60例实体肿瘤患者外周血干细胞的动员和采集

目的:对60例实体肿瘤患者造血干细胞的动员和采集效果进行分析。方法:采用常规化疗联合造血因子动员剂方法动员肿瘤患者外周血干细胞,CS-3000plus血细胞分离仪和程控冷冻降温方法采集、冷冻保存干细胞。结果:60例患者平均年龄41岁(24～57),Ⅰ期3.4%,Ⅱ期25.0%,Ⅲ期38.3%,Ⅳ期33.3%;肿瘤负荷情况,CR46.6%,PR31.6%。平均采集次数2.6次,MNC5.6×108/kg,CFU-GM2.4×105/kg,BFU-E1.7×104/kg,CD34+10.1×106/kg,CFU-GM第1次收获率50.0%,第2次36.0%。各病种间除CD34+外均无统计学差异。恶性淋巴瘤组CD34+细胞数高于其他病种。一次动员成功率90.0%。干细胞冷冻复苏后平均MNC回收率77.0%,CFU-GM回收率69.0%,BFU-E回收率72.0%。各病种之间回收率无差异。结论:常规化疗联合造血干细胞因子是实体肿瘤外周血干细胞移植的一种有效动员剂。     

rHuG-CSF动员健康供者外周血造血干细胞的效果观察

目的:观察重组人粒细胞集落刺激因子(recombinant human granulocyte-colony stimulating factor,rHuG-CSF)动员健康供者外周血造血干细胞的效果及影响因素。方法:将本研究中心异基因造血干细胞移植健康供者163例,分别采用3种不同厂家生产的rHuG-CSF进行外周血造血干细胞动员,对其动员效果、受者移植后造血重建等情况进行比较。结果:不同种rHuG-CSF动员后采集的单个核细胞(MNC)及CD34 细胞均能满足临床造血干细胞移植的需要,130例人类白细胞抗原(human leucocyte antigens,HLA)配型相合的同胞受者移植后均获得顺利植入。动员的单个核细胞数及CD34 细胞数与性别无关,而CD34 细胞数在41~60岁年龄组中明显减少(P<0.05);对采集时机的分析显示:第5天采集的单个核细胞数及CD34 细胞数最高(P<0.05),此后逐渐下降。结论:糖基化的及两个非糖基化的rHuG-CSF制剂均能有效地在异基因移植中作为外周血造血干细胞动员剂。     

超高CD34+采集的动员方案序贯二次自体造血干细胞移植治疗难治性 霍奇金淋巴瘤

目的:探讨超高CD34+采集的动员方案后序贯二次自体造血干细胞移植治疗难治性霍奇金淋巴瘤的疗效和安全性。方法:对1例经过多疗程一线、二线、新药、免疫等均难治的霍奇金淋巴瘤患者，予以IA+C方案化疗+G-CSF动员干细胞后采集出超高水平CD34+细胞，之后行自体造血干细胞移植，移植后获得完全缓解，再予序贯第二次自体造血干细胞移植进行巩固治疗。结果:总计输注单个核细胞数13.67×108/kg，CD34+细胞48.68×106/kg，第一次自体造血干细胞移植术后第7天造血功能恢复，复查全身PET-CT提示获得完全缓解，第二次自体造血干细胞移植术后第8天造血功能恢复，两次自体造血干细胞移植相关并发症均在可控范围内。结论:超高CD34+细胞采集的IA+C方案化疗+G-CSF动员可以让患者有机会进行多次自体造血干细胞移植，是临床动员的创新方案。对于难治性霍奇金淋巴瘤，序贯二次自体造血干细胞移植可达到更深层次缓解，且安全性较高，延长患者无疾病生存期及总生存期，为难治性霍奇金淋巴瘤治疗提供更多临床依据。     

急性白血病异基因外周血造血干细胞移植血缘供者安全性分析

目的：探讨急性白血病异基因外周血造血干细胞移植血缘供者近期的不良事件及远期的安全性。方法185例急性白血病异基因外周血造血干细胞移植血缘供者,干细胞动员后,用COBE Spectra血细胞分离机采集外周血干细胞。检测供者动员时血常规及形态学分类、CD34＋细胞百分比、干细胞混悬液中单个核细胞（ MNC）数量及CD34＋细胞计数,同时记录供者动员和采集过程中的不良事件、采集后第1、3、7天血常规变化及长期随访。结果血缘供者干细胞动员前白细胞计数为（6.16±1.58）x 109·L-1,采集时白细胞计数为（41.55±9.77）x109·L-1,是动员前6.75（4.18-10.87）倍。干细胞混悬液MNC为（247.61±105.99）x 108,CD34＋细胞为（3.54±3.42）x 108。动员时血缘供者的常见不良事件有头痛、腰背困痛、四肢痛、全身痛,合计占94.6%;外周血干细胞采集过程中,静脉持续输注葡萄糖酸钙,供者口周和指尖麻木等低钙症状发生率为3.2%;所有供者的不良事件均可耐受,无一例供者因不良事件终止干细胞动员或采集。供者干细胞采集后1周血象基本恢复正常;随访11 a血缘供者健康状况良好,无与动员及采集相关的远期并发症发生。结论急性白血病异基因外周血造血干细胞移植血缘供者动员采集无明显的近期不良事件及远期并发症,安全性非常高,为非血缘移植供者提供可靠的安全保障依据,减少恐惧感,降低反悔率。     

CD34+造血干细胞阳性提取进行异基因造血干细胞移植

CD34抗原在造血干细胞中有表达,因而将提取的CD34+造血细胞进行造血干细胞移植是可能的,是合理的,CD34阳性细胞的提取及移植是有其特点的,这样的异基因造血干细胞移植已有不少成功的报告,现将其主要方法介绍如下.     

自体外周血造血干细胞的动员和采集及冷冻保存研究

目的 评价自体外周血造血干细胞的动员和采集及冷冻保存效果。方法 20例病人采用大剂量化疗加刺激因子动员自体外周血干细胞(APBSC)后用CS—3000血细胞分离机和程控降温仪进行了65次APBSC采集和冷冻保存。结果 经化疗 rhG-CSF动员后采集的PBSC总数、CD34~ 细胞总数和CFU—GM总数不同病人相差较大,分别为MNC5.56±2.00×10~8/kg,CD34~ 23.25±41.90×10~6/kg,CFU—GM 21.68±15.39×10~4/kg。化疗后平均15.1天,用rhG—CSF7.9天CD34~ 细胞达峰值。经冷冻保存的干细胞回输后均使病人造血重建,采集与回输的PBSC数与造血重建时间相关。结论 本研究APBSC动员和采集及冷冻保存的效果肯定,APBSCT后全部病人造血重建,移植成功。     

胎盘脐带血造血干细胞库的建立与临床移植

1　胎盘脐带血干细胞库的建立我国多为独生子女 ,同胞间造血干细胞移植的供者来源日益匮乏 ,因此 ,建立非血缘关系胎盘脐带血库 ( PCBB)具有重要意义。北京大学血液病研究所提供技术 ,北京大学人民医院提供后勤支持 ,北京纬晓生物技术公司提供资金 ,于 1 996年开始筹建非血缘关系 PCBB,到 2 0 0 0年 7月已冻存经过 HLA配型的胎盘脐带血 3744余份。现将部分结果总结如下 :1 .1　库用材料与方法　 ( 1 )胎盘脐带血的采集 :来自经检查符合要求的足月顺产或剖宫产新生儿 ,经CPD- A抗凝。采用密闭式血袋采集法采集 ;( 2 )胎盘脐带血的分离 …     

外周血造血干细胞移植治疗恶性血液病53例

背景与目的:造血干细胞移植使恶性血液病的预后得到很大的改观,外周血造血干细胞移植(transplantation of peripheral blood stem cells,PBSCT)逐渐取代了骨髓移植(bone marrow transplantation,BMT)而成为造血干细胞移植的主要方式.本研究观察了自体或异基因外周血造血干细胞移植对53例恶性血液病患者的治疗效果.方法:53例恶性血液病患者于2003年7月～2006年5月在郑州大学第一附属医院血液科接受PBSCT治疗,中位年龄37岁.采用G-CSF或化疗联合G-CSF动员外周血干细胞.自体移植患者接受CD34 细胞的中位数为3.0×106/kg,异基因移植患者接受CD34 细胞的中位数为6.2×106/kg;自体移植采用MAC预处理方案,异基因移植采用改良的Bu/Cy预处理方案;移植物抗宿主病(graft versus host disease,GVHD)的预防采用MTX、环孢菌素A联合骁悉,1例1个点不合患者加用抗淋巴细胞球蛋白.结果:移植后中性粒细胞≥0.5×109/L、血小板≥20×109/L的天数在自体移植中分别为13天和19天,在异基因移植中分别为12天和15天;异基因移植中Ⅰ～Ⅲ度急性GVHD(aGVHD)的发生率为31.4%,慢性GVHD(cGVHD)的发生率为71.4%,复发率在自体移植和异基因移植患者中分别为38.9%和5.7%,700天无病生存率在自体移植和异基因移植患者中分别为57.9%和69.5%.结论:自体和异基因外周血造血干细胞移植均能很快地重建造血,是治疗恶性血液病的重要手段之一.     

-80℃直接冷冻保存造血干细胞移植治疗恶性血液病

:[目的]探讨 -80℃直接冷冻保存自体造血干细胞移植(APBSCT)治疗恶性血液病的疗效。[方法]ABSCT5例 ,移植前采用粒细胞集落刺激因子(G CSF)动员外周血干细胞(PBSC) ,分离后 ,将采集的PBSC分袋直接置于 -80℃冰箱冷冻保存。[结果]PBSC短期冻存后检测回收率和台盼蓝拒染率均在80%以上 ;接受移植的5例患者均获成功 ,并持续缓解(CCR) ,中位CCR时间为18(5～31)个月 ,无复发。[结论] -80℃直接冷冻短期保存PBSC具有良好效果 ;具有简单、方便、费用低等优点 ;ABSCT造血重建快并发症少 ,值得进一步推广     

外周血造血祖细胞检测对外周血干细胞动员采集的预测意义

 目的　通过血细胞分析仪检测外周血造血祖细胞（HPC）含量,探寻一种快速预测采集物干细胞含量、判断外周血造血干细胞采集时机的手段,并评价其应用意义。方法　对27例化疗联合粒细胞集落刺激因子（G-CSF）进行外周血造血干细胞动员采集者及17例单用G-CSF动员的采集者,利用血细胞分析仪检测外周血HPC计数,血液治疗和移植工程国际组织（ISHAGE）法检测外周血及采集物CD+34 细胞计数,并进行相关回归分析。对外周血HPC计数预测采集物CD+34 含量进行受试者工作曲线（ROC）分析。结果　无论化疗组或非化疗组,外周血HPC计数与CD+34 计数均具有线性相关性（r＝0.711,P＝0.000及r＝0.656,P＝0.004）。化疗组外周血CD+34 计数＝-0.829+0.648×外周血HPC计数;非化疗组外周血CD+34 细胞计数＝45.033+0.460×外周血HPC计数。化疗组患者外周血HPC计数与采集物CD+34 细胞量呈线性相关（r＝0.602,P＝0.001）,采集物CD+34 计数＝1.106+0.046×外周血HPC计数。以HPC≥85／μl预测采集物CD+34 计数≥5×106／kg的灵敏度为78 %,特异度为82 %。结论　在自体干细胞移植动员患者中,外周血HPC计数可部分替代外周血CD+34 计数预测采集效果,HPC≥85／μl为较好的预测阈值。     

异基因造血干细胞移植治疗白血病

目的探讨异基因造血干细胞移植(Allo-HSCT)治疗白血病的疗效、造血重建及生存情况.方法白血病患者10例,其中同胞间HLA相合的异基因外周血干细胞移植(Allo-PBSCT)7例,无亲缘关系HLA不全相合脐血移植(UCBT)3例.结果9/10例受者获造血重建,UCBT患者造血重建速度较HLA相合的同胞PBSCT慢,1例UCBT移植后35天造血未重建,回输自体外周血干细胞后,仍未能重建造血,于72天死亡.其余至今均无病生存.结论Allo-HSCT是目前治愈白血病的有效方法,对于无同胞HLA相合的供者,选择细胞数量较高、HLA 1～2个位点不合的UCBT仍然有效可行.     

Sustained molecular remission by non-myeloablative stem cell transplantation after autologous hematopoietic stem cell transplantation in a patient with multiple myeloma

Multiple myeloma (MM) is refractory to conventional chemotherapy. To achieve a sustained complete remission, we performed planned non-myeloablative allogeneic stem cell transplantation (NST) after autologous hematopoietic stem cell transplantation (HSCT) in a patient with stage III MM. Autologous HSCT was performed using high-dose melphalan after conventional chemotherapy, followed by NST from an HLA-identical sibling using low-dose total body irradiation (200 cGy) for conditioning. Cyclosporine and mycophenolate mofetil were used for graft-vs-host disease (GVHD) prophylaxis. Acute GVHD was transiently seen in the skin and intestine, while, in addition, mild chronic GVHD was seen in the oral mucosa and skin. Complete donor chimerism was achieved and the disappearance of tumor-derived monoclonal B cells was confirmed based on an analysis of immunoglobulin light chain messenger signals on day 156 when chronic GVHD occurred. The clinical course in this case strongly suggested the existence of a graft-vs-myeloma effect.     

Hematopoietic stem cell transplantation in mantle cell lymphoma.

BACKGROUND: Patients with mantle cell lymphoma (MCL) have in general, lower response rates and overall survival (OS) than those with other B-cell non-Hodgkin's lymphomas. The role of hematopoietic stem cell transplantation (HSCT) in MCL is unclear. Hence we decided to study the clinical course of patients who received autologous and allogeneic HSCT for MCL. METHODS: Ninety-seven patients, (80 patients-autologous; 17 patients-allogeneic) who received a HSCT for mantle cell lymphoma were included in the study. RESULTS: The complete response rates at day 100 between the two groups were similar (73% vs. 62%). Day-100 mortality was higher in the allogeneic HSCT group (19% vs. 0%) (P < 0.01). The estimated 5-year relapse rates, 5-year event-free survival (EFS) and 5-year OS among the allogeneic HSCT patients were 21%, 44% and 49%, respectively, similar to 56%, 39% and 47% in the autologous group. Ten patients received HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone + high-dose methotrexate and cytarabine) +/- rituximab prior to transplant. There have been no relapses or deaths amongst these patients at a median follow-up of 16 months. CONCLUSIONS: Patients treated with allogeneic HSCT had a lower relapse rate, but similar EFS and OS to autologous HSCT. Treatment of MCL with HyperCVAD +/- rituximab followed by HSCT seems promising.     

自体造血干细胞移植治疗复发难治恶性淋巴瘤十例效果观察

目的 探讨自体造血干细胞移植(AHSCT)治疗复发难治恶性淋巴瘤的疗效和安全性.方法 回顾性分析济南军区总医院2011年8月至2015年6月收治的10例接受AHSCT治疗的复发难治恶性淋巴瘤患者的临床资料,其中男性6例,女性4例;中位年龄34岁(20~50岁);复发4例,难治6例;霍奇金淋巴瘤(HL)5例,非霍奇金淋巴瘤(NHL)5例.移植前经过多个疗程的放化疗,予大剂量甲氨蝶呤(CTX)+粒细胞集落刺激因子(G-CSF)动员外周血造血干细胞,采用BEAM(卡莫司汀+依托泊苷+阿糖胞苷+美法仑)、CBV(环磷酰胺+卡莫司汀+依托泊苷)或全身照射(TBI)方案进行预处理.结果 10例AHSCT患者单个核细胞(MNC)中位计数为7.385×108/kg,移植后8例完全缓解,2例复发.中位随访时间为18个月(20~50个月),患者总生存率及无病生存率均为80%(8/10).患者均出现不同程度的恶心、呕吐、腹泻、口腔黏膜炎等不良反应,均可耐受.结论 AHSCT是治疗复发难治恶性淋巴瘤的有效方法,安全性较高.     

短程大剂量格拉诺赛特动员APBSC移植(附1例报告)

目的：报导短程大剂量格拉诺赛特（ｒｈＧ－ＣＳＦ）动员外周血造血干细胞,进行自体外周血造血干细胞移植（ＡＰＢＳＣＴ）治疗急性白血病。方法：ｒｈＧ－ＣＳＦ,５００μｇ／ｄ皮下注射４天,第５、６天单采外周血单个核细胞（ＭＮＣ）,行ＣＦＵ－ＧＭ培养,ＣＤ３４＾＋细胞由流式细胞仪检测。于ＭＡＣ方案处理,回输自体外周围血造血干细胞（ＡＰＢＳＣ）。结果：动员后ＣＦＵ－ＧＭ明显增高,ＣＤ３４＾＋细胞增多,骨髓造血     

骨髓间充质干细胞在造血干细胞移植中的应用研究

造血干细胞移植(HSCT)后,干细胞的成活、分化、增殖及造血功能的恢复,影响治疗的效果,移植过程中难免会遇到诸多问题。如造血微环境的破坏,干细胞归巢问题及移植后的移植物抗宿主反应(GVHR)均影响移植成败。近年研究发现骨髓间充质干细胞(MSC)为造血微环境的重要组成成分,可分泌多种细胞因子,能够促进造血,加速干细胞归巢,还能参与免疫反应,降低T淋巴细胞反应。而MSC的这些特性恰好可以减少HSC中的以上问题。因此,国内外已将HSC与MSC共移植治疗恶性肿瘤应用于临床,并取得了良好的临床效果。     

Current Status of Retroviral Vector Mediated Gene Transfer into Human Hematopoietic Stem Cells

Genetic modification of hematopoietic stem cells (HSCs) has been proposed as a treatment strategy for a variety of hematologic diseases, tracking marked cells or conferring resistance to chemotherapeutic agents. Despite early enthusiasm, the results of clinical studies involving gene transfer into HSCs has not resulted in therapeutic benefits for the vast majority of treated patients. This review describes the limitations and advances that have been made in the areas of gene transfer vectors, identification of the appropriate HSCs to target for genetic modifications and the methods used to perform gene transfer.     

Hematopoietic Stem Cell Transplants for Multiple Myeloma

Standard chemotherapy with melphalan-prednisone or a combination of alkylating agents has not extended the overall survival of patients with multiple myeloma during the last 30 years and strictly defined complete remissions (CR) are exceedingly rare. The early mortality with conventional therapy varies between 2 and 10 percent. A substantial increase in the dose of melphalan (100-140 mg/m²) has resulted in a 30-45% CR rate in newly diagnosed patients and an overall survival advantage of approximately 1 year. However, treatment related morbidity and mortality, due to prolonged cy-topenia was unacceptably high. Based on these findings the dose intensity was further increased by either escalating melphalan to 200 mg/m² or by adding total body irradiation, while at the same time providing stem cell support to shorten the duration of cytopenia. Autologous transplants, especially with peripheral blood stem cells and hematopoietic growth factors, can now be performed safely up to the age of 70 with a low transplant-related mortality (2-10%). A CR is attained in approximately 50% of previously untreated patients and 10-20% of refractory cases. Overall survival of newly diagnosed and refractory patients treated with autotransplants appears superior to that of patients receiving conventional chemotherapy. Therefore, autotransplantation should be considered as a treatment option in all patients with multiple myeloma at least up to the age of 65. Despite these encouraging findings, most myeloma patients ultimately relapse and the survival curves do not suggest that autotransplantation as currently performed is a curative approach in a substantial proportion of patients. Further improvement with autotransplants should be achieved by providing tumor-free grafts and by introducing post-transplantation manipulations, aimed at eradicating minimal residual disease.     

The Hematopoietic Stem Cell Transplantation in Hodgkin's Disease: Questions and Controversies

Most patients with Hodgkin's disease (HD) are cured with chemotherapy and/or radiotherapy. However, half of those with advanced stage disease (IIIB, IV) do not respond adequately to treatment or relapse. Salvage therapy used in such cases gives from 10% to 50% complete remission but only 10% long term survival. The results of bone marrow transplantation reported in acute leukemia and non-Hodgkin's lymphoma encouraged some authors to develop this new therapeutic strategy in Hodgkin's disease. In the early 1980's promising results were achieved when refractory and relapsed patients were selected to receive myeloablative therapy followed by bone marrow transplantation. Today, high dose chemotherapy with hematopoietic stem cell transplantation (HSCT) is used more and more often in poor prognosis Hodgkin's disease.