Elmaagacli A H, Ditschkowski M, Steckel N K, Gromke T, Ottinger H, Hillen U, Baba H A, Trenschel R, Beelen D W, Koldehoff M
Department of Hematology and Oncology, Helios Klinik Schwerin, Schwerin, Germany.
Department of Bone Marrow Transplantation (AHE), West German Cancer Center, all University Hospital Essen, Essen, Germany.
Bone Marrow Transplant. 2014 Jun;49(6):800-5. doi: 10.1038/bmt.2014.59. Epub 2014 Mar 31.
GVHD is a major complication following allogeneic hematopoietic SCT, and is associated with substantial morbidity and mortality. Based on the results of our previous clinical study with females treated with human chorionic gonadotropin (hCG) as preconditioning therapy for in vitro fertilization, we hypothesized that low-dose hCG stimulates indoleamine-2,3-dioxygenase (IDO), IL 10 and regulatory T cells (Treg), thereby suppressing clinical manifestations of chronic GVHD. Active chronic GVHD localized at skin, subcutaneous tissue, joints or gastrointestinal tract that was refractory or intolerant to glucocorticoid therapy improved substantially in 12 of 20 patients treated with hCG for 8 weeks (off-label), enabling a glucocorticoid dose reduction of 28% (average). Twelve of 19 patients with chronic GVHD of the skin responded to hCG therapy with a reduction of 25% (average) in their total skin score. HCG treatment increased IDO expression at median by sevenfold in peripheral mononuclear cells and IL10 levels in serum up to twofold at median from the pretreatment baseline. Further, an expansion of the Treg cell population was measured in one patient, which is also associated with the induction of tolerance. This novel application of low-dose hCG was well tolerated and is of clinical interest for GVHD treatment.
移植物抗宿主病（GVHD）是异基因造血干细胞移植后的主要并发症，与显著的发病率和死亡率相关。基于我们之前对接受人绒毛膜促性腺激素（hCG）作为体外受精预处理治疗的女性进行的临床研究结果，我们推测低剂量hCG刺激吲哚胺-2,3-双加氧酶（IDO）、白细胞介素10（IL 10）和调节性T细胞（Treg），从而抑制慢性移植物抗宿主病（GVHD）的临床表现。20例接受hCG治疗8周（超适应症用药）的患者中，有12例对糖皮质激素治疗难治或不耐受的、局限于皮肤、皮下组织、关节或胃肠道的活动性慢性移植物抗宿主病有显著改善，糖皮质激素剂量平均降低28%。19例皮肤慢性移植物抗宿主病患者中有12例对hCG治疗有反应，其总皮肤评分平均降低25%。hCG治疗使外周单核细胞中IDO表达中位数增加7倍，血清中IL10水平从预处理基线起中位数最高增加2倍。此外，在1例患者中检测到Treg细胞群体扩大，这也与耐受性诱导相关。低剂量hCG的这种新应用耐受性良好，并对移植物抗宿主病治疗具有临床意义。
