Josting A, Sieniawski M, Glossmann J-P, Staak O, Nogova L, Peters N, Mapara M, Dörken B, Ko Y, Metzner B, Kisro J, Diehl V, Engert A
University Hospital Cologne, First Department of Internal Medicine, Germany.
Ann Oncol. 2005 Aug;16(8):1359-65. doi: 10.1093/annonc/mdi248. Epub 2005 Jun 6.
Combination chemotherapy can cure patients with non-Hodgkin's lymphoma (NHL), but those who suffer treatment failure or relapse still have a poor prognosis. High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) can improve the outcome of these patients. We evaluated an intensified high-dose sequential chemotherapy program with a final myeloablative course.
Inclusion criteria were age 18-65 years, histologically proven primary progressive or relapsed aggressive NHL and eligibility for HDCT. The therapy consists of two cycles DHAP: dexamethasone 40 mg (day 1-4), high-dose cytarabine 2 g/m2 12q (day 2), cisplatin 100 mg/m2 (day 51); patients with partial (PR) or complete remission (CR) received cyclophosphamide 4 g/m2 (day 37), followed by peripheral blood stem cell (PBSC) harvest; methotrexate 8 g/m2 (day 1) plus vincristine 1.4 mg/m2 (day 51); and etoposide 500 mg/m2 (day 58-62). The final myeloblative course was BEAM: cytarabine 200 mg/m2 12q (day 81-84), etoposide 150 mg/m2 12q (day 81-84), melphalan 140 mg/m2 (day 80), carmustin 300 mg/m2 (day 80) followed by PBSCT.
Fifty-seven patients (median age 43 years, range 24-65) were enrolled: 23 (40%) patients were refractory to primary therapy and 34 (60%) patients had relapsed NHL. The response rate (RR) after 2 cycles of DHAP was 72% (9% CR, 63% PR) and at the final evaluation (100 days post transplantation) 43% (32% CR, 11% PR). Toxicity was tolerable. Median follow-up was 25 months (range 1-76 months). Freedom from second failure (FF2F) and overall survival (OS) at 2 years were 25% and 47% for all patients, respectively. FF2F at 2 years for patients with relapse and for patients refractory to primary therapy were 35% and 9% (P=0.0006), respectively. OS at 2 years for patients with relapse and for patients refractory to primary therapy were 58% and 24% (P=0.0044), respectively.
We conclude that this regimen is feasible, tolerable and effective in patients with relapsed NHL. In contrast, the results in patients with progressive disease are unsatisfactory. This program is currently being modified by addition of rituximab for patients with relapsed aggressive NHL.
联合化疗可治愈非霍奇金淋巴瘤（NHL）患者，但治疗失败或复发的患者预后仍较差。大剂量化疗（HDCT）联合自体干细胞移植（ASCT）可改善这些患者的预后。我们评估了一种强化的大剂量序贯化疗方案，其最后一个疗程为清髓性化疗。
纳入标准为年龄18 - 65岁、组织学确诊为原发性进展期或复发性侵袭性NHL且适合进行HDCT。治疗方案包括两个周期的DHAP：地塞米松40mg（第1 - 4天）、大剂量阿糖胞苷2g/m² 每12小时一次（第2天）、顺铂100mg/m²（第5 - 1天）；部分缓解（PR）或完全缓解（CR）的患者接受环磷酰胺4g/m²（第3 - 7天），随后进行外周血干细胞（PBSC）采集；甲氨蝶呤8g/m²（第1天）加长春新碱1.4mg/m²（第5 - 1天）；依托泊苷500mg/m²（第58 - 62天）。最后一个清髓性疗程为BEAM：阿糖胞苷200mg/m² 每12小时一次（第81 - 84天）、依托泊苷150mg/m² 每12小时一次（第81 - 84天）、美法仑140mg/m²（第80天）、卡莫司汀300mg/m²（第80天），随后进行PBSCT。
共纳入57例患者（中位年龄43岁，范围24 - 65岁）：23例（40%）患者对初始治疗耐药，34例（60%）患者为复发性NHL。两个周期的DHAP治疗后缓解率（RR）为72%（9% CR，63% PR），在最终评估（移植后100天）时为43%（32% CR，11% PR）。毒性可耐受。中位随访时间为25个月（范围1 - 76个月）。所有患者2年时无二次失败生存期（FF2F）和总生存期（OS）分别为25%和47%。复发患者和对初始治疗耐药患者2年时的FF2F分别为35%和9%（P = 0.0006）。复发患者和对初始治疗耐药患者2年时的OS分别为58%和24%（P = 0.0044）。
我们得出结论，该方案对复发性NHL患者可行、可耐受且有效。相比之下，进展期疾病患者的结果并不理想。目前正在对该方案进行修改，为复发性侵袭性NHL患者添加利妥昔单抗。
