Gökbuget Nicola, Dombret Hervé, Giebel Sebastian, Bruggemann Monika, Doubek Michael, Foà Robin, Hoelzer Dieter, Kim Christopher, Martinelli Giovanni, Parovichnikova Elena, Rambaldi Alessandro, Ribera Josep-Maria, Schoonen Marieke, Stieglmaier Julia M, Zugmaier Gerhard, Bassan Renato
a Department of Medicine II, Department of Hematology/Oncology , University Hospital , Frankfurt , Germany.
b Hôpital Saint-Louis, University Paris Diderot , Paris , France.
Hematology. 2019 Dec;24(1):337-348. doi: 10.1080/16078454.2019.1567654.
Detectable minimal residual disease (MRD) after therapy for acute lymphoblastic leukemia (ALL) is the strongest predictor of hematologic relapse. This study evaluated outcomes of patients with B-cell precursor ALL with MRD of ≥10 Methods: Study population was from ALL study groups in Europe managed in national study protocols 2000-2014. MRD was measured by polymerase chain reaction or flow cytometry. Patients were age ≥15 years at initial ALL diagnosis. Patients were excluded if exposed to blinatumomab within 18 months of baseline or prior alloHSCT.
Of 272 patients in CR1, baseline MRD was ≥10, 10 to <10, 10 to <10, and 10 to <10 in 15 (6%), 71 (26%), 109 (40%), and 77 (28%) patients, respectively. Median duration of complete remission (DoR) was 18.5 months (95% confidence interval [CI], 11.9-27.2), median relapse-free survival (RFS) was 12.4 months (95% CI, 10.0-19.0) and median overall survival (OS) was 32.5 months (95% CI, 23.6-48.0). Lower baseline MRD level (P ≤ .0003) and white blood cell count <30,000/µL at diagnosis (P ≤ .0053) were strong predictors for better RFS and DoR. Allogeneic hematopoietic stem cell transplantation (alloHSCT) was associated with longer RFS (hazard ratio [HR], 0.59; 95% CI, 0.41-0.84) and DoR (HR, 0.43; 95% CI, 0.29-0.64); the association with OS was not significant (HR, 0.72; 95% CI, 0.50-1.05).
In conclusion, RFS, DoR, and OS are relatively short in patients with MRD-positive ALL, particularly at higher MRD levels. AlloHSCT may improve survival but has limitations. Alternative approaches are needed to improve outcomes in MRD-positive ALL.
急性淋巴细胞白血病（ALL）治疗后可检测到的微小残留病（MRD）是血液学复发的最强预测指标。本研究评估了微小残留病≥10的B细胞前体ALL患者的预后。方法：研究人群来自2000 - 2014年按照国家研究方案管理的欧洲ALL研究组。通过聚合酶链反应或流式细胞术检测MRD。患者初诊ALL时年龄≥15岁。如果患者在基线前18个月内接受过博纳吐单抗治疗或之前接受过异基因造血干细胞移植（alloHSCT），则被排除。
在272例处于完全缓解期1（CR1）的患者中，基线MRD≥10、10至＜10、10至＜10以及10至＜10的患者分别有15例（6%）、71例（26%）、109例（40%）和77例（28%）。完全缓解持续时间（DoR）的中位数为18.5个月（95%置信区间[CI]，11.9 - 27.2），无复发生存期（RFS）的中位数为12.4个月（95%CI，10.0 - 19.0），总生存期（OS）的中位数为32.5个月（95%CI，23.6 - 48.0）。较低的基线MRD水平（P≤0.0003）和诊断时白细胞计数＜30,000/µL（P≤0.0053）是更好的RFS和DoR的强预测指标。异基因造血干细胞移植（alloHSCT）与更长的RFS（风险比[HR]，0.59；95%CI，0.41 - 0.84）和DoR（HR，0.43；95%CI，0.29 - 0.64）相关；与OS的相关性不显著（HR，0.72；95%CI，0.50 - 1.05）。
总之，MRD阳性ALL患者的RFS、DoR和OS相对较短，尤其是在MRD水平较高时。alloHSCT可能改善生存，但有局限性。需要其他方法来改善MRD阳性ALL的预后。
