母供子非去T细胞性单倍体异基因造血干细胞移植治疗恶性血液病

目的:对18例恶性血液病进行母供子非去T细胞性单倍体异基因造血干细胞移植(Allo-HSCT)治疗,探讨其疗效及毒性反应。方法:6例急性髓系白血病(AML-M23例,AML-M41例,AML-M5b2例),3例慢性粒细胞白血病(伴骨髓纤维化1例),8例急性淋巴细胞白血病(ALL),非霍奇金淋巴瘤(Ⅳ期B组)1例,以母亲为供者进行非去T细胞性单倍体Allo-HSCT。供者动员方案:G-CSF300μg/12h×5d后采集造血干细胞。输注D34 细胞(3.58~8.90)×106/kg。预处理方案为:MeCCNC250mg·m-2·d-1×1d,Ara-C4g·m-2·d-1×2d,Bu4mg·kg-1·d-1×3d,CTX1.8g·m-2·d-1×2d。ALL患者以全身放疗(TBI)代替Bu。以CsA、MMF、MTX和ALG预防移植物抗宿主病(GVHD)。结果:所有患者均顺利完成预处理。移植后发生急性GVHD16例、慢性GVHD10例,出血性膀胱炎1例。全部患者在移植后10~20d获造血重建。18例患者中12例存活。结论:非去T细胞性单倍体Allo-HSCT是治疗恶性血液病的一种安全、有效的方法;同时提示在以后的单倍体异基因造血干细胞移植中优先选择母亲供体,对降低GVHD的严重程度、提高移植成功率是有帮助的。     

母供子非去T细胞性单倍体异基因造血干细胞移植治疗恶性血液病

异基因造血干细胞移植（allo-HSCT）是治愈恶性血液病的有效手段，但HLA相合（血缘相关或无关）供者来源的不足极大限制了allo—HSCT的应用。随着研究的进展，单倍体半相合allo-HSCT逐渐应用于临床，它有来源广、易获得、移植快等优点，使其成为allo-BMT研究的热点。我们对18例恶性血液病开展了母供子非去T细胞性单倍体allo-HSCT，探讨其有效性及毒副反应。     

异基因造血干细胞移植治疗恶性血液病

目的：探讨异基因造血干细胞移植(Allo—HSCT)治疗恶性血液病的疗效、造血重建、免疫重建及长期生存的情况。方法：血液系统恶性疾病患者12例，其中同胞HLA相合异基因骨髓移植(Allo-BMT)及外周血干细胞移植(Allo—PBSCT)7例；无亲缘关系HLA不全相合脐血移植(UCBT)5例。结果：11／12例受者获造血重建，UCBT患者造血重建速度较同胞PBSCT或BMT慢，1例UCBT移植后46d造血功能未重建，回输自体骨髓后恢复自体造血。11例Allo—HSCT受者免疫功能重建开始于移植后30d，死亡2例，均为移植后复发病例。结论：Allo—HSCT是目前治愈恶性血液病的最佳方法，对于无同胞HLA相合的供者，选择较高细胞数量、HLA1～2个位点不合的UCBT仍然安全有效。     

单倍体与同胞相合异基因造血干细胞移植治疗恶性血液病疗效观察

目的:探讨单倍体与同胞相合异基因造血干细胞移植治疗恶性血液病疗效及影响预后的相关因素。方法:分析2013年6月—2019年12月于山西白求恩医院行异基因造血干细胞移植的82例恶性血液病患者的临床资料，急性髓系白血病51例，骨髓增生异常综合征11例，急性淋巴细胞白血病20例。同胞全相合异基因造血干细胞移植(MSD-HSCT)30例，单倍体异基因造血干细胞移植(Haplo-HSCT)52例。结果:82例患者中位随访时间为15个月，总植入率为87.8%,移植前疾病未缓解者MSD-HSCT组占26.7%(8/30),Haplo-HSCT组占15.4%(8/52),Haplo-HSCT组和MSD-HSCT组移植后2年总生存率(OS)分别为63.3%和65.4%,差异无统计学意义(P=0.771),其中Haplo-HSCT组患者Ⅰ～Ⅱ度急性移植物抗宿主病(aGVHD)发生率为73.1%(38/52),明显高于MSD-HSCT组的46.7%(14/30),差异有统计学意义(P=0.017),其余移植相关并发症包括植入失败率、Ⅲ～Ⅳ度aGVHD、外周血巨细胞病毒、EB病毒、出血性膀胱炎，2组比较均差异...     

异基因造血干细胞移植治疗恶性血液病临床观察

目的观察异基因造血干细胞移植(allo-SCT)治疗恶性血液病的疗效.方法选择HLA-A、B、DR位点完全相同的同胞作为供者,对13例恶性血液病患者进行allo-SCT,其中急性白血病10例,慢性白血病2例,恶性淋巴结瘤1例.采用BUCY预处理方案7例,TBI CY预处理方案4例,非清髓预移植方案2例.输入CD34细胞数(4.6～11.4)×106/kg.患者均用环孢菌素A加甲氨蝶呤预防移植物抗宿主病.结果 11例清髓性移植患者移植后9～19天外周血白细胞≥1.0×109/L,14～34天血小板≥20×109/L.移植后4例死于移植相关并发症,9例完全缓解,中位生存期26(8～73)个月.结论 allo-SCT治疗恶性血液病疗效可靠.     

造血干细胞移植治疗恶性血液病151例

造血干细胞移植（ＨＳＣＴ）是近２０多年来治疗恶性血液病的重要方法，使恶性血液病根治率提高到５０％以上，使某些恶性肿瘤疗效大为提高，现介绍我们近年来所进行的１５１例ＨＳＣＴ治疗恶性血液病的经验，并对有关问题进行讨论。一、资料与方法（一）病例选择１９８７...     

减低剂量预处理对异基因造血干细胞移植治疗恶性血液病疗效观察

目的:探讨应用减低剂量的氟达拉宾、白消安和环磷酰胺(FBC)方案预处理对异基因造血干细胞移植(alloHSCT)治疗恶性血液病疗效的影响。方法:19例恶性血液病患者移植前进行减低剂量的FBC预处理。采用磷酸氟达拉宾(Flud)30mg/m2·d-1静脉滴注5d。白消安(Bu)0.6mg/kg、4次/d,共3d。环磷酰胺(CTX)30mg/kg·d-1静脉滴注,共2d,随后施行HLA配型的同胞或父亲供者的造血干细胞移植。术后采用环孢素及霉酚酸酯预防移植物抗宿主病(GVHD)。结果:全部患者的造血功能均获得快速重建。白细胞升至1.0×109/L以上,中位时间为(11.4±4.6)d。中性粒细胞升至0.5×109/L以上,中位时间为(11.9±6.7)d;血小板升至20×109/L以上,中位时间为(12.2±3.5)d。供者细胞完全植入15例,混合嵌合性植入4例,1例出现宿主排斥移植物(HVG)反应,进行供者淋巴细胞输注(DLI)2次后,达到完全供者嵌合。11例出现急性GVHD(57.89%),7例出现慢性GVHD(36.83%),2例HLA配型不完全相合者死于急性GVHD。结论:减毒的FBC预处理方案allo-HSCT治疗恶性血液病疗效肯定,并发症少,是治疗恶性血液病的有效方法。     

异基因造血干细胞移植治疗恶性血液病临床分析

异基因造血干细胞移植（allo-HSCT）是治疗血液系统疾病的重要手段,能够使恶性血液疾病得到治愈,明显改善预后.我们自2001年5月～2010年5月对37例恶性血液病患者进行了allo-HSCT.现报道如下。     

改良BU/CY预处理异基因造血干细胞移植治疗恶性血液病

异基因造血干细胞移植是治疗恶性血液病的有效方法,造血干细胞移植中预处理方案的选择和顺利进行是保证移植成功的重要部分。我们自2003年以来用改良BU/CY方案对39例恶性血液病患者进行了异基因造血干细胞移植,现报道如下。1资料与方法1.1临床资料39例均为2003年3月-2007年12月在我院住院患者,男22例,女17例;中位年龄30（6-55）岁。     

自体造血干细胞移植治疗恶性血液病及实体瘤的临床研究

目的探讨自体造血干细胞移植(AHSCT)治疗恶性血液病及实体瘤的疗效。方法1996年5月至2005年2月广州医学院第一附属医院肿瘤血液中心用AHSCT治疗的白血病及恶性淋巴瘤患者共20例,年龄18～50岁。预处理化疗方案选用以下药物中任意2种或3种联合:阿糖胞苷3～4g/m2,环磷酰胺4～6g/m2,依托泊苷(VP-16)0.5～1.0g/m2,司莫司汀300mg/m2,马法兰140mg/m2,塞替哌600mg/m2,卡铂1.0g/m2,白消安(Bu)16mg/kg。除2例ALL联合全身照射(剂量为8Gy)外,其余均单用化疗。结果所有患者移植后均重建造血,无移植相关死亡;随访中位值39.5(2～109)个月,无病生存者15例,占全部移植患者的75.0%。其中无病生存1年12例(60%),2年8例(40%),3年8例(40%),最长存活9年余。结论自体造血干细胞移植可明显提高完全缓解肿瘤患者的治愈率;对于复发或难治者,可以提高完全缓解率,延长生存期,提高生活质量。     

外周血造血干细胞移植治疗恶性血液病疗效观察

目的:观察外周血干细胞移植治疗恶性血液病的疗效、探讨移植相关并发症的预防及处理.方法:回顾分析了我院自2005年5月～2006年3月,其中2例采用HLA相合的同胞异基因外周血干细胞移植(AlloPBSCT),9例采用自体外周血造血干细胞移植(Auto-PBSCT).结果:全部病例均成功获得造血重建,中性粒细胞≥0.5×109/L,平均时间为11.3 d,血小板≥20×109/L平均时间为16.3 d;无严重并发症发生,无严重GVHD发生,中位随访时间11(2～24)个月,无复发及死亡病例.结论:外周血干细胞移植是治疗恶性血液病安全、有效的方法.     

Myeloablative haploidentical hematopoietic stem cell transplantation using basiliximab for graft-versus-host disease prophylaxis

Abstract

Objectives

We retrospectively compared the prophylactic effect of basiliximab and antithymocyte globulin (ATG) after haploidentical hematopoietic stem cell transplantation (HSCT) in patients with leukemia.

Methods

Haploidentical HSCT using basiliximab for graft-versus-host disease (GVHD) prophylaxis in 10 patients with leukemia was retrospectively compared to ATG for GVHD prophylaxis in 24 patients.

Results

All the patients achieved neutrophil engraftment. One patient in the ATG group did not achieve platelet engraftment. The incidence of grade II–IV and grade III–IV acute GVHD was 30 and 20%, respectively, in the basiliximab group and 16.7 and 4.2%, respectively, in the ATG group (P > 0.05). Extensive cGVHD developed in 40 and 22.2% of patients in the basiliximab group and ATG group, respectively (P > 0.05). Basiliximab resulted in mild infection and a low incidence (10%) of infection-related mortality; ATG resulted in relative severe infection with 29.2% infection-related mortality (P > 0.05). During the follow-up period, 20% of the basiliximab group and 22.7% of the ATG group relapsed (P > 0.05). In the basiliximab group and the ATG group, the 3-year accumulative overall survival rate was, respectively, 80 and 52.5% and the 3-year leukemia-free survival, respectively, was 60 and 49.6% (P > 0.05).

Discussion

The incidences of grade II–IV and grade III–IV aGVHD in the basiliximab group were similar to those in halpoidentical HSCT containing ATG. Compared to the ATG group, the basiliximab group had a lower rate of transplantation-related mortality and better long-term survival, but without statistical significance.

Conclusion

The prophylactic regimen of basiliximab with haploidentical HSCT against GVHD seems safe and promising. More studies needed to verify this.     

Alternative donor: αß/CD19 T-cell-depleted haploidentical hematopoietic stem cell transplantation for sickle cell disease

Sickle cell disease (SCD) is an inherited disorder; despite significant improvements in supportive care, SCD continues to cause substantial morbidity, mortality, and reduced life expectancy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only widely available curative therapy for SCD, which is offered as a standard of care for patients with a matched sibling donor (MSD). Donor availability is limited to a minority of patients. Thus, αβ/CD3-depleted haploidentical HSCT, as an efficient means for depletion of graft-versus-host disease (GvHD)-mediating T cells, can be offered as an alternative curative therapy, particularly for nonmalignant diseases such as SCD.Out of 38 patients with advanced stage SCD, 25 were transplanted with CD3/CD19- or T-cell receptor αβ/CD19 T-cell-depleted peripheral stem cell grafts (T-haplo-HSCT group), whereas 13 transplanted from MSD (MSD group); both groups received an almost identical conditioning regimen. Engraftment was achieved in all. However, in the T-haplo-HSCT group, three patients succumbed to an uncontrolled cytomegalovirus pneumonitis, a macrophage activation syndrome, and a major blood group incompatibility with a late graft failure and multiorgan failure. The overall survival was 88% and 100% in T-haplo-HSCT and MSD groups, respectively. None of our patients developed a Glucksberg Grade III–IV acute GvHD. Four patients (16%) in the T-haplo-HSCT group and two patients (15%) in the MSD group developed a steroid-sensitive, mild-to-moderate chronic GvHD that resolved within 18 months posttransplant.These results are encouraging and demonstrate the feasibility, safety, and efficacy of T-haplo-HSCT in advanced stage SCD in children and adults, thus offering a curative alternative to majority of patients.     

异基因造血干细胞移植治疗恶性血液病(附9例报告)

9例恶性血液病患者 ,采用异基因外周血干细胞移植 ( allo- HSCT)治疗 7例 ,外周血与骨髓干细胞混合移植 2例 ;供者均为人白细胞相关抗原 ( HL A)完全相合同胞兄妹。预处理方案用马利兰 ( BU)、环磷酰胺( CY) ,环孢霉素 A ( Cs A)联合短程甲氨蝶呤 ( MTX)预防移植物抗宿主病 ( GVHD)。结果 :患者治疗后均重建造血 ,中性粒细胞≥ 0 .5× 10 9/ L 的中位数为 14天 ,血小板≥ 2 0× 10 9/ L 的中位数为 16天。发生急性 GVHD5例 ,慢性 GVHD2例 ,肝静脉闭塞病 ( VOD) 1例 ,巨细胞病毒血症 9例。2例 ABO血型不合者移植后未发生溶血及纯红再障。1例耐药复发淋巴瘤 ,供、受者均为乙肝病毒携带者 ,移植后达完全缓解。中位随访时间 15个月 ,无病生存 8例。认为 allo- HSCT是治疗恶性血液病 (尤其是耐药复发者 )的有效方法 ,ABO血型不合及乙肝供者不是移植的障碍     

IL-2 activated NK cell immunotherapy of three children after haploidentical stem cell transplantation

Natural killer (NK) cells are thought to be of benefit in HLA-mismatched hematopoietic transplantation (H-SCT). Therefore, we developed a protocol for clinical-use expansion of highly enriched and IL-2-stimulated NK cells. Purification of unstimulated leukaphereses by a two-step T cell depletion with a final CD56 enrichment procedure leads to a mean purity of 95% CD56(+)CD3- NK cells with a four- to five-log depletion of T cells. So far, three pediatric patients with multiply relapsed acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) were treated with repeated transfusions post-H-SCT. Directed killer immunoglobulin-like receptor (KIR) mismatches were demonstrated in all three cases. Although all patients showed blast persistence at the time of transplant, they reached complete remission and complete donor chimerism within 1 month post-H-SCT. NK cell therapy was tolerated well without graft-versus-host disease (GvHD) induction or other adverse events. The AML patient died of early relapse on day +80, while the ALL patients died of thrombotic-thrombocytopenic purpura and atypical viral pneumonia on days +45 and +152, respectively. This initial trial showed the feasibility of good manufacturing practice (GMP)-compliant NK cell isolation and expansion for clinical applications. We now launch a clinical phase I trial with activated NK cells post-H-SCT.