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伊马替尼治疗后行异基因造血细胞移植序贯首次缓解的费城染色体阳性急性淋巴细胞白血病患儿的结局及预后因素

Outcome and prognostic factors of children with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib followed by allogeneic hematopoietic cell transplantation in first remission.

作者信息

Shin Juae, Lee Na Yeong, Kim Seongkoo, Lee Jae Wook, Jang Pil-Sang, Chung Nack-Gyun, Cho Bin

机构信息

Department of Pediatrics, The Catholic University of Korea, Seoul, Korea.

出版信息

Blood Res. 2019 Mar;54(1):45-51. doi: 10.5045/br.2019.54.1.45. Epub 2019 Mar 21.

Abstract

BACKGROUND

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a subset of ALL with poor prognosis. Here, we analyzed the outcomes and prognostic factors of children with Ph+ ALL who received imatinib and chemotherapy followed by allogeneic hematopoietic cell transplantation (HCT) in first complete remission (CR).

METHODS

Thirty-one Ph+ ALL patients (female 10) diagnosed from January 2005 to December 2016 were included in the study. All patients were treated with imatinib and chemotherapy before HCT. Bone marrow (BM) evaluations included real-time quantitative polymerase chain reaction (RQ-PCR) study of the fusion transcript. All patients received HCT with total body irradiation (TBI)-based conditioning at a median of 6.4 (range, 4.2-47.1) months from diagnosis.

RESULTS

Compared to values at diagnosis, the median decrement of RQ-PCR value post-consolidation, and prior to HCT was -3.7 Log and -4.8 Log, respectively. The 5-year event-free survival (EFS) and overall survival of the patients were 64.5±9.4% (20/31) and 75.0±8.3% (23/31) respectively. Events included relapse (N=5) and death in CR post-HCT (N=6). The 5-year incidence of molecular relapse was 30.9±9.1% (9/31). An RQ-PCR decrement of at least -4 Log post-consolidation significantly predicted lower incidence of molecular relapse: 7.7±7.7% for ≥-4 Log decrement, 50.0±13.8% for <-4 Log decrement (=0.027).

CONCLUSION

Decrement in RQ-PCR for the transcript that was determined after consolidation was the only significant prognostic factor for incidence of molecular relapse. In the post-induction TKI initiation setting, steadfast imatinib treatment during consolidation may allow for optimum post-HCT outcomes.

摘要

背景

费城染色体阳性急性淋巴细胞白血病(Ph+ ALL)是急性淋巴细胞白血病的一个预后较差的亚型。在此,我们分析了在首次完全缓解(CR)期接受伊马替尼和化疗后进行异基因造血细胞移植(HCT)的Ph+ ALL患儿的治疗结果及预后因素。

方法

本研究纳入了2005年1月至2016年12月期间诊断的31例Ph+ ALL患者(女性10例)。所有患者在进行HCT前均接受伊马替尼和化疗。骨髓(BM)评估包括融合转录本的实时定量聚合酶链反应(RQ-PCR)研究。所有患者在诊断后中位6.4(范围4.2 - 47.1)个月接受基于全身照射(TBI)的预处理进行HCT。

结果

与诊断时的值相比,巩固治疗后及HCT前RQ-PCR值的中位下降分别为-3.7 Log和-4.8 Log。患者的5年无事件生存率(EFS)和总生存率分别为64.5±9.4%(20/31)和75.0±8.3%(23/31)。事件包括复发(N = 5)和HCT后CR期死亡(N = 6)。5年分子复发发生率为30.9±9.1%(9/31)。巩固治疗后RQ-PCR下降至少-4 Log显著预示分子复发发生率较低:下降≥-4 Log时为7.7±7.7%,下降<-4 Log时为50.0±13.8%(P = 0.027)。

结论

巩固治疗后测定的转录本RQ-PCR下降是分子复发发生率的唯一显著预后因素。在诱导后开始使用酪氨酸激酶抑制剂(TKI)的情况下,巩固治疗期间持续使用伊马替尼可能会带来最佳的HCT后治疗结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b906/6439289/aa4984c224ed/br-54-45-g001.jpg

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