93例成人急性淋巴细胞白血病的临床分析

摘要/Abstract

摘要：

目的分析成人急性淋巴细胞白血病(ALL)患者诱导治疗完全缓解后接受不同巩固治疗方案的生存情况及预后影响因素。方法纳入北京大学深圳医院2012年1月至2019年6月收治的93例成人ALL患者,所有患者经VDLCP方案诱导治疗达完全缓解,根据巩固治疗方案分为标准组、强化组及移植组。标准组34例,接受VDLCP或Hyper-CVAD方案为基础的ALL样方案巩固4~6个疗程;强化组29例,接受BFM90/95方案巩固维持治疗2年;移植组30例,经原诱导方案巩固2~3疗程,接受异基因造血干细胞移植(allo-HSCT)。中位随访时间18(3~96)个月,主要随访指标为总生存期(OS)及无瘤生存期(DFS)。分析成人ALL患者的预后影响因素及各组治疗相关死亡情况。结果标准组、强化组和移植组3年OS率分别为54.0%(95%CI为35.3%~72.6%)、71.8%(95%CI为41.0%~94.5%)、62.3%(95%CI为43.6%~80.9%),差异有统计学意义(χ²=6.110,P=0.047);3年DFS率分别为31.4%(95%CI为12.9%~49.8%)、72.1%(95%CI为52.3%~91.9%)、65.7%(95%CI为45.3%~86.1%),差异有统计学意义(χ²=13.831,P=0.001);强化组和移植组OS及DFS差异均无统计学意义(χ²=0.709,P=0.400;χ²=0.046,P=0.830),强化组OS及DFS显著优于标准组(χ²=5.346,P=0.021;χ²=10.326,P=0.010)。多因素分析提示化疗第14~21天骨髓微小残留病(MRD)转阴为影响成人ALL的独立预后因素(HR=0.114,95%CI为0.015~0.841,P=0.033)。接受与未接受allo-HSCT的Ph⁺ALL患者3年OS率分别为53.5%(95%CI为23.1%~83.8%)、52.4%(95%CI为23.8%~81.0%),3年DFS率分别为77.1%(95%CI为54.2%~100.0%)、35.0%(95%CI为4.8%~65.2%),两组比较差异均无统计学意义(χ²=3.600,P=0.223;χ²=3.824,P=0.050)。非移植组(标准组+强化组)和移植组治疗相关死亡率分别为3.2%(2/63)、20.0%(6/30),非移植组治疗相关死亡率明显低于移植组(χ²=7.318,P=0.007)。结论成人ALL预后差,采用BFM方案强化巩固治疗3年OS率、3年DFS率均优于标准巩固治疗,达到了与allo-HSCT相似的疗效,而治疗相关死亡率没有显著升高。化疗第14~21天骨髓MRD转阴患者OS、DFS更优。

关键词:前体细胞淋巴母细胞白血病淋巴瘤,临床特征,总生存,无病生存,异基因造血干细胞移植

Abstract:

ObjectiveTo analyze the survival and prognostic factors of adult acute lymphoblastic leukemia (ALL) with different consolidation regimens after complete remission by induction therapy.MethodsA total of 93 adult patients with ALL were enrolled from January 2012 to June 2019 in Peking University Shenzhen Hospital. All the patients achieved complete remission induced by VDLCP regimen, and were divided into the standard group, intensive group and transplantation group according to the consolidation treatment. Thirty-four patients in the standard group received an ALL-like chemotherapy regimen based on VDLCP or Hyper-CVAD consolidation for 4-6 courses. Twenty-nine patients in the intensive group received BFM90/95 consolidation treatment for 2 years. Thirty patients in the transplantation group received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after 2-3 courses of consolidation with the original induction regimen. The median follow-up was 18 (3-96) months, and the main follow-up indicators were overall survival (OS) and disease free survival (DFS). Prognostic factors of adult ALL patients and treatment-related deaths in each group were analyzed.ResultsThe 3-year OS rates of the standard group, intensive group and transplantation group were 54.0% (95%CI: 35.3%-72.6%), 71.8%(95%CI: 41.0%-94.5%), 62.3%(95%CI: 43.6%-80.9%), with a statistically significant difference (χ²=6.110,P=0.047). The 3-year DFS rates of the three groups were 31.4% (95%CI: 12.9%-49.8%), 72.1%(95%CI: 52.3%-91.9%), 65.7%(95%CI: 45.3%-86.1%), with a statistically significant difference (χ²=13.831,P=0.001). There were no significant differences in OS and DFS between the intensive group and the transplantation group (χ²=0.709,P=0.400;χ²=0.046,P=0.830). OS and DFS of the intensive group were better than those of the standard group (χ²=5.346,P=0.021;χ²=10.326,P=0.010). Multivariate analysis suggested that bone marrow minimal residual disease (MRD) negative on day 14-21 of chemotherapy was an independent prognostic factor affecting adult ALL (HR=0.114, 95%CI: 0.015-0.841,P=0.033). The 3-year OS rates of Ph⁺ALL patients who received and did not receive allo-HSCT were 53.5% (95%CI: 23.1%-83.8%), 52.4%(95%CI: 23.8%-81.0%), the 3-year DFS rates were 77.1% (95%CI: 54.2%-100.0%), 35.0%(95%CI: 4.8%-65.2%), and there were no significant differences between the two groups (χ²=3.600,P=0.223;χ²=3.824,P=0.050). The treatment-related mortalities of the non-transplantation group (standard group + intensive group) and the transplantation group were 3.2% (2/63) and 20.0% (6/30), and the treatment-related mortality of the non-transplantation group was significantly lower than that of the transplantation group (χ²=7.318,P=0.007).ConclusionAdult ALL has a poor prognosis. The 3-year OS rate and 3-year DFS rate of BFM intensive consolidation therapy are better than those of standard consolidation therapy, achieving a similar effect to allo-HSCT, but treatment-related mortality does not increase significantly. Patients with bone marrow MRD negative on the day 14-21 of chemotherapy have the better OS and DFS.

Key words:Precursor cell lymphoblastic leukemia-lymphoma,Clinical features,Overall survival,Disease-free survival,Allogeneic hematopoietic stem cell transplantation

许蕾, 戴婧, 张倩, 张文丽, 李晋萌, 张红宇. 93例成人急性淋巴细胞白血病的临床分析[J]. 国际肿瘤学杂志, 2020, 47(9): 535-541.

Xu Lei, Dai Jing, Zhang Qian, Zhang Wenli, Li Jinmeng, Zhang Hongyu. Clinical analysis of 93 cases of adult patients with acute lymphoblastic leukemia[J]. Journal of International Oncology, 2020, 47(9): 535-541.

图/表7

表1

3组ALL患者基本临床特征(例)"

特征	标准组 (n=34)		强化组 (n=29)		移植组 (n=30)		χ²值		P值
性别
男	19		18		20		0.790		0.670
女	15		11		10
年龄(岁)
18~39	20		19		21		0.888		0.641
40~60	14		10		9
免疫表型
T-ALL	6		14		5		9.821		0.007
B-ALL	28		15		25
Ph染色体
阳性	11		1		14		14.189		0.001
阴性	23		28		16
特征		标准组 (n=34)		强化组 (n=29)		移植组 (n=30)		χ²值		P值
WBC(×10⁹/L)
<30		19		24		16
30~100		7		4		7		7.866		0.097
>100		8		1		7
危险分层
标危		6		6		1		4.615		0.099
高危		28		23		29
CNSL
发生		2		2		4		1.232		0.648
未发生		32		27		26
MRD
转阴		7		6		5		0.205		0.903
未转阴		27		23		25

表1

图1

图2

因素	HR值	95%CI	P值
性别(男vs.女)	0.853	0.420~1.735	0.661
年龄(18~35岁vs.36~60岁)	1.062	0.522~2.162	0.869
免疫表型(T-ALLvs.B-ALL)	1.186	0.575~2.448	0.644
Ph染色体(阳性vs.阴性)	1.373	0.675~2.793	0.381
WBC(×10⁹/L)	0.991	0.628~1.564	0.968
(<30vs.30~100vs.>100)
分层(高危vs.标危)	0.845	0.410~1.744	0.649
CNSL(发生vs.未发生)	1.621	0.623~4.217	0.322
MRD(转阴vs.未转阴)	0.087	0.009~0.862	0.037

表2

因素	HR值	95%CI	P值
性别(男vs.女)	0.707	0.365~1.642	0.505
年龄(18~35岁vs.36~60岁)	1.015	0.376~1.861	0.661
免疫表型(T-ALLvs. B-ALL)	1.164	0.467~2.462	0.870
Ph染色体(阳性vs.阴性)	1.116	0.600~3.005	0.474
WBC(×10⁹/L)	0.898	0.474~1.425	0.485
(<30vs.30~100vs.>100)
分层(高危vs.标危)	0.645	0.362~1.725	0.554
CNSL(发生vs.未发生)	1.815	0.640~5.150	0.262
MRD(转阴vs.未转阴)	0.114	0.015~0.841	0.033

表3

图3

图4

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