拓扑替康联合化疗用于转化型慢性粒细胞白血病和晚期骨髓增生异常综合征患者。

Topotecan-based combination chemotherapy in patients with transformed chronic myelogenous leukemia and advanced myelodysplastic syndrome.

作者信息

Park S J, Kim D W, Kim H J, Eom H S, Min C K, Lee J W, Min W S, Kim C C

机构信息

Catholic Hemopoietic Stem Cell Transplantation Center, Department of Internal Medicine, Catholic University of Korea, College of Medicine, Seoul, Korea.

出版信息

Korean J Intern Med. 2000 Jul;15(2):122-6. doi: 10.3904/kjim.2000.15.2.122.

DOI:10.3904/kjim.2000.15.2.122

PMID:10992724

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4531761/

Abstract

BACKGROUND

Patients with transformed chronic myelogenous leukemia(CML) and advanced myelodysplastic syndrome(MDS) have poor prognosis. The aim of this study is to evaluate the feasibility of second chronic phase induction in accelerated phase(CML-AP) or blastic crisis of CML(CML-BC) and remission induction in advanced MDS by combining topoisomerase I inhibitor (topotecan) with topoisomerase II inhibitor(mitoxantrone).

METHODS

Twenty-four evaluable patients were entered on this study with a median age of 34 years. Eighteen patients with transformed CML(7 CML-AP, 11 CML-BC) and 6 patients with advanced MDS were treated. Topotecan was administered as 1.5 mg/m2/day by continuous infusion over 24 hours daily for 5 days every 4 to 8 weeks until remission. To enhance the tumoricidal effects, mitoxantrone(12 mg/m2/day, Days 1-3) was added.

RESULTS

Eight patients(33%) achieved a complete remission(CR). Four of 7 patients with CML-AP(57%), 2 of 4 patients with CML-lymphoid blastic crisis (-LBC)(50%) and 2 of 6 patients with advanced MDS(33%) had CR lasting more than 45 days(45 to 400 days). There was no CR in the patients with CML-myeloid blastic crisis(-MBC). The dose level of 1.5 mg/m2/day(7.5 mg/m2/course) of topotecan was well tolerated in all patients. Mucositis occurred in 69% of patients (severe in 5%) and diarrhea in 67%(severe in 8%). In addition, there were no new or unexpected toxicities in the patients who were treated at this dose(7.5 mg/m2/course). In patients who recovered their neutrophil count, the absolute neutrophil count(ANC) remained below 500/microL for a period of 13 to 58 days(median 21 days) and the time to ANC recovery was associated with pretreatment severity of bone marrow fibrosis(mainly CML patients). Likewise, in the patients who recovered unsupported platelets, the platelets remained below 20,000/microL for a period of 0 to 37 days (median 19 days).

CONCLUSION

The combination of topotecan-mitoxantrone has shown modest activity in CML-AP, CML-LBC and advanced MDS with acceptable toxicities.

摘要

背景

转化型慢性粒细胞白血病（CML）和晚期骨髓增生异常综合征（MDS）患者预后较差。本研究旨在评估拓扑异构酶I抑制剂（拓扑替康）与拓扑异构酶II抑制剂（米托蒽醌）联合用于慢性粒细胞白血病加速期（CML-AP）或急变期（CML-BC）的二次慢性期诱导以及晚期MDS缓解诱导的可行性。

方法

24例可评估患者进入本研究，中位年龄34岁。其中18例转化型CML患者（7例CML-AP，11例CML-BC）和6例晚期MDS患者接受治疗。拓扑替康以1.5mg/m²/天的剂量，通过24小时持续输注，每4至8周进行5天，直至缓解。为增强杀瘤效果，加入米托蒽醌（12mg/m²/天，第1 - 3天）。

结果

8例患者（33%）达到完全缓解（CR）。7例CML-AP患者中有4例（57%）、4例CML-淋巴母细胞急变期（-LBC）患者中有2例（50%）以及6例晚期MDS患者中有2例（33%）获得持续超过45天（45至400天）的CR。CML-髓母细胞急变期（-MBC）患者无CR。所有患者对1.5mg/m²/天（7.5mg/m²/疗程）的拓扑替康剂量耐受性良好。69%的患者发生黏膜炎（5%为重度），67%的患者发生腹泻（8%为重度）。此外，接受此剂量（7.5mg/m²/疗程）治疗的患者未出现新的或意外的毒性反应。在中性粒细胞计数恢复的患者中，绝对中性粒细胞计数（ANC）在13至58天（中位21天）内持续低于500/μL，ANC恢复时间与预处理时骨髓纤维化的严重程度相关（主要为CML患者）。同样，在血小板恢复且无需支持的患者中，血小板在0至37天（中位19天）内持续低于20,000/μL。