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异基因造血干细胞移植后慢性期和晚期复发的慢性髓性白血病患者对酪氨酸激酶抑制剂治疗的反应。

Response to tyrosine kinase inhibitor therapy in patients with chronic myelogenous leukemia relapsing in chronic and advanced phase following allogeneic hematopoietic stem cell transplantation.

机构信息

Leukemia/BMT Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada.

出版信息

Biol Blood Marrow Transplant. 2010 May;16(5):639-46. doi: 10.1016/j.bbmt.2009.11.026. Epub 2010 Feb 4.

DOI:10.1016/j.bbmt.2009.11.026
PMID:20005967
Abstract

Tyrosine kinase inhibitors (TKI) have been used to treat relapse of chronic myelogenous leukemia (CML) after allogeneic stem cell transplant (HSCT), with responses seen predominantly in chronic phase (CP) patients. This study aimed to analyze the response to TKI therapy and overall survival for patients relapsing predominantly in advanced phase. We retrospectively reviewed 22 patients treated with imatinib (n=20) and/or dasatinib (n=6) for relapsed CML after HSCT; 8 patients were in CP, and 14 patients had advanced disease. Seven patients also received donor lymphocyte infusions. Hematologic, cytogenetic, and molecular responses were analyzed. Nineteen patients (86%) achieved complete hematologic response (CHR), 17 patients (77%) achieved complete cytogenetic response (CCR), and 14 patients (64%) achieved complete molecular response (CMR). In advanced phase patients, 11 (79%) achieved CHR, 10 (71%) CCR, and 8 (57%) achieved CMR. Grade 3 or 4 cytopenias occurred in 10 cases. With median follow-up of 31.5 months from relapse, 14 (64%) patients remain alive, 13 in CMR. In multivariate analysis, the achievement of CMR was significantly correlated with OS with an odds ratio of 20.5 (95% confidence interval 2.3-182) P=.007. TKI therapy is capable of inducing durable molecular responses for CML relapsing after HSCT, both in chronic and advanced phases. The achievement of CMR appears to be crucial in providing long-term disease control for these patients.

摘要

酪氨酸激酶抑制剂 (TKI) 已被用于治疗异基因干细胞移植 (HSCT) 后慢性髓性白血病 (CML) 的复发,主要在慢性期 (CP) 患者中观察到应答。本研究旨在分析 TKI 治疗对主要在晚期复发的患者的反应和总生存期。我们回顾性分析了 22 例接受伊马替尼(n=20)和/或达沙替尼(n=6)治疗的 HSCT 后复发的 CML 患者;8 例患者处于 CP,14 例患者处于晚期疾病。7 例患者还接受了供体淋巴细胞输注。分析了血液学、细胞遗传学和分子反应。19 例患者(86%)达到完全血液学缓解(CHR),17 例患者(77%)达到完全细胞遗传学缓解(CCR),14 例患者(64%)达到完全分子缓解(CMR)。在晚期疾病患者中,11 例(79%)达到 CHR,10 例(71%)达到 CCR,8 例(57%)达到 CMR。发生 3 级或 4 级血细胞减少症的有 10 例。从复发到中位随访 31.5 个月,14 例(64%)患者存活,13 例达到 CMR。多变量分析显示,CMR 的获得与 OS 显著相关,优势比为 20.5(95%置信区间 2.3-182)P=.007。TKI 治疗能够诱导 HSCT 后复发的 CML 产生持久的分子反应,无论是在慢性期还是在晚期。CMR 的获得似乎对这些患者的长期疾病控制至关重要。

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