Frickhofen N, Kaltwasser J P, Schrezenmeier H, Raghavachar A, Vogt H G, Herrmann F, Freund M, Meusers P, Salama A, Heimpel H
Department of Medicine III, University of Ulm, Germany.
N Engl J Med. 1991 May 9;324(19):1297-304. doi: 10.1056/NEJM199105093241901.
Immunosuppression is the most effective treatment for patients with aplastic anemia, except for bone marrow transplantation. The best results are achieved with antilymphocyte globulin or cyclosporine. Patients have been treated successfully with a combination of both agents, but there has been no controlled evaluation of its efficacy. We conducted a randomized, multicenter trial in 84 patients not eligible for bone marrow transplantation, comparing treatment with antilymphocyte globulin and methylprednisolone (41 patients--the control group) with antilymphocyte globulin, methylprednisolone, and cyclosporine (43 patients--the cyclosporine group).
At three months significantly more patients in the cyclosporine group had a complete or partial remission in response to treatment than did patients in the control group (65 percent vs. 39 percent, P less than 0.03); this difference was confirmed at six months (70 percent vs. 46 percent, P less than 0.05). The superior results of the regimen including cyclosporine were most evident in the patients with severe or very severe aplastic anemia, whose response rate at six months was 65 percent, as compared with 31 percent of such patients in the control group (P less than 0.02). Granulocyte and hemoglobin levels became normal in most patients who responded, but platelet counts continued to be subnormal in 61 percent of the patients. Ten of 52 patients with responses (3 in the cyclosporine group and 7 in the control group) relapsed 4 to 37 months after treatment. The actuarial survival of all patients at 41 months is 64 percent in the cyclosporine group and 58 percent in the control group (P = 0.16); among the patients with severe or very severe disease, survival is 80 percent and 44 percent, respectively (P = 0.077). Cyclosporine had substantial but reversible side effects.
Immunosuppressive treatment of aplastic anemia with antilymphocyte globulin, methylprednisolone, and cyclosporine appears to be more effective than a regimen of antilymphocyte globulin and methylprednisolone without cyclosporine and may thus represent a treatment of choice for patients who are not eligible for bone marrow transplantation.
除骨髓移植外，免疫抑制是再生障碍性贫血患者最有效的治疗方法。抗淋巴细胞球蛋白或环孢素治疗效果最佳。两种药物联合使用已成功治疗了患者，但尚未对其疗效进行对照评估。我们对84例不符合骨髓移植条件的患者进行了一项随机、多中心试验，比较抗淋巴细胞球蛋白和甲泼尼龙治疗（41例患者——对照组）与抗淋巴细胞球蛋白、甲泼尼龙和环孢素治疗（43例患者——环孢素组）的效果。
三个月时，环孢素组中对治疗有完全或部分缓解的患者明显多于对照组（65%对39%，P<0.03）；六个月时这一差异得到证实（70%对46%，P<0.05）。包括环孢素的治疗方案的优越效果在重度或极重度再生障碍性贫血患者中最为明显，这些患者六个月时的缓解率为65%，而对照组此类患者的缓解率为31%（P<0.02）。大多数有反应的患者粒细胞和血红蛋白水平恢复正常，但61%的患者血小板计数仍低于正常。52例有反应的患者中有10例（环孢素组3例，对照组7例）在治疗后4至37个月复发。环孢素组所有患者41个月时的精算生存率为64%，对照组为58%（P = 0.16）；在重度或极重度疾病患者中，生存率分别为80%和44%（P = 0.077）。环孢素有显著但可逆的副作用。
用抗淋巴细胞球蛋白、甲泼尼龙和环孢素进行免疫抑制治疗再生障碍性贫血似乎比不使用环孢素的抗淋巴细胞球蛋白和甲泼尼龙治疗方案更有效，因此可能是不符合骨髓移植条件患者的首选治疗方法。
