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俄罗斯联邦卫生部国家医学研究血液中心急性髓系白血病治疗方案的应用结果。

Results of program acute myeloid leukemia therapy use in National Medical Research Center for Hematology of the Ministry of Health of Russian Federation.

作者信息

Parovichnikova E N, Loukianova I A, Troitskaya V V, Drokov M Y, Lobaova T I, Kuzmina L A, Sokolov A N, Kokhno A V, Fidarova Z T, Baskhaeva G A, Gavrilina O A, Vasilyeva V A, Obukhova T N, Kuznetsova S A, Sudarikov A B, Dvirnik V N, Galtseva I V, Davidiva J O, Kulikov S M, Savchenko V G

机构信息

National Research Center for Hematology, Moscow, Russia.

出版信息

Ter Arkh. 2018 Aug 17;90(7):14-22. doi: 10.26442/terarkh201890714-22.

Abstract

AIM

To analyze treatment results of 172 patients with acute myeloid leukemia (AML) aged 18-60 years in National Medical Research Center for Hematology of MHRF.

MATERIALS AND METHODS

Inductive and consolidation program for 139 (80%) patients was based on a standardized protocol: 4 courses "7+3" with different anthracycline use (2 courses of daunorubicin, idarubicin, mitoxantrone) and continuous use of cytarabine on the second inductive course. In 20% of patients cytarabine courses at the dose of 1 g/m2 2 times a day for 1-3 days combined with idarubicin and mitoxantrone were used as two consolidation courses. Allogenic bone marrow transplantation was performed in the first complete remission (CR) period in 40% of patients.

RESULTS

The frequency of CR achievement in all patients was 78.6%, refractory forms were observed in 13.9% of patients, early mortality - in 7.5% of patients. Seven-year overall survival (OS) rate was 40.7%, relapse free survival (RFS) - 43.2%. When estimating effectiveness depending on cytogenetic risk group it was demonstrated that 5-year OS and RFS in patients with translocation (8; 21) cannot be considered as satisfying, it accounted for 50 and 34%, respectively. At the same time in patients with 16th chromosome inversion (inv16) these characteristics accounted for 68.6 and 63.5%. Acquired results forced reconsidering of the consolidation program in AML patients of this subgroup. The median time to allogenic blood stem cells transplantation (allo-BSCT) in patients with first CR was 6.5 months that was taken as a reference point in landmark analysis of patients in whom allo-BSCT was not performed. Landmark analysis showed that in AML patients of favorable prognosis group allo-BSCT does not significantly reduce the probability of relapse (0 and 36%) and does not influence RFS (33 and 64%). In patients of border-line and poor prognosis allo-BSCT significantly reduces relapse probability (26 and 66%; 20 and 100%) and significantly increases a 7-year RFS (68.7 and 30%; 45.6 and 0%). Allo-BSCT also results in significant RFS increase and reduces the probability of relapse (25 и 78%) in patients in whom CR was achieved only after the second induction course. At the same time allo-BSCT does not influence patients who achieved CR after the first treatment course: 55 and 50%.

CONCLUSION

Multivariate analysis showed that cytogenetic risk group (HR=2.3), time of CR achievement (HR=2.9), and allo-BSCT transplantation (HR=0.16) are independent factors for disease relapse prognosis after achieving CR.

摘要

目的

分析俄罗斯卫生部国家血液学医学研究中心172例年龄在18至60岁的急性髓系白血病(AML)患者的治疗结果。

材料与方法

139例(80%)患者的诱导和巩固方案基于标准化方案:4个疗程的“7+3”方案,使用不同的蒽环类药物(柔红霉素、伊达比星、米托蒽醌各2个疗程),并在第二个诱导疗程持续使用阿糖胞苷。20%的患者使用剂量为1 g/m²、每日2次、共1 - 3天的阿糖胞苷疗程联合伊达比星和米托蒽醌作为两个巩固疗程。40%的患者在首次完全缓解(CR)期进行异基因骨髓移植。

结果

所有患者的CR达成率为78.6%,13.9%的患者出现难治性形式,7.5%的患者早期死亡。七年总生存率(OS)为40.7%,无复发生存率(RFS)为43.2%。根据细胞遗传学风险组评估疗效时发现,伴有(8;21)易位的患者5年OS和RFS并不理想,分别为50%和34%。同时,伴有16号染色体倒位(inv16)的患者,这些指标分别为68.6%和63.5%。所得结果促使重新考虑该亚组AML患者的巩固方案。首次CR患者接受异基因造血干细胞移植(allo - BSCT)的中位时间为6.5个月,这被用作未进行allo - BSCT患者的里程碑分析中的参考点。里程碑分析表明,在预后良好组的AML患者中,allo - BSCT并未显著降低复发概率(0%和36%),也未影响RFS(33%和64%)。在临界和预后不良组患者中,allo - BSCT显著降低复发概率(26%和66%;20%和100%),并显著提高七年RFS(68.7%和30%;45.6%和0%)。allo - BSCT还使仅在第二个诱导疗程后才达到CR的患者的RFS显著增加并降低复发概率(25%和78%)。同时,allo - BSCT对首次治疗疗程后达到CR的患者无影响:分别为55%和50%。

结论

多因素分析表明,细胞遗传学风险组(HR = 2.3)、达到CR的时间(HR = 2.9)和allo - BSCT移植(HR = 0.16)是达到CR后疾病复发预后的独立因素。

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