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
Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Rome, Italy.
Haematologica. 1997 Nov-Dec;82(6):664-7.
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.
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).
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.
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.
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。
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。
70例患者中有55例（78%）达到完全缓解（CR），4例因感染死于再生障碍，11例无反应。血细胞计数从治疗开始起中位21天恢复。非血液学副作用极为有限，主要为感染。
鉴于所选患者病情极为不利，本研究证实了HD-伊达比星 + HD-ARA-C联合方案在难治性和早期复发ALL及NHL患者中的可行性和抗白血病活性。该方案的良好耐受性并不排除缓解后进行骨髓移植治疗。
