自体外周血造血干细胞移植治疗重症天疱疮三例

目的 探讨自体外周血造血干细胞移植治疗天疱疮的疗效及安全性.方法 选择经糖皮质激素、免疫抑制剂等治疗6个月以上病情仍难以控制或病情进展、且出现治疗相关并发症的3例寻常型天疱疮患者进行自体外周血造血干细胞移植治疗,并随访5年以上.3例中男1例,女2例,平均年龄27.3(21～39)岁.造血干细胞的动员方案为环磷酰胺4g/m2、重组人粒细胞集落刺激因子(G-CSF)、利妥昔单抗375 mg/m2;预处理方案为环磷酰胺50 mg·kg-1·d-1连用4d(移植前第6天到移植前第3天)、抗胸腺细胞球蛋白2.5 mg·kg-1·d-1连用4d(移植前第3天至移植当天)、利妥昔单抗600 mg/d于移植当天和移植后第7天静脉滴注.结果 3例天疱疮患者均获得成功植入,平均植活时间白细胞13.3 d(11 ～ 16d),血小板16.3 d(16～ 17d).监测各项免疫指标及相关抗体未见异常,免疫重建良好.随访期间,所有患者无严重并发症,生活质量较前明显提高.结论 自体外周血造血干细胞移植可能是治疗天疱疮有效且安全的新方法之一.     

SLE患者自体外周血纯化造血干细胞移植后自身抗体的变化

目的研究自体外周血纯化造血干细胞移植对系统性红斑狼疮(SLE)患者自身抗体的影响并评估治疗效果。方法16例接受自体外周血纯化造血干细胞移植的SLE患者列入研究。应用酶联免疫吸附试验动态监测移植前及移植后3,6,12个月血清中自身抗体含量,并进行定量分析。结果自体外周血造血干细胞移植治疗SLE后,ANA、抗双链DNA抗体、抗Sm抗体、抗RNP抗体的滴度均较移植前下降。其中移植后3,6,12个月的血清中ANA、抗RNP抗体的含量均明显低于移植前。结论自体外周血纯化造血干细胞移植能减少血清中的自身抗体,有效治疗SLE。     

自体造血干细胞移植对SLE患者生活质量的影响

目的探讨自体外周血造血干细胞移植(APBSCT)对系统性红斑狼疮(SLE)患者生活质量的影响。方法对21例住院的SLE患者进行APBSCT治疗。动员方案为环磷酰胺(CTX)4 g/m2,粒细胞集落刺激因子(G-CSF)5μg/(kg.d),4~5天。预处理方案为CTX 50 mg/(kg.d),4天;抗胸腺球蛋白(ATG)15~25 mg/(kg.d),3天。预处理结束后回输采集到的CD34+造血干细胞。采用WHOQOL-BREF中文版,观察并评价移植前后患者的生活质量评分。结果21例患者造血干细胞均成功植入。移植相关的死亡率为0%。WHOQOL-BREF表的五个方面,包括生理、心理、社会关系、环境、总体感觉等在移植后均有明显改善(P<0.05或P<0.01)。结论APBSCT治疗SLE有良好的疗效,患者在移植后生活质量明显改善。     

自体外周血纯化造血干细胞移植治疗系统性红斑狼疮

目的 探讨自体外周血纯化造血干细胞移植治疗系统性红斑狼疮(SLE)的疗效和安全性。方法 对9例SLE患者进行自体外周血纯化造血干细胞移植。采集的干细胞的计数为(2.37～9.9)×10⁸/kg。预处理方案是环磷酰胺50 mg·kg^-1·d^-1静脉滴注,连用4 d(造血干细胞回输前2～5d)。抗胸腺球蛋白抗体2.5 mg·kg^-1·d^-1静脉滴注,连用4d。同时碱化和水化尿液,保护心、肝和肾功能。从移植后临床表现、SLE相关的免疫学指标的变化,移植后造血重建情况,移植的并发症等方面进行评价。结果 9例患者均获得成功植入,外周血白细胞总数>1.0×10>/L的时间为移植后7～15 d,血小板>20×10⁹/L时间为移植后0～21d。所有患者均于移植后面部红斑等临床症状完全消失,大部分患者自身抗体转阴。9例患者均出现轻重不一的血清病样反应,1例出现严重的肾衰和心衰,3例有出血性膀胱炎,1例出现心因性精神障碍,1例发生会阴部念珠菌感染。结论 随访1年结果表明,自体外周血纯化造血干细胞移植治疗SLE的近期疗效显著,且相对安全。     

自体外周血造血干细胞移植治疗难治性寻常型天疱疮1例

目的观察自体外周血造血干细胞移植治疗难治性寻常型天疱疮1例的效果。方法患者男,45岁。口腔、头面部、躯干、四肢水疱、糜烂6年。诊断为寻常型天疱疮。经糖皮质激素和免疫抑制剂及抗CD20单克隆抗体治疗,疾病反复发作。同时合并糖尿病和高血压。半年前,全身水疱加重,行自体外周血造血干细胞移植。应用环磷酰胺、粒细胞集落刺激因子（G-CSF）进行动员。用环磷酰胺（CTX）＋磷酸氟达拉滨（Flud）＋抗胸腺细胞球蛋白（ATG）进行预处理。结果患者移植结束后,皮疹消退,自身抗体滴度明显降低。移植2个月后皮疹轻度反复,小量糖皮质激素联合甲氨蝶呤可以控制。目前移植后6个月,病情稳定。结论自体外周血造血干细胞移植治疗难治性寻常天疱疮疗效显著。可作为治疗难治性寻常型天疱疮的一种新方法。但其远期治疗效果需进一步观察。     

自体外周血干细胞移植治疗难治性天疱疮一例

目的 探讨自体外周血干细胞移植治疗天疱疮的可能性.病历资料男性患者,35岁,全身反复大疱4年余,根据临床表现、组织病理和免疫荧光检查确诊为天疱疮.经糖皮质激素和免疫抑制剂治疗效果不佳,2月前出现髓关节疼痛,经X线和CT检查诊断为股骨头无菌性坏死.采取环磷酞胺及粒细胞集落刺激因子作为动员剂,利妥昔单抗联合净化.用环磷酞胺联合抗胸腺细胞球蛋白、利妥昔单抗进行预处理,同时碱化和水化尿液,保护心、肝和肾功能.观察移植后临床表现、造血和免疫指标等的变化.结果 患者移植结束即停用糖皮质激素,3周后自觉双侧靛关节疼痛减轻,复查CT示股骨头缺血性改变减轻.移植6周后直接免疫荧光和间接免疫荧光检查转阴并持续阴性.经一年复诊,临床及免疫学检查均无复发迹象.结论 本研究结果提示自体外周血干细胞移植治疗天疙疮近期疗效显著,可能是治疗存在治疗抵抗的重症天疤疮潜在的“根治”方法,但其风险收益比尚需进一步评价.     

Stem cell transplantation in the treatment of systemic lupus erythematosus: reports from China

回顾近10年国内期刊上关于干细胞移植治疗系统性红斑狼疮的报道,绝大部分为自体外周造血干细胞移植,异体骨髓间充质干细胞移植仅有2例报道,尚无自体骨髓间充质干细胞移植治疗系统性红斑狼疮的报道.     

结缔组织病

20063165自体造血干细胞移植对SLE患者生活质量的影响/李建华(广州市南方医院皮肤风湿科),曾抗,周再高…∥中国皮肤性病学杂志.-2006,20(2).-84~85,96对21例住院的SLE患者进行APBSCT治疗。动员方案为环磷酰胺(CTX)4 g/m2,粒细胞集落刺激因子(G-CSF)5μg/(kg·d),4~5天。预处理方案为CTX 50mg/(kg·d),4天;抗胸腺球蛋白(ATG)15~25 mg/(kg·d),3天。预处理结束后回输采集到的CD34 造血干细胞。采用WHOQOL-BREF中文版,观察并评价移植前后患者的生活质量评分。结果:21例患者造血干细胞均成功植入。移植相关的死亡率为0%。WHOQO…     

大剂量化疗联合造血干细胞移植治疗严重SLE患者的初步研究

具有多器官功能损害的ＳＬＥ患者 ,尽管作了静脉内环磷酰胺治疗 ,但仍有很高的早期死亡率。研究者用大剂量的免疫抑制剂和输入自体造血干细胞治疗严重的ＳＬＥ患者 ,获得较好疗效。该研究选择了 9例ＳＬＥ患者 ,即有ＷＨＯ规定的Ⅲ～Ⅳ级肾小球肾炎 ,狼疮性脑炎或横贯性脊髓炎 ,狼疮性血管炎 ,包括心肺实质性损害 ;与狼疮有关、对生命构成严重威胁、有严重血细胞减少症 ;具有以上情况 ,同时用普通剂量环磷酰胺治疗 6个疗程无效的患者 ;或严重的抗磷脂抗体综合征的患者作为入选对象。患者在移植造血干细胞前用药 :移植前 3～ 6天开始静脉给予…     

免疫吸附联合非清髓性CD34+细胞自身移植治疗难治性SLE三例

目的 观察免疫吸附联合非清髓性化疗结合CD34+细胞分选的自体外周血干细胞移植治疗难治性SLE的疗效。方法 难治性SLE 3例，均经肾活检确诊为狼疮性肾炎Ⅳ型，狼疮处于活动期，病情进展，常规治疗无效；应用以葡萄球菌A蛋白作为免疫吸附剂的吸附柱进行免疫吸附，一个疗程共6次，每次吸附血浆3 L；随后采用异环磷酰胺加重组人粒细胞集落刺激因子动员、Baxter CS-3000血细胞分离机采集外周血，获取单一核细胞，通过CD34+细胞分选仪分别得到2.6 × 106/kg、2.1 × 106/kg、2.4 × 106/kg CD34+细胞，采集物中分别含3 × 105/kg、2.1 × 105/kg、2.0 × 105/kg CD3+细胞，预处理为回输前6 d，每日应用氟达拉滨50 mg/d 共5 d，回输前3 d始每日应用抗胸腺细胞球蛋白90 mg/kg共5 d。 结果 ①3例患者吸附后血浆中抗dsDNA、ANA抗体、IgG均明显下降，补体C3明显上升。②3例患者均于移植后2 ~ 3 d获得造血重建。③移植后3例患者临床症状均明显缓解，SLEDAI评分均 < 3分。④移植后6个月，患者血浆中抗dsDNA、ANA抗体均转阴性，补体C3升至正常，尿蛋白转阴性，肾功能恢复正常。结论 移植治疗难治性SLE近期疗效满意。     

造血干细胞移植治疗系统性红斑狼疮1例报告并文献复习

目的探讨自体骨髓干细胞移植(ABMSCT)对系统性红斑狼疮(SLE)的疗效。方法患者为SLE迁延不愈并伴有自身免疫性溶血性贫血(AIHA),采集自体骨髓造血干细胞,预处理用环磷酰胺(CTX)2.4 g静滴连用2天,依托泊苷(VP-16)0.4 g/m2d1,0.5 g/m2d2(即依据病人体表面积第1天用0.4 g/m2,第2天用0.5 g/m2),预处理后回输自体骨髓悬液。用惠尔血(rhG-CSF)刺激粒细胞的恢复,观察ABMSCT前后临床表现和免疫学指标的变化。结果ABM-SCT后患者的临床症状明显缓解,血象各指标恢复正常。结论ABMSCT对SLE有较好的疗效,远期疗效还需长期随访。     

A case of acute graft-versus-host disease following autologous peripheral blood stem cell transplantation

A 42-year-old woman developed severe erythema with exfoliative scaling on the bilateral palms and soles and erosive dermatitis on the axillae and groin eight days after an autologous peripheral blood stem cell transplantation for the treatment of non-Hodgkin's lymphoma. She also developed exanthema; however she did not show intestinal, hepatic, or renal involvement. The skin biopsy revealed characteristic apoptotic cell death of the epidermis with eosinophilic necrosis, and she was diagnosed with acute graft-versus-host disease (GVHD). The cutaneous lesions responded to topical corticosteroid treatments and improved within a month without systemic immunosuppressing therapies. The cutaneous GVH reaction did not recur. However, she was treated with an intermittent thrombocyte transfusion because of persistent thrombocytopenia. On day 130, she developed intestinal pneumonia and died due to respiratory dysfunction. Unlike an allo-bone marrow graft, GVHD after an autologous stem cell transplantation is not common. Even for an autologous transplantation, GVH may develop with less characteristic clinical manifestations.     

Muscle regeneration and cell-mediated cytotoxicity in the autologous muscle culture of dermatomyositis

Muscle culture from a dermatomyositis patient was performed to investigate the muscle regeneration and cell-mediated cytotoxicity. In the primary culture, spindle-shaped mononuclear myoblasts exponentially increased in number. In the secondary culture, the myotubes fused with the myoblasts and/or other myotubes into large thick syncytia. The cell morphology and growth pattern of the cultured muscle cells in dermatomyositis were identical to those of normal healthy controls. The autologous mononuclear cells added in the secondary culture of day 14 adhered to the surface membrane of the myotubes. Three days after this treatment, the myotubes underwent degenerative changes. On the other hand, in two series of sister cultures, each added with the autologous serum and control medium, no remarkable morphological changes were observed. The results of the present study suggest that dermatomyositis could be precipitated by the associated abnormal cell-mediated cytotoxicity, but not by abnormalities in muscle fibers per se.     

Autologous hematopoietic stem cell transplantation followed by oral bexarotene in a patient with advanced mycosis fungoides

We describe the case of a 17-year-old patient with rapidly progressing and aggressive mycosis fungoides, with multiple cutaneous tumors and large cell transformation. She was initially treated with 3 cycles of high-dose chemotherapy with mega-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) without response, leading to the decision to undertake autologous hematopoietic stem cell transplantation. Partial remission of the disease was achieved with this treatment and subsequent introduction of oral bexarotene led to complete remission, which has been maintained for more than 3 years with good tolerance of oral therapy. We discuss the advantages and disadvantages of autologous hematopoietic stem cell transplantation and the use of oral bexarotene.     

Flexural erythematous eruption following autologous peripheral blood stem cell transplantation: a study of four cases

Autologous bone marrow transplantation and autologous peripheral blood stem cell transplantation (APBSCT) are alternative therapeutic options in the treatment of various malignancies. We describe four patients undergoing APBSCT for malignancies; they developed a cutaneous eruption characterized by confluent erythematous and hyperpigmented patches within the flexural areas during the first month after transplantation. The lesions were poorly circumscribed without epidermal changes such as scaling, xerosis, erosions or atrophy. The skin patches were treated with topical corticosteroids and resolved within a few days with discoloration. Histopathological findings were characterized by focal vacuolar degeneration of the basal layer with epidermal dysmaturation. We believe that these cutaneous eruptions are consistent with an interplay of high-dose chemotherapy and local factors such as friction, local skin temperature and eccrine gland distribution, which could explain the constant location of this eruption in the axillae and genital area.