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流式细胞术检测微小残留病对急性髓系白血病患者异基因造血干细胞移植前后的预后影响

Prognostic impact of minimal residual disease analysis by flow cytometry in patients with acute myeloid leukemia before and after allogeneic hemopoietic stem cell transplantation.

作者信息

Bastos-Oreiro Mariana, Perez-Corral Ana, Martínez-Laperche Carolina, Bento Leyre, Pascual Cristina, Kwon Mi, Balsalobre Pascual, Muñoz Cristina, Buces Elena, Serrano David, Gayoso Jorge, Buño Ismael, Anguita Javier, Diéz-Martín José Luís

机构信息

Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.

出版信息

Eur J Haematol. 2014 Sep;93(3):239-46. doi: 10.1111/ejh.12336. Epub 2014 Apr 29.

DOI:10.1111/ejh.12336
PMID:24702162
Abstract

Allogeneic stem cell transplantation (allo-SCT) has become the treatment of choice in patients with intermediate-risk and high-risk acute myeloid leukemia (AML). The quality of response to treatment, assessed in terms of detection of minimal residual disease (MRD), has been consistently associated with prognosis and clinical outcome in patients with AML. The aim of the present study was to evaluate the prognostic impact of analyzing MRD in bone marrow using 4-color multiparametric flow cytometry (MFC) in 29 patients with AML before and after allo-SCT. Eighteen patients who were shown to be MRD-negative [≤0.1% leukemia-associated immunophenotypes (LAIPs)] by MFC at transplantation and underwent allo-SCT had lower rates of relapse (15% vs. 66%, P = 0.045), better overall 1-yr survival (83% vs. 52%, P = 0.021) and a lower cumulative incidence of relapse (P = 0.032) than patients who were MRD-positive (>0.1%). All post-transplant MRD-positive patients underwent a therapeutic intervention after transplant (tapering of immunosuppression, donor lymphocyte infusion, or re-transplant) with the intention of preventing relapse. Disease was controlled and MRD disappeared in five of these patients. Disease recurred in the other seven patients. We can conclude that follow-up with MFC for the detection of MRD in AML before and after SCT is useful for predicting relapse. In the post-transplant setting, monitoring of MRD by MFC could be a key preemptive intervention.

摘要

异基因干细胞移植(allo-SCT)已成为中危和高危急性髓系白血病(AML)患者的首选治疗方法。以检测微小残留病(MRD)来评估的治疗反应质量,一直与AML患者的预后和临床结局相关。本研究的目的是评估在29例AML患者allo-SCT前后,使用四色多参数流式细胞术(MFC)分析骨髓中MRD的预后影响。18例在移植时经MFC检测显示为MRD阴性[白血病相关免疫表型(LAIPs)≤0.1%]并接受allo-SCT的患者,其复发率较低(15%对66%,P = 0.045),1年总生存率更好(83%对52%,P = 0.021),复发累积发生率更低(P = 0.032),优于MRD阳性(>0.1%)的患者。所有移植后MRD阳性患者在移植后均接受了治疗性干预(免疫抑制减量、供体淋巴细胞输注或再次移植),以预防复发。其中5例患者疾病得到控制且MRD消失。其他7例患者疾病复发。我们可以得出结论,在SCT前后用MFC随访检测AML中的MRD有助于预测复发。在移植后阶段,通过MFC监测MRD可能是一项关键的预防性干预措施。

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