Crump M, Smith A M, Brandwein J, Couture F, Sherret H, Sutton D M, Scott J G, McCrae J, Murray C, Pantalony D
University of Toronto Autologous Bone Marrow Transplant Program, Canada.
J Clin Oncol. 1993 Apr;11(4):704-11. doi: 10.1200/JCO.1993.11.4.704.
To evaluate an intensive therapy regimen of high-dose etoposide and melphalan and autologous bone marrow transplantation (ABMT) in advanced Hodgkin's disease; and to determine possible prognostic factors that predict for long-term disease-free survival (DFS).
Seventy-three patients with advanced Hodgkin's disease who had failed to achieve remission with front-line chemotherapy (n = 16) or who had relapsed (n = 57) were treated with high-dose etoposide 60 mg/kg and melphalan 160 mg/m2 and ABMT. Previous therapy included mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), or hybrid MOPP/ABV. All patients received pretransplant cytoreduction with conventional-dose salvage chemotherapy and 40 also received pretransplant extended-field radiation to areas of bulky nodal disease (> 5 cm).
Response to high-dose etoposide and melphalan was determined at 3 months post-ABMT. The complete response (CR) rate was 75% (95% confidence interval [CI], 64% to 84%), including 35 of 50 patients with measurable disease before ABMT (70%; 95% CI, 60% to 86%). There were three early deaths (septicemia) and four late deaths (three interstitial pneumonitis, one intracerebral hemorrhage). Actuarial DFS is 38.6% at 4 years. Multivariate regression analysis showed that disease status at the time of ABMT (no evidence of disease [NED], nonbulky residual disease [NBRD], or bulky disease) was the most important factor determining DFS: 68% of those transplanted with NED versus 26% for patients with NBRD and 0% for bulky disease (P = .0002, log-rank test). Relapse in a previous radiation field was the only other significant prognostic factor.
Etoposide and melphalan is an effective and well-tolerated intensive therapy regimen in advanced Hodgkin's disease. Patients in complete remission after conventional-dose salvage therapy transplanted with this regimen enjoy superior long-term DFS.
评估高剂量依托泊苷和马法兰强化治疗方案及自体骨髓移植（ABMT）用于晚期霍奇金淋巴瘤的疗效；并确定可能预测长期无病生存（DFS）的预后因素。
73例晚期霍奇金淋巴瘤患者，其中16例一线化疗未缓解，57例复发，接受高剂量依托泊苷60mg/kg和马法兰160mg/m²及ABMT治疗。既往治疗包括氮芥、长春新碱、丙卡巴肼和泼尼松（MOPP）与多柔比星、博来霉素、长春碱和达卡巴嗪（ABVD）交替使用，或混合MOPP/ABV方案。所有患者在移植前接受常规剂量挽救化疗进行细胞减灭，40例患者还接受了移植前对大块淋巴结疾病区域（>5cm）的扩大野放疗。
在ABMT后3个月确定对高剂量依托泊苷和马法兰的反应。完全缓解（CR）率为75%（95%置信区间[CI]，64%至84%），包括ABMT前50例可测量疾病患者中的35例（70%；95%CI，60%至86%）。有3例早期死亡（败血症）和4例晚期死亡（3例间质性肺炎，1例脑出血）。4年时的精算DFS为38.6%。多变量回归分析显示，ABMT时的疾病状态（无疾病证据[NED]、非大块残留疾病[NBRD]或大块疾病）是决定DFS的最重要因素：NED患者移植后的DFS为68%，而NBRD患者为26%，大块疾病患者为0%（P = .0002，对数秩检验）。既往放疗野内复发是唯一的其他显著预后因素。
依托泊苷和马法兰是晚期霍奇金淋巴瘤一种有效且耐受性良好的强化治疗方案。采用该方案移植的患者在常规剂量挽救治疗后完全缓解，其长期DFS更佳。
