI）的预处理方案相较于化疗预处理方案用于异基因造血干细胞移植（allo-HSCT）具有优越性。该研究将417例年龄在4至18岁处于完全缓解（CR）期的患者随机分组，这些患者接受了来自人类白细胞抗原（HLA）匹配的同胞或无关供者的allo-HSCT。由于某些地区无法开展TBI且要考虑个体禁忌证，本研究报告了2013年至2018年接受基于白消安（BU）或曲奥舒凡（TREO）方案治疗的患者结局的预先设定比较。总体而言，分别有180例和128例患者接受了BU/硫替派（THIO）/氟达拉滨（FLU）或TREO/THIO/FLU方案。截至2023年2月进行数据分析，中位随访时间为4.2年（范围0.3至9.1年）。3年总生存率分别为0.71（BU，95%置信区间[0.64 - 0.77]）和0.72（TREO，[0.63 - 0.79]），3年无事件生存率分别为0.60（BU，[0.53 - 0.67]）和0.55（TREO，[0.46 - 0.63]）。3年累积复发率（BU，0.31[0.25 - 0.38]；TREO，0.36[0.27 - 0.44]）以及非复发死亡率（BU，0.08[0.05 - 0.13]；TREO，0.09[0.05 - 0.15]）具有可比性。每组均发生1例致命性静脉闭塞性疾病。急性和慢性移植物抗宿主病（GVHD）或3年无GVHD且无复发生存率（BU，0.48[0.41 - 0.55]；TREO，0.45[0.37 - 0.54]）无显著差异。无论采用何种方案，首次和第二次CR期患者的结局相似。总之，对于年龄大于4岁有禁忌证或无法进行TBI的ALL患者，BU/THIO/FLU或TREO/THIO/FLU方案可作为TBI的替代方案。本试验已在www.ClinicalTrials.gov注册，注册号为#NCT01949129。
