学科主题临床医学
Administration of imatinib in the first 90 days after allogeneic hematopoietic cell transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia
Chen Huan; Liu Kai-yan; Xu Lan-ping; Liu Dai-hong; Chen Yu-hong; Shi Hong-xia; Han Wei; Zhan Xiao-hui; Wang Yu; Zhao Ting; Huang Xiao-jun
关键词Philadelphia chromosome acute lymphoblastic leukemia allogeneic hematopoietic cell transplantation minimal residual disease
刊名CHINESE MEDICAL JOURNAL
2011-01-20
DOI10.3760/cma.j.issn.0366-6999.2011.02.018
124期:2页:246-252
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, General & Internal
研究领域[WOS]General & Internal Medicine
关键词[WOS]BONE-MARROW-TRANSPLANTATION ; RESIDUAL DISEASE DETECTION ; POLYMERASE-CHAIN-REACTION ; CANCER PROGRAM ; CHEMOTHERAPY ; TRANSCRIPTS ; MESYLATE ; RELAPSE ; EUROPE
英文摘要

Background Relapse happens frequently after allogeneic hematopoietic cell transplantation (allo-HCT) in the patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Detection of the minimal residual disease (MRD) before and after allo-HCT is associated with higher relapse rate. Early administration of imatinib after allo-HCT may prevent recurrent Ph+ ALL. The aim of this study was to evaluate the safety and efficacy of imatinib in preventing hematological relapse when imatinib was administrated in the first 90 days after allo-HCT.

Methods Patients with Ph+ ALL that underwent allo-HCT were enrolled in a prospective study. A TaqMan-based real-time quantitative polymerase chain reaction (RQ-PCR) technique was used to detect the MRD (bcr-abl transcript levels). Imatinib therapy was initiated prior to 90 days after allo-HCT if the patient′s absolute neutrophil count (ANC) was above 1.0x10(9)/L (without granulocyte colony-stimulating factor (G-CSF) administration) and the platelet count was greater than 50.0x10(9)/L, or if the bcr-abl transcript levels were elevated in two consecutive tests, or if the bcr-abl transcript levels were >= 10(-2) after the initial engraftment. The initial daily dose of imatinib was 400 mg/d for adults and 260 mg/m(2) for children (younger than 17 years). Imatinib was administered for at least 1 month and the bcr-abl TaqMan results were negative for 3 consecutive tests, or complete molecular remission (CRmol) was sustained for at least 3 months.

Results From May 2005 to October 2008, 29 patients were enrolled in this study, of whom, 19 patients were male and 10 were female. The median age of the enrolled patients was 33 years (range 6-50 years). Imatinib therapy was started at a median time of 60 days (range 20-122 days) post HCT (only one patient started Imatinib therapy at 122nd day after HCT). Twenty-five adult patients could tolerate a dose of 300-400 mg/d of imatinib, and three children tolerated a dose of 260 mg.m(-2).d(-1). Sixty-eight percent of the patients experienced various adverse events during imatinib therapy, hematological toxicity being the most common adverse event. The median duration of imatinib treatment was 3 months (range 7 days-18 months). During the median follow-up of 24 months (range 16.0-54.5 months), 3 out of 27 patients that could be evaluated for efficacy died from relapse. The 3-year probability of relapse for the evaluated patients was (11.3 +/- 0.61)%. The relapse rates among the subgroup of positive and negative bcr-abl patients before allo-HCT were 13.6% and 0, respectively (P >0.05). The relapse rates among the subgroups of bcr-abl positive and negative patients after allo-HCT were 20.0% and 5.9%, respectively (P >0.05). The relapse rates among the patients in first complete remission (CR1) and second complete remission/non-remission (CR2/NR) before transplantation were 0 and 31.4%, respectively (P <0.05). The 3-year probability of overall survival (OS) and disease-free survival (DFS) for the all enrolled patients were (75.3 +/- 8.1)%. The 3-year probabilities for OS and DFS among the subgroup of patients in CR1 and CR2/NR before transplantation were (87.7 +/- 8.2)% and (54.6 +/- 15.0)%, respectively (P <0.05).

Conclusions Administration of imatinib at a dose of 300-400 mg/d in the first 90 days after allo-HCT is feasible in Ph+ ALL patients. With this treatment, bcr-abl positive patients before or after transplantation do not have a higher relapse rate after allo-HCT compared with the bcr-abl negative patients. Because of lower relapse rate and better OS and DFS, we recommend that Ph+ ALL patients receive allo-HCT in CR1.

语种英语
WOS记录号WOS:000286787300020
项目编号30725038 ; IRT0702 ; RDC2009-36
资助机构National Outstanding Young Scientist&prime ; s Foundation of China ; Program for Innovative Research Team in University ; People&prime ; s Hospital
引用统计
被引频次:9[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61864
专题北京大学第二临床医学院_北京大学血液病研究所
医学人文研究院/公共教学部_哲学与社会科学系
北京大学第二临床医学院_血液科
作者单位Peking Univ Peoples Hosp, Peking Univ Inst Hematol, Beijing 100044, Peoples R China
推荐引用方式
GB/T 7714
Chen Huan,Liu Kai-yan,Xu Lan-ping,et al. Administration of imatinib in the first 90 days after allogeneic hematopoietic cell transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia[J]. CHINESE MEDICAL JOURNAL,2011,124(2):246-252.
APA Chen Huan.,Liu Kai-yan.,Xu Lan-ping.,Liu Dai-hong.,Chen Yu-hong.,...&Huang Xiao-jun.(2011).Administration of imatinib in the first 90 days after allogeneic hematopoietic cell transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.CHINESE MEDICAL JOURNAL,124(2),246-252.
MLA Chen Huan,et al."Administration of imatinib in the first 90 days after allogeneic hematopoietic cell transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia".CHINESE MEDICAL JOURNAL 124.2(2011):246-252.
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