Gratwohl Alois, Duarte Rafael, Snowden John A, van Biezen Anja, Baldomero Helen, Apperley Jane, Cornelissen Jan, Greinix Hildegard T, Grath Eoin Mc, Mohty Mohamad, Kroeger Nicolaus, Nagler Arnon, Niederwieser Dietger, Putter Hein, Brand Ronald
Hematology, Medical Faculty, University of Basel, Basel, Switzerland.
Department of Hematology, University Hospital Puerta de Hierro Majadahonda, Madrid, Spain.
EClinicalMedicine. 2019 Aug 9;15:33-41. doi: 10.1016/j.eclinm.2019.07.019. eCollection 2019 Oct.
The role of conditioning intensity and stem cell source on modifying pre-transplantation risk in allogeneic haematopoietic stem cell transplantation (HSCT) is a matter of debate, but crucial when benchmarking centres.
This Retrospective, multicenter exploratory-validation analysis of 9103 patients, (55.5% male, median age 50 years; 1-75 years range) with an allogeneic HSCT between 2010 and 2016 from a matched sibling (N = 8641; 95%) or matched unrelated donor (N = 462; 5%) for acute myeloid (N = 6432; 71%) or acute lymphoblastic (N = 2671; 29%) leukaemia in first complete remission, and reported by 240 centres in 30 countries to the benchmark database of the European Society for Blood and Marrow Transplantation (EBMT) searched for factors associated with use of transplant techniques (standard N = 6375;70% or reduced intensity conditioning N = 2728;30%, respectively bone marrow N = 1945;21% or peripheral blood N = 7158;79% as stem cell source), and their impact on outcome.
Treatment groups differed significantly from baseline population (p < 0.001), and within groups regarding patient-, disease-, donor-, and centre-related pre-transplantation risk factors (p < 0.001); choice of technique did depend on pre-transplantation risk factors and centre (p < 0.001). Probability of overall survival at 5 years decreased systematically and significantly with increasing pre-transplantation risk score (score 2 vs 0/1 HR: 1·2, 95% c.i. [1·1-1·.3], p = 0.002; score 3 vs 0/1 HR: 1·5, 95% c.i. [1·3-1·7], p < 0.001; score 4/5/6 vs 0/1 HR: 1·9, 95% c.i. [1·6-2·2], p < 0.001) with no significant differences between treatment groups (likelihood ratio test on interaction: p = 0.40). Overall survival was significantly associated with selection steps and completeness of information (p < 0.001).
Patients' pre-transplantation risk factors determine survival, independent of transplant techniques. Transplant techniques should be regarded as centre policy, not stratification factor in benchmarking. Selection criteria and completeness of data bias outcome. Outcomes may be improved more effectively through better identifying pre-transplantation factors as opposed to refinement of transplant techniques.
The study was funded by EBMT.
预处理强度和干细胞来源对异基因造血干细胞移植（HSCT）中移植前风险的影响存在争议，但在对各移植中心进行基准对比时至关重要。
本研究对9103例患者进行回顾性、多中心探索性-验证性分析（男性占55.5%，中位年龄50岁；年龄范围1 - 75岁），这些患者在2010年至2016年间接受了来自同胞匹配供者（N = 8641；95%）或无关匹配供者（N = 462；5%）的异基因HSCT，用于治疗首次完全缓解的急性髓系白血病（N = 6432；71%）或急性淋巴细胞白血病（N = 2671；29%），由30个国家的240个中心向欧洲血液与骨髓移植学会（EBMT）的基准数据库报告，研究寻找与移植技术使用相关的因素（标准预处理N = 6375；70%或减低强度预处理N = 2728；30%，分别以骨髓N = 1945；21%或外周血N = 7158；79%作为干细胞来源）及其对结局的影响。
治疗组与基线人群有显著差异（p < 0.001），且组内患者、疾病、供者和中心相关的移植前危险因素也有显著差异（p < 0.001）；技术选择确实取决于移植前危险因素和中心（p < 0.001）。随着移植前风险评分增加，5年总生存概率系统性且显著降低（评分2 vs 0/1，HR：1.2，95%置信区间[1.1 - 1.3]，p = 0.002；评分3 vs 0/1，HR：1.5，95%置信区间[1.3 - 1.7]，p < 0.001；评分4/5/6 vs 0/1，HR：1.9，95%置信区间[1.6 - 2.2]，p < 0.001），治疗组间无显著差异（交互作用似然比检验：p = 0.40）。总生存与选择步骤和信息完整性显著相关（p < 0.001）。
患者的移植前危险因素决定生存，与移植技术无关。移植技术应被视为中心策略，而非基准对比中的分层因素。选择标准和数据完整性会影响结局。相较于改进移植技术，通过更好地识别移植前因素可能更有效地改善结局。
本研究由EBMT资助。
