Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts, and Harvard School of Public Health, Boston, Massachusetts.
Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin.
Clin Cancer Res. 2019 Aug 15;25(16):5143-5155. doi: 10.1158/1078-0432.CCR-18-3988. Epub 2019 Jun 28.
To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT).
We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research.
On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or ≥5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high ( < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years).
In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.
为先前接受过慢性淋巴细胞白血病(CLL)治疗的患者开发一个预后模型和细胞遗传学风险分类,这些患者接受了强度降低的调理(RIC)异基因造血细胞移植(HCT)。
我们对 2008 年至 2014 年期间向国际血液和骨髓移植研究中心报告的 606 例接受 RIC 异基因 HCT 的 CLL 患者的结果进行了回顾性分析。
基于多变量模型,疾病状态、合并症指数、HCT 时的淋巴细胞计数和白细胞计数被选择用于开发预后模型。使用预后评分,我们将患者分层为低、中、高和极高风险[4 年无进展生存率(PFS)分别为 58%、42%、33%和 25%,<0.0001;4 年总生存率(OS)分别为 70%、57%、54%和 38%,<0.0001]。我们还评估了细胞遗传学异常以及 del(17p),发现 del(17p)或≥5 异常与 PFS 较差相关。使用多变量模型,我们将细胞遗传学风险分类为低、中和高(<0.0001)。当预后评分和细胞遗传学风险相结合时,低预后评分和低细胞遗传学风险的患者具有更长的 PFS(4 年时为 61%)和 OS(4 年时为 75%)。
在这一大群先前接受过 CLL 治疗的患者中,我们开发了一个强大的异基因 HCT 结果预后评分系统和一个新的基于细胞遗传学的风险分层系统。这些预后模型可用于为患者提供咨询、比较研究数据,并为未来的干预措施提供基准。未来的研究将进一步验证这些模型在接受 HCT 前接受靶向治疗的患者中的应用。