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微小残留病(MRD)在具有良好细胞遗传学特征[t(8;21)和inv(16)]的急性髓系白血病(AML)中的预后价值

Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia (AML) with favorable cytogenetics [t(8;21) and inv(16)].

作者信息

Perea G, Lasa A, Aventín A, Domingo A, Villamor N, Queipo de Llano M Paz, Llorente A, Juncà J, Palacios C, Fernández C, Gallart M, Font L, Tormo M, Florensa L, Bargay J, Martí J M, Vivancos P, Torres P, Berlanga J J, Badell I, Brunet S, Sierra J, Nomdedéu J F

机构信息

Hematology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.

出版信息

Leukemia. 2006 Jan;20(1):87-94. doi: 10.1038/sj.leu.2404015.

Abstract

Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with current anthracycline- and cytarabine-based protocols. Tandem analysis with flow cytometry (FC) and real-time RT-PCR (RQ-PCR) was applied to 55 patients, 28 harboring a t(8;21) and 27 an inv(16), including one case with a novel CBFbeta/MYH11 transcript. A total of 31% (n=17) of CR patients relapsed: seven with t(8;21) and 10 with inv(16). The mean amount of minimal residual disease (MRD) detected by FC in relapsed and nonrelapsed patients was markedly different: 0.3 vs 0.08% (P=0.002) at the end of treatment. The mean number of fusion transcript copies/ ABL x 10(4) also differed between relapsed and non-relapsed patients: 2385 vs 122 (P=0.001) after induction, 56 vs 7.6 after intensification (P=0.0001) and 75 vs 3.3 (P=0.0001) at the end of chemotherapy. Relapses were more common in patients with FC MRD level >0.1% at the end of treatment than in patients with < or = 0.1%: cumulative incidence of relapse (CIR) was 67 and 21% (P=0.03), respectively. Likewise, using RQ-PCR, a cutoff level of >10 copies at the end of treatment correlated with a high risk of relapse: CIR was 75% for patients with RQ-PCR >10 compared to 21% for patients with RQ-PCR levels < or = 10 (P=0.04). Combined use of FC and RQ-PCR may improve MRD detection, and provide useful clinical information on relapse kinetics in AML patients.

摘要

大多数患有急性髓系白血病(AML)且伴有t(8;21)或inv(16)的患者,采用目前基于蒽环类药物和阿糖胞苷的治疗方案,预后良好。对55例患者进行了流式细胞术(FC)和实时逆转录聚合酶链反应(RQ-PCR)的串联分析,其中28例携带t(8;21),27例携带inv(16),包括1例具有新型CBFβ/MYH11转录本的病例。共有31%(n = 17)的完全缓解(CR)患者复发:7例t(8;21)患者和10例inv(16)患者。复发患者和未复发患者通过FC检测到的微小残留病(MRD)平均量明显不同:治疗结束时分别为0.3%和0.08%(P = 0.002)。复发患者和未复发患者之间融合转录本拷贝数/ABL×10⁴的平均数也有所不同:诱导后为2385对122(P = 0.001),强化后为56对7.6(P = 0.0001),化疗结束时为75对3.3(P = 0.0001)。治疗结束时FC MRD水平>0.1%的患者比≤0.1%的患者更容易复发:复发累积发生率(CIR)分别为67%和21%(P = 0.03)。同样,使用RQ-PCR时,治疗结束时>10拷贝的截断水平与高复发风险相关:RQ-PCR>10的患者CIR为75%,而RQ-PCR水平≤10的患者为21%(P = 0.04)。联合使用FC和RQ-PCR可能会改善MRD检测,并为AML患者的复发动力学提供有用的临床信息。

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