伊马替尼治疗Ph^＋急性淋巴细胞白血病的临床研究  

Clinical study of imatinib for treatment of Philadelphia chromosome positive acute lymphoblastic leukemia

作　　者：李彩霞[1] 吴德沛[1] 刘红[1] 刘跃均[1] 马骁[1] 吴小津[1] 陈晓晨[1] 孙道萍[1] 

机构地区：[1]苏州大学附属第一医院、江苏省血液研究所,卫生部血栓与止血重点实验室,215006

出　　处：《中华血液学杂志》2010年第3期181-185,共5页Chinese Journal of Hematology

基　　金：江苏省自然科学基金（BK2006056）;江苏省医学领军人才项目（LJ200626）

摘　　要：目的探讨伊马替尼联合化疗和异基因造血干细胞移植（allo—HSCT）治疗Ph^＋急性淋巴细胞白血病（Ph^＋-ALL）的疗效及转归。方法总结我院2006年1月至2009年3月的初诊Ph^＋-ALL患者30例。诱导化疗均采用CDOLP方案，其中16例化疗不敏感者联合伊马替尼治疗。11例进行allo—HSCT，19例采用大剂量的阿糖胞苷、甲氨蝶呤、环磷酰胺巩固治疗。维持化疗采用VP方案联合伊马替尼。结果30例患者中17例WBC〉30×10^9／L；29例细胞免疫学标记为B系表达；1例为T系表达；24例伴附加染色体异常。诱导化疗总完全缓解（CR）率96．7％，中位CR时间9（2～20）个月。1年和3年总体生存（OS）率分别为（64．7±9．8）％和（30．0±12．4）％；1年和3年无事件生存（EFS）率分别为（28．8±9．5）％和（19．2±10．1）％。30例中13例bcr—abl融合基因持续转阴，持续bcr—abl阴性者较持续阳性及复发者OS率高（70．7％对61．3％，P=0．267）、EFS率高（61．7％对17．3％，P=0．01）。移植与化疗患者中位生存时间分别为18（5～36）个月和14（4～22）个月；移植组比化疗组OS率高（71．6％对58．8％，P=0．189）、EFS率高（36．4％对21．8％，P=0．045）。高白细胞组患者和非高白细胞组患者中位生存时间分别为10（4～18）个月和29（5～36）个月。高白细胞组比非高白细胞组OS率低（46．9％对83．1％，P=0．003）、EFS率低（15．5％对50．8％，P=0．009）。结论伊马替尼能够显著提高Ph^＋-ALL患者的CR率和bcr—abl融合基因的转阴率，延长非移植患者的缓解期。伊马替尼联合allo—HSCT有望提高Ph^＋-ALL患者的治愈率。Objective To explore the efficacy and therapeutic outcome of imatinib combined with chemotherapy or allogeneic hematopoictic stem cell transplantation （allo-HSCT） for Philadelphia chromosome positive acute lymphoblastie leukemia（ALL）. Methods Thirty patients from Jan 2006 to Mar 2009 were enrolled in this study. All patients received CDOLP induction chemotherapy regimen. Sixteen patients insensitive to chemotherapy were given imatinib simultaneously. Eleven of 30 patients underwent HSCT. The other 19 cases received consolidation therapy including HD-Ara-C, HD-MTX and HD-CTX. Maintenance therapy regimens were VP combined with imatinib. Results The white blood cell （WBC） count in 17 patients was higher than 30 × 10^9/L. Of 30 patients, 29 were B cell phenotype and 1 T cell phenotype, 24 had additional chromosomal abnormalities. The overall complete remission（CR） rate was 96.7%. The median CR duration was 9 （ 2 - 20 ） months. The 1 -year and 3-year overall survival （OS） rates were （ 64.7 ± 9.8 ） % and （ 30.0 ± 12.4） % , and the event free survival （EFS） rates were （ 28.8 ± 9.5 ） % and （ 19.2 ± 10.1 ） % , respectively. The ber-abl transcripts in 13 of 30 patients were continuous negative. The OS rate in patients with negative ber-abl transcripts was higher than that with positive bcr-abl （70.7% vs 61.3% ） （P =0. 189）. The EFS rate of patients with continuous negative ber-abl transcripts was significantly higher than that of patients with continuous positive ber-ab1 transcripts （ P = 0.01 ）. The median overall survival duration of higher WBC count group and normal WBC count group were 10（4 -18） and 29 （5 -36）months, respectively. The patients of higher WBC count had lower OS and EFS rates than that of normal WBC count （46.9% and 15.5% vs 83.5% and 50. 8%, respectively） （P = 0. 003 and 0. 009, respectively）. Conclusion Imatinib can significantly improve molecular CR rate and CR duration for Ph^＋ ALL patients. Imatinib combined with allo- HSC

关 键 词：白血病 淋巴细胞 急性 费城染色体 伊马替尼 化疗 造血干细胞移植 

分 类 号：R733.71[医药卫生—肿瘤]