异基因造血干细胞移植治疗白血病12例临床观察

目的 探讨异基因造血干细胞移植(Allo-HSCT)治疗白血病的疗效.方法 选择2007年4月至2009年4月进行异基因造血干细胞移植的患者12例,其中急性淋巴细胞白血病(ALL)2例,急性髓系白血病(AML)4例,慢性粒细胞白血病6例.预处理方案均为BU/CY,采用以CsA、MMF、ATG加短程MTX常规预防移植物抗宿主病,非亲缘移植加用抗胸腺细胞球蛋白(ATG).结果 12例患者移植后均造血重建,发生急性移植物抗宿主病(aGVHD)1例,慢性移植物抗宿主病(cGVHD)2例.移植后100d内移植相关死亡率(TRM)8.3%(1/12),死于aGVHD、感染;移植后100d至2年内TRM为16.7%(2/12),分别死于cGVHD、感染及白血病复发.其余9例无病生存1～24个月,DFS为75%(9/12).结论 异基因外周血干细胞移植是目前惟一可能治愈白血病的方法,值得推广和进一步总结.     

异基因造血干细胞移植后重度肠道急性移植物抗宿主病的临床分析

目的 探讨异基因造血干细胞移植(Allo-HSCT)后重症肠道急性移植物抗宿主病(aGVHD)的发生情况及预后.方法 2例慢性粒细胞白血病(慢性期)患者接受异基因造血干细胞移植,预处理方案为BU/CY、GIAC方案,以CsA、MMF、ATG加短程MTX预防aGVHD.结果 2例分别于移植后21、40d并发重度肠炎,诊断为肠道aGVHD,予以糖皮质激素为主的综合治疗包括FK506、抗CD25单克隆抗体后缓解.结论 重度肠道aGVHD是异基因造血干细胞移植后常见的最严重并发症之一,有效治疗直接关系到疾病的预后.     

输注淋巴细胞防治造血干细胞移植后白血病复发的观察

目前能治愈白血病的最有效方法仍然是异基因造血干细胞移植(Allo-HSCT),但对于移植后复发的病例,过去只能采用二次移植,其疗效多数都不理想。自从1995年Kolb[1]等报道了异基因骨髓移植(all-BMT)治疗慢性粒细胞白血病患者复发,经过供者淋巴细胞输注(DLI)后再次获得血液学和细胞遗传学缓解以来,许多研究报告已经肯定DLI对治疗和预防各类白血病Allo-HSCT后复发有很好的疗效。我院于2004年3月至2007年1月应用DLI治疗10例Allo-HSCT后患者,现报道如下。资料和方法1.病例资料10例均为我院2004年3月至2007年1月住院患者,其中慢性粒细胞…     

无关供体异基因外周造血干细胞(URD-PBSCT)移植术后肺部感染的护理

近年来,随着血液学及相关领域基础和临床研究的不断发展,造血干细胞移植(HSCT)已成为治疗恶性血液病的有效手段.但人白细胞抗原(HLA)配型相合的血缘相关供者来源不足,极大限制了异基因造血干细胞移植(Allo-HSCT)的应用[1].无关供体异基因外周造血干细胞(URD-PBSCT)作为造血干细胞移植供体来源的补充,已成为拯救恶性血液病患者生命的一种治疗方法.但由于必须采用较强的预处理方案,故移植后也需应用强免疫抑制剂,移植后相关并发症较高.肺部感染是无关供体异基因外周血造血干细胞移植术中及术后的主要并发症之一.我科2008年5月～2010年3月共实行URD-PBSCT 35例,其中10例发生不同程度的肺部感染.现将护理体会总结如下.     

异基因造血干细胞移植55例GVHD的临床观察

目的 探索异基因造血干细胞GVHD的有效防治方法.方法 异基因移植患者55例,慢性粒细胞白血病(CML)30例,急性髓系白血病(ALM)12例,急性淋巴细胞白血病(ALL)11例,急性混合细胞白血病(MAL)2例.同胞间人类白细胞抗原(HLA)全相合移植45例,非血缘异基因移植7例,HLA半相合移植3例.43例患者采用MMF、CsA联合短程MTX方案.12例患者采用MMF、CsA、短程MTX联合ATG方案.结果 所有患者造血均顺利重建,12例(21.1%)发生Ⅰ～Ⅱ度aGVHD;11例(20%)发生cGVHD,局限型8例,广泛型3例.aGVHD和广泛型cGVHD经甲强龙冲击治疗后均得到控制.结论 MMF、CsA、MTX、ATG三联方案能有效控制同胞间HLA全相合移植的aGVHD,加用ATG能理想的预防同胞间HLA半相合移植和非血缘异基因移植aGVHD的发生.     

Cy-VP16-fTBI预处理的干细胞移植治疗恶性血液病的长期疗效

目的 Cy-VP16-fTBI预处理方案的造血干细胞移植治疗血液系统恶性疾病的长期疗效观察. 方法 造血干细胞移植治疗16例恶性血液病患者,其中异基因外周血干细胞移植8例,异基因骨髓移植5例,自体外周血干细胞移植3例.所有患者均予环磷酰胺(Cy)+依托泊苷(VP16)+标准分次全身放疗(fTBI)预处理方案. 结果 所有患者均成功植活,白细胞、血小板植入中位时间分别为第15(10～22)天和第20(10～65)天.Ⅱ-Ⅳ度急性移植物抗宿主病(aGVHD)3例(19%),慢性GVHD(cGVHD)7例(43%).11例(68.75%)患者长期生存,中位生存期75(34～82)个月.6年总体生存率(OS)68.75%,其中第一次完全缓解或慢性粒细胞白血病慢性期患者6年OS为78.75%.6年复发率14.29%,移植满2 a后无患者复发. 结论 Cy-VP16-fTBI预处理方案的造血干细胞移植安全、有效,其长期疗效明显优于常规化疗.aGVHD发生率较低,但cGVHD在异基因外周血干细胞移植中发生率较高;其他毒副作用较少.     

伊马替尼联合干细胞移植治疗慢性粒细胞白血病临床观察

目的探讨甲磺酸伊马替尼(IM)联合亲缘异基因造血干细胞移植治疗进展期慢性粒细胞性白血病(CML)的临床疗效。方法回顾性分析2011年1月至2012年10月采用亲缘异基因造血干细胞移植联合甲磺酸伊马替尼治疗的进展期CML 8例的疗效。结果 8例患者移植后均获得造血重建,移植后中性粒细胞和血小板植活的中位时间分别为16d和18.5d;发生Ⅰ度急性移植物抗宿主病(aGVHD)1例,Ⅱ度aGVHD 5例,局限型慢性移植物抗宿主病(cGVHD)7例,广泛型cGVHD 2例;无白血病存活率为75.0%,移植相关死亡率为12.5%。总体存活率为87.5%,平均无病生存8月(7~17个月),BCR/ABL转阴时间1~5个月。结论亲缘异基因造血干细胞造移植前、后联合格列卫治疗进展期CML,具有降低移植前白血病细胞负荷,争取移植机会,促进供者完全嵌合状态的转变,延长患者生存,是一种安全有效的治疗方法。     

Clinical efficacy of allogeneic hematopoietic stem cell transplantation on myelodysplastic syndrome

回顾性分析异基因造血干细胞移植(Allo-HSCT)治疗骨髓增生异常综合征(MDS)的适应证、治疗时机、移植物的选择、移植预处理方案的选择和移植疗效.22例患者中21例获得造血重建,1例非血缘脐血移植(UCBT)未获得植入的成人患者,于非血缘脐血移植(UCBT)后38 d进行母亲HLA4/6相合的外周血联合骨髓造血干细胞移植解救治疗获得植入.22例中死亡3例,无1例复发.MDS患者何时进行Allo-HSCT需依据国际预后积分系统(IPSS )对患者分组,评分属于高危组的患者宜在疾病确诊后尽早进行移植,而低危组的患者可在其他药物治疗效果不佳的时候进行;不仅可选择血缘关系的骨髓移植(BMT)和外周血造血干细胞移植(PBSCT),也可进行非血缘人类白细胞共同抗原(HLA)不全相合的UCBT;移植预处理如采用减低强度的方案(RIC)并不影响移植效果.     

亲缘间外周血异基因移植后白血病复发的危险因素分析

目的 分析急慢性白血病患者行亲缘间、外周血异基因造血干细胞移植（Allo-HSCT）后复发的危险因素。方法 选取2016年1月至2020年10月期间行Allo-HSCT的62例白血病患者为研究对象,其中急性髓系白血病（AML）30例,急性淋巴细胞白血病（ALL）24例,慢性粒细胞白血病（CML）8例。造血干细胞来源均为亲缘供者外周血,给予改良BU/CY±ATG清髓性预处理方案,统计移植后疾病复发情况,分析复发的危险因素。结果 随访至2021年10月,中位随访时间为38(12～52)个月,共20例患者复发,总体复发率为32.3%(20/62),其中,AML复发率为33.3%(10/30),ALL复发率为37.5%(9/24),CML复发率为12.5%(1/8)。单因素分析显示,移植后复发的发生与患者性别、年龄、疾病类型、血型、人类白细胞抗原（HLA）配型、初诊时伴髓外病变、急性移植物抗宿主病（aGVHD）的发生、巨细胞病毒（CMV）感染无明显关系（P>0.05）;与移植前微小残留病（MRD）水平、慢性移植物抗宿主病（cGVHD）的发生有关,移植前MRD阳性、移植后未并发cGVHD患...     

异基因外周血造血干细胞移植治疗重型再生障碍性贫血

目的：探索异基因外周血造血干细胞移植(allo—PBSCT)治疗重型再生障碍性贫血(SAA)的疗效及其长期造血重建，分析其治疗过程中移植物抗宿主病(GVHD)的发生状况，探讨其有效治疗方法。方法：1例SAA患者，男性，26岁，供者为其胞妹，HLA配型完全相合。预处理采用全身照射(TBI) 环磷酰胺(CTX) 抗胸腺细胞球蛋白(ATG)方案；GVHD预防采用常规环胞菌素，A(CsA) 短程甲氨蝶呤(MTX)方案；治疗慢性GVHD(cGVHD)采用霉酚酸酯(MMF) CsA 硫唑嘌吟(6—MP) 泼尼松 酞咪哌啶酮(反应停，Thalido-mide)。结果：移植后23d造血重建。同时检测染色体核型为46，XX(G)，第63天血型由B型转变为O型。移植133d发生cGVHD，随访28个月，cGVHD已控制。结论：异基因外周血造血干细胞移植可有效治疗重型再障。本例造血重建迅速，cGVHD有效治疗后可被控制。     

Cyclosporin A as prophylaxis against graft-versus-host disease in 36 patients

Oral cyclosporin A was used as prophylaxis against graft-versus-host disease in (a) 31 patients with acute leukaemia or aplastic anaemia given transplants of HLA-matched bone marrow and (b) five patients with inborn errors of metabolism given transplants of haplotype-identical (parental) bone marrow. Twenty-six patients survived longer than two months after the operation. Despite the cyclosporin A, 31 patients (86%) suffered an acute form of graft-versus-host disease and 22 (61%) a chronic form. Nevertheless, the disease was usually treatable with immunosuppressive agents and caused the death of only one patient. Cyclosporin A caused renal toxicity in all cases; occasionally this was associated with a "capillary leak" syndrome, fatal in two patients. In children hypertension, fits, and fluid retention were common side effects. Blood concentrations of cyclosporin A correlated with blood urea values and blood pressure but did not predict the occurrence of graft-versus-host disease. Four different dose schedules were used to find the optimum way to administer this drug. Oral cyclosporin A is extremely effective at reducing the severity of graft-versus-host disease, but prevention of the disease is limited by toxicity of the drug and variable absorption. Better results might be achieved with parenteral administration or by using the drug in combination with other methods.     

Risk factors for bronchiolitis obliterans syndrome in allogeneic hematopoietic stem cell transplantation

Background The occurrence of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare but severe. We examine the role of pre-HSCT chemotherapeutic exposure, pre-HSCT comorbidities, and transplant-related complications in the development of BOS after allo-HSCT.

Methods A nested case-control study was designed. Cases with BOS and controls matched for the year of allo-HSCT and length of the follow-up were identified from a cohort of 1646 patients who underwent allo-HSCT for treatment of hematologic malignancies between 2006 and 2011. Antithymocyte globulin was used in the partial matched related and unrelated matched donor HSCT, or patients with severe aplastic anemia.

Results Thirty-six patients suffered from BOS; the mean age at the time of presentation was (32.7±12.4) years, and the mean time to presentation was (474±350) days post-HSCT. A pre-HSCT cyclophosphamide dose of ≥3.2 g/m2 (OR=8.74, P=0.025), chronic graft-versus-host disease (moderate to severe) (OR=12.02, P=0.000), and conditioning regimens without antithymocyte globulin (OR=2.79, P=0.031) were independently associated with BOS.

Conclusions We found that higher pre-HSCT cyclophosphamide exposure, a conditioning regimen without antithymocyte globulin, and moderate to severe chronic graft-versus-host disease are significantly and independently associated with BOS. Based on these results, we can identify patients who are at a higher risk of developing BOS after allo-HSCT, select a more appropriate therapeutic strategy, and improve the outcome of HSCT recipients.

     

异基因联合脐带间充质干细胞移植术后患者的护理

目的探讨异基因联合脐带间充质干细胞（Mesenchymal Stem Cell,MSC）移植术的护理。方法采取规范的治疗方案护理,严格控制脐带MSC、外周造血干细胞（PBSC）、骨髓干细胞输入时间及方法,注意观察病情,加强aGVHD皮肤、肠道及肝脏护理。结果联合移植后1个月复查患者嵌合体均为100%完全供者嵌合;白细胞植入中位时间13.5d,血小板植入中位时间14d;半年内无死亡病例。结论对移植后发生的植入综合征、感染及出血性膀胱炎并发症采取有效的预防和护理是保证移植术成功的关键。     

Long-term outcomes in adults with leukemia treated with transplantation of two unrelated umbilical cord blood units

Background  Wide application of umbilical cord blood transplantation (UCBT) in adult patients is limited by low cell-dose available in one umbilical cord blood (UCB) unit. The aim of this study was to investigate the safety and long-term outcomes of UCBT from unrelated donors in adult and adolescent patients with leukemia.

Methods  Thirteen patients with leukemia received double-unit UCBT with human leukocyte antigen (HLA) mismatched at 0–2 loci. We analyzed the engraftment, graft-versus-host disease (GVHD) and survival.

Results  Twelve evaluable patients (92.3%) had neutrophil and platelet engraftment at a median of 21 days (range, 16–38 days) and 34 days (range, 25–51 days), respectively. At day 30, engraftment was derived from one donor in 8 patients (66.7%, 95% CI 40.0%–93.4%), and from both donors in 4 patients (33.3%, 95% CI 6.7%–60.0%) with 1 unit predominated. Unit with larger nucleated cell (NC) dose would predominate in engraftment (P=0.039), whereas CD34⁺ cell dose or HLA-match failed to demonstrate any relationship with unit predominance. Only one patient developed grade II acute graft-versus-host disease (aGVHD). Chronic GVHD (cGVHD) was observed in 2 of 11 patients who survived more than 100 days, and both were limited. The median follow-up after transplantation for the 13 patients was 45 months (range 1.5–121.0 months) and 72 months (range 41.0–121.0 months) for the 8 alive and with full donor chimerism. The 5-year cumulative disease free survival (DFS) was (61.5±13.5)%. Of the 13 patients, 5 patients died in 1 year and 1-year transplantation related mortality (TRM) was 23.1% (95% CI 0.2%–46.0%).

Conclusion  Double-unit UCBT from unrelated donors with HLA-mismatched at 0–2 loci may overcome the cell-dose barrier and be feasible for adults and adolescents with leukemia.

     

造血干细胞移植女性患者的若干问题

造血干细胞移植(HSCT)是根治多种造血及非造血系统良恶性疾病的重要方法,应提高临床医生对于女性患者移植前后可能出现的问题的认识,如人乳头瘤样病毒感染、异常子宫出血、早发性卵巢功能不全、生育力保护措施、激素补充治疗与青春期诱导、生殖器移植物抗宿主病等,从而推动HSCT患者的全生命周期医疗管理.     

不同强度预处理方案用于系列不明急性白血病异基因造血干细胞移植的疗效比较

目的 分析两种不同强度预处理方案对系列不明急性白血病(ALAL)异基因造血干细胞移植(allo-HSCT)的疗效.方法 回顾性分析南方医科大学附属南方医院血液内科2002年3月至2010年8月38例ALAL患者临床资料.标准清髓性预处理方案为全身放疗+环磷酰胺或白消安+环磷酰胺;超强预处理方案为氟达拉滨+阿糖胞苷+全身放疗+环磷酰胺.移植物抗宿主病(GVHD)预防在人白细胞抗原(HLA)全相合相关移植患者用环孢素A(CsA)+甲氨蝶呤(MTX),HLA不相合相关移植及无关移植患者采用CsA+MTX+抗胸腺细胞球蛋白和(或)霉酚酸酯.COX模型分析影响长生存的因素.结果 19例患者接受标准预处理方案;19例接受超强预处理方案.移植后38例患者均获造血重建,5年累计总体总生存(OS)和无病生存(DFS)率分别为35.5%和25.7%;标准预处理组和超强预处理组5年0s率分别为20.2%与48.1%(P=0.233)、DFS为6.5%与43.1%(P:0.031).38例患者移植后5年白血病累计复发率为58.9%,标准预处理组和超强预处理组分别为87.6%和30.4%(P=0.003).COX单因素分析显示:超强预处理及慢性GVHD为DFS的保护因素(P=0.001、0.031).结论 在allo-HSCT中应用超强预处理能改善ALAL患者的生存及减少复发,移植物抗白血病效应对ALAL患者具有一定疗效.

Abstract：

objective To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT)in the conditionings of different intensities for acute leukemias of ambiguous lineage(ALJAL). Methods A total of 38 ALAL patients were treated with two conditionings of different intensities in our hospital from March 2002 to August 2010. The standard conditioning included TBI+Cy or Bu+Cy,intensified conditioning included Fludarabine+Ara-C+TBI+Cy. Cyelosporine A(CsA)and methotrexate (MTX) were administered in patients with human leukocyte antigen-matched sibling donor. And CsA, MTXplus antihuman thymocyte globulin and/or mycophenolate were used in all patients with HLA-A-mismatched related donor and unrelated donors transplants for graft-versus-host disease(GVHD)prophylaxis. COX regression was used to evaluate the prognostic factors of ALAL Results Among 38 ALAL patients,19received the standard conditioning while another 19 the intensified conditioning. All patients achieved hematopoietic reconstitution. The 5-year overall survival(OS)and the disease-free survival(DFS)were 35. 5%and25. 7%respectivelv. The 5-year OS rates were 20. 2%and48. 1%(P=0. 233)and DFS 6. 5%and 43. 1%(P=0. 031)in the standard and intensified conditioning groups respectively. The 5-year cumulative relapsing incidence was 58. 9%in all patients and 87. 6% vs 30. 4% in the standard and intensifted conditioning groups respectively(P=0. 003). Through a COX regression model for univariate analysis, the intensified conditioning and chronic GVHD were protective factors for DFS (P = 0. 001,0. 031 ). Conclusions The intensified conditioning in ALAL patients undergoing allo-HSCT may improve the long-term patient survival and decrease the relapse of leukemia. The graft versus leukemic effect has some efficacy in ALAL patients undergoing allo-HSCT.     

马利兰和环磷酰胺预处理方案的非亲缘异基因骨髓移植治疗骨髓增生异常综合征

目的:评估以马利兰和环磷酰胺(Bu-CY2)为预处理方案的非亲缘异基因骨髓移植治疗骨髓增生异常综合征(MDS)的临床疗效。方法:对6例MDS患者进行非亲缘异基因骨髓移植术,以Bu-CY2为预处理方案,Bu 4 m g.k-g 1.d-1,-7 d~-4 d,CY 60 m g.k-g 1.-d 1,-3 d~-2 d。输入单个核细胞数(MNC)为3.38×108/kg(2.4×108/kg~4.6×108/kg),CD 34+细胞数5.81×106/kg(1.2×106/kg~8.5×106/kg),粒-巨噬细胞集落形成单位(CFU-GM)数2.88×105/kg(1.61×105/kg~4.56×105/kg)。以霉酚酸酯加环孢素A(C sA)和短程氨甲蝶呤(MTX)预防移植物抗宿主病,前列腺素E1脂质微球预防肝静脉阻塞病。结果:6例患者中性粒细胞≥0.5×109/L的中位时间为18 d(13~21 d),血小板≥20×109/L的中位时间为21 d(13~24 d)。经DNA短串联重复序列多态性分析和染色体检查,均为供者骨髓植活。早期死亡率为0,移植后随访时间为27个月(6~60个月)。目前实际无病生存6例,缓解期实际生存率100%。结论:以Bu-CY2为预处理方案的非亲缘异基因骨髓移植是治疗MDS的有效方法。     

128例急诊内科呼吸困难患者的临床诊治分析

目的：分析128例急诊内科呼吸困难患者临床诊治情况。方法整群选取2014年3月—2016年3月在该院急诊科室接受呼吸困难治疗的128例患者,并进行回顾分析。判断患者正确诊断率、误诊率和心肺疾病误诊率、心肺疾病外误诊率。结果128例呼吸困难患者的正确诊断率、误诊率以及心肺疾病误诊率、心肺疾病外误诊率分别为93.75%（120/128）、6.25%（8/128）、5.56%（6/108）、10%（2/20）。结论急诊内科呼吸困难患者的诊治水平同急诊科医师专业诊断技术的全面性以及临床经验密切相关。