甲氨蝶呤、长春新碱、聚乙二醇缀合门冬酰胺酶和泼尼松联合治疗难治性或复发性急性淋巴细胞白血病患者。

Combination therapy with methotrexate, vincristine, polyethylene-glycol conjugated-asparaginase, and prednisone in the treatment of patients with refractory or recurrent acute lymphoblastic leukemia.

作者信息

Aguayo A, Cortes J, Thomas D, Pierce S, Keating M, Kantarjian H

机构信息

The Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Cancer. 1999 Oct 1;86(7):1203-9. doi: 10.1002/(sici)1097-0142(19991001)86:7<1203::aid-cncr15>3.0.co;2-3.

DOI:10.1002/(sici)1097-0142(19991001)86:7<1203::aid-cncr15>3.0.co;2-3

PMID:10506705

Abstract

BACKGROUND

L-asparaginase in combination with methotrexate has synergistic antileukemic activity in a schedule-dependent fashion. A new preparation of L-asparaginase, polyethylene-glycol conjugated (PEG)-asparaginase, is a pharmacologically different formulation of L-asparaginase with distinct properties including a longer half-life and less immunogenic properties.

METHODS

Patients with refractory or recurrent acute lymphoblastic leukemia (ALL) were treated with a combination of methotrexate (MTX), vincristine, PEG-asparaginase, and prednisone (MOAP). The treatment was comprised of MTX, 100 mg/m(2) intravenously (i.v.), over 15 minutes on Days 1 and 14; PEG-asparaginase, 2500 IU/m(2), with a maximum dose of 3750 IU i.v. approximately 4-6 hours after MTX on Days 1 and 14; vincristine, 1.4 mg/m(2) (maximum dose, 2 mg) i.v., over 15 minutes on Days 1, 7, and 14; and prednisone, 200 mg daily orally, on Days 1-5 and 14-19.

RESULTS

Thirty-two patients with a median age of 34 years (range, 20-74 years) were treated. Eight patients (25%) had ALL that was refractory to prior therapy and 24 patients (75%) had recurrent disease. Seven patients (22%) achieved a complete remission (CR). Five patients (16%) died early due to infections. Features associated with a poor response were high pretreatment lactate dehydrogenase levels and Philadelphia chromosome positive disease. The median duration of CR was 16 weeks and the overall median survival after MOAP therapy was 12 weeks. Anaphylactic reactions were not observed during MOAP combination therapy.

CONCLUSIONS

MOAP is an active regimen in patients with refractory or recurrent ALL. This regimen is well tolerated and is not associated with allergic reactions. However, further studies regarding the pharmacologic interaction of MTX with PEG-asparaginase are needed to optimize this regimen.

摘要

背景

L-天冬酰胺酶与甲氨蝶呤联合使用时，具有依时间顺序的协同抗白血病活性。一种新的L-天冬酰胺酶制剂，聚乙二醇缀合（PEG）-天冬酰胺酶，是一种药理学上不同的L-天冬酰胺酶制剂，具有不同的特性，包括更长的半衰期和更低的免疫原性。

方法

难治性或复发性急性淋巴细胞白血病（ALL）患者接受甲氨蝶呤（MTX）、长春新碱、PEG-天冬酰胺酶和泼尼松（MOAP）联合治疗。治疗方案包括：第1天和第14天，MTX 100 mg/m²静脉注射（i.v.），持续15分钟；第1天和第14天，在MTX静脉注射约4 - 6小时后，PEG-天冬酰胺酶2500 IU/m²，最大剂量3750 IU静脉注射；第1天、第7天和第14天，长春新碱1.4 mg/m²（最大剂量2 mg）静脉注射，持续15分钟；第1 - 5天和第14 - 19天，泼尼松200 mg每日口服。

结果

32例患者接受治疗，中位年龄34岁（范围20 - 74岁）。8例患者（25%）的ALL对先前治疗难治，24例患者（75%）为复发性疾病。7例患者（22%）实现完全缓解（CR）。5例患者（16%）因感染早期死亡。与反应不佳相关的特征是治疗前乳酸脱氢酶水平高和费城染色体阳性疾病。CR的中位持续时间为16周，MOAP治疗后的总体中位生存期为12周。MOAP联合治疗期间未观察到过敏反应。