Moore John, Brooks Peter, Milliken Sam, Biggs Jim, Ma David, Handel Malcolm, Cannell Paul, Will Rob, Rule Simon, Joske David, Langlands Bob, Taylor Kerry, O'Callaghan Joe, Szer Jeff, Wicks Ian, McColl Geoff, Passeullo Frances, Snowden John
St. Vincents Hospital, Sydney, Australia.
Arthritis Rheum. 2002 Sep;46(9):2301-9. doi: 10.1002/art.10495.
Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high-dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA.
Thirty-three patients with severe RA who had been treated unsuccessfully with methotrexate and at least 1 other disease-modifying agent were enrolled in the trial. The patients received high-dose immunosuppressive treatment with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected or unmanipulated. Safety, efficacy (based on American College of Rheumatology [ACR] response criteria), and time to recurrence of disease were assessed on a monthly basis for up to 12 months.
All patients were living at the end of the study, with no major unexpected toxicities. Overall, on an intent-to-treat basis, ACR 20% response (ACR20) was achieved in 70% of the patients. An ACR70 response was attained in 27.7% of the 18 patients who had received CD34-selected cells and 53.3% of the 15 who had received unmanipulated cells (P = 0.20). The median time to disease recurrence was 147 days in the CD34-selected cell group and 201 days in the unmanipulated cell group (P = 0.28). There was no relationship between CD4 lymphopenia and response, but 72% of rheumatoid factor (RF)-positive patients had an increase in RF titer prior to recurrence of disease.
HSCT can be performed safely in patients with RA, and initial results indicate significant responses in patients with severe, treatment-resistant disease. Similar outcomes were observed in patients undergoing HSCT with unmanipulated cells and those receiving CD34-selected cells. Larger studies are needed to confirm these findings.
动物研究、病例报告及Ⅰ期研究的证据表明，造血干细胞移植（HSCT）可能对类风湿关节炎（RA）的治疗有效。然而，高剂量化疗后输注的干细胞产品中T细胞的清除是否通过减少输注的自身反应性T细胞数量而有助于延长疗效尚不清楚。开展这项多中心试点随机试验，以获取关于自体干细胞移植物的CD34选择（作为一种T细胞清除形式）在重症难治性RA患者的HSCT过程中是否有益的可行性数据。
33例接受甲氨蝶呤及至少1种其他改善病情药物治疗失败的重症RA患者纳入该试验。患者接受200mg/kg环磷酰胺的高剂量免疫抑制治疗，随后输注经CD34选择或未处理的自体干细胞。每月评估安全性、疗效（基于美国风湿病学会[ACR]反应标准）及疾病复发时间，最长评估12个月。
研究结束时所有患者均存活，无重大意外毒性反应。总体而言，在意向性分析的基础上，70%的患者达到ACR 20%反应（ACR20）。在接受CD34选择细胞的18例患者中，27.7%达到ACR70反应，在接受未处理细胞的15例患者中，53.3%达到ACR70反应（P = 0.20）。CD34选择细胞组疾病复发的中位时间为147天，未处理细胞组为201天（P = 0.28）。CD4淋巴细胞减少与反应之间无关联，但72%的类风湿因子（RF）阳性患者在疾病复发前RF滴度升高。
RA患者可安全进行HSCT，初步结果表明重症难治性疾病患者有显著反应。接受未处理细胞和接受CD34选择细胞的HSCT患者观察到相似的结果。需要更大规模的研究来证实这些发现。
