Hematologic Malignancy Program, Texas Oncology-Amarillo Cancer Center, Amarillo, Texas 79109, USA.
Leuk Lymphoma. 2010 Dec;51(12):2258-61. doi: 10.3109/10428194.2010.527404. Epub 2010 Nov 11.
The treatment options for patients with myelodysplastic syndrome (MDS) who have failed DNA hypomethylating agents are limited. In this study, we set out to investigate the efficacy of low dose clofarabine in 10 patients with MDS (four intermediate-2/high risk disease) who had failed 5-azacytidine. The median age was 73 years (range 65-78) and median cycles of clofarabine received were 2 (range 1-4). Nine patients were evaluable for response. An overall response rate of 44% was observed (one CR, one PR, and two HI). All responders had low risk disease. The median duration of response was 12 months (range 6.5-15.5). Although the doses of clofarabine administered were only 12.5-25% of that used in other studies, significant hematologic toxicities were observed. Severe and prolonged pancytopenia occurred in all 10 patients. One patient who had a history of thrombocytopenic gastrointestinal bleed died due to an intracranial bleed despite aggressive platelet support. Low dose clofarabine may, therefore, induce response, but with significant toxicities, in patients with low risk MDS who fail 5-azacytidine. Future work involving a larger patient population is needed to establish the role of low dose clofarabine in low risk MDS.
对于接受去甲基化药物治疗失败的骨髓增生异常综合征（MDS）患者，治疗选择有限。在这项研究中，我们旨在研究小剂量氯法拉滨在 10 名接受去甲基化药物治疗失败的 MDS 患者（4 名中间 2/高危疾病）中的疗效。中位年龄为 73 岁（范围 65-78 岁），接受氯法拉滨的中位周期数为 2（范围 1-4）。9 名患者可评估反应。观察到总缓解率为 44%（1 例完全缓解，1 例部分缓解，2 例血液学改善）。所有缓解者均为低危疾病。缓解的中位持续时间为 12 个月（范围 6.5-15.5）。尽管给予的氯法拉滨剂量仅为其他研究中使用剂量的 12.5-25%，但仍观察到明显的血液学毒性。所有 10 名患者均出现严重且持久的全血细胞减少症。一名有血小板减少性胃肠道出血史的患者因颅内出血而死亡，尽管给予了积极的血小板支持。因此，小剂量氯法拉滨可能会在接受去甲基化药物治疗失败的低危 MDS 患者中诱导缓解，但毒性较大。需要进行涉及更大患者人群的进一步研究，以确定小剂量氯法拉滨在低危 MDS 中的作用。
