Bosch Francesc, Ferrer Anna, López-Guillermo Armando, Giné Eva, Bellosillo Beatriz, Villamor Neus, Colomer Dolors, Cobo Francesc, Perales María, Esteve Jordi, Altés Albert, Besalduch Joan, Ribera Josep M, Montserrat Emili
Department of Haematology, Institut d'Investigacions Biomèdiques 'August Pi i Sunyer' (IDIBAPS), Hospital Clinic, Department of Haematology, Hospital de Sant Pau, Barcelona, Spain.
Br J Haematol. 2002 Dec;119(4):976-84. doi: 10.1046/j.1365-2141.2002.03959.x.
We evaluated the efficacy and toxicity of fludarabine combined with cyclophosphamide and mitoxantrone (FCM) in patients with relapsed or resistant chronic lymphocytic leukaemia (CLL). In total, 37 patients with recurrent or resistant CLL received FCM: fludarabine 25 mg/m2 intravenously (IV), d 1-3; cyclophosphamide 200 mg/m2 IV, d 1-3; and mitoxantrone 6 mg/m2 IV, d 1, at 4-week intervals for up to six courses. Moreover, 23 patients received FCM with cyclophosphamide 600 mg/m2 i.v. and mitoxantrone 8 mg/m2 i.v. on d 1. In addition to clinical methods, response was assessed using cytofluorometric and molecular techniques. 'In vitro' sensitivity to the FCM regimen was also analysed in 20 samples. The median number of courses given was 3 (range: 1-6). Overall, 30 patients (50%) achieved complete response (CR), including 10 cases of negative minimal residual disease (MRD(-)) (17%), and 17 (28%) partial response (PR). The median duration of response was 19 months. 'In vitro' sensitivity also correlated with CR achievement (P = 0.04). Main toxicity consisted of neutropenia, infections (8% of courses), and nausea and vomiting. The treatment-related mortality was 5%. FCM did not hamper stem cell harvesting in patients who were candidates for autologous stem cell transplantation. FCM induced a high CR rate, including an important number of MRD(-), in patients with previously treated CLL.
我们评估了氟达拉滨联合环磷酰胺和米托蒽醌（FCM）治疗复发或难治性慢性淋巴细胞白血病（CLL）患者的疗效和毒性。共有37例复发或难治性CLL患者接受FCM治疗：氟达拉滨25mg/m²静脉注射（IV），第1 - 3天；环磷酰胺200mg/m²静脉注射，第1 - 3天；米托蒽醌6mg/m²静脉注射，第1天，每4周进行一次，最多六个疗程。此外，23例患者在第1天接受FCM联合环磷酰胺600mg/m²静脉注射和米托蒽醌8mg/m²静脉注射。除临床方法外，还使用细胞荧光分析和分子技术评估反应。对20个样本进行了FCM方案的“体外”敏感性分析。给予的疗程中位数为3（范围：1 - 6）。总体而言，30例患者（50%）达到完全缓解（CR），包括10例微小残留病阴性（MRD(-)）（17%），17例（28%）部分缓解（PR）。反应的中位持续时间为19个月。“体外”敏感性也与CR的实现相关（P = 0.04）。主要毒性包括中性粒细胞减少、感染（占疗程的8%）以及恶心和呕吐。治疗相关死亡率为5%。FCM并未妨碍适合自体干细胞移植的患者进行干细胞采集。FCM在先前接受治疗的CLL患者中诱导出高CR率，包括大量MRD(-)的病例。
