Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial
Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial
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DOI：
10.1182/blood-2015-07-657981
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发表时间：
2016-01-07
期刊：
影响因子：
20.3
通讯作者：
Teachey, David T.
中科院分区：
文献类型：
--
作者：
Bride, Karen L.;Vincent, Tiffaney;Teachey, David T.
自身免疫性多系细胞减少症的患者通常对需要慢性免疫抑制的标准治疗方案无效，这些药物疗效有限，毒性高。我们介绍了一项多中心前瞻性临床试验中使用西罗莫司作为单一疗法治疗的30名患者的数据。所有患有自身免疫淋巴增殖性综合征(ALPS)的儿童(N=12)在服用西罗莫司后1至3个月内均获得持久的完全缓解(CR)，包括自身免疫性疾病、淋巴结病和脾肿大的迅速改善。在大多数患者中不再检测到双阴性T细胞，但其他淋巴细胞群体幸免于难，这表明西罗莫司具有靶向作用。我们还治疗了12例继发于常见变异性免疫缺陷(CVID)、埃文斯综合征(ES)或系统性红斑狼疮(SLE)的多系细胞减少症患者，大多数患者获得了完全缓解(N=8)，尽管达到完全缓解的时间通常比阿尔卑斯山慢。6名患有单系自身免疫性细胞减少症的儿童接受了治疗，只有2人有反应。西罗莫司耐受性良好，副作用极少。所有有反应的患者都继续接受治疗超过1年(中位数为2年；范围为1至4.5年)。综上所述，西罗莫司在大多数患有难治性多系自身免疫性红细胞减少症的儿童中导致了CR和持久的反应。阿尔卑斯山患者的反应是深刻的，这表明西罗莫司应该被视为需要慢性治疗的患者的一线非类固醇治疗。其他多系自身免疫性细胞减少队列的结果令人鼓舞，西罗莫司应考虑用于SLE、ES和CVID儿童。
Patients with autoimmune multilineage cytopenias are often refractory to standard therapies requiring chronic immunosuppression with medications with limited efficacy and high toxicity. We present data on 30 patients treated on a multicenter prospective clinical trial using sirolimus as monotherapy. All children (N = 12) with autoimmune lymphoproliferative syndrome (ALPS) achieved a durable complete response (CR), including rapid improvement in autoimmune disease, lymphadenopathy, and splenomegaly within 1 to 3 months of starting sirolimus. Double-negative T cells were no longer detectable in most, yet other lymphocyte populations were spared, suggesting a targeted effect of sirolimus. We also treated 12 patients with multilineage cytopenias secondary to common variable immunodeficiency (CVID), Evans syndrome (ES), or systemic lupus erythematosus (SLE), and most achieved a CR (N = 8), although the time to CR was often slower than was seen in ALPS. Six children with single-lineage autoimmune cytopenias were treated and only 2 responded. Sirolimus was well tolerated with very few side effects. All of the responding patients have remained on therapy for over 1 year (median, 2 years; range, 1 to 4.5 years). In summary, sirolimus led to CR and durable responses in a majority of children with refractory multilineage autoimmune cytopenias. The responses seen in ALPS patients were profound, suggesting that sirolimus should be considered as a first-line, steroid-sparing treatment of patients needing chronic therapy. The results in other multilineage autoimmune cytopenia cohorts were encouraging, and sirolimus should be considered in children with SLE, ES, and CVID.