马利兰和氟达拉滨与马利兰和环磷酰胺预处理方案在急性髓性白血病异基因造血干细胞移植中的比较

 目的 比较马利兰（Bu）和氟达拉滨（Flu）组成的预处理方案（Bu/Flu）与Bu和环磷酰胺（Cy）组成的预处理方案（Bu/Cy）在急性髓性白血病第一次完全缓解（AML-CR1）患者异基因造血干细胞移植（allo-HSCT）中的移植相关毒性和疗效的差异。方法 32例接受allo-HSCT的AML-CR1患者按移植顺序交替分至Bu/Cy组（Bu 3.2 mg·kg^-1·d^-1,移植前第7~4天;Cy 60 mg·kg^-1·d^-1,移植前第3~2天）或Bu/Flu组（Bu 3.2 mg·kg^-1·d^-1,移植前第5～2天;Flu 30 mg·m^-2·d^-1,移植前第6～2天）。评价两组预处理相关毒性（RRT）、移植物抗宿主病（GVHD）发生率与严重程度、3年累积复发率、非复发死亡率（NRM）、3年无病生存（EFS）率和总生存（OS）率等方面的差异。结果 中位随访时间为617.5（6~1261）d。两组中性粒细胞和血小板中位重建时间无明显差异（P=0.121和P=0.171）,移植后30 d嵌合状态分析提示两组患者均达到完全植入。Bu/Cy组预处理后中性粒细胞持续<0.1×10⁹/L和血小板持续﹤20×10⁹/L中位时间明显长于Bu/Flu组［6（3~14）d比2.5（1~9）d,P=0.000;3（1~36）d比1（0~4）d,P=0.047］。Bu/Cy组与Bu/Flu组Ⅱ～Ⅳ度RRT发生率分别为68.8%和25.0%（P=0.032）;急性GVHD发生率分别为46.7%和75.0%（P=0.149）,慢性GVHD发生率分别为46.7%和80.0%（P=0.149）;NRM分别为25.0%和6.3%（P=0.333）;3年累积复发率分别为（17.9±11.7）%和（14.1±9.3）%（P=0.834）;3年EFS率分别为（65.5±12.7）%和（80.2±10.3）%（P=0.362）;3年OS率分别为（68.8±11.6）%和（87.5±8.3）%（P=0.111）。结论 Bu/Flu是一种清髓性预处理方案,与Bu/Cy方案比较具有低骨髓抑制毒性及RRT。Bu/Flu作为AML-CR1患者allo-HSCT预处理方案其疗效不低于Bu/Cy。     

做好实习前准备提高临床实习质量

文章论述了医学专业的学生在实习前的各项准备工作,并从知识、技能、心理方面提出了建议,对提高学生的临床实习质量有一定的帮助.     

血缘关系供者外周血干细胞移植中移植物细胞组分对造血重建移植物抗宿主病的影响

目的 探讨HLA全相合血缘关系供者外周血干细胞移植(PBSCT)中移植物细胞组分对恶性血液病患者移植后造血重建、移植物抗宿主病(GVHD)的影响.方法 回顾性分析我科107例接受HLA全相合血缘关系供者PBSCT的恶性血液病患者,其移植物细胞组分与移植后患者造血重建、GVHD的关系.结果 移植物各细胞组分与粒细胞重建时间无关;单个核细胞(MNC)、CD34+细胞数与血小板重建时间呈负相关(r值分别为-0.32和-0.21,P值均＜0.05).CD34+、CD34+CD38-细胞数与急性GVHD发生呈负相关(r分别为-0.24和-0.29,P值均＜0.05).淋巴细胞各亚群数量与急性GVHD发生均无明显关系.CD25+ CD4+、CD3+、CD4+ CD3+细胞数及CD4+/CD8+细胞比值与慢性GVHD发生均呈正相关(P值均＜0.05),且相关系数均大于0.4,其中CD25+ CD4+细胞数与慢性GVHD相关系数高达0.78.CD34+、CD34+ CD38-细胞数与慢性GVHD发生无明显关系.结论PBSCT中输入MNC、CD34+、CD34+ CD38-细胞数增加到一定阈值后,增加细胞数并不能进一步有效促进患者造血重建,反而有可能因输入淋巴细胞数增加而增加患者慢性GVHD、广泛慢性GVHD的发生率.     

间充质干细胞治疗糖皮质激素耐药性慢性移植物抗宿主病临床疗效观察

Objective To assess whether treatment with mesenchymal stem cells (MSCs) is an effective adjunct therapy for refractory extensive chronic graft-versus-host disease (GVHD) resistant to conventional therapy. Methods 12 patients with steroid-resistant extensive chronic GVHD were treated with MSCs. One patient received one dose, 10 received two doses, and the remaining three doses. The MSCs were obtained from HI,A-identical sibling donors (n = 14), haploidentical donors (n = 2), unrelated mismatched donor (n = 1) and third-party HLA-mismatched donors (n = 7). Of the 11 patients treated with multiple infusions, 5 received cells derived from two donors. The median first dose of MSCs was 1.0 (0. 4-2. 1) × 106/kg , the median second dose was 1.2(0. 8-1.9) × 106/kg , and the third dose in one patient was 1.1 × 106/kg. Meanwhile the proportion of CD3+ ,CD4+,CD8+ ,CD19+,CD4+ CD25+ ,FOXP3+,FOXP3+CD4+ and FOXP3+ CD25+ was determined with double fluorescent-labeled antibodies and flow cytometry before and 4 weeks after the MSCs infusion. Results No patients had side-effects during or immediately after the infusions of MSCs. After a treatment course of one to three doses, 3 patients had complete response(CR), 6 showed partial response(PR) and 3 did not respond; the total effective rate was 75% (9/12). Complete resolution was seen in the involvement of skin (3/12), lung (1/3), joints (1/5), liver (3/10), oralcavity (4/12) and eye (2/7). Response rate was not related to donor HLA-match. 3 CR patients discontinued all of the immunosuppressive agents without relapse 100 to 292 days after the MSC infusion and 6 PR patients taped all immunosuppressive agents after 60 to 79 days. Mean follow-up period was 1152(795-1914) days, leukemia free survival rate was 91.7% (11/12) and the overall survival rate was 75% (9/12). The ratio of CD4/CD8 and the proportion of regulatory T cells were significantly higher than that before MSCs treatment. Conclusion Third-party MSCs were as effective as HLA-identical or haploidentical cells. This finding has practical implications and suggests that third-party cells can be prepared and stored frozen to be used for steroid-resistant extensive chronic GVHD therapy. It is concluded that MSCs may prevent the lethal cGVHD after allogeneic hematopoietic stem cell transplantation and raise the survival rate by increasing the ratio of CD4/CD8 and proportion of regulatory T cells in vivo.     

格拉司琼透皮贴片预防抗肿瘤治疗所致恶心呕吐的前瞻性、多中心的真实世界研究报告

目的 探讨采用真实世界研究模式,在中国癌症患者中评价格拉司琼透皮贴片(granisetron transdermal delivery system,GTDS)预防抗肿瘤治疗所致恶心呕吐(antitumor drugs-induced nausea and vomiting,DINV)的效果、安全性和治疗价值.方法 本...     

异基因造血干细胞移植后EB病毒再激活的危险因素分析

背景:异基因造血干细胞移植后EB病毒再激活可导致致死性的移植后淋巴细胞增殖性疾病及相关疾病,目前国内尚未建立完整的EB病毒再激活及其相关性疾病的诊疗体系。目的:前瞻性研究异基因造血干细胞移植后患者EB病毒再激活的发生和相关危险因素。方法:纳入129例接受异基因造血干细胞移植的患者,采用实时定量PCR方法定期测定外周血中EB病毒载量,Kaplan-Meier模型分析其再激活的发生率,Logistic回归分析模型分析其再激活的相关危险因素。结果与结论:异基因造血干细胞移植后EB病毒再激活及其相关疾病发生率高,EB病毒再激活发生的危险因素有HLA配型不合、应用抗胸腺细胞球蛋白、Ⅲ～Ⅳ度急性移植物抗宿主病及年龄小于20岁。     

间充质干细胞治疗糖皮质激素耐药性慢性移植物抗宿主病临床疗效观察

Objective To assess whether treatment with mesenchymal stem cells (MSCs) is an effective adjunct therapy for refractory extensive chronic graft-versus-host disease (GVHD) resistant to conventional therapy. Methods 12 patients with steroid-resistant extensive chronic GVHD were treated with MSCs. One patient received one dose, 10 received two doses, and the remaining three doses. The MSCs were obtained from HI,A-identical sibling donors (n = 14), haploidentical donors (n = 2), unrelated mismatched donor (n = 1) and third-party HLA-mismatched donors (n = 7). Of the 11 patients treated with multiple infusions, 5 received cells derived from two donors. The median first dose of MSCs was 1.0 (0. 4-2. 1) × 106/kg , the median second dose was 1.2(0. 8-1.9) × 106/kg , and the third dose in one patient was 1.1 × 106/kg. Meanwhile the proportion of CD3+ ,CD4+,CD8+ ,CD19+,CD4+ CD25+ ,FOXP3+,FOXP3+CD4+ and FOXP3+ CD25+ was determined with double fluorescent-labeled antibodies and flow cytometry before and 4 weeks after the MSCs infusion. Results No patients had side-effects during or immediately after the infusions of MSCs. After a treatment course of one to three doses, 3 patients had complete response(CR), 6 showed partial response(PR) and 3 did not respond; the total effective rate was 75% (9/12). Complete resolution was seen in the involvement of skin (3/12), lung (1/3), joints (1/5), liver (3/10), oralcavity (4/12) and eye (2/7). Response rate was not related to donor HLA-match. 3 CR patients discontinued all of the immunosuppressive agents without relapse 100 to 292 days after the MSC infusion and 6 PR patients taped all immunosuppressive agents after 60 to 79 days. Mean follow-up period was 1152(795-1914) days, leukemia free survival rate was 91.7% (11/12) and the overall survival rate was 75% (9/12). The ratio of CD4/CD8 and the proportion of regulatory T cells were significantly higher than that before MSCs treatment. Conclusion Third-party MSCs were as effective as HLA-identical or haploidentical cells. This finding has practical implications and suggests that third-party cells can be prepared and stored frozen to be used for steroid-resistant extensive chronic GVHD therapy. It is concluded that MSCs may prevent the lethal cGVHD after allogeneic hematopoietic stem cell transplantation and raise the survival rate by increasing the ratio of CD4/CD8 and proportion of regulatory T cells in vivo.     

造血干细胞移植后病毒性肺炎(附视频)

造血干细胞移植(HSCT)后肺部并发症是影响HSCT受者预后的一个重要因素.近年来随着人们对肺部细菌、真菌及非感染性并发症等认识的深入,由病毒感染引起的肺部并发症再次成为人们关注的焦点.病毒性肺炎的病原体主要分为两大类:疱疹病毒和社区获得性呼吸道病毒.本文重点介绍HSCT后病毒性肺炎的流行病学、预防、诊断及治疗等方面的新进展.     

两种方案预防无血缘关系供者造血干细胞移植后移植物抗宿主病的效果比较

移植物抗宿主病（GVHD）是引起无血缘关系供者造血干细胞移植（URD—HSCT）后患者死亡的主要原因，降低URD—HSCT后GVHD发生率和严重程度是提高患者长期生存率的关键。现将我院40例接受URD—HSCT的白血病患者分别采用环孢菌素A（CsA）、甲氨蝶呤（MTX）、抗胸腺细胞球蛋白（ATG）、霉酚酸酯（MMF）四联方案以及CsA、MTX、ATG三联方案预防GVHD的效果报道如下。     

造血干细胞移植治疗慢性粒细胞白血病疗效分析

目的 评价自体(auto-)造血干细胞移植(HSCT)或异体(allo-)HSCT治疗慢性粒细胞白血病(CML)的临床疗效。方法 57例CML接受HSCT治疗,其中8例采用净化auto-HSCT、39例相关allo-HSCT、10例无关allo-HSCT。预处理方案:32例接受全身放疗+环磷酰胺(TBI+CY)、24例改良BuCY(羟基脲、马利兰、阿糖胞苷、环磷酰胺)、1例MACC(马法兰、阿糖胞苷、环磷酰胺、环已亚硝脲)。移植物抗宿主病(GVHD)预防:相关移植环孢素A+甲氨蝶呤(CsA+MTX)、无关移植CsA+MTX+霉酚酸酯(MMF)+抗胸腺细胞球蛋白(ATG)方案.Kaplan-Meier生存模型评估移植后无病生存期。结果 8例接受激活骨髓联合反义寡核苷酸或联合STI571体内外净化自体移植后,除1例死于移植中相关并发症外,其余均获得部分或完全细胞或分子遗传学缓解。49例allo-HSCT患者除1例死于肝静脉闭塞综合征(VOD)和1例移植前急变患者移植后无效,其余患者均获完全缓解。移植中感染发生率为33.3%,VOD发生率7.0%,出血性膀胱炎发生率22.8%,巨细胞病毒间质性肺炎8.8%,VOD、出血性膀胱炎和巨细胞病毒间质性肺炎均发生在异体移植患者。急性和慢性GVHD在相关与无关移植分别为41.0%和48.6%与40.0%和42.9%。移植后白血病复发率自体移植57.1%、异体移植12.8%。移植后5年无病生存率在自体与异体移植分别为25.0%和61.7%。移植前慢性期与加速期和急变期患者allo-HSCT后5年无病生存率分别为70.7%和34.1%,相关与无关allo-HSCT后无病生存期存在差异(P<0.05)。结论 allo-HSCT对CML患者,尤其是移植前慢性期患者具有较高的临床治愈率;CsA+MTX+MMF+ATG四联预防无关allo-HSCT中GVHD能降低移植后GVHD的发生率及程度;采用净化骨髓自体移植能延长CML患者生存期,甚至少部分患者可获得临床治愈。