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1.
目的 探讨人类白细胞抗原(HLA)单倍相合造血干细胞移植(HSCT)治疗恶性血液病的疗效和主要并发症.方法 对2004年7月至2006年12月第三军医大学附属新桥医院收治的35例恶性血液病患者进行HLA单倍相合亲缘供者HSCT.采用延长、强化联合免疫抑制促进植入、抗胸腺细胞球蛋白(ATG)加强预防移植物抗宿主病(GVHD)、粒细胞集落刺激因子(G-CSF)动员的骨髓(BM)加外周血干细胞(PBSC)混合移植方案.结果 所有患者均重建供者造血.18例(51.4%)发生急性GVHD(aGVHD),其中Ⅰ度8例,Ⅱ度5例,Ⅲ度3例,Ⅳ度2例,Ⅱ~Ⅳ度aGVHD累积发生率为28.6%.12例(34.3%)发生慢性CVHD(cGVHD),均为局限性.23例患者存活,总存活率为65.7%,2年无病存活率(DFS)为62.9%.12例患者死亡,7例死于复发,5例死于移植相关合并症,其中肺部感染2例,Ⅳ度GVHD 2例,巨细胞病毒(CMV)感染1例.结论 随着预处理方案、GVHD预防方案及移植物成分的优化,HLA单倍相合造血干细胞移植的疗效明显改善,已成为治疗恶性血液病的重要方法. 相似文献
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随着人口寿命的延长,老年人恶性血液病的发病率明显增高。除急性淋巴细胞白血病(ALL)的发病率仅次于5岁以下儿童外,其余各种类型恶性血液病的发病率均居各年龄段之首[1] 。然而到目前为止,老年人恶性血液病的常规治疗效果远不如年轻患者。随着造血干细胞移植(HSCT)技术的不断成 相似文献
3.
静脉滴注白消安和氟达拉滨预处理方案行异基因造血干细胞移植治疗髓系血液病疗效观察 总被引:1,自引:0,他引:1
目的探讨静脉滴注白消安(Bu)和氟达拉滨(Flu)作为预处理方案,进行异基因造血干细胞移植治疗髓系血液病的疗效。方法选取2003年10月至2005年4月成都军区昆明总医院血液科髓系血液病患者9例,其中急性非淋巴细胞白血病(ANLL)3例,慢性粒细胞白血病(CML)5例,骨髓增生异常综合征(MDS)1例,均进行同胞白细胞抗原(HLA)全相合异基因造血干细胞移植。预处理方案采用移植前第6天至移植前第3天静脉滴注白消安3.2mg/(kg.d),共4d;移植前第6天至移植前第2天静脉滴注氟达拉滨30mg/(m2.d),共5d。环孢素A和霉酚酸酯(骁悉)联合应用预防移植物抗宿主病(GVHD)。结果9例患者均成功植入,中性粒细胞>0.5×109/L的平均时间为12d;血小板(PLT)>20×109/L的平均时间为14d。中位观察时间为31个月。除轻微胃肠道反应外,无严重的预处理相关毒性,移植后1个月检测证实均为供者型完全植入。发生急性GVHD2例,慢性GVHD1例。9例患者中8例无病存活。结论静脉滴注Bu/Flu预处理方案,移植相关毒性小,治疗髓系血液病安全有效。 相似文献
4.
目的:探讨HLA不全相合外周血造血干细胞移植(PBSCT)治疗急性白血病(AL)的可行性。方法:应用HLA1个位点不合亲缘供体PBSCT治疗急性白血病2例,采用BUCY加ALG进行预处理,采用环孢素A、甲氨喋呤、霉酚酸酯和抗CD25单抗等联合预防移植物抗宿主病(GVHD)。结果:2例患者均获造血重建,并发Ⅱ度急性GVHD及局限性慢性GVHD。随访19个月均无病生存,恢复正常生活。结论:对缺乏HLA完全相合同胞供体的白血病患者,应用HLA不全相合的亲缘供体PBSCT治疗急性白血病具有一定的应用前景。 相似文献
5.
患者男 ,4 5岁。因乏力 1个月 ,于 1999年 2月入院。血象 :Hb 6 9g/L ,WBC 4 7× 10 9/L ,血小板 5 0× 10 9/L ,诊断为急性非淋巴细胞白血病 (M2b)。给予DA方案 :柔红霉素(DNR) 4 0mg ,3d ,阿糖胞苷 (Ara c) 15 0mg ,7d ;MCA方案 :米托蒽醌 (MIT) 6mg ,5d ,环磷酰胺 (CTX) 4 0 0mg ,3d ,Ara c 15 0mg ,7d ;化疗 2个疗程后达部分缓解。此后又给予DA和IDA方案 :去甲氧柔红霉素 (IDR) 10mg ,5d ,Ara c10 0mg ,7d ;IDEA方案 :IDR 10mg ,5d ,Ara c 10 0mg ,7d ,VP 16 10 0mg ,5d ;各化疗一疗程 ,骨髓达完全缓解(CR)。患者男… 相似文献
6.
脐血移植治疗恶性血液病的临床研究 总被引:1,自引:0,他引:1
目的 :研究脐血移植 (CBT)在恶性血液病长期造血重建和移植物抗宿主病 (GVHD)及其他移植相关并发症发生情况。方法 :用CBT治疗恶性血液病 11例。供者均为患儿同胞 ,并于产前HLA配型 ,其中 9例完全相合 ,2例 4个位点相合。预处理选用Bu/Cy方案。仅用环孢素A(CsA)预防GVHD。脐血平均采集量 14 1(76~ 2 0 8)ml,输入有核细胞 (NCs)中位数 3.5 (1.5~ 10 .0 )× 10 7/kg。 结果 :9例造血重建 ,ANC >0 .5× 10 9/L的中位时间为 17(13~ 4 2 )d ,>1.0× 10 9/L中位时间为 2 1(16~ 5 0 )d ,PLT >2 0× 10 9/L中位时间为 2 6 (2 1~ 4 8)d ,>5 0× 10 9/L的中位时间为 4 5 (31~ 80 )d。DNA微卫星位点检测 ,2 8~ 90d呈现完全嵌合。其中 3例发生Ⅰ~Ⅱ度急性GVHD ,1例Ⅲ~Ⅳ度急性GVHD ,3例发生慢性局限性GVHD ,2例未植活。结论 :①同胞HLA相合脐血移植安全、有效。②CBT造血恢复时间与输入有核细胞数有关 ,最好NCs≥ 3.5× 10 7/kg。③Bu/Cy方案副作用小 ,是儿童造血干细胞移植安全有效的预处理方案。④HLA相合者仅用CsA即可预防GVHD。 相似文献
7.
HLA部分不相合异基因外周血干细胞移植造血重建 总被引:2,自引:0,他引:2
目的:了解HLA部分不相合异基因外周血干细胞移植(ALLo-PBSCT)后造血功能重建情况,及在发生严重移植物抗宿主病(GVHD)时对造血功能的影响。方法:对患者移植后的血象、骨髓象,生化指标进行动态观察并分析结果。结果:移植后,+ 13 d 白细胞达2.2×109/L;+ 20 d 骨髓增生活跃;+ 46 d ABO 血型、MN 血型、HLA表型、HLA DNA分型均转为供型者,显示移植物植入成功。+ 10 d 开始出现GVHD征象,+ 29 d 达GVHDⅢ度,经用马抗人胸腺细胞球蛋白(ATG)、CD3 单抗、CD25单抗后,症状消失。同时造血功能明显受抑。结论:①ALLo-PBSCT造血重建过程中,应用G-CSF可促使移植干细胞加快分化、增殖。②发生严重GVHD后,用ATG等药物抑制T细胞,同时减少T细胞分泌GM-CSF等相关细胞因子,致造血功能受抑制。 相似文献
8.
异基因造血干细胞移植(allo-HSCT)是根治恶性血液病的有效手段,在全球范围内广泛应用。近20年allo-HSCT蓬勃发展,移植数量逐年增加,移植方案不断优化,移植疗效和安全性不断提高。该文介绍allo-HSCT治疗恶性血液病的现状并对未来可能的发展方向进行展望。 相似文献
9.
目的探讨异基因造血干细胞移植治疗年龄较大的白血病患者安全性和疗效。方法采用HSCT治疗10例45—63岁恶性血液病患者,HLA6/6位点相合8例,5/6位点相合2例。以清髓性方案预处理4例,减低强度方案预处理6例。HLA不全相合患者加用ATG。采用环孢素联合霉酚酸酯预防移植物抗宿主病(GVHD)。结果本组10例受者均获造血重建。中性粒细胞绝对计数≥0.5×10^9/L,血小板≥20×10^9/L的中位时间分别为移植后12(9~16)天和15(12~21)天。3例发生了急性GVHD(30%),Ⅱ度以上2例。可评估的9例患者中2例出现了慢性GVHD(22%)。复发2例,死亡3例。可评估的2年无病生存率为70%。结论造血干细胞移植对于高龄白血病患者是一种有效、安全的根治疗法。 相似文献
10.
目的 :探讨应用单倍体相合骨髓移植对难治高度恶性非霍奇金淋巴瘤 (NHL)治疗的可行性。方法 :6例难治高度恶性NHL伴有骨髓浸润患者接受人白细胞抗原 (HLA) 2~ 3个位点不合的单倍体相合移植 ,供者用粒细胞集落刺激因子 (G CSF)促进后采髓 ,急性移植物抗宿主病 (GVHD)预防例 1采用环孢菌素A(CSA)、短程甲氨蝶呤 (MTX)、霉酚酸酯 (MMF)和抗胸腺细胞球蛋白 ,余 5例除上述药物外 ,还加用CD2 5单克隆抗体。结果 :6例移植后均获造血重建 ,粒细胞绝对数 >0 .5× 10 9/L中位天数是 17d ,血小板 >2 0× 10 9/L的中位天数是 2 2d ,骨髓植活直接证据检测证实为完全供者造血。 1例于移植后 2 0d时发生急性Ⅳ度肠道GVHD ,可评价慢性GVHD病例4例 ,均发生慢性GVHD ,其中 1例广泛性慢性GVHD ,口服泼尼松和CSA病情控制。中位随访 2 0 (7~ 4 2 )个月 ,1例重度GVHD于移植后 2个月死亡 ,1例在移植后 4个月并发真菌感染死亡 ,无病存活 4例 ,Karnofshy生存质量评价为 10 0 %。结论 :研究表明单倍体相合未经体外去T细胞骨髓移植对难治高度恶性NHL具有一定治疗价值 ,能够降低急性重症aGVHD发生和减少移植相关死亡。 相似文献
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12.
自19世纪60年代末期第1例造血干细胞移植成功以来,造血干细胞移植为血液系统疾病、实体肿瘤、遗传和代谢性疾病提供了一种重要的治疗方式。但移植后感染性并发症很常见,尤其肺部感染具有较高的发病率和病死率。本文即对造血干细胞移植后肺部感染的诊治特点作一综述。 相似文献
13.
Shimazaki C Ochiai N Uchida R Okano A Fuchida S Ashihara E Inaba T Fujita N Maruya E Nakagawa M 《Blood》2003,101(8):3334-3336
Feto-maternal microchimerism suggests that immunologic tolerance exists between mother and fetus. Based on this hypothesis, we performed haploidentical stem cell transplantation (SCT) without T-cell depletion (TCD) in 5 patients with advanced hematologic malignancies. HLA incompatibilities for graft-versus-host disease (GVHD) direction included 3-loci mismatches in 4 patients, and 2-loci mismatches in one patient. Recipient chimeric cells were detected in all patients. The prophylaxis against GVHD was tacrolimus with minidose methotrexate. Engraftment was obtained in all patients. An acute GVHD of less than or equal to grade 2 developed in all patients except one who developed tacrolimus encephalopathy. Two patients died, 1 from fungal pneumonia and 1 from disease progression. The other 3 patients survived, with one patient in complete remission. These observations suggest that haploidentical SCT based on the feto-maternal microchimerism without TCD is possible. 相似文献
14.
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。 相似文献
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用低强度Bu/Cy预处理方案进行异基因造血干细胞移植治疗恶性血液病的疗效观察 总被引:1,自引:1,他引:1
目的探讨使用低强度Bu/Cy预处理方案进行异基因造血干细胞移植治疗恶性血液病的疗效。方法在哈尔滨医科大学附属第二医院采用低强度的Bu/Cy方案,进行异基因造血干细胞移植,治疗5例恶性血液病,预处理方案是:马利兰3~4mg/(kg·d)×3,环磷酰胺50mg/(kg·d)×2,阿糖胞苷2g/(m2·d)×1~2d,移植前7d开始环孢素A(CsA)3mg/(kg·d),霉酚酸酯(MMF)1g/d。结果5例病人均重建造血,未发生预处理相关严重并发症,5例病人已无病存活3~22个月(中位时间10·5个月)。结论低强度的Bu/Cy预处理方案,移植相关毒性减小,该方法治疗恶性血液病是安全可行的。 相似文献
16.
Detrait M Dubois V Sobh M Morisset S Tedone N Labussière H Gillis L Barraco F Cannas G Ducastelle S Fatoum J Thomas X Chelgoum Y Nicolini FE Michallet M 《Experimental hematology》2012,40(10):792-799
Anti-human leukocyte antigen (HLA) antibodies are associated with several complications in solid organ transplantations, but their impact after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not yet well defined. To evaluate the relevance of anti-HLA antibodies, we have retrospectively analyzed 107 peripheral blood allo-HSCTs after reduced-intensity conditioning regimen between 2005 and 2010. Acute myeloid leukemia and multiple myeloma were the most frequent malignancies in the cohort. The detection of anti-HLA antibodies was systematically performed in all patients before transplantation. Anti-HLA antibodies were present in 24 patients (22%). There was no significant impact of anti-HLA antibodies on engraftment, incidence of relapse, and incidence of acute graft-vs-host disease. The presence of anti-HLA antibodies was associated with significantly worse overall survival (p = 0.006) and event-free survival (p = 0.024) after stratification on sex. The 3-year probability of overall survival was 34% without anti-HLA antibodies and 16% in their presence. Patients with anti-HLA antibodies had a higher transplant-related mortality associated with life-threatening vascular complications. Our study supports that anti-HLA antibodies should be tested and considered as an important impacting factor for transplantation outcomes after reduced-intensity conditioning allo-HSCT. We recommend its consideration before allo-HSCT in the donor-recipient selection parameters. 相似文献
17.
Huang XJ 《Best Practice & Research: Clinical Haematology》2011,24(3):351-358
Currently, human leukocyte antigen (HLA)-mismatched/haploidentical allografts have been validated as an alternative stem cell source for patients who have no immediate access to an HLA-matched related or unrelated donor. However, relapse remains a challenge after HLA-mismatched/haploidentical hematopoietic stem cell transplantation (HSCT) that is employed in the treatment of patients with hematological malignancies. In recent years, newly developed immunomodulatory strategies, which include prophylactic and therapeutic donor lymphocyte/natural killer (NK) cell infusion, donor selection based on NK alloreactivity/non-inherited maternal antigen (NIMA), immune reconstitution promotion, and application of exogenous cytokines, have made it possible to decrease the relapse rate and improve outcomes following haploidentical HSCT. Further elucidation of the underlying mechanisms that govern leukemia stem cell escape from immunosurveillance after haploidentical HSCT may broaden our understanding and lead to therapies that control relapse. 相似文献
18.
An overview of conditioning regimens for haploidentical stem cell transplantation with post‐transplantation cyclophosphamide 下载免费PDF全文
Munira Shabbir‐Moosajee Lindsey Lombardi Stefan O. Ciurea 《American journal of hematology》2015,90(6):541-548
Haploidentical related donors are an attractive alternative source of stem cells for allogeneic stem cell transplantation due to widespread availability and ease of stem cell procurement. Historically, haploidentical stem cell transplantation (HaploSCT) with extensive T‐cell depletion has been associated with high rates of infectious complications and nonrelapse mortality (NRM). Post‐transplantation cyclophosphamide (PTCy) has been shown to induce immune tolerance, effectively control graft‐versus‐host‐disease (GVHD), and is associated with lower NRM, making it a preferred option for patients undergoing HaploSCT. Over the last decade, several groups investigated PTCy for GVHD prevention in HaploSCT; it is now successfully utilized with both myeloablative and nonmyeloablative conditioning regimens with survival comparable to HLA‐matched transplantation. Future directions will focus on optimizing conditioning regimens by diagnosis, improving donor selection, and enhancing graft‐versus‐leukemia effect. Am. J. Hematol. 90:541?548, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
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《Haematologica》2021,106(6):1599
We have used a non-myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation for the past 20 years. During that period, changes in clinical practice have been aimed at reducing morbidity and mortality from infections, organ toxicity, and graft-versus-host disease. We hypothesized that improvements in clinical practice led to better transplantation outcomes over time. From 1997–2017, 1,720 patients with hematologic malignancies received low-dose total body irradiation ± fludarabine or clofarabine before transplantation from HLAmatched sibling or unrelated donors, followed by mycophenolate mofetil and a calcineurin inhibitor ± sirolimus. We compared outcomes in three cohorts by year of transplantation: 1997–2003 (n=562), 2004–2009 (n =594), and 2010–2017 (n=564). The proportion of patients ≥60 years old increased from 27% in 1997–2003 to 56% in 2010–2017, and with scores from the Hematopoietic Cell Transplantation Comorbidity Index of ≥3 increased from 25% in 1997–2003 to 45% in 2010–2017. Use of unrelated donors increased from 34% in 1997–2003 to 65% in 2010–2017. When outcomes from 2004–2009 and 2010–2017 were compared to 1997–2003, improvements were noted in overall survival (P=0.0001 for 2004–2009 and P≤0.0001 for 2010–2017), progression-free survival (P=0.002 for 2004–2009 and P<0.0001 for 2010–2017), non-relapse mortality (P<0.0001 for 2004– 2009 and P<0.0001 for 2010–2017), and in rates of grades 2–4 acute and chronic graft-versus-host disease. For patients with hematologic malignancies who underwent transplantation with non-myeloablative conditioning, outcomes have improved during the past two decades. Trials reported are registered under clinicaltrials gov. Identifiers: , NCT00003145, 005803, NCT00003196, NCT00006251, NCT00014235, NCT00027820, NCT00031655, NCT00036738, NCT00052546, NCT00045435, NCT00060424, NCT00075478, NCT00078858, NCT00089011, NCT00104858, NCT00105001, NCT00110058, NCT00397813, NCT00793572, NCT01231412, NCT01252667. NCT01527045相似文献
20.
非去T细胞单倍型相合的造血干细胞移植31例临床分析 总被引:2,自引:0,他引:2
目的 探讨HLA单倍型相合造血干细胞移植(HSCT)对恶性血液病的疗效及其预后。方法 总结2002年7月至2006年7月在我院治疗的31例恶性血液病患者(标危组11例,高危组20例)接受HLA单倍型相合HSCT临床资料,分析急性移植物抗宿主病(aGVHD)发生及其相关因素。结果 31例患者中30例获得稳定的造血重建,移植后中性粒细胞〉0.5×10^9/L及血小板〉20×10^9/L的中位时间分别为13d和22d,发生Ⅱ-Ⅳ度aGVHD的累积发生率为61.3%,慢性GVHD的累积发生率为41.9%。标危组33个月累积无病生存率(DFS)为62.3%,高危组33个月的DFS为35.0%。移植物中CD3^+T细胞数量和供受体HLA—A、B、DR位点不相合的程度是影响aGVHD发生的主要因素。结论 HLA单倍型相合的HSCT对于恶性血液病是一种有效的治疗方法,移植物中CD3^+T细胞数量和HLA—A、B、DR位点不相合的程度是影响单倍型相合的HSCT的aGVHD发生的主要因素。 相似文献