Ph染色体阳性白血病患者经伊马替尼治疗后行异基因造血干细胞移植的疗效观察

目的探讨Ph染色体阳性白血病患者经伊马替尼治疗后行异基因造血干细胞移植的疗效。方法回顾性分析2001年6月至2005年6月北京大学人民医院血液病研究所住院的难治性Ph染色体阳性的39例白血病患者经伊马替尼治疗后再行异基因造血干细胞移植的效果,观察伊马替尼对造血重建、移植物抗宿主病(GVHD)、总存活率(OS)、无病存活率(DFS)、复发率和移植相关并发症的影响。结果伊马替尼治疗后,18例患者血液学完全缓解,9例骨髓缓解,4例部分缓解,4例无效或疾病进展,总有效率79.49%,无重度非血液学毒性反应;移植后中性粒细胞和血小板植活中位时间分别为14d和13.5d;Ⅱ~Ⅳ度和Ⅲ~Ⅳ度急性GVHD累积发生率分别为61.53%和15.38%;根据对伊马替尼治疗的效应分为完全缓解组和未完全缓解组,其3年预期OS和DFS分别为(73.51±9.61)%对(36.36±14.50)%和(61.28±12.37)%对(31.25±13.98)%,3年累积复发率为20.41%对75.00%;4例患者死于重度移植相关并发症。结论应用伊马替尼后行异基因造血干细胞移植是一种安全、有效的治疗难治性Ph染色体阳性白血病的方法,尤其达完全缓解后行移植,可望提高此类患者的临床治愈率。     

CAG预激方案联合伊马替尼治疗复发/难治性Ph+急性淋巴细胞白血病首例报道

目的:寻找有效治疗复发/难治性Ph染色体阳性急性淋巴细胞白血病(Ph ALL)的疗法。方法:以CAG预激方案联合伊马替尼诱导治疗复发/难治性Ph ALL病例1例。结果:该复发/难治Ph ALL患者经CAG方案联合伊马替尼诱导治疗后达缓解。结论:对于复发/难治性Ph ALL,CAG联合伊马替尼是一个值得尝试的方案。     

Role of p21<Superscript>WAF1/CIP1</Superscript> as an attenuator of both proliferative and drug-induced apoptotic signals in <Emphasis Type="Italic">BCR-ABL</Emphasis>-transformed hematopoietic cells

The constitutive tyrosine kinase activity of the BCR-ABL fusion protein plays a crucial role in the pathogenesis of chronic myeloid leukemia and promotes growth factor-independent survival of hematopoietic cells. In 32D cells, expression levels of retrovirally transduced BCR-ABL were positively correlated with the levels of the cell cycle regulator protein p21, and this upregulation of p21 expression depended on the kinase activity of BCR-ABL. To assess the role of p21 on BCR-ABL-positive hematopoietic cells, we compared proliferation and drug-induced apoptosis in bone marrow (BM) cells from wild-type and p21 knockout mice after retroviral transfer of the BCR-ABL fusion gene. As compared with wild-type cells, p21 knockout cells showed increased proliferation, suggesting that p21 acted as an attenuator of BCR-ABL-mediated cell proliferation. In marked contrast, deletion of p21 promoted apoptosis induction by imatinib and taxol in BCR-ABL-transformed BM cells. These findings demonstrate that p21 has a dual function in BCR-ABL-transformed murine BM cells: It attenuates the effects of two apparently opposed phenomena such as BCR-ABL-mediated cell proliferation and drug-induced apoptosis. This dual function of p21 calls for a cautious evaluation of the suitability of p21 as a secondary target in anticancer therapy.     

复发性胃肠间质瘤的临床治疗

目的：探讨复发转移性胃肠道间质瘤（CIST）的治疗。方法：回顾分析我院2008-2012年5年间收治的30例复发转移性GIST患者的临床资料。结果：30例患者均予伊马替尼治疗后接受手术治疗。治疗有效（RD组）的18例中有13例、疾病进展（PD组）的12例中有1例共计14例（46.7%）患者肿瘤获得完全切除。RD组无疾病进展生存时间（PFS）为24.9个月,PD组的PFS为2.7个月,两组比较,差异有统计学意义（P〈0.01）。结论：在复发转移性GIST患者中,口服伊马替尼治疗有效的患者行二次手术切除是可行的;但是对于口服伊马替尼治疗无效的GIST患者分为两类：局限性进展的GIST,在评估手术可以完整切除局限进展肿瘤的情况下,仍建议实施手术治疗,术后可继续原剂量伊马替尼或增加剂量治疗,也可选择舒尼替尼治疗;广泛进展的GIST,不建议采取手术,可以增加伊马替尼治疗,或改用舒尼替尼治疗。     

伊马替尼为基础治疗骨破坏为首发表现的费城染色体阳性急性淋巴细胞白血病一例并文献复习

目的报道并分析1例以骨破坏为首发表现的费城染色体阳性（Ph^＋）急性淋巴细胞白血病（ALL）,采用伊马替尼为基础个体化方案的诊断和治疗。方法采用病例报告及文献复习的方式对以骨破坏起病的ALL患者及Ph^＋ALL治疗进展进行描述。结果患者诊断Ph^＋ALL明确,经伊马替尼为基础治疗获得诱导缓解,维持分子学缓解17个月。结论对以骨破坏为首发表现者,应考虑ALL诊断可能;伊马替尼为基础的标准化疗方案有可能改善Ph^＋ALL的治疗模式和预后。     

Inhibition of c-Kit signaling is associated with reduced heat and cold pain sensitivity in humans

The tyrosine kinase receptor c-Kit is critically involved in the modulation of nociceptive sensitivity in mice. Ablation of the c-Kit gene results in hyposensitivity to thermal pain, whereas activation of c-Kit produces hypersensitivity to noxious heat, without altering sensitivity to innocuous mechanical stimuli. In this study, we investigated the role of c-Kit signaling in human pain perception. We hypothesized that subjects treated with Imatinib or Nilotinib, potent inhibitors of tyrosine kinases including c-Kit but also Abl1, PDFGFRα, and PDFGFRβ, that are used to treat chronic myeloid leukemia (CML), would experience changes in thermal pain sensitivity. We examined 31 asymptomatic CML patients (14 male and 17 female) receiving Imatinib/Nilotinib treatment and compared them to 39 age- and sex-matched healthy controls (12 male and 27 female). We used cutaneous heat and cold stimulation to test normal and noxious thermal sensitivity, and a grating orientation task to assess tactile acuity. Thermal pain thresholds were significantly increased in the Imatinib/Nilotinib-treated group, whereas innocuous thermal and tactile thresholds were unchanged compared to those in the control group. In conclusion, our findings suggest that the biological effects of c-Kit inhibition are comparable in mice and humans in that c-Kit activity is required to regulate thermal pain sensitivity but does not affect innocuous thermal and mechanical sensation. The effect on experimental heat pain observed in our study is comparable to those of several common analgesics; thus modulation of the c-Kit pathway can be used to specifically modulate noxious heat and cold sensitivity in humans.     

A Case Report of Multiple Capillary Hemangioma in a Chronic Myeloid Leukemia Patient Taking Tyrosine Kinase Inhibitors

A capillary hemangioma is a vascular tumor with small capillary sized vascular channel. Multiple capillary hemangioma in relation with drugs have been rarely reported. Here in, we report a case of multiple capillary hemangioma in patient diagnosed with chronic myeloid leukemia who received tyrosine kinase inhibitors (TKIs). Histopathological findings have shown capillary proliferation in the upper dermis, which is consistent with capillary hemangioma. Since TKIs can paradoxically activate the MEK/ERK pathway which is required for angiogenesis, we presumed that the lesions as the cutaneous side effects of TKIs.     

Imatinib治疗转移性、不能手术切除的胃肠间质瘤

1 文献类型 治疗2 证据水平 2b3 文献来源Demetri G D, Mehren M V, Blanke C D, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors [J]. N Engl J Med, 2002,347:472-4804 背景 Imatinib(Gleevec,甲磺酸伊马替尼,STI571)是一种小分子酪氨酸激酶抑制剂。最初,Imatinib用于治疗慢性粒细胞白血病。2000年Joensuu首先报道1例