Miyamoto Koji, Nishigami Kazuhiro, Nagaya Noritoshi, Akutsu Koichi, Chiku Masaaki, Kamei Masataka, Soma Toshihiro, Miyata Shigeki, Higashi Masahiro, Tanaka Ryoichi, Nakatani Takeshi, Nonogi Hiroshi, Takeshita Satoshi
Department of Medicine, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
Circulation. 2006 Dec 12;114(24):2679-84. doi: 10.1161/CIRCULATIONAHA.106.644203. Epub 2006 Dec 4.
The short-term clinical benefits of bone marrow mononuclear cell transplantation have been shown in patients with critical limb ischemia. The purpose of this study was to assess the long-term safety and efficacy of bone marrow mononuclear cell transplantation in patients with thromboangiitis obliterans.
Eleven limbs (3 with rest pain and 8 with an ischemic ulcer) of 8 patients were treated by bone marrow mononuclear cell transplantation. The patients were followed up for clinical events for a mean of 684+/-549 days (range 103 to 1466 days). At 4 weeks, improvement in pain was observed in all 11 limbs, with complete relief in 4 (36%). Pain scale (visual analog scale) score decreased from 5.1+/-0.7 to 1.5+/-1.3. An improvement in skin ulcers was observed in all 8 limbs with an ischemic ulcer, with complete healing in 7 (88%). During the follow-up, however, clinical events occurred in 4 of the 8 patients. The first patient suffered sudden death at 20 months after transplantation at 30 years of age. The second patient with an incomplete healing of a skin ulcer showed worsening of the lesion at 4 months. The third patient showed worsening of rest pain at 8 months. The last patient developed an arteriovenous shunt in the foot at 7 months, which spontaneously regressed by 1 year.
In the present unblinded and uncontrolled pilot study, long-term adverse events, including death and unfavorable angiogenesis, were observed in half of the patients receiving bone marrow mononuclear cell transplantation. Given the current incomplete knowledge of the safety and efficacy of this strategy, careful long-term monitoring is required for future patients receiving this treatment.
骨髓单个核细胞移植的短期临床益处已在严重肢体缺血患者中得到证实。本研究的目的是评估骨髓单个核细胞移植治疗血栓闭塞性脉管炎患者的长期安全性和疗效。
8例患者的11条肢体（3条有静息痛，8条有缺血性溃疡）接受了骨髓单个核细胞移植治疗。对患者进行临床事件随访，平均随访时间为684±549天（范围103至1466天）。4周时，所有11条肢体的疼痛均有改善，4条（36%）完全缓解。疼痛量表（视觉模拟量表）评分从5.1±0.7降至1.5±1.3。所有8条有缺血性溃疡的肢体的皮肤溃疡均有改善，7条（88%）完全愈合。然而，在随访期间，8例患者中有4例发生了临床事件。第一例患者在移植后20个月、30岁时突然死亡。第二例皮肤溃疡未完全愈合的患者在4个月时病变恶化。第三例患者在8个月时静息痛加重。最后一例患者在7个月时足部出现动静脉分流，1年后自行消退。
在本项非盲法、非对照的初步研究中，接受骨髓单个核细胞移植的患者中有一半观察到了包括死亡和不良血管生成在内的长期不良事件。鉴于目前对该策略安全性和疗效的认识尚不完整，未来接受该治疗的患者需要进行仔细的长期监测。
