小剂量地西他滨在异基因造血干细胞移植后早期复发及cGVHD治疗中的作用

目的 分析小剂量地西他滨(decitabine/dacogen,DAC)治疗异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)后慢性移植物抗宿主病(chronic graft versus host disease,cGVHD)患者的转归情况.方法 收集2013年6月25日至2015年7月7日我院行allo-HSCT术后早期复发及发生cGVHD,并接受小剂量DAC治疗的4例患者,包括急性髓系白血病(acute myeloid leukemia,AML)3例,骨髓增生异常综合征(myelodysplastic syndrome,MDS)1例.对其诊断、移植方式、cGVHD分型及评分、以及DAC治疗后转归进行分析.结果 4例接受小剂量DAC的患者,cGVHD症状减轻,无严重的血液学毒性.1例因严重肺部感染放弃治疗,3例目前病情稳定.结论 小剂量DAC可减轻allo-HSCT术后cGVHD症状,改善患者生存质量,并对早期复发的控制有一定的效果.     

成人难治急性髓细胞白血病的诊治及其进展

急性髓细胞白血病(acute myeloid leukemia,AML)是一种较为常见的危及人类生命的血液系统恶性肿瘤.成人AML的治疗仍面临着巨大的挑战.尤其是难治AML的预后更差,再次达完全缓解的比例一般不超过30%,治愈率不到5%(除非行异基因干细胞移植).因此,难治急性髓细胞白血病(refractory acute myeloid leukemia)的治疗就成为白血病治疗中的难题之一.本文从成人难治AML发生的可能机制、诊断及治疗进展做一综述.     

细胞因子在造血干细胞移植中诱导免疫耐受的基础和应用研究

血液恶性疾病是严重危害人类生命健康的重大疾病,异基因造血干细胞移植(allogeneic hemopoietic stem cell transplantation,Allo-HSCT)是绝大多数血液恶性疾病患者的有效乃至唯一的根治手段,Allo-HSCT的基础是异体植入及随后的移植物抗白血病(graft versus leukemia,GVL)效应,但Allo-HSCT同时发生移植物抗宿主病(graft versus host disease,GVHD),导致GVHD相关死亡.     

移植前状态对难治复发急性淋巴细胞白血病异基因造血干细胞移植预后的影响

目的 探讨难治复发急性淋巴细胞白血病(acute lymphocytic leukemia,ALL)的缓解状态对异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)预后的影响.方法 回顾性分析我研究所不同缓解状态下行allo-HSCT的52例难治复发ALL患者,其中19例处于未缓解(non-remission,NR)状态,33例达到第2次及以上完全缓解(complete remission,≥CR2).所有患者均采用清髓性预处理,其中改良白消安加环磷酰胺37例,全身照射加环磷酰胺14例.结果 除1例患者早期死亡外,其余51例均获得造血重建,NR和≥CR2患者100 d内移植相关死亡为10.5％和12.1％ (P=1.000).移植后急性移植物抗宿主病(graft versus host disease,GVHD)发生率为52.6％和57.6％ (P =0.730),其中Ⅰ～Ⅱ度为42.1％和33.3％ (P =0.527),Ⅲ～Ⅳ度为10.5％和24.3％(P=0.399),慢性GVHD发生率为41.6％和57.9％ (P =0.660).中位随访时间为12(1.8 ～44.5)个月,26例患者无白血病生存至今.NR与≥CR2患者的预计2年总生存(overall survival,Os)和无白血病生存(leukemia-free survival,LFS)分别为42.6％、45.7％ (P =0.740)和46.3％、46.2％(P=0.998),累积复发率为47.0％、34.3％ (P =0.425).影响预后的单因素和多因素分析显示,移植前疾病缓解状态与生存无关,移植后发生慢性GVHD才是影响OS、LFS的独立预后因素.结论 移植前NR患者与≥CR2患者相比,移植预后无统计学差异,提示allo-HSCT挽救性治疗NR状态下难治复发的ALL是可行的.     

16.2.Leukocyte and leukocyte function

930341 Prophylaxis against graft versus hostdisease with low dose cyclosporin.CHEN Hu(陈虎),et al.North Taiping Road Hosp,Bei-jing,100039.Chin J Hematol 1993;14 (2):66—68.Graft versus host disease (GVHD) is a majorcomplication of allogeneic bone marrow trans-plantation (BMT).Combination of methotrex-ate (MTX) and cyclosporin (CSA) has reducedthe incidence of acute GVHD in HLA—identicalBMT.However,long term and high dose CSAcan increase side deffects of itself and the inci-dence of leukemia relapse following BMT.Ourresults of 23 leukemia patients receiving low     

难治复发性白血病患者造血干细胞移植后复发的分析

目的分析难治复发性白血病患者接受异基因造血干细胞移植(allo-HSCT)后复发的生存预后情况及影响因素。方法回顾性分析140例难治复发性白血病患者,其中急性髓系白血病69例,急性淋巴细胞白血病46例,慢性粒细胞白血病11例,急性混合型白血病10例,淋巴瘤白血病4例;移植前处于完全缓解(CR)49例,未缓解(NR)91例;诊断为中枢神经系统白血病(CNSL)28例。结果观察期内87例死亡,总死亡率为62.1%(87/140),复发率为39.3%(55/140),复发相关死亡为25.7%(36/140)。5年总生存率(OS)为(36.7±5.2)%,无病生存率(DFS)为(31.2±5.5)%。年龄≥40岁、移植前疾病NR状态、中枢侵犯、Ⅱ~Ⅳ°移植物抗宿主病均为影响难治复发白血病患者造血干细胞移植后复发相关死亡的独立危险因素。结论 allo-HSCT是挽救性治疗难治复发性白血病患者的有效手段,移植后复发是影响患者生存率的主要因素之一。降低移植后复发率是提高难治复发性白血病患者allo-HSCT后DFS的关键。     

复发难治性急性髓系白血病的治疗进展

<正>近年来,急性髓系白血病(acute myeloid leukemia,AML)发病率逐渐增高,其中,复发难治性急性髓系白血病所占比例的增加尤为明显^([1])。复发难治性急性髓系白血病因其自身特性难以达到完全缓解,并发症多,生存期短,治疗极为困难,是目前国内外本领域研究的重点和难点。本文就复发难治性急性髓系白血病的治疗进展做一简要综述。1复发难治性AML的发病机制对化疗耐药是AML复发、难治的主要原因之一,其机制复杂,为多因素作用的结果([1])。复发难治性急性髓系白血病因其自身特性难以达到完全缓解,并发症多,生存期短,治疗极为困难,是目前国内外本领域研究的重点和难点。本文就复发难治性急性髓系白血病的治疗进展做一简要综述。1复发难治性AML的发病机制对化疗耐药是AML复发、难治的主要原因之一,其机制复杂,为多因素作用的结果^([2])。主要包括:(1)细胞膜上能量依赖外排泵。多药耐药(MDR)是AML耐药的重要机制之一,白血病细胞对多种化疗药物同时产生耐药,是治愈白血病的最大障     

HLA半相合异基因外周血造血干细胞移植治疗AA克隆演变继发MDS疗效分析

目的：回顾性分析应用HLA半相合异基因外周血造血干细胞移植（haploidentical hematopoietic stem cell transplantation,haplo?HSCT）治疗再生障碍性贫血（aplastic anemia,AA）克隆演变继发骨髓增生异常综合征（secondary myelodysplastic syndrome,sMDS）的疗效和安全性。方法：本中心5例AA患者经强化免疫抑制治疗后演变为sMDS,均采用haplo?HSCT,观察植入情况,移植物抗宿主病（graft versus host disease,GVHD）、移植相关并发症和移植相关病死率（transplant related modify,TRM）、总体生存（overall survival,OS）时间等。结果：5例中位OS时间63个月（41.9~149.3个月）,移植后中位OS时间12.9个月（2.4~36.5个月）,1年累积生存率60%,TRM 40%。移植后粒系植入时间18 d（14~22 d）,血小板植入时间21 d（15~65 d）,总植入率100%。60%（3/5）患者发生Ⅰ~Ⅲ度急性移植物抗宿主病（acute graft versus host disease,aGVHD）,无Ⅳ度aGVHD发生,20%（1/5）患者发生慢性移植物抗宿主病（chronic graft versus host disease,cGVHD）。中位随访时间63个月（41.9~149.3个月）。结论：在无合适HLA相合供者情况下,haplo?HSCT可作为AA演变MDS患者的有效治疗策略。     

难治性白血病异基因造血干细胞移植超强预处理的疗效

目的 探讨异基因造血干细胞移植超强预处理联合移植后诱导移植物抗白血病(GVL)治疗难治未缓解白血病的预处理相关毒性(RRT)和疗效。方法 18例移植前难治未缓解白血病和62例移植前完全缓解的急性白血病或慢性粒细胞白血病慢性期病人分别接受超强预处理方案和全身放疗+环磷酰胺或改良BuCY(羟基脲、马利兰、阿糖胞苷、环磷酰胺)方案(对照组)。在难治性白血病移植后30d未出现移植物抗宿主病(GVHD)病人,采用早期快速递减环孢素A或供体淋巴细胞输注诱导GVL。统计移植后RRT发生率与致死率、移植后完全缓解率、GVHD发生率、白血病复发和无病生存率等。结果 移植后除超强预处理组1例和对照组2例死于移植相关并发症外,其余病人均获得造血重建。两组总RRT发生率均为100%,各脏器RRT发生均以胃肠最常见,超强预处理组和对照组分别为83.3%和85.5%,两组口腔RRT发生率分别为44.4%和62.9%,膀胱RRT发生率分别为16.7%和33.9%,各组比较未见差异。超强预处理组RRT致死率为0,对照组为5%,两组比较无差异(P=0.341)。18例接收超强预处理病人除1例死于移植中感染外,其余病人均获完全缓解。超强预处理组和对照组移植后急性GVHD发生率分别为11.8%和18.3%,移植后3年估计无病生存率分别为(61.2±12.3)%和(65.0±7.4)%(P=0.6311)。结论 连续序惯超强预处理方案能提高移植前未缓解的难治性白血病移植后完全缓解率和无病生存率,不增加移植中RRT发生率和致死率。     

Comparative outcomes between cord blood transplantation and bone marrow or peripheral blood stem cell transplantation from unrelated donors in patients with hematologic malignancies: a single-institute analysis

Background Umbilical cord blood (UCB) has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients. Our aim was to assess the leukemia-free survival (LFS) and some primary results, such as hematologic recovery, risk of graft-versus-host disease (GVHD), relapse, and long-term survival, after unrelated cord blood transplantation compared with the outcomes of transplantations from other unrelated graft source.

Methods The clinical outcomes of 112 consecutive patients with acute leukemia who received umbilical cord blood (UCBT) as a primary unrelated stem cell source (n=38), bone marrow (UBMT n=28, transplanted before January 2003), or peripheral blood stem cells (UPBSCT n=46, transplanted after January 2003) between July 2000 and July 2008 were analyzed.

Results Except that the patients were much younger in the UCBT group (median age, 10.5 years in UCBT, 30 years in UPBSCT, and 20 years in UBMT), other pre-transplant parameters, such as gender, diagnosis, and the phase of disease, were comparable. All patients received myeloablative regimens, primarily including BUCY; however, there was less anti-thymocyte globulin (ATG) used for the UBMT patients (2/38 in UCBT, 0/46 in UPBSCT, and 8/28 in UBMT did not use ATG, P=0.000). Significant delays in engraftment occurred after UCBT for both neutrophil cells and platelets. The cumulative allo-engraftment rates were also significantly lower (87.8% vs. 97.8% vs. 100% for WBC, P=0.000; 73.0% vs. 97.5% vs. 89.5% for PLT, P=0.000) for UCBT. The incidence of Grade 2?4 and 3?4 acute graft versus host disease (aGVHD) was much higher in the UBMT group but did not differ among the other groups (51% and 13.2%, 40.2% and 10.5%, and 77.4% and 41.2%, respectively, for UCBT, UPBSCT, and UBMT, P=0.000). The occurrence of extensive chronic GVHD (cGVHD) was significantly decreased for recipients of UCBT (4%) compared with that of UPBSCT (39.1%) and UBMT (49.1%, P=0.000), although the rates of whole cGVHD were not significantly different (30.3%, 63.1%, and 60.1% for UCBT, UPBSCT, and UBMT, respectively). The patients had a similar rate of CMV infection (21/38, 28/46, and 22/28 for UCBT, UPBSCT, and UBMT, respectively), while the HC occurrence was lower after UCBT (7/38, 16/46, and 14/28 for UCBT, UPBSCT, and UBMT, respectively). As of August 2012, there was no apparent difference in 5-year overall survival (OS), LFS, or the relapse rate for each graft source (52.5%, 52.6%, and 20.8% in UCBT; 48.7%, 46.4%, and 27.9% in UPBSCT; and 46.4%, 42.9%, and 16.0% in UBMT).

Conclusion These data support the use of UCB donors as an alternative allogeneic donor.

     

清髓性异基因造血干细胞移植治疗成人急性淋巴细胞白血病非血缘脐血与血缘相关移植的比较——单中心临床研究

目的 评估并比较异基因造血干细胞移植清髓方案治疗成人急性淋巴细胞白血病(ALL)的疗效及安全性.方法 异基因造血干细胞移植治疗37例成人急性淋巴细胞白血病患者:其中17例行非血缘脐血移植(UCBT)患者中位年龄25(14～37)岁、中位体质量55(31～84)kg、男性占82%,UCBT组中高危难治患者共15例(88%...     

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.

     

异基因造血干细胞移植治疗儿童急性髓系白血病的临床观察

目的 总结分析异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation,allo-HSCT）治疗儿童急性髓系白血病（acute myeloid leukemia,AML）的临床疗效,发现可能影响预后的相关因素。方法 收集2006年1月至2016年1月首都医科大学附属北京儿童医院血液肿瘤中心确诊为AML并进行allo-HSCT治疗的病例,采用Kaplan-Meier生存曲线评估患者的总生存率（overall survival,OS）,采用Log-rank检验进行不同组别比较。多因素分析采用Cox回归法分析影响预后的相关因素。结果 共收集46例病例,中位随访时间27个月。存活31例,15例死亡,8例复发。5年OS为（61.1±8.7）%,中位生存时间为77.3个月,5年累积复发率为（16.0±6.0）%。Log-rank检验结果显示前期后期不同移植方案、移植前缓解状态、缓解次数、不同供者来源、是否合并移植物抗宿主病在对OS影响上差异无统计学意义（P>0.05）。多因素分析显示,合并髓系肉瘤和复发是影响患者预后的危险因素（P<0.05）。结论 异基因造血干细胞移植是治疗AML尤其是难治/复发AML的有效治疗手段,随着移植方案的改良及支持治疗的发展,生存率逐年提高。合并髓系肉瘤及复发是影响AML移植治疗预后的重要不良因素。     

术前外周血淋巴细胞与单核细胞比值评估T1期非肌层浸润型膀胱癌预后的临床价值

目的 评估术前外周血淋巴细胞与单核细胞比值(LMR)在评估T1期非肌层浸润型膀胱癌(NMIBC)患者术后预后中的临床价值。方法 纳入行经尿道膀胱肿瘤切除术治疗的T1期NMIBC患者215例,收集临床资料,随访并记录患者无病生存(DFS)和总生存(OS)情况。作术前LMR与患者预后关系的受试者工作特征(ROC)曲线,确定LMR的最佳分界值,将患者分为低LMR组(LMR<3.86,n=77)和高LMR组(LMR≥3.86,n=138);采用Kaplan-Meier生存曲线比较不同LMR水平患者的累积DFS率和OS率,COX比例风险回归模型分析影响患者DFS和OS的因素。 结果 215例T1期NMIBC患者随访2~92个月,DFS率为59.07%,OS率为65.12%。Kaplan-Meier曲线示,低LMR组患者累积DFS率(χ ²=4.784,P=0.029)与累积OS率(χ ²=7.146,P=0.008)均明显低于高LMR组。肿瘤大小≥3 cm(HR=1.398,95%CI:1.042~1.875,P=0.025)、病理G3级(HR=1.266,95%CI:1.026~1.563,P=0.028)、LMR≥3.86(HR=2.347,95%CI:1.080~5.101,P=0.031)是影响T1期NMIBC患者DFS的独立因素;肿瘤大小≥3 cm(HR=1.228,95%CI:1.015~1.484,P=0.034)、病理G3级(HR=1.366,95%CI:1.017~1.834,P=0.038)、LMR<3.86(HR=2.008,95%CI:1.052~3.832,P=0.035)是影响T1期NMIBC患者OS的独立因素。结论 术前外周血LMR水平是影响T1期NMIBC患者预后的独立因素,低水平LMR患者术后的NMIBC进展风险与死亡风险更高。     

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.     

CIG方案治疗急性髓系白血病疗效分析

目的观察阿糖胞苷(Ara-C)、去甲氧柔红霉素(IDA)和粒细胞集落刺激因子(G-CSF)联合方案(CIG方案)治疗急性髓系白血病(acute myeloid leukemia,AML)的临床疗效及不良反应。方法初治、难治/复发和老年AML患者中36例采用CIG方案治疗,完成1个疗程后评估疗效,治疗失败患者则退出观察,有效者继续接受1个疗程治疗。随访分析患者总体生存期(overall survival,OS),评判CIG方案的疗效。结果 CIG组36例中完全缓解(completely remission,CR)20例(55.5%),部分缓解(partial remission,PR)9例(25%),未缓解(non remission,NR)7例,死亡1例,总有效率80.55%。其中第1个疗程达CR者14例,第2个疗程达CR者6例。CIG组中位OS 26个月。结论初治、难治/复发和老年AML患者治疗中,CIG方案是有效且不良反应低的治疗方法。     

FLAG方案治疗复发或难治性急性髓系白血病临床观察

目的:探讨FLAG方案治疗复发或难治性急性髓系白血病患者的疗效。方法:采用FLAG方案治疗复发或难治性急性髓系白血病患者37例。FLAG方案为氟达拉滨(Flu)30 mg/m2,dl～d5,阿糖胞苷(Ara-C)2 g,d1～d5,粒细胞集落刺激因子(G-CSF)5μg/kg d0直到白细胞恢复超过>1.5×109/L。结果:37例患者中12例完全缓解(CR),CR率为32.4%。随访中位总生存期(overall survival,OS)为6.2个月,中位无进展生存期(progression-freesurvival,PFS)为10.3个月。26例复发患者FLAG方案治疗前少于3个疗程化疗的患者与3个及3个以上化疗疗程的患者疗效比较,差异有统计学意义(P<0.01)。结论:FLAG方案治疗复发、难治的急性髓系白血病患者效果良好。