Zhang Xiao-hui, Huang Xiao-Jun, Liu Kai-yan, Xu Lan-ping, Liu Dai-hong, Chen Huan, Chen Yu-hong, Wang Jing-zhi, Han Wei, Lu Dao-pei
Institute of Hematology, Peking University People's Hospital, Beijing 100044, China.
Chin Med J (Engl). 2007 Mar 20;120(6):463-8.
Allogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma. The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment modality. The challenge for clinical investigators is to reduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem cell transplantion for multiple myeloma. In this study the toxicity and efficacy of modified myeloablative conditioning regimen followed by allogeneic stem cell transplantation was investigated in patients with multiple myeloma.
The conditioning regimen consisted of hydroxyurea, cytarabine, busulfan, cyclophosphamide, and semustine. Ten patients underwent allogeneic transplantation among them hydroxyurea (40 mg/kg) was administered twice on day-10 and cytarabine (2 g/m(2)) was given on day-9, busulfan was administered orally in four divided doses daily for 3 days (days-8 to -6). The dose of busulfan was 12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1 hour on days-5 and -4 (1.8 g/m(2)), and with semustine (Me-CCNU) 250 mg/m(2) on day -3.
Chimerism data were available on all patients and all patients achieved full donor chimerism without graft failure. Six patients had not acute graft-versus-host disease (GVHD, 36.4%; 95% CI: 13.9% - 38.6%). Two patients (18.2%) developed grade I acute GVHD (95% CI: 10.9% - 35.9%) and grade II acute GVHD occurred in one patient (9.1%; 95% CI: 8.4% - 32.3%). Severe grade IVa GVHD was seen in one patient, who died from acute GVHD. The incidence of chronic GVHD was 22.2% (95% CI: 11.7% - 36.7%), among them one died of severe grade IV GVHD and one developed multiorgan failure on day +170; the treatment-related mortality was 22.0% (95% CI: 10.3% - 34.1%). The overall 4-year survival rate was 67.8% (95% CI: 16.3% - 46.7%). The estimated 4-year progression-free survival rate was 58.5% (95% CI: 13.7% - 41.8%). The 4-year complete remission was 72.7% (95% CI: 27.8% - 49.6%). One patient relapsed after 4 months and achived the complete remission after receiving the donor lymphocyte infusion.
Modified conditioning regimen busulfan-cyclophosphamide with peripheral blood stem cells + bone marrow cells transplantation result in a low incidence of severe GVHD with a relatively low treatment-related mortality, high complete remission rates and a long-term survival.
异基因干细胞移植是多发性骨髓瘤患者一种潜在的治愈方法。与标准异基因干细胞移植相关的极高移植相关死亡率是目前限制这种潜在治愈性治疗方式更广泛应用的主要因素。临床研究人员面临的挑战是降低接受自体造血干细胞移植治疗多发性骨髓瘤患者的移植后并发症发生率。在本研究中，对接受改良清髓预处理方案后进行异基因干细胞移植的多发性骨髓瘤患者的毒性和疗效进行了研究。
预处理方案包括羟基脲、阿糖胞苷、白消安、环磷酰胺和司莫司汀。10例患者接受了异基因移植，其中羟基脲（40mg/kg）在第-10天给药两次，阿糖胞苷（2g/m²）在第-9天给药，白消安口服，分4次每日给药，共3天（第-8天至-6天）。方案中白消安的剂量为12mg/kg，随后在第-5天和-4天静脉输注环磷酰胺1小时（1.8g/m²），并在第-3天给予司莫司汀（甲环亚硝脲）250mg/m²。
所有患者均有嵌合数据，所有患者均实现完全供体嵌合且无移植失败。6例患者未发生急性移植物抗宿主病（GVHD，36.4%；95%置信区间：13.9% - 38.6%）。2例患者（18.2%）发生I级急性GVHD（95%置信区间：10.9% - 35.9%），1例患者发生II级急性GVHD（9.1%；95%置信区间：8.4% - 32.3%）。1例患者出现严重的IVa级GVHD，死于急性GVHD。慢性GVHD的发生率为22.2%（95%置信区间：11.7% - 36.7%），其中1例死于严重的IV级GVHD，1例在第+170天发生多器官功能衰竭；治疗相关死亡率为22.0%（95%置信区间：10.3% - 34.1%）。总体4年生存率为67.8%（95%置信区间：16.3% - 46.7%）。估计4年无进展生存率为58.5%（95%置信区间：13.7% - 41.8%）。4年完全缓解率为72.7%（95%置信区间：27.8% - 49.6%）。1例患者在4个月后复发，接受供体淋巴细胞输注后实现完全缓解。
改良预处理方案白消安-环磷酰胺联合外周血干细胞+骨髓细胞移植导致严重GVHD发生率低，治疗相关死亡率相对较低，完全缓解率高且长期生存。
