氟达拉滨/大剂量阿糖胞苷双重强化可增强自体干细胞移植对急性髓系白血病患者的疗效。

Double reinforcement with fludarabine/high-dose cytarabine enhances the impact of autologous stem cell transplantation in acute myeloid leukemia patients.

作者信息

Visani G, Lemoli R M, Isidori A, Piccaluga P P, Martinelli G, Malagola M, Gugliotta L, Bonini A, Bonifazi F, Motta M R, Rizzi S, Castellani S, Tura S

机构信息

Institute of Hematology and Medical Oncology 'L and A Seragnoli', Bologna University, Bologna, Italy.

出版信息

Bone Marrow Transplant. 2001 Apr;27(8):829-35. doi: 10.1038/sj.bmt.1703003.

DOI:10.1038/sj.bmt.1703003

PMID:11477440

Abstract

Reinforced chemotherapy based on a double high-dose consolidation regimen could be a different way to enhance in vivo purging prior to autologous stem cell transplantation (auto-SCT) in acute myeloid leukemia (AML). We investigated the impact on outcome of auto-SCT after two different strategies of early intensification performed after an identical induction regimen in adult patients with AML. Between January 1993 and December 1998, 140 consecutive AML patients were enrolled in a program consisting of an identical anthracycline-based induction (ICE) and two different consolidation regimens: one cycle, cytarabine-based (single-NOVIA: 91 patients); two cycles, fludarabine-based (double-FLAN: 49 patients). Seventy out of 91 patients received single-NOVIA consolidation: 60 underwent a transplantation procedure (allogeneic bone marrow transplantation (allo-BMT):16 patients; auto-SCT: 44). Thirty-five out of 49 patients received double-FLAN consolidation: 31 underwent a transplantation procedure (allo-BMT: 10; auto-SCT: 21). The double consolidation regimen was well-tolerated with only minor side-effects. Median follow-up observation time for surviving patients was 38 months (range, 17-71) for the double-FLAN consolidation group and 70 months (range: 48-93) for the single-NOVIA consolidation group. Among the patients who received auto-SCT, the double consolidation strategy produced a superior disease-free survival curve at 36 months (78.6% (95%CI: 59.4-97.8) vs 47.7% (95%CI: 33-62.4)) compared with the single-NOVIA group. This difference was confirmed when the patients were analyzed for intention to treat (P = 0.04). In addition, the double-FLAN consolidation group showed a superior overall survival and lower relapse rate (P = 0.02). We conclude that the double-FLAN reinforcement strategy is safe and enhances the clinical impact of auto-SCT for AML patients in first complete remission. It may provide specific clinical benefit for patients undergoing auto-SCT.

摘要

基于双高剂量巩固方案的强化化疗可能是一种在急性髓系白血病（AML）自体干细胞移植（auto-SCT）前增强体内净化的不同方法。我们研究了在成年AML患者中，采用相同诱导方案后进行两种不同早期强化策略对auto-SCT结局的影响。1993年1月至1998年12月，140例连续的AML患者参加了一个项目，该项目包括相同的基于蒽环类药物的诱导方案（ICE）和两种不同的巩固方案：一个周期，基于阿糖胞苷的方案（单周期NOVIA：91例患者）；两个周期，基于氟达拉滨的方案（双周期FLAN：49例患者）。91例患者中的70例接受了单周期NOVIA巩固治疗：60例接受了移植手术（异基因骨髓移植（allo-BMT）：16例患者；auto-SCT：44例）。49例患者中的35例接受了双周期FLAN巩固治疗：31例接受了移植手术（allo-BMT：10例；auto-SCT：21例）。双巩固方案耐受性良好，仅有轻微副作用。双周期FLAN巩固治疗组存活患者的中位随访观察时间为38个月（范围17 - 71个月），单周期NOVIA巩固治疗组为70个月（范围48 - 93个月）。在接受auto-SCT的患者中，与单周期NOVIA组相比，双巩固策略在36个月时产生了更好的无病生存曲线（78.6%（95%CI：59.4 - 97.8）对47.7%（95%CI：33 - 62.4））。在对患者进行意向性治疗分析时，这一差异得到了证实（P = 0.04）。此外，双周期FLAN巩固治疗组显示出更好的总生存率和更低的复发率（P = 0.02）。我们得出结论，双周期FLAN强化策略是安全的，并且增强了auto-SCT对首次完全缓解的AML患者的临床影响。它可能为接受auto-SCT的患者提供特定的临床益处。