Department of Internal Medicine, Division of Cardiovascular and Regenerative Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
Rheumatology (Oxford). 2014 May;53(5):854-9. doi: 10.1093/rheumatology/ket432. Epub 2014 Jan 3.
SSc causes intractable ischaemic ulcers. To avoid major amputation, we examined the safety and efficacy of therapeutic vascular angiogenesis for digital ulcers due to SSc.
A single-centre, open-label pilot study was conducted in patients with an ischaemic digital ulcer [n = 40, mean age 65 years (s.d. 8), Rutherford class III-5 or III-6) due to lcSSc (n = 11) or arteriosclerosis obliterans (ASO; n = 29). Bone marrow mononuclear cells (0.4-5.1 × 10(10) cells in total) were administered into the ischaemic limbs. We evaluated short-term safety and efficacy by means of a pain scale, (99m)Tc-tetrofosmin scintigraphy and transcutaneous oxygen tension (TcPO2) before and 4 weeks after treatment. Also, the 2-year outcome was compared.
There was a case of amputation in each group within 4 weeks after therapy. The pain scale significantly decreased in both groups [lcSSc 93 mm (s.d. 9) to 11 (s.d. 16), P < 0.01; ASO 77 mm (s.d. 22) to 16 (s.d. 13), P < 0.01] and TcPO2 significantly improved [lcSSc 9.0 mmHg (s.d. 9) to 35 (s.d. 14), P < 0.01; ASO 18 mmHg (s.d. 10) to 29 (s.d. 21), P < 0.05). At the 2-year follow-up, the limb amputation rate was 9.1% in lcSSc and 20.7% in ASO (P = 0.36), while the recurrence rate was 18.2% in lcSSc and 17.2% in ASO (P = 0.95). All-cause mortality was 27.3% in lcSSc and 17.2% in ASO (P = 0.65).
In patients with lcSSc, bone marrow mononuclear cell implantation provides clinical benefit and is safe, without major adverse reactions, and may become an effective strategy.
UMIN-CTR, http://www.umin.ac.jp/ctr/index-j.htm, no. UMIN000004112.
硬皮病可导致难治性缺血性溃疡。为避免进行大截肢，我们研究了治疗性血管生成治疗硬皮病相关的指端缺血性溃疡的安全性和有效性。
在因局限性硬皮病（lcSSc，n=11）或动脉硬化性闭塞症（ASO，n=29）而发生缺血性指端溃疡的患者中开展了一项单中心、开放性标签的初步研究（n=40，平均年龄 65 岁（标准差 8），Rutherford 分级 3-5 级或 3-6 级）。将骨髓单核细胞（0.4-5.1×10(10)细胞）注入缺血肢体。我们通过疼痛量表、（99m）Tc-四氟甲基磷酸钠闪烁扫描和经皮氧分压（TcPO2）在治疗前和治疗后 4 周评估短期安全性和疗效。还比较了 2 年的结果。
治疗后 4 周内每组各有 1 例截肢。两组的疼痛评分均显著下降[lcSSc 从 93mm（标准差 9）降至 11（标准差 16），P<0.01；ASO 从 77mm（标准差 22）降至 16（标准差 13），P<0.01]，TcPO2 也显著改善[lcSSc 从 9.0mmHg（标准差 9）升至 35（标准差 14），P<0.01；ASO 从 18mmHg（标准差 10）升至 29（标准差 21），P<0.05]。在 2 年随访时，lcSSc 的肢体截肢率为 9.1%，ASO 为 20.7%（P=0.36），lcSSc 的复发率为 18.2%，ASO 为 17.2%（P=0.95）。lcSSc 的全因死亡率为 27.3%，ASO 为 17.2%（P=0.65）。
在局限性硬皮病患者中，骨髓单核细胞植入提供了临床获益且安全，无重大不良反应，可能成为一种有效的治疗策略。
UMIN-CTR，http://www.umin.ac.jp/ctr/index-j.htm，编号 UMIN000004112。
