Knauf W U, Koenigsmann M P, Notter M, Hoppe B, Reufi B, Oberberg D, Thiel E, Berdel W E
Department of Hematology & Oncology, Klinikum Benjamin Franklin, Free University of Berlin, Germany.
Leuk Lymphoma. 1996 Oct;23(3-4):305-11. doi: 10.3109/10428199609054833.
High-dose chemotherapy followed by autologous peripheral blood progenitor cell transplantation (PBPCT) is increasingly applied in patients with relapsed, poor risk malignant lymphomas. Different strategies for progenitor cell mobilization using cytoreductive chemotherapy, hematopoietic growth factors, or both have been described. We studied the safety and efficacy of a modified DexaBEAM regimen (dexamethasone, BCNU [carmustine], etoposide, ara-C, melphalan) followed by granulocyte-colony stimulating factor (G-CSF) that was administered in order to minimize any residual disease and to obtain a sufficient amount of progenitor cells in the autografts. Until now, 16 patients at poor risk (8 with Hodgkin's disease, 8 with non-Hodgkin's lymphoma) entered the study. All the 12 patients with measurable disease at study entry responded to DexaBEAM. Median time of subsequent leukopenia (leukocytes < 1.000/microL) was 6 days (range 5-8 days). Peak numbers of CD34+ hematopoietic progenitor cells appeared in the peripheral blood after a median of 20 days (range 18-22 days) after onset of therapy. At that time, peripheral mononuclear cells were collected for autografting. Thereafter, the leukapheresis products were frozen until the day of transplantation, either unpurged in the case of Hodgkin's disease or purged with the ether lipid edelfosine in cases of non-Hodgkin's lymphoma. After high-dose chemotherapy with the CBV regimen (cyclophosphamide, BCNU, etoposide) the patients received their autografts, followed again by G-CSF treatment. A stable hematopoietic recovery was reached with granulocytes > 2.000/muL within 11 days (range 8-17 days), and platelets > 50.000/microL within 15 days (range 10-31 days), respectively, without significant differences between the purged and unpurged transplants. After a median follow-up of 28 months (range 1-40 months) 7 patients are alive without signs of recurrent disease, while 1 patient has died due to acute treatment related toxicity. Three patients had refractory disease, and 5 have relapsed of whom 4 have died. In summary, the DexaBEAM/G-CSF/CBV strategy appears to be safe and effective for salvage treatment in patients with poor risk malignant lymphomas.
大剂量化疗后行自体外周血祖细胞移植(PBPCT)越来越多地应用于复发的高危恶性淋巴瘤患者。已经描述了使用细胞减灭性化疗、造血生长因子或两者结合进行祖细胞动员的不同策略。我们研究了改良的DexaBEAM方案(地塞米松、卡莫司汀、依托泊苷、阿糖胞苷、美法仑)联合粒细胞集落刺激因子(G-CSF)的安全性和有效性,该方案旨在尽量减少任何残留疾病并在自体移植中获得足够数量的祖细胞。到目前为止,16例高危患者(8例霍奇金病,8例非霍奇金淋巴瘤)进入了该研究。所有在研究开始时患有可测量疾病的12例患者对DexaBEAM均有反应。随后白细胞减少(白细胞<1000/μL)的中位时间为6天(范围5-8天)。治疗开始后中位20天(范围18-22天)外周血中CD34+造血祖细胞数量达到峰值。此时,采集外周单个核细胞用于自体移植。此后,白细胞分离产品被冷冻直至移植日,霍奇金病患者的产品未进行净化处理,非霍奇金淋巴瘤患者的产品用醚脂依地福新进行净化处理。在采用CBV方案(环磷酰胺、卡莫司汀、依托泊苷)进行大剂量化疗后,患者接受自体移植,随后再次接受G-CSF治疗。分别在11天(范围8-17天)内粒细胞>2000/μL,15天(范围10-31天)内血小板>50000/μL时达到稳定的造血恢复,净化处理和未净化处理的移植之间无显著差异。中位随访28个月(范围1-40个月)后,7例患者存活且无复发迹象,而1例患者因急性治疗相关毒性死亡。3例患者患有难治性疾病,5例复发,其中4例死亡。总之,DexaBEAM/G-CSF/CBV策略对于高危恶性淋巴瘤患者的挽救治疗似乎是安全有效的。