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达沙替尼联合化疗后行异基因造血干细胞移植治疗费城染色体阳性急性淋巴细胞白血病的临床分析

[Clinical Analysis of Dasatinib and Chemotherapy Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia].

作者信息

Li Yuan, Wang Bing-Jie, Liu Wei, Liang Ze-Yin, Yin Yue, Dong Yu-Jun, Wang Qian, Sun Yu-Hua, Xu Wei-Lin, Ren Han-Yun

机构信息

Department of Hematology, Peking University First Hospital, Beijing 100034, China.

Department of Hematology, Peking University First Hospital, Beijing 100034, China,E-mail:

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):18-23. doi: 10.19746/j.cnki.issn.1009-2137.2020.01.004.

Abstract

OBJECTIVE

To investigate the clinical efficacy, related side-effectt and long-term survival condition of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph ALL) patients treated with second generation TKI dasatinib and chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODS

Clinical data of 19 newly diagnosed as Ph ALL patients treated by dasatinib, chemotherapy and allo-HSCT from January 2012 to September 2018 were collectd and analyzed.

RESULTS

There were 10 males and 9 females with median age of 29 years old. 14 patients were BCR/ABL P190 positive while 5 with BCR/ABL P210 positive. Three patients had complex karyotype, and 3 cases were confirmed to have central nervous system leukemia. All the patients received treatment with the induction chemotherapy regimen of VDCLP and consolidation regimens such as HD-MTX and MAE. 11 patients (57.9%) received dasatinib during induction chemotherapy, 3 patients (15.8%) received dasatinib after remission and 5 patients (26.3%) received dasatinib to replace imatinib. Side-effect appeared in 3 patients including rash, edema and nausea. All the patients got morphological remission and 7 patients(63.6%) got MMR after 4 weeks of induction chemotheraphy. 17 patients (89.5%) got MMR and 15 patients(78.9%) got CMR before allo-HSCT. All the patients received related bone marrow and peripheral hematopoietic stem cell transplantation from related donors, the median time of WBC and platelet engraftment were 12 d and 14 d after transplantation, respectively. The incidence rate of aGVHD and cGVHD were 42.1% and 57.9% respectivety. 13 patients received therapy of dasatinib after HSCT but 7 patients discontinued because of severe headache, vomiting and serious effusions. All the patients were followed-up for the median time of 42 months, the 3-year and 5-year OS both were 94.4%, and 3-year and 5-year RFS of 81.9% and 71.6%, respectively.

CONCLUSION

First-line administration of dasatinib and chemotherapy followed by allo-HSCT for treatment of PhALL is effective and patients can well-tolerate, the patients long-tern survival maybe superior to that of the patients treated with first generation TKI.

摘要

目的

探讨第二代酪氨酸激酶抑制剂(TKI)达沙替尼联合化疗后行异基因造血干细胞移植(allo-HSCT)治疗费城染色体阳性急性淋巴细胞白血病(Ph ALL)患者的临床疗效、相关副作用及长期生存情况。

方法

收集并分析2012年1月至2018年9月期间19例新诊断为Ph ALL患者接受达沙替尼、化疗及allo-HSCT治疗的临床资料。

结果

男性10例,女性9例,中位年龄29岁。14例患者BCR/ABL P190阳性,5例BCR/ABL P210阳性。3例患者核型复杂,3例确诊有中枢神经系统白血病。所有患者均接受VDCLP诱导化疗方案及HD-MTX、MAE等巩固方案治疗。11例患者(57.9%)在诱导化疗期间接受达沙替尼治疗,3例患者(15.8%)在缓解后接受达沙替尼治疗,5例患者(26.3%)接受达沙替尼替代伊马替尼治疗。3例患者出现副作用,包括皮疹、水肿和恶心。所有患者诱导化疗4周后均获形态学缓解,7例患者(63.6%)获主要分子学缓解(MMR)。17例患者(89.5%)在allo-HSCT前获MMR,15例患者(78.9%)获完全分子学缓解(CMR)。所有患者均接受来自相关供者的亲缘骨髓及外周造血干细胞移植,移植后白细胞和血小板植入中位时间分别为12天和14天。急性移植物抗宿主病(aGVHD)和慢性移植物抗宿主病(cGVHD)发生率分别为42.1%和57.9%。13例患者在HSCT后接受达沙替尼治疗,但7例患者因严重头痛、呕吐及严重积液而停药。所有患者中位随访时间42个月,3年和5年总生存率(OS)均为94.4%,3年和5年无复发生存率(RFS)分别为81.9%和71.6%。

结论

一线应用达沙替尼联合化疗后行allo-HSCT治疗PhALL有效,患者耐受性良好,患者长期生存可能优于第一代TKI治疗的患者。

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