Venetoclax联合化疗治疗复发/难治性急性髓系白血病的临床研究

doi:10.12114/j.issn.1007-9572.2022.02.005

摘要/Abstract

摘要： 背景成人复发/难治性急性髓系白血病（AML）的预后较差，长期生存率和治愈率极低，化疗方案有限。目的探讨Venetoclax（VEN）联合阿扎胞苷（Aza）、HAAG〔高三尖杉酯碱（HHT）、阿糖胞苷（Ara-C）、阿克拉霉素（Acla）、粒细胞刺激因子（G-CSF）〕方案治疗复发/难治性AML的安全性和有效性。方法回顾性分析蚌埠医学院第一附属医院收治的10例复发/难治性AML患者的临床资料，包括：临床特征（年龄、性别、诊断、染色体、基因突变、预后）、外周血及骨髓细胞学、VEN+Aza+HAAG方案治疗效果。结果10例患者中男7例、女3例，平均年龄（47.9±11.3）岁；FAB分型：M24例、M56例；预后良好3例、中等2例、不良5例。化疗前中位白细胞计数（WBC）、血红蛋白（Hb）、血小板计数（PLT）、骨髓原始细胞百分比（Blasts%）分别为4.10×109/L、87.5 g/L、66.00×109/L 、63.5%，化疗后分别为3.28×109/L、107.0 g/L、78.00×109/L、5.5%。VEN+Aza+HAAG方案联合化疗前中位化疗次数为5次，化疗后完全缓解（CR）1例，形态学完全缓解而血细胞计数未完全恢复（CRi）4例，部分缓解（PR）3例，未缓解（NR）2例。10例患者客观缓解率（ORR）为80%，中位生存期（OS）为6.5（3.0，8.5）个月。毒副作用主要为骨髓抑制、感染等，无患者死于治疗相关并发症及其他毒副作用。结论与传统化疗方案相比，复发/难治性AML患者使用VEN+Aza+HAAG化疗方案可以明显提高ORR及缓解深度，延长患者生存时间，值得进一步研究并有望在临床推广应用。

关键词: 白血病, 髓样, 急性, Venetoclax, 复发, 药物疗法, 联合, 治疗结果, 抗肿瘤联合化疗方案

Abstract: Background

Adults with relapsed/refractory acute myeloid leukemia (AML) have poor prognosis, very low long-term survival rate and cure rate, and limited chemotherapy regimens.

Objective

To investigate the safety and efficacy of venetoclax (VEN) with HAAG 〔homoharringtonine (HHT) , Cytarabine (Ara-C) , aclacinomycin (Acla) , granulocyte stimulating factor (G-CSF) 〕 in relapsed/refractory AML.

Methods

The clinical data of 10 adult patients with relapsed/refractory AML treated in the First Affiliated Hospital of Bengbu Medical College were analyzed retrospectively, including: clinical characteristics (sex, age, diagnosis, chromosome, gene mutation, prognosis) , peripheral blood and bone marrow cytology, and the effect of Ven+Aza+HAAG regimen.

Results

Among the 10 patients, there were 7 men and 3 women, with an average age of (47.9±11.3) years; 4 cases of M₂ and 6 cases of M₅ by FAB classification; 3 cases of good prognosis, 2 cases of fair and 5 cases of poor. The median levels of WBC count, hemoglobin content, and platelet count, as well as median percentage of bone marrow blast cells before chemotherapy of the patients were 4.10×10⁹/L, 87.5 g/L, 66.00×10⁹/L, and 63.5%, respectively, and after chemotherapy, the values of these four indicators were 3.28×10⁹/L, 107.0 g/L, 78.00×10⁹/L and 5.5%, respectively. Before VEN+Aza+HAAG regimen combined chemotherapy, the median number of chemotherapy used by the patients was 5. And after the combined therapy, there were 1 case of complete remission (CR) and 4 cases of CR with incomplete count recovery (CRi) , 3 cases of partial remission (PR) , and 2 cases of non-remission (NR) . The objective response rate of 10 patients was 80%, and median survival time was 〔6.5 (3.0, 8.5) 〕months. The toxic and side effects were mainly bone marrow suppression and infection. No patients died of treatment-related complications and other toxic and side effects.

Conclusion

Compared with traditional chemotherapy regimen, the use of Ven + Aza + HAAG with chemotherapy could significantly improve the objective response rate and remission degree, and prolong the survival in patients with relapsed/refractory AML, which is worthy of further study and has a prospect of clinical application.

Key words: Leukemia, myeloid, acute, Venetoclax, Recurrence, Drug therapy, combination, Treatment outcome, Antineoplastic combined chemotherapy protocols

中图分类号:

R733.71

陈晓奉,王蒙,李忠玉,等. Venetoclax联合化疗治疗复发/难治性急性髓系白血病的临床研究[J]. 中国全科医学, 2022, 25(08): 957-962. DOI: 10.12114/j.issn.1007-9572.2022.02.005.

CHEN Xiaofeng, WANG Meng, LI Zhongyu, LI Jiajia.

Clinical Study of Venetoclax with Chemotherapy for Relapsed/Refractory Acute Myeloid Leukemia [J]. Chinese General Practice, 2022, 25(08): 957-962.

图/表 5

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病例	WBC（×10⁹/L）		Hb（g/L）		PLT（×10⁹/L）		Blasts（%）
病例	化疗前	化疗后	化疗前	化疗后	化疗前	化疗后	化疗前	化疗后
1	39.80	4.60	67.0	130.0	528.00	118.00	70.00	2.00
2	1.06	3.28	83.0	110.0	54.00	84.00	67.00	1.00
3	5.00	2.98	92.0	102.0	28.00	79.00	73.00	4.00
4	20.55	12.56	61.0	42.0	39.00	17.00	81.00	44.00
5	3.20	4.00	113.0	122.0	28.00	74.00	70.00	1.00
6	1.39	2.42	57.0	86.0	20.00	12.00	60.00	16.00
7	5.39	3.27	120.0	111.0	211.00	194.00	40.00	7.00
8	1.26	0.97	100.0	104.0	150.00	77.00	41.00	33.00
9	1.04	2.47	53.0	98.0	78.00	150.00	21.00	0
10	54.77	4.64	94.0	112.0	79.00	64.00	52.00	7.00

病例	WBC（×10⁹/L）		Hb（g/L）		PLT（×10⁹/L）		Blasts（%）
病例	化疗前	化疗后	化疗前	化疗后	化疗前	化疗后	化疗前	化疗后
1	39.80	4.60	67.0	130.0	528.00	118.00	70.00	2.00
2	1.06	3.28	83.0	110.0	54.00	84.00	67.00	1.00
3	5.00	2.98	92.0	102.0	28.00	79.00	73.00	4.00
4	20.55	12.56	61.0	42.0	39.00	17.00	81.00	44.00
5	3.20	4.00	113.0	122.0	28.00	74.00	70.00	1.00
6	1.39	2.42	57.0	86.0	20.00	12.00	60.00	16.00
7	5.39	3.27	120.0	111.0	211.00	194.00	40.00	7.00
8	1.26	0.97	100.0	104.0	150.00	77.00	41.00	33.00
9	1.04	2.47	53.0	98.0	78.00	150.00	21.00	0
10	54.77	4.64	94.0	112.0	79.00	64.00	52.00	7.00

病例	化疗方案	疗效	CR/PR持续时间（月）	复发次数	OS（月）
1	IA×2、HD-Ara-C×4、DA/VEN+Aza+HAAG×4	CR/CR	10/7	4/0	10
2	IA×4、Decitabine +CAG/VEN+Aza+HAAG×3	CR/CR	5/5	2/0	6
3	HD-Ara-C×2、IA、Decitabine+HAG×2、Chidamide +CLAG /VEN+Aza+HAAG×2	CR/CR	12/3	3/0	3
4	IA、Decitabine +HAG×2/VEN+Aza+HAAG	CR/NR	2/-	2/-	1
5	IA×3、MD-Ara-C、FLAG×2、HA、Decitabine+Chidamide+CLAG/VEN+Aza+HAAG×4	CR/CR	11/7	2/0	9
6	HD-Ara-C、IA×2、Decitabine +CAG×2/VEN+Aza+HAAG×2	PR/PR	3/1	3/1	3
7	Decitabine+CAG、Decitabine+HAAG/ VEN+Aza+HAAG×2	CR/PR	7/6	1/0	7
8	IA×2、HD-Ara-C×2、Decitabine +HAG/ VEN+Aza+HAAG×2	CR/NR	2/-	2/-	2
9	Decitabine +HAG、IA/ VEN+Aza+HAAG×5	PR/CR	1/10	1/0	13
10	IA、Decitabine +HAAG/VEN+Aza+HAAG×4	NR/CR	2/4	2/1	7

病例	化疗方案	疗效	CR/PR持续时间（月）	复发次数	OS（月）
1	IA×2、HD-Ara-C×4、DA/VEN+Aza+HAAG×4	CR/CR	10/7	4/0	10
2	IA×4、Decitabine +CAG/VEN+Aza+HAAG×3	CR/CR	5/5	2/0	6
3	HD-Ara-C×2、IA、Decitabine+HAG×2、Chidamide +CLAG /VEN+Aza+HAAG×2	CR/CR	12/3	3/0	3
4	IA、Decitabine +HAG×2/VEN+Aza+HAAG	CR/NR	2/-	2/-	1
5	IA×3、MD-Ara-C、FLAG×2、HA、Decitabine+Chidamide+CLAG/VEN+Aza+HAAG×4	CR/CR	11/7	2/0	9
6	HD-Ara-C、IA×2、Decitabine +CAG×2/VEN+Aza+HAAG×2	PR/PR	3/1	3/1	3
7	Decitabine+CAG、Decitabine+HAAG/ VEN+Aza+HAAG×2	CR/PR	7/6	1/0	7
8	IA×2、HD-Ara-C×2、Decitabine +HAG/ VEN+Aza+HAAG×2	CR/NR	2/-	2/-	2
9	Decitabine +HAG、IA/ VEN+Aza+HAAG×5	PR/CR	1/10	1/0	13
10	IA、Decitabine +HAAG/VEN+Aza+HAAG×4	NR/CR	2/4	2/1	7

病例	骨髓抑制（级）	脱发（级）	感染（级）	出血（级）	恶心（级）	腹泻（级）	肝功能异常（级）
1	3	1	1	0	1	1	0
2	3	1	1	2	1	1	0
3	4	1	2	1	2	0	1
4	3	1	4	2	2	2	1
5	4	2	2	2	2	1	0
6	4	1	2	2	1	0	0
7	4	1	2	1	1	1	0
8	4	2	2	4	2	1	0
9	3	0	1	0	1	1	0
10	4	1	1	2	1	0	0