高剂量伊达比星联合大剂量阿糖胞苷（MSKCC ALL-3方案）治疗成人及儿童急性淋巴细胞白血病。罗马“La Sapienza”大学的经验。

A single high dose of idarubicin combined with high-dose ARA-C (MSKCC ALL-3 protocol) in adult and pediatric patients with acute lymphoblastic leukemia. Experience at the University "La Sapienza" of Rome.

作者信息

Testi A M, Moleti M L, Giona F, Annino L, Chiaretti S, Del Giudice I, Todisco E, D'Elia G, Ferrari A, Arcese W, Mandelli F

机构信息

Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Rome, Italy.

出版信息

Haematologica. 1997 Nov-Dec;82(6):664-7.

PMID:9499665

Abstract

BACKGROUND AND OBJECTIVE

The anthracycline analogue idarubicin, either alone or in combination with other antineoplastic drugs, has shown antileukemic activity in relapsed and refractory acute lymphoblastic leukemia (ALL). In an attempt to minimize the non-hematologic toxicity and obtain a potent antileukemic effect, MSKCC activated a pilot study in previously treated adult ALL, using HD-ARA-C combined with idarubicin administered as a single high-dose infusion. We herein report our experience with a series of pediatric and adult high risk ALL and NHL patients treated with the protocol above, which confirms its feasibility, response rate and individual compliance.

METHODS

In a clinical phase II study, the combination of a single high dose (HD) of idarubicin and HD cytosine-arabinoside (ARA-C), as designed at the Memorial Sloan Kettering Cancer Center, was applied to 70 adults and children with refractory or early relapse acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic non-Hodgkin's lymphoma (NHL). Therapy consisted of HD-ARA-C 3 g/m2/d on days 1-5, idarubicin 40 mg/m2 on day 3, prophylactic intrathecal methotrexate on days 1 and 4, and G-CSF 5 mg/kg/d s.c. from day 7 to hematopoietic reconstitution (PMN > 0.5 x 10(9)/L).

RESULTS

Fifty-five of the 70 patients (78%) achieved complete remission (CR), four died in aplasia due to infection and 11 were non-responders. Recovery of blood counts occurred at a median of 21 days from the start of treatment. Non-hematologic side effects were extremely limited and consisted predominantly of infections.

INTERPRETATION AND CONCLUSIONS

In view of the highly unfavorable series of patients selected, this study confirms the feasibility and antileukemic activity of the HD-idarubicin + HD-ARA-C combination in patients with refractory and early relapse ALL and NHL. The excellent tolerance to this regimen does not preclude bone marrow transplantation as post-remission treatment.

摘要

背景与目的

阿霉素类似物伊达比星，无论是单独使用还是与其他抗肿瘤药物联合使用，在复发和难治性急性淋巴细胞白血病（ALL）中均显示出抗白血病活性。为了尽量减少非血液学毒性并获得强效的抗白血病效果，纪念斯隆凯特琳癌症中心（MSKCC）开展了一项针对先前接受过治疗的成年ALL患者的试点研究，采用大剂量阿糖胞苷（HD-ARA-C）联合伊达比星单次大剂量输注的方案。我们在此报告我们对一系列采用上述方案治疗的儿科和成年高危ALL及NHL患者的经验，证实了该方案的可行性、缓解率及个体依从性。

方法

在一项临床II期研究中，按照纪念斯隆凯特琳癌症中心的设计，将单次大剂量（HD）伊达比星与大剂量阿糖胞苷（ARA-C）联合应用于70例难治性或早期复发的急性淋巴细胞白血病（ALL）及T细胞淋巴母细胞性非霍奇金淋巴瘤（NHL）的成人和儿童患者。治疗方案包括第1 - 5天给予HD-ARA-C 3 g/m²/d，第3天给予伊达比星40 mg/m²，第1天和第4天给予预防性鞘内注射甲氨蝶呤，从第7天至造血重建（中性粒细胞>0.5×10⁹/L）给予G-CSF 5 mg/kg/d皮下注射。