Authors' Affiliations: Laboratories of Molecular Biology, Pathology, and Metabolism Branch, National Cancer Institute; and Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, Maryland.
Clin Cancer Res. 2013 Dec 15;19(24):6873-81. doi: 10.1158/1078-0432.CCR-13-1752. Epub 2013 Nov 25.
In contrast with the classic form, variant hairy cell leukemia (HCLv) responds poorly to single-agent purine analogs, expresses unmutated BRAF, has shorter overall survival, and lacks effective standard therapy. No treatment has achieved a high complete remission (CR) rate even in small series, and of 39 reported cases from six studies, overall response rate after cladribine was 44% with 8% CRs. Rituximab has been found to increase the sensitivity of malignant cells to cladribine, suggesting that combination with cladribine might improve response in HCLv. To test this hypothesis, patients with HCLv were treated with simultaneous cladribine and rituximab.
Patients with HCLv with 0 to 1 prior courses of cladribine received cladribine 0.15 mg/kg for days 1 to 5, with eight weekly doses of rituximab 375 mg/m(2) beginning day 1. Restaging was performed, and minimal residual disease (MRD) in blood and marrow was quantified using PCR, immunohistochemistry, and flow cytometry.
By 6 months, 9 (90%) of 10 patients achieved CR, compared with 3 (8%) of 39 reported cases treated with cladribine alone (P < 0.0001). Of the 9 CRs, 8 remain free of MRD at 12 to 48 (median 27) months of follow-up. No dose-limiting toxicities were observed when beginning cladribine and rituximab on the same day, although most patients required short-term steroids to prevent and treat rituximab infusion reactions. Cytopenias in CRs resolved in 7 to 211 (median 34) days without major infections.
Although cladribine alone lacks effectiveness for early or relapsed HCLv, cladribine with immediate rituximab achieves CRs without MRD and is feasible to administer.
与经典型相比，变异型毛细胞白血病（HCLv）对单药嘌呤类似物反应不佳，表达未突变的 BRAF，总生存期较短，且缺乏有效标准疗法。即使在小系列中，没有一种治疗方法能达到高完全缓解（CR）率，在来自六项研究的 39 例报告病例中，克拉屈滨后的总缓解率为 44%，CR 率为 8%。已经发现利妥昔单抗可增加恶性细胞对克拉屈滨的敏感性，这表明克拉屈滨联合治疗可能改善 HCLv 的反应。为了验证这一假设，对 HCLv 患者进行了克拉屈滨和利妥昔单抗同时治疗。
接受过 0 至 1 次克拉屈滨治疗的 HCLv 患者接受克拉屈滨 0.15mg/kg，第 1 至 5 天，第 1 天开始每周 8 次利妥昔单抗 375mg/m2。重新分期，并使用 PCR、免疫组织化学和流式细胞术定量血液和骨髓中的微小残留疾病（MRD）。
6 个月时，10 例患者中的 9 例（90%）达到 CR，而单独用克拉屈滨治疗的 39 例报告病例中仅 3 例（8%）达到 CR（P<0.0001）。在 9 例 CR 中，8 例在 12 至 48 个月（中位 27 个月）的随访中无 MRD。当在同一天开始使用克拉屈滨和利妥昔单抗时，没有观察到剂量限制毒性，尽管大多数患者需要短期类固醇来预防和治疗利妥昔单抗输注反应。CR 中的细胞减少症在 7 至 211 天（中位 34 天）内无主要感染而得到解决。
虽然克拉屈滨单独治疗早期或复发的 HCLv 效果不佳，但克拉屈滨联合立即利妥昔单抗可达到无 MRD 的 CR，并且易于给药。
