van Gelder Michel, Ziagkos Dimitris, de Wreede Liesbeth, van Biezen Anja, Dreger Peter, Gramatzki Martin, Stelljes Matthias, Andersen Niels Smedegaard, Schaap Nicolaas, Vitek Antonin, Beelen Dietrich, Lindström Vesa, Finke Jürgen, Passweg Jacob, Eder Matthias, Machaczka Maciej, Delgado Julio, Krüger William, Raida Luděk, Socié Gerard, Jindra Pavel, Afanasyev Boris, Wagner Eva, Chalandon Yves, Henseler Anja, Schoenland Stefan, Kröger Nicolaus, Schetelig Johannes
Department of Internal Medicine, University Medical Center Maastricht, Maastricht, the Netherlands.
Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
Clin Lymphoma Myeloma Leuk. 2017 Oct;17(10):667-675.e2. doi: 10.1016/j.clml.2017.06.007. Epub 2017 Jun 17.
Patients with genetically high-risk relapsed/refractory chronic lymphocytic leukemia have shorter median progression-free survival (PFS) with kinase- and BCL2-inhibitors (KI, BCL2i). Allogeneic hematopoietic stem cell transplantation (alloHCT) may result in sustained PFS, especially in younger patients because of its age-dependent non-relapse mortality (NRM) risk, but outcome data are lacking for this population.
Risk factors for 2-year NRM and 8-year PFS were identified in patients < 50 years in an updated European Society for Blood and Marrow Transplantation registry cohort (n = 197; median follow-up, 90.4 months) by Cox regression modeling, and predicted probabilities of NRM and PFS of 2 reference patients with favorable or unfavorable characteristics were plotted.
Predictors for poor 8-year PFS were no remission at the time of alloHCT (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.1-2.5) and partially human leukocyte antigen (HLA)-mismatched unrelated donor (HR, 2.8; 95% CI, 1.5-5.2). The latter variable also predicted a higher risk of 2-year NRM (HR, 4.0; 95% CI, 1.4-11.6) compared with HLA-matched sibling donors. Predicted 2-year NRM and 8-year PFS of a high cytogenetic risk (del(17p) and/or del(11q)) patient in remission with a matched related donor were 12% (95% CI, 3%-22%) and 54% (95% CI, 38%-69%), and for an unresponsive patient with a female partially HLA-matched unrelated donor 37% (95% CI, 12%-62%) and 38% (95% CI, 13%-63%).
Low predicted NRM and high 8-year PFS in favorable transplant high cytogenetic risk patients compares favorably with outcomes with KI or BCL2i. Taking into account the amount of uncertainty for predicting survival after alloHCT and after sequential administration of KI and BCL2i, alloHCT remains a valid option for younger patients with high cytogenetic risk chronic lymphocytic leukemia with a well-HLA-matched donor.
基因高危复发/难治性慢性淋巴细胞白血病患者使用激酶抑制剂和BCL2抑制剂（KI，BCL2i）时，中位无进展生存期（PFS）较短。异基因造血干细胞移植（alloHCT）可能导致PFS持续，尤其是在年轻患者中，因为其非复发死亡率（NRM）风险与年龄相关，但该人群缺乏结局数据。
在欧洲血液和骨髓移植学会登记队列的更新队列（n = 197；中位随访时间90.4个月）中，通过Cox回归模型确定年龄<50岁患者2年NRM和8年PFS的危险因素，并绘制2例具有有利或不利特征的参考患者的NRM和PFS预测概率。
alloHCT时未缓解（风险比[HR]，1.7；95%置信区间[CI]，1.1 - 2.5）和部分人类白细胞抗原（HLA）不匹配的无关供体（HR，2.8；95%CI，1.5 - 5.2）是8年PFS较差的预测因素。与HLA匹配的同胞供体相比，后一变量还预测2年NRM风险更高（HR，4.0；95%CI，1.4 - 11.6）。一名处于缓解期、具有匹配相关供体的高细胞遗传学风险（del(17p)和/或del(11q)）患者的预测2年NRM和8年PFS分别为12%（95%CI，3% - 22%）和54%（95%CI，3
