血液肿瘤患者急性药物性肺损伤的临床特征、诊断及治疗

 目的　回顾性分析急性药物性肺损伤病例的临床特征及诊断治疗经过,总结血液肿瘤患者急性药物性肺损伤的临床规律。方法　从2007年7月至2011年11月南方医院血液科住院患者中选择符合急性药物性肺损伤诊断标准患者,分析其临床特征、诊断治疗及预后转归。急性药物性肺损伤诊断标准：突发胸闷、气促、呼吸困难,排除心源性呼吸困难、支气管哮喘和肺栓塞;影像学以弥漫性肺间质浸润为主;抗感染治疗无改善,病原学检查阴性;停用药物、予糖皮质激素和机械通气治疗有效。结果　诊断急性药物性肺损伤4例,药物分别为伊马替尼、硼替佐米、利妥昔单抗和博来霉素,相应原发病分别为慢性粒细胞白血病、多发性骨髓瘤、弥漫大B细胞淋巴瘤和外周T细胞淋巴瘤。除1例患者放弃治疗外,其余3例患者均获得临床治愈,随访未见复发。结论　伊马替尼、硼替佐米、利妥昔单抗和博来霉素可导致急性药物性肺损伤,临床表现为急性呼吸窘迫综合征,机械通气和大剂量糖皮质激素治疗可有效改善预后。     

强化培门冬酶化学药物治疗方案降低成人费城染色体阴性ALL移植后复发

目的分析成人费城染色体阴性急性淋巴细胞白血病(ALL)移植后复发的影响因素。方法总结南方医科大学南方医院血液科2016年至2018年期间,接受异基因造血干细胞移植(allo-HSCT)的成人费城染色体阴性ALL患者移植前后临床资料,进行回顾性分析。65例费城染色体阴性成人ALL接受首次allo-HSCT的患者,男性37例,女性28例,年龄14～58岁,中位年龄25岁。结果中位随访27个月,2年的总存活(OS)率为78.8%(95%CI 67.8%～89.8%),2年的无复发生存(RFS)率为70.7%(95%CI 58.2%～83.2%);移植前化学药物治疗3～7疗程(中位数4疗程),培门冬酶中位剂量为3剂(2 000 IU/m2,每次1剂)。多因素分析发现,强化培门冬酶组(移植前化疗方案中培门冬酶剂量≥4剂)是移植后复发的保护性因素(HR=4.067,P=0.046),高危染色体核型是移植后复发的高危因素(HR=0.193,P=0.009)。生存分析显示,强化培门冬酶组(32例)2年RFS显著高于对照组(33例)(90.0%,95%CI 79.2%～100%和56.9%,95%CI ...     

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.     

不同血液静化方式治疗终末期肾病的效果观察

目的：探讨高通量血液透析与血液透析滤过两种血液静化方式治疗终末期肾病的临床效果和临床推广价值。方法选取2012年1月～2014年6月中国人民解放军153中心医院收治的终末期肾病患者120例,随机分为观察组和对照组,每组60例,观察组患者运用高通量血液透析方法进行治疗,对照组采用血液透析滤过方法对患者进行治疗,观察对比2组患者的血压、血管紧张素2、甲状旁腺激素、肾功能水平的差异。结果治疗后,观察组患者的血压、血管紧张素2、甲状旁腺激素、肾功能水平（肌酐、血清尿素）均明显优于对照组（P＜0．05）。结论高通量血液透析在对终末期肾病患者的治疗中,效果明显优于血液透析滤过,值得临床推广应用。     

加速康复外科理念在泌尿外科腹腔镜围术期的护理应用

目的：探讨加速康复外科理念在泌尿外科腹腔镜围术期的护理效果。方法选取泌尿外科腹腔镜患者60例,随机分成观察组和对照组,每组各30例,对照组采用常规护理,观察组在常规护理基础上采用加速康复外科理念进行护理,观察2组患者并发症发生率、置管引流时间、尿管留置时间、住院时间等。结果观察组术后住院时间平均（4．6±2．6） d,对照组平均（7．8±3．9） d,2组比较,差异有统计学意义（P＜0．05）。观察组术后并发症4例（13．33％）,对照组术后并发症13例（38．24％）,2组比较差异有统计学意义（P＜0．05）。置管引流时间和尿管留置时间观察组均明显低于对照组,2组比较差异有统计学意义（ P＜0．05）。结论加速康复外科理念在泌尿外科腹腔镜围术期护理中,能够明显缩短住院时间,减少并发症。     

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.     

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.     

急性氨茶碱中毒引起双重性心动过速1例

双重性心动过速为同时存在两种快速心律失常,病因多见于洋地黄中毒,临床较为少见。急性氨茶硷中毒所致双重性心动过速似未见报道,现报告我院最近遇到的1例。     

自体造血干细胞移植可改善多发性骨髓瘤患者的临床状态

目的 探究蛋白酶体抑制剂和来那度胺治疗下,自体造血干细胞移植（ASCT）对初发多发性骨髓瘤（MM）患者缓解深度和生存的影响。方法 回顾性收集2015年1月~2019年12月在南方医科大学南方医院接受蛋白酶体抑制剂和或来那度胺治疗的初发及适合移植的MM患者临床资料,按照患者是否接受自体干细胞移植分为移植组及未移植组。移植组纳入接受4~6疗程蛋白酶体抑制剂和或来那度胺为基础的诱导治疗后序贯ASCT的患者,未移植组纳入仅接受8疗程以上的蛋白酶体抑制剂和或来那度胺为基础的诱导及巩固的患者,比较两组患者的治疗疗效及生存的差异。结果 总共105例患者纳入研究,移植组48例 （45.7%）、未移植组57例（54.3%）,两组患者在性别、年龄及4疗程诱导治疗后疗效等方面相似（P>0.05）。两组患者在首次复发前获得过的最佳缓解程度有统计学差异（P<0.001）,移植组获得完全缓解（85.4% vs 54.4%,P=0.001））和完全缓解+非常好的部分缓解（95.8% vs 73.7%,P=0.002）的比例高于未移植组;截止2020年12月31日末次随访时,移植组和未移植组的中位无进展生存期（PFS）分别为未达到和 29 月（P=0.013）,两组患者的中位总生存期（OS）均未达到,但移植组 OS 优于未移植组（P= 0.022）。结论 在新药时代,ASCT仍能进一步提高初发MM患者的缓解深度并改善患者的生存。     

IKZF1基因缺失在急性B淋巴细胞白血病患者中的预后意义北大核心CSCD

目的分析IKZF1基因缺失在急性B淋巴细胞白血病(B-ALL)患者中的预后意义。方法回顾性分析2016年3月至2019年9月南方医科大学附属南方医院收治的142例接受儿童样化疗方案的B-ALL患者的临床资料,分析IKZF1缺失患者的临床特征。无事件生存(EFS)和总生存(OS)的多因素分析使用Cox回归模型。将患者分为IKZF1缺失/单纯化疗组(A组)、IKZF1缺失/移植组(B组)、IKZF1非缺失/单纯化疗(C组)、IKZF1非缺失/移植(D组)四组比较患者生存。结果142例患者,50例(35.2%)检出IKZF1基因缺失,其中4~7号外显子缺失占44.0%;与非缺失型比较,IKZF1缺失组B-ALL患者初诊时白细胞计数升高比例更高(52.0%对28.3%,P=0.005)、诱导治疗第14天微小残留病转阴率更低(MRD1,40.0%对70.7%,P<0.001)以及Ph染色体阳性比例更高(52.0%对21.7%,P<0.001)。单因素分析显示,IKZF1缺失组3年EFS率、OS率明显低于IKZF1非缺失组[(37.1±7.3)%对(54.7±5.4)%,P=0.025;(51.8±7.9)%对(73.9±4.7)%,P=0.013];多因素分析显示IKZF1缺失是影响B-ALL患者EFS(HR=1.744,95%CI 1.082~2.812,P=0.022)、OS(HR=2.036,95%CI 1.119~3.705,P=0.020)的独立危险因素。其中,A组的3年EFS、OS、无病生存率(DFS)均明显低于其他亚组。在IKZF1缺失患者中,接受异基因造血干细胞移植(allo-HSCT)组3年OS率为(67.9±10.4)%,3年EFS率为(46.6±10.5)%,均明显高于非移植组的(31.9±11.0)%和(26.7±9.7)%(P值分别为0.005、0.026)。结论IKZF1基因缺失的B-ALL患者整体预后差,儿童样化疗方案不能完全纠正IZKF1缺失对预后的不良影响;儿童样方案联合allo-HSCT可显著改善IKZF1缺失B-ALL的整体预后。