Schetelig J, de Wreede L C, van Gelder M, Andersen N S, Moreno C, Vitek A, Karas M, Michallet M, Machaczka M, Gramatzki M, Beelen D, Finke J, Delgado J, Volin L, Passweg J, Dreger P, Henseler A, van Biezen A, Bornhäuser M, Schönland S O, Kröger N
Medical Department I, University Hospital, Technische Universität Dresden, Dresden, Germany.
Clinical Trials Unit, DKMS, gemeinnützige GmbH, Tübingen, Germany.
Bone Marrow Transplant. 2017 Apr;52(4):552-560. doi: 10.1038/bmt.2016.329. Epub 2017 Jan 23.
For young patients with high-risk CLL, BTK-/PI3K-inhibitors or allogeneic stem cell transplantation (alloHCT) are considered. Patients with a low risk of non-relapse mortality (NRM) but a high risk of failure of targeted therapy may benefit most from alloHCT. We performed Cox regression analyses to identify risk factors for 2-year NRM and 5-year event-free survival (using EFS as a surrogate for long-term disease control) in a large, updated EBMT registry cohort (n= 694). For the whole cohort, 2-year NRM was 28% and 5-year EFS 37%. Higher age, lower performance status, unrelated donor type and unfavorable sex-mismatch had a significant adverse impact on 2-year NRM. Two-year NRM was calculated for good- and poor-risk reference patients. Predicted 2-year-NRM was 11 and 12% for male and female good-risk patients compared with 42 and 33% for male and female poor-risk patients. For 5-year EFS, age, performance status, prior autologous HCT, remission status and sex-mismatch had a significant impact, whereas del(17p) did not. The model-based prediction of 5-year EFS was 55% and 64%, respectively, for male and female good-risk patients. Good-risk transplant candidates with high-risk CLL and limited prognosis either on or after failure of targeted therapy should still be considered for alloHCT.
对于高危慢性淋巴细胞白血病（CLL）的年轻患者，可考虑使用布鲁顿酪氨酸激酶（BTK）抑制剂/磷脂酰肌醇-3-激酶（PI3K）抑制剂或异基因造血干细胞移植（alloHCT）。非复发死亡率（NRM）低但靶向治疗失败风险高的患者可能从alloHCT中获益最大。我们进行了Cox回归分析，以确定在一个大型的、更新的欧洲血液和骨髓移植协会（EBMT）登记队列（n = 694）中2年NRM和5年无事件生存期（使用无进展生存期（EFS）作为长期疾病控制的替代指标）的危险因素。对于整个队列，2年NRM为28%，5年EFS为37%。较高年龄、较低体能状态、无关供体类型和不良的性别错配对2年NRM有显著不利影响。计算了低危和高危参考患者的2年NRM。男性和女性低危患者预测的2年NRM分别为11%和12%，而男性和女性高危患者分别为42%和33%。对于5年EFS，年龄、体能状态、既往自体造血干细胞移植、缓解状态和性别错配有显著影响，而17p缺失则没有。男性和女性低危患者基于模型预测的5年EFS分别为55%和64%。对于高危CLL且在靶向治疗失败时或失败后预后有限的低危移植候选者，仍应考虑进行alloHCT。
