加强预处理方案异基因造血干细胞移植克服<i>t(6；9)/DEK-NUP214</i>急性髓系白血病患者不良预后

何海; 曹星玉; 赵艳丽; 熊敏; 卢岳; 张建平; 魏志杰; 刘德琰; 孙瑞娟

doi:10.13201/j.issn.1004-2806.2024.07.011

加强预处理方案异基因造血干细胞移植克服t(6；9)/DEK-NUP214急性髓系白血病患者不良预后

- 1.
  河北燕达陆道培医院骨髓移植科(河北廊坊，065000)
- 2.
  北京陆道培医院骨髓移植科

详细信息

通讯作者: 孙瑞娟，E-mail：15901388773@163.com

中图分类号: R733.71

收稿日期: 2024-05-09

刊出日期: 2024-07-01

Intensive pretreatment protocol allogeneic hematopoietic stem cell transplantation to overcome poor prognosis in patients with t(6;9)/DEK-NUP214 acute myeloid leukemia

- 1.
  Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, 065000, China
- 2.
  Department of Bone Marrow Transplantation, Beijing Lu Daopei Hospital

More Information

Corresponding author: SUN Ruijuan, E-mail: 15901388773@163.com

Received Date: 09 May 2024

Publish Date: 01 July 2024

摘要

摘要: 目的探讨加强预处理方案异基因造血干细胞移植(allo-HSCT)治疗t(6；9)/DEK-NUP214急性髓系白血病(AML)的疗效。方法对2015年3月—2023年4月应用加强预处理方案allo-HSCT治疗t(6；9)/DEK-NUP214 AML的32例患者资料进行回顾分析，观察疗效。结果 32例患者均获得造血重建，白细胞和血小板植活中位天数分别为+13(10~20) d、+12(6~29) d。预处理相关毒性(RRT)多发生于预处理2周内，Ⅰ/Ⅱ级RRT发生率为59.4%(19/32)，最常见的是胃肠道反应(13/32)，其次为肝损伤(9/32)。32例患者均未发生Ⅲ/Ⅳ级RRT。移植后中位随访44(3~107)个月，3年总生存(OS)率90.3%、无复发生存(RFS)率86.2%、累计复发率3.1%、移植相关死亡率9.4%。移植时完全缓解患者20例与未缓解患者12例二组比较，其3年OS率和RFS率比较差异无统计学意义(OS率：95.0% vs 82.5%，P=0.28；RFS率：87.7% vs 82.5%，P=0.61)。20例患者发病时携带FLT3-ITD与12例非携带FLT3-ITD患者比较，3年OS率和RFS率比较差异无统计学意义(OS率：95.0% vs 82.5%，P=0.3；RFS率：87.7% vs 82.5%，P=0.63)。结论加强预处理方案allo-HSCT可克服t(6；9)/DEK-NUP214 AML患者不良预后和具有良好的耐受性，生存不受移植前状态和携带FLT3-ITD影响。
- DEK-NUP214 /
- t(6;9) /
- 急性髓系白血病 /
- 预处理 /
- 异基因造血干细胞移植
Abstract: Objective To explore the efficacy of an intensified conditioning regimen allogeneic hematopoietic stem cell transplantation(allo-HSCT) for t(6;9)/DEK-NUP214 acute myeloid leukemia(AML).Methods Between 2015 and 2023, 32 AML patients with t(6;9)/DEK-NUP214 fusion gene who underwent allo-HSCT were analyzed. All patients underwent an intensified conditioning regimen.Results Hematopoietic reconstitution was achieved in all 32 patients, with median days to leukocyte and platelet viability of 13(10-20) and 12(6-29) days, respectively. Pretreatment-related toxicity(RRT) occurred mostly within 2 weeks of pretreatment, with a grade Ⅰ/Ⅱ RRT incidence of 59.3%(19/32), most commonly gastrointestinal reactions(13/32), followed by hepatic injury(9/32). No patients experienced grade Ⅲ/Ⅳ RRT. With a median follow-up of 44(3-107) months after transplantation, the 3-year overall survival(OS) was 90.3%, relapse-free survival(RFS) was 86.2%, cumulative relapse rate was 3.1%, and transplant-related mortality was 9.4%. There were 20 patients in complete remission at the time of transplantation and 12 patients in no remission, and there was no difference in the comparison of 3-year OS and RFS between the two groups(OS: 95.0% vs 82.5%, P=0.28; RFS: 87.7% vs 82.5%, P=0.61). There was no difference in the 3-year OS and RFS in the 20 patients with FLT3-ITD compared with 12 patients without FLT3-ITD (OS: 95.0% vs 82.5%, P=0.3; RFS: 87.7% vs 82.5%, P=0.63).Conclusion Intensive pretreatment regimen allo-HSCT overcame poor prognosis and was well tolerated in patients with t(6;9)/DEK-NUP214 AML. Survival was not influenced by the state at transplant and FLT3-ITD.
- DEK-NUP214 /
- t(6;9) /
- acute myeloid leukemia /
- intensive pretreatment regimen /
- allo-HSCT

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图 1 32例患者allo-HSCT后3年OS、RFS曲线

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图 2 移植前CR组患者与NR组患者OS(a)及RFS(b)曲线

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图 3 移植前CR患者中MRD⁺组与MRD^-组患者RFS曲线

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图 4 32例患者中FLT3-ITD⁺组与FLT3-ITD^-组患者RFS曲线

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图 5 地西他滨组、嘌呤核苷酸类似物组、伊达比星组患者RFS曲线

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表 1 患者一般资料

序号	性别	年龄/岁	FLT3-ITD基因突变	移植时CR情况	移植类型	移植方案	+1个月MRD	转归	复发
1	男	24	有	NR^b	半合	FA/Bu/Cy/ATLG	阴	存活	否
2	女	36	有	CR1	半合	FA/Bu/Cy/ATLG	阴	存活	否
3	男	15	有	CR1	半合	CLAG/Bu/Cy/ATG	阴	存活	是
4	女	28	无	CR1	半合	FA/Bu/Cy/ATG	阴	死亡	否
5	女	47	无	NR^a	半合	FA/Bu/Cy/ATG	阴	死亡	否
6	男	35	有	NR^b	全合	CLAG/Bu/Cy/ATG	阴	存活	否
7	女	12	无	CR1	半合	Dec/Ara-C/Bu/Cy/ATLG	阴	存活	否
8	男	7	无	NR^b	半合	FA/Bu/Cy/ATG	阴	存活	否
9	女	18	有	CRi	半合	Dec/Ara-C/Bu/Cy/ATLG	阴	存活	否
10	男	16	无	CRi	半合	IA/Bu/Cy/ATG	阴	存活	否
11	男	10	无	CR1	半合	FA/Bu/Cy/ATG	阴	存活	否
12	男	38	有	NR^a	半合	CLAG/Bu/Cy/ATG	阴	存活	否
13	男	12	有	NR^b	半合	Dec/Ara-C/Bu/Cy/ATG	阴	存活	否
14	女	54	有	NR^a	半合	Dec/Ara-C/BU/Cy/ATG	阴	存活	否
15	女	15	有	CR1	半合	IA/Bu/Cy/ATG	阴	存活	否
16	男	9	无	CR1	半合	IA/Bu/Cy/ATLG	阴	存活	否
17	女	24	无	CRi	全合	Dec/Ara-C/Bu/Cy/ATG	阴	存活	否
18	男	12	无	NR^a	半合	CLAG/Bu/Cy/ATG	阴	存活	否
19	男	15	无	NR^b	半合	Dec/Ara-C/TBI/Cy/ATLG	阴	存活	否
20	女	30	有	CR1	半合	IA/Bu/Cy/ATG	阴	存活	否
21	男	22	无	CR1	半合	IA/Bu/Cy/ATG	阴	存活	否
22	女	46	有	NR^a	半合	Dec/Ara-C/TBI/Cy/ATLG	阴	存活	否
23	女	6	有	CRi	半合	IA/Bu/Cy/ATG	阴	存活	否
24	女	24	有	NR^b	半合	Dec/Ara-C/BU/Cy/ATLG	阴	死亡	否
25	女	25	有	CR1	半合	Dec/Ara-C/BU/Cy/ATLG	阴	存活	否
26	男	28	有	CR2	半合	FA/Bu/Cy/ATG	阴	存活	否
27	男	12	有	CR1	全合	IA/Bu/Cy/ATG	阴	存活	否
28	男	8	有	CR1	半合	Dec/Ara-C/Bu/Cy/ATLG	阴	存活	否
29	男	39	有	NR^b	半合	FA/Bu/Cy/ATG	阴	存活	否
30	女	35	无	CR1	无关	Dec/Ara-C/Bu/Cy/ATG	阴	存活	否
31	女	51	有	CR1	半合	Dec/Ara-C/Bu/Cy/ATG	阴	存活	否
32	女	32	有	CR1	半合	Dec/Ara-C/Bu/Cy/ATG	阴	存活	否
注：NR^a难治性白血病；NR^b复发状态白血病；FA：氟达拉滨、阿糖胞苷；CLAG：克拉屈滨、阿糖胞苷、重组人粒细胞刺激因子。

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表 2 预处理相关毒性情况例(%)

部位	地西他滨强化组(n=13)	嘌呤核苷酸类似物强化组(n=12)	伊达比星强化组(n=7)
胃肠道	5(38.5)	5(41.7)	3(42.8)
口腔黏膜	2(15.4)	3(25.0)	1(14.2)
心脏	1(7.7)	0	0
肝脏	1(7.7)	5(41.7)	3(42.8)
肾脏	0	0	0
肺脏	0	0	0
神经系统	0	0	0
出血性膀胱炎	1(7.7)	0	0

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