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环磷酰胺依赖性激酶抑制剂 flavopiridol 治疗慢性淋巴细胞白血病患者肿瘤溶解综合征的风险因素。

Risk factors for tumor lysis syndrome in patients with chronic lymphocytic leukemia treated with the cyclin-dependent kinase inhibitor, flavopiridol.

机构信息

Division of Hematology, Department of Internal Medicine, The Arthur G James Comprehensive Cancer Center and The Ohio State University, Columbus, OH 43210, USA.

出版信息

Leukemia. 2011 Sep;25(9):1444-51. doi: 10.1038/leu.2011.109. Epub 2011 May 24.

Abstract

Tumor lysis syndrome (TLS) has been described in over 40% of patients with chronic lymphocytic leukemia treated with the cyclin-dependent kinase inhibitor, flavopiridol. We conducted a retrospective analysis to determine predictive factors for TLS. In 116 patients, the incidence of TLS was 46% (95% CI: 36-55%). In univariable analysis, female gender, greater number of prior therapies, Rai stages III-IV, adenopathy ≥ 10 cm, splenomegaly, del(11q), decreased albumin and increased absolute lymphocyte count, white blood cell count (WBC), β2-microglobulin, and lactate dehydrogenase were associated (P < 0.05) with TLS. In multivariable analysis, female gender, adenopathy ≥ 10 cm, elevated WBC, increased β2-microglobulin, and decreased albumin were associated with TLS (P < 0.05). With respect to patient outcomes, 49 and 44% of patients with and without TLS, respectively, responded to flavopiridol (P = 0.71). In a multivariable analysis, controlling for number of prior therapies, cytogenetics, Rai stage, age and gender, progression-free survival (PFS) was inferior in patients with TLS (P = 0.01). Female patients and patients with elevated β2-microglobulin, increased WBC, adenopathy ≥ 10 cm and decreased albumin were at highest risk and should be monitored for TLS with flavopiridol. TLS does not appear to be predictive of response or improved PFS in patients receiving flavopiridol.

摘要

肿瘤溶解综合征(TLS)在接受细胞周期蛋白依赖性激酶抑制剂 flavopiridol 治疗的慢性淋巴细胞白血病患者中超过 40%的患者中被描述过。我们进行了一项回顾性分析以确定 TLS 的预测因素。在 116 例患者中,TLS 的发生率为 46%(95%CI:36-55%)。在单变量分析中,女性、更多的既往治疗、Rai 分期 III-IV、淋巴结病≥10cm、脾肿大、del(11q)、白蛋白降低和绝对淋巴细胞计数、白细胞计数(WBC)、β2-微球蛋白和乳酸脱氢酶升高与 TLS 相关(P<0.05)。在多变量分析中,女性、淋巴结病≥10cm、WBC 升高、β2-微球蛋白升高和白蛋白降低与 TLS 相关(P<0.05)。就患者结局而言,分别有 TLS 的患者和无 TLS 的患者中有 49%和 44%对 flavopiridol 有反应(P=0.71)。在多变量分析中,控制既往治疗的次数、细胞遗传学、Rai 分期、年龄和性别后,有 TLS 的患者无进展生存期(PFS)更差(P=0.01)。女性患者和β2-微球蛋白升高、WBC 升高、淋巴结病≥10cm 和白蛋白降低的患者风险最高,应监测接受 flavopiridol 治疗的患者的 TLS。TLS 似乎不能预测接受 flavopiridol 治疗的患者的反应或改善 PFS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e6b/3162125/e04824d551e6/nihms-288737-f0001.jpg

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