Department of Medicine, Stanford University School of Medicine, Stanford, CA.
Department of Medicine, Oregon Health & Science University, Portland, OR.
Blood Adv. 2023 Jul 25;7(14):3395-3402. doi: 10.1182/bloodadvances.2023009856.
Measurable residual disease (MRD) is an adverse prognostic factor in adult patients with acute lymphoblastic leukemia (ALL) undergoing hematopoietic cell transplant (HCT). Next-generation sequencing (NGS) can detect MRD with a sensitivity of 10-6, but the prognostic value of NGS-based MRD in adult patients with ALL undergoing HCT remains minimally studied. To evaluate the prognostic value of NGS-based MRD in adult patients with ALL undergoing HCT, patients aged ≥18 years with ALL who underwent allogeneic HCT at Stanford University or Oregon Health & Science University between January 2014 and April 2021 and were evaluated for MRD using the NGS-based clonoSEQ assay were included in this study. MRD was assessed before HCT (MRDpre) and up to 1 year after HCT (MRDpost). Patients were followed up for leukemia relapse and survival for up to 2 years after HCT. In total, 158 patients had a trackable clonotype for MRD monitoring. The cumulative incidence of relapse was increased at all levels of MRDpre, including in patients who had low MRDpre of <10-4 (hazard ratio [HR], 3.56; 95% confidence interval [95% CI], 1.39-9.15). In multivariable analysis, MRDpre level remained significantly prognostic; however, detectable MRDpost was the strongest predictor of relapse (HR, 4.60; 95% CI, 3.01-7.02). In exploratory analyses limited to patients with B-cell ALL, the detection of post-HCT immunoglobulin H (IgH) MRD clonotypes, rather than non-IgH MRD clonotypes, was associated with relapse. In this analysis across 2 large transplant centers, we found that the detection of MRD by NGS at a level of 10-6 offers significant prognostic value in adults with ALL undergoing HCT.
可测量残留疾病（MRD）是接受造血细胞移植（HCT）的成人急性淋巴细胞白血病（ALL）患者的不良预后因素。下一代测序（NGS）可以以 10-6 的灵敏度检测 MRD，但 NGS 检测的 MRD 在接受 HCT 的成人 ALL 患者中的预后价值研究甚少。为了评估 NGS 检测的 MRD 在接受 HCT 的成人 ALL 患者中的预后价值，我们纳入了 2014 年 1 月至 2021 年 4 月期间在斯坦福大学或俄勒冈健康与科学大学接受异基因 HCT 的年龄≥18 岁的 ALL 患者，这些患者使用基于 NGS 的 clonoSEQ 检测进行了 MRD 评估。MRD 在 HCT 前（MRDpre）和 HCT 后 1 年内（MRDpost）进行评估。患者接受了长达 2 年的 HCT 后白血病复发和生存随访。总共有 158 例患者具有可监测的 MRD 监测克隆型。MRDpre 水平在所有水平的复发率均增加，包括 MRDpre 水平低（<10-4）的患者（风险比[HR]，3.56；95%置信区间[95%CI]，1.39-9.15）。多变量分析显示，MRDpre 水平仍然具有显著的预后意义；然而，可检测的 MRDpost 是复发的最强预测因子（HR，4.60；95%CI，3.01-7.02）。在仅限于 B 细胞 ALL 患者的探索性分析中，HCT 后免疫球蛋白 H（IgH）MRD 克隆型的检测，而不是非 IgH MRD 克隆型的检测，与复发相关。在这两项大型移植中心的分析中，我们发现 NGS 在 10-6 水平检测到的 MRD 在接受 HCT 的 ALL 成人中具有显著的预后价值。
