Clark Andrew D, Douglas Kenneth W, Mitchell Lyndsay D, McQuaker I Grant, Parker Anne N, Tansey Patrick J, Franklin Ian M, Cook Gordon
Academic Transfusion Medicine Unit, Department of Medicine, University of Glasgow, Glasgow, Scotland, UK.
Br J Haematol. 2002 Jun;117(3):605-12. doi: 10.1046/j.1365-2141.2002.03519.x.
A phase I-II study of high-dose (HD) alkylating agents in newly diagnosed patients with multiple myeloma after maximum response to Z-Dex (idarubicin, dexamethasone) therapy and DHAP (cisplatin, HD cytosine arabinoside, dexamethasone), stem cell mobilization is reported. Twenty-six patients, median age 56 years (range 42-66), completed Z-Dex chemotherapy and peripheral blood stem cells (PBSC) were mobilized with DHAP. Patients then preceded to cyclophosphamide (HD Cy: 6 g/m(2)) with granulocyte colony-stimulating factor followed by busulphan-melphalan-conditioned PBSC autograft. Interferon alpha was introduced at 3 months post transplant as maintenance therapy. Six patients failed to complete the full protocol. Median time from diagnosis to transplantation was 8 months (range 6-12). Mean CD34+ cell dose collected was 15.8 x 10(6)/kg (CI 11.8, 19.8). Median time from DHAP to HD-Cy was 6 weeks (range 4-12) and from HD-Cy to transplant was 8 weeks (range 6-12). The median follow-up was 36 months (range 6-63). On an intent-to-treat basis, the response rates were three complete response (CR, 12%), 21 partial response (PR, 80%) and two stable disease (SD, 8%) post Z-Dex, five CR (19%) and 21 PR (81%) post HD-Cy, and 14 CR (54%) and 12 PR (46%) post transplant. The treatment-related mortality (TRM) was 4% (1 patient). Median overall survival (OS) and progression-free survival (PFS) have not been reached; estimated values were 60 and 48 months respectively. The 3-year OS and PFS were 72% and 62%. Actuarial 5-year OS and event-free survival were 49% and 32%. DHAP produces effective PBSC mobilization and sequential HD therapy, including autologous PBSCT, in patients who received Z-Dex; this offers significant durable disease response rates with acceptable TRM.
报告了一项针对新诊断的多发性骨髓瘤患者的I-II期研究，这些患者在对Z-Dex（伊达比星、地塞米松）疗法和DHAP（顺铂、大剂量阿糖胞苷、地塞米松）达到最大反应后接受大剂量（HD）烷基化剂治疗及干细胞动员。26例患者，中位年龄56岁（范围42 - 66岁），完成了Z-Dex化疗，并用DHAP动员外周血干细胞（PBSC）。患者随后接受环磷酰胺（大剂量Cy：6 g/m(2)）并联合粒细胞集落刺激因子，接着进行白消安-美法仑预处理的PBSC自体移植。移植后3个月引入干扰素α作为维持治疗。6例患者未完成完整方案。从诊断到移植的中位时间为8个月（范围6 - 12个月）。收集的平均CD34 +细胞剂量为15.8×10(6)/kg（可信区间11.8，19.8）。从DHAP到HD-Cy的中位时间为6周（范围4 - 12周），从HD-Cy到移植的中位时间为8周（范围6 - 12周）。中位随访时间为36个月（范围6 - 63个月）。在意向性分析基础上，Z-Dex治疗后缓解率为3例完全缓解（CR，12%）、21例部分缓解（PR，80%）和2例疾病稳定（SD，8%），HD-Cy治疗后5例CR（19%）和21例PR（81%），移植后14例CR（54%）和12例PR（46%）。治疗相关死亡率（TRM）为4%（1例患者）。中位总生存期（OS）和无进展生存期（PFS）尚未达到；估计值分别为60个月和48个月。3年OS和PFS分别为72%和62%。精算5年OS和无事件生存期分别为49%和32%。DHAP能在接受Z-Dex治疗的患者中有效动员PBSC并进行序贯大剂量治疗，包括自体PBSCT；这能带来显著持久的疾病缓解率且TRM可接受。
