外周血干细胞移植治疗11例急性白血病和恶性实体瘤

目的:观察外周血干细胞移植(PBSCT)治疗急性白血病和恶性实体瘤的临床疗效观察。方法:自1999年11月至2004年3月,用PBSCT治疗急性白血病和恶性实体瘤11例,其中:急性淋巴细胞白血病(ALL)1例;急性非淋巴细胞白血病(ANLL)3例;非霍奇金淋巴瘤(NHL)4例;霍奇金淋巴瘤(HD)1例;乳腺癌1例;恶性黑色素瘤1例。除1例异基因外周血干细胞移植患者采用重组人粒细胞集落刺激因子(rhGCSF,惠尔血)对供者进行动员外,其他患者均为自体外周血干细胞移植,动员方案为化疗 rhGCSF。经2次采集,获得MNC为(5.91±2.34)×108/kg,CD34 细胞为(14.05±6.65)×106/kg,CFUGM(4.80±2.80)×105/kg。预处理方案3例患者采用FTBI加化疗,8例患者采用高剂量化疗方案。结果:所有患者移植后均重建造血。外周血WBC于移植后(6±1)天降至0。PLT于(7±1)天降至30×109/L以下。WBC>1.0×109/L、中性粒细胞>0.5×109/L、PLT>50×109/L,分别为(11±2)天、(11±2)天、(13±3)天。3例患者于移植后1～12个月死于肝功能衰竭或病情复发,2例患者带瘤生存3～5个月,其余患者均无瘤存活3～46个月,疗效仍在近一步随访中。结论:PBSCT对急性白血病和恶性实体瘤是一种安全有效的治疗方法。     

外周血干细胞移植治疗恶性淋巴瘤15例

 目的　观察自体外周血干细胞移植治疗恶性淋巴瘤（ML）的疗效。方法　对15例中、高度ML[其中非霍奇金淋巴瘤（NHL）13例,霍奇金淋巴瘤（HL）2例]在首次完全缓解（CR）后行自体外周血干细胞移植,患者采用大剂量环磷酰胺联合粒细胞集落刺激因子动员外周血干细胞,在干细胞采集结束后,予CBV方案行预处理,预处理结束48～72 h后回输自体外周血干细胞。结果　全部病例获造血重建。随访6～36个月,15例患者中13例持续CR（86.7 %）,2例患者分别于+120天和+185天复发,复发后经局部放疗加白细胞介素-2治疗,再次获缓解,至今无复发倾向。结论　自体外周血干细胞移植是一种治疗ML安全有效的方法,是延长ML无瘤生存的有效措施。     

自体造血干细胞移植治疗侵袭性恶性淋巴瘤

[目的]探讨自体外周血十细胞移植对侵袭性恶性非霍奇金淋巴瘤的疗效。[方法]31例侵袭性恶性非霍奇金淋巴瘤（NHL）患者使用化疗或放化疗同步进行的诱导缓解治疗达部分缓解（PR）或完全缓解（CR）后，行自体外周血干细胞移植治疗，部分患者移植后进行免疫治疗6～12个月。[结果]31例患者中位随访时间53个月，总生存率（OS）87．0％，无事件生存率（EFS）80．6％、其中CR后移植持续缓解率为88．0％，PR后移植持续缓解率为50．0％。[结论]自体外周血干细胞移植治疗侵袭性恶性非霍奇金淋巴瘤疗效确切，移植前达到CR患者疗效更佳。     

脐带血血清体外培养的人骨髓间充质干细胞对干细胞移植病人造血重建的影响

目的：观察脐带血血清体外培养体系培养的人骨髓间充质干细胞对干细胞移植病人造血重建的影响及不良反应。方法：用10%脐带血血清体外培养体系培养的人骨髓间充质干细胞联合自体外周血干细胞移植治疗3例恶性淋巴瘤患者,计数BM-MSC的数目,观察其造血重建时间、不良反应。结果：采用10%脐带血血清培养体系培养BM-MSC,回输时达到2.82-3.96×106/kg,3例患者中性粒细胞〉0.1×109/L的时间为移植后第9-12天,血小板〉20×109/L的时间为移植后第9-15天,无明显不良反应。结论：10%脐带血血清培养体系是一种基于临床移植需要的分离、培养人BM-MSC的方法,此法培养的BM-MSC联合APBSC移植治疗恶性淋巴瘤患者,加速了造血重建,未见明显不良反应,具有临床应用价值。     

自体外周血造血干细胞移植治疗非霍奇金淋巴瘤疗效分析

目的观察高剂量化疗联合自体造血干细胞移植治疗复发和难治性非霍奇金淋巴瘤的疗效。方法1995年至2005年采用大剂量化疗联合自体外周血造血干细胞移植治疗非霍奇金淋巴瘤30例。外周血干细胞动员方法为将常规剂量CHOP方案中CTX增至2500mg/m2,化疗后予G-CSF3.5~5μg/kg的动员方案,当骨髓功能恢复WBC计数达(2~5)×109/L,外周血单核细胞(MNC)计数达20%~30%时分离外周血造血干细胞。预处理方案为异环磷酰胺(IFO)12g/m2,阿糖胞苷(Ara-c)4.5g/m2,足叶乙甙(Vp-16)0.75g/m2。结果30例患者移植后缓解时间为1~108个月,中位缓解期42个月。其中1年无病生存25例(83%),2年22例(73%),3年20例(66.7%)。最长存活9年。全组无移植相关死亡。结论高剂量化疗联合自体造血干细胞移植治疗复发和难治性恶性淋巴瘤的疗效优于常规化疗。     

化疗联合单一剂量rhG-CSF用于自体外周血造血干细胞移植的临床研究

背景与目的:总结广东省干细胞多中心研究协作组自1999年6月至2001年12月间55例自体外周血造血干细胞移植治疗造血系统恶性疾病的资料,对化疗联合单一剂量rhG-CSF用于自体外周血造血干细胞移植前动员及移植后造血重建的效果进行研究和评价。方法:全部病例(急性髓细胞性白血病28例,急性淋巴细胞性白血病9例,非霍奇金淋巴瘤14例,其他4例)采用化疗+重组粒系集落刺激因子(rhG-CSF,格拉诺赛特)联合动员方案,其中白血病患者主要采用EA方案,恶性淋巴瘤患者主要采用以CTX为主的方案。rhG-CSF用量为250μg/d,WBC升至>4×109/L后,连续1～2天采集PBSC。移植后+3天开始使用rhG-CSF250μg/d,并观察造血重建情况。结果:动员所需的时间即自化疗开始至采集的平均时间为(18.08±3.63)天,rhG-CSF平均应用剂量为4.15μg·(kg·d)-1,应用时间平均7.12天。55例患者平均采集1.38次,采集到的MNC细胞数为(4.09±1.69)×109/kg,CD34+细胞平均值为8.5×106/kg,CFU-GM平均为(6.1±5.8)×105/kg。WBC恢复至>1.0×109/L及中性粒细胞绝对值>0.5×109/L的中位天数分别为10天和10.5天,全部移植患者均获满意的造血重建。结论:我们采用的EA和以CTX为主的化疗联合单一剂量rhG-CSF,是一种安全有效的动员自体外周血造血干细胞的方法,单一剂量rh     

高剂量化疗并自体外周血干细胞移植治疗实体瘤九例分析

目的 探讨高剂量化疗并自体外周血干细胞移植治疗高危实体瘤的可行性及疗效,了解外周血干细胞动员及采集时机、造血功能重建等问题.方法 9例经病理组织学确诊的高危乳腺癌2例,非霍奇金淋巴瘤(NHL)3例及4例小细胞肺癌经过诱导化疗后,进行了高剂量化疗并自体外周血干细胞的移植.结果 随访7(1.6～13.8)个月,9例全部生存,7例无瘤生存.回输的单个核细胞(MNC)＞1.5×108/kg时,中性粒细胞(ANC)恢复≥0.5×109/L和血小板20×109/L所需的天数分别为9天和9.4天,无1例骨髓功能重建不全.结论 高剂量化疗并自体外周血干细胞移植对化疗敏感的乳腺癌、NHL及小细胞肺癌具有较好疗效且较安全,回输足够数量的造血干细胞,可使造血功能快速重建.     

自体造血干细胞移植治疗恶性淋巴瘤15例临床分析

目的:评价自体造血干细胞移植(AHSCT)治疗恶性淋巴瘤患者的疗效。方法:采用AHSCT治疗恶性淋巴瘤患者15例,其中霍奇金淋巴瘤患者3例(均为复发病例),非霍奇金淋巴瘤患者12例(Ⅲ、Ⅳ期或复发病例,IPI评分2-4分)。采集外周血造血干细胞前均经化疗及动员剂动员(CHOP方案9例,CHOP+MTX 3例,CEP、大剂量MTX、单用G-CSF各1例)。预处理方案为联合化疗10例(BEAC、CBV方案为主),联合化疗加放射治疗5例(TBI、TLI各1例,提前局部照射3例)。结果:移植后白细胞≥1.0×109/L的中位时间为10(9-13)天,血小板≥50×109/L的中位时间为14(11-17)天。随访时间为1-110.5个月。中位生存时间为43(1-110.5个月)个月,3年总生存率(OS)为66.7%。结论:AHSCT是一种治疗复发难治恶性淋巴瘤的安全有效的方法。     

自体造血干细胞移植支持下BEAC方案治疗晚期复发恶性淋巴瘤

目的：报告 20例恶性淋巴瘤在自体造血干细胞移植支持下接受超大剂量化疗的初步治疗经验 ,评价所用外周血造血干细胞 (peripheral blood progenitors,PBPC )动员方案的动员效果,预处理方案的远期疗效和耐受性,以及回输后造血重建情况。方法： 20例复发、晚期恶性淋巴瘤中, 1例复发霍奇金病 (Hodgkin s disease,HD),19例非霍奇金淋巴瘤 (non- Hodgkin s lymphoma,NHL）。经常规化疗获缓解后, 3例采用自体骨髓移植 (autologous bone marrow transplantation,ABMT), 17例采用自体外周血干细胞移植 (autologous peripheral blood stem cell transplantation,APBSCT);动员方案为环磷酰胺 (CTX)3 500 mg/m2＋ G- CSF 3.5～ 5μ g/kg＋地塞米松 10 mg,预处理方案为 BEAC(CTX 3 600～ 4 000 mg/m2,Vp- 16 1 200 mg/m2,BCNU 300 mg/m2和 Ara- C 1 500～ 2 000 mg/m2),化疗结束后 24～ 48 h回输自体造血干细胞。结果： ABMT病人回输单核细胞 (MNC)1.3(1.0～ 1.7)× 108/kg, APBSCT病人回输 MNC 1.8(1.0～ 4.4)× 108、 CFU- GM 5.1 (1.9～ 9.6 )× 105/kg和 CD34＋细胞 2.9(1.9～ 8.7)× 106/kg。回输造血干细胞后均获快速造血功能重建,中性粒细胞 (ANC)≥ 0.5× 109/L时间为 9(6～ 17)天,血小板≥     

聚乙二醇重组人粒细胞集落刺激因子在复发难治恶性淋巴瘤自体外周血造血干细胞动员中的应用研究

  目的  比较聚乙二醇重组人粒细胞集落刺激因子（pegylated recombinant human granulocyte colony stimulating factor,PEGrhG-CSF）与粒细胞集落刺激因子（granulocyte colony stimulating factor,G-CSF）在复发难治恶性淋巴瘤自体外周血造血干细胞动员（peripheral blood stem cell mobilization,PBSCM）及自体外周血造血干细胞移植（autologous peripheral stem cell transplantation,APBSCT）后造血重建中疗效及药物经济学差异。  方法  选择2014年7月至2016年10月上海交通大学附属第一人民医院收治的复发难治恶性淋巴瘤患者15例,应用PEG-rhG-CSF动员（试验组）;选择2013年1月至2015年8月上海交通大学附属第一人民医院收治的复发难治恶性淋巴瘤患者15例,应用G-CSF动员（对照组）,进行回顾性分析。  结果  两组患者外周血造血干细胞均动员采集成功,其中试验组和对照组采集物的中位CD34+细胞计数分别为16.2×106/kg和8.9×106/kg（P=0.414）;中位总单核细胞（mononuclear cell,MNC）数量分别为12.4×108/kg和9.9×108/kg（P=0.519）。试验组和对照组的平均动员时间分别为（10.66±1.45）d和（9.33±1.83）d（P=0.234）。动员期间,试验组和对照组的平均粒缺时间分别为（4.20±2.17）d和（3.80±2.04）d（P=0.608）。干细胞回输后,试验组和对照组粒系重建的平均时间分别为（10.14±1.29）d和（10.93±2.69）d（P=0.327）。血小板重建平均时间分别为（10.36±2.27）d和（12.27±3.38）d（P=0.121）。两组在干细胞动员和造血系统重建方面无显著差异。在药物经济学方面,PEG-rhGCSF平均费用明显低于G-CSF,分别为3 960元和（11 479.3±2 401.3）元（P < 0.001）。  结论  PEG-rhG-CSF在复发难治恶性淋巴瘤的自体PBSCM中疗效与传统的G-CSF相当,且可明显降低患者费用,应用前景广泛。      

Effect of cyclosporine and irradiation on experimental pancreatic allografts in the primate

The present study assessed the effectiveness of cyclosporine (CSA) and subtotal marrow irradiation (TL1) alone, and CSA in combination with TL1 in a primate segmental pancreatic allotransplantation model. Continuous administration of CSA 25 mg/kg/day and 50 mg/kg/day resulted in mean graft survival of 21.5 days and 24.5 days, respectively. Administration of fractionated TL1 800 rad (8 Gy) and 1,000 rad (10 Gy) alone resulted in mean graft survival of 13.3 days and 14.5 days, respectively. Of 20 animals that received TL1 1,000 rad (10 Gy) and CSA 25 mg/kg/day orally for 5 days then 10 mg/kg/day intramuscularly indefinitely, 3 had graft survival of greater than 100 days. Likewise, of a group of 15 animals that received TL1 800 rad (8 Gy) and combined indefinite administration of CSA, 6 had graft survival of greater than 100 days. Although CSA and TL1 administration alone produced modest pancreatic allograft survival, a combination of IL1 (800 or 1,000 rad) and CSA resulted in highly significant segmental pancreatic allograft survival in the primate.     

Efficacy of up-front treatment with a double stem cell transplantation in multiple myeloma

BACKGROUND: We report the outcome of 53 patients with multiple myeloma (MM), who received autologous stem cell transplantation (ASCT) from April 1996 to September 2004 at our institution and who survived for more than 3 months after the transplant. METHODS: Following the first ASCT, 36 patients underwent an up-front second SCT, which consisted of either an ASCT (n = 24) or a reduced-intensity conditioning allogeneic stem cell transplant (RIST) (n = 12). Seventeen patients were given maintenance treatment. RESULTS: Seventy-seven percent of the patients (n = 41) showed an objective response to the initial therapy prior to the first ASCT. Overall, 60.4% (32 out of 53) and 32.1% (17 out of 53) of the patients had a complete response (CR) and partial response (PR) after the first ASCT, respectively. At the time of analysis, 34 patients (64.2%) were still alive. With a median follow-up of 32 months (range 9-98), the estimated progression-free survival (PFS) and overall survival (OS) at 5 years were 17.0 and 34.9%, respectively. Multivariate analysis revealed that the second SCT, normal hemoglobin and <50% marrow plasma cells were associated with an improved PFS. A second SCT, CR to the first SCT, female gender and an absence of advanced bone lesions were associated with a better OS. CONCLUSIONS: A second SCT is the most significant factor for an improved PFS and OS after the first ASCT (P < 0.001, respectively). Up-front double SCT is needed to improve the OS and PFS in patients with MM.     

Primate endocrine function after pancreatico-duodenal-splenic allotransplantation

In this study the endocrine function following intraperitoneal hetero- and orthotopic pancreatico-duodenal-splenic allotransplantation (PDS) in hemipancreatectomized, non-immune-suppressed chacma baboons was assessed. Significantly reduced K-values and insulin release together with glucose intolerance during IVGTT were observed in hemipancreatectomized recipients (HPS) without grafts. Orthotopic and heterotopic PDS transplantation improved the glucose intolerance of HPS recipients; orthotopically sited grafts rendering the best curves. Normal glucose tolerance was not achieved. Both orthotopic and heterotopic PDS transplantation rendered suboptimal insulin release during IVGTT; heterotopically draining grafts released significantly more insulin than orthotopic grafts. Hyperglucagonaemia during IVGTT was a constant feature in both groups, heterotopic grafts releasing the most glucagon during stimulation. C-peptide release was significantly lower in orthotopic grafts compared to normal animals or heterotopically drained insulin. It is concluded that glucose tolerance was not directly related to insulin or glucagon release in this study as orthotopic grafts rendered near-normal IVGTT curves in the presence of hypoinsulinaemia, hyperglucagonaemia, and reduced C-peptide values. The hormonal response after PDS transplantation was variable and the advantages of portal vs systemic insulin drainage remain to be defined.     

Costs of Allogeneic Hematopoietic Cell Transplantation Using Reduced Intensity Conditioning Regimens

Reduced intensity conditioning (RIC) regimens have allowed older patients and those with comorbidities to receive hematopoietic cell transplantation (HCT). We analyzed medical costs from the beginning of conditioning to 100 days after HCT for 484 patients and up to 2 years for 311 patients who underwent a RIC HCT at two institutions from January 2008 to December 2010. Multiple linear regression was used to analyze the association between clinical variables, center effect, and costs. Patient and transplant characteristics were comparable between the sites, although differences were seen in pretransplant performance scores. Significant predictors for lower costs for the first 100 days included a diagnosis of lymphoma/myeloma and use of human leukocyte antigen‐matched related donors. Grade II‐IV acute graft‐versus‐host disease (GVHD) was associated with higher costs. The overall short‐term costs between the two institutions were comparable when adjusted for clinical variables (p = .43). Late costs between 100 days and 2 years after HCT were available for one cohort (n = 311); median costs during this period were $39,000 and accounted for 39% of costs during the first 2 years. Late costs were not associated with any pretransplant variables, but were higher with extensive chronic GVHD and death. After adjustment for clinical characteristics, the overall costs of the RIC transplants were similar between the two institutions despite different management approaches (inpatient vs. outpatient conditioning) and accounting methodologies. Use of unrelated/alternative donors, transplant for diseases other than lymphoma or myeloma, and acute GVHD were predictors for higher early costs, and extensive chronic GVHD and death were associated with higher late costs.     

造血干细胞移植研究和应用的回顾与展望

 结合第54届美国血液学会年会教育论坛的相关内容着重复习造血干细胞移植（HSCT）领域的一些进展。在论述人类白细胞抗原（HLA）配型技术和供者来源扩展的基础上,分别简述了各类HSCT（HLA-相合同胞供者移植、脐带血移植、无关供者移植、 HLA-单倍型相合的移植）疗效的提升,也回顾了疾病种类和病期对HSCT结局的影响;结合自身的理解与经验,强调确保供者安全的注意事项与意义。     

肾移植术后恶性肿瘤:14例病例

目的总结肾移植术后恶性肿瘤的发生率、发生机制及治疗方法。方法回顾性分析我院1991～2006年间500例肾移植后并发恶性肿瘤的诊断、治疗情况。结果14例病例发生恶性肿瘤,占肾移植病例总数的2．8％。治疗方法包括：停用或减少部分免疫抑制剂的用量,更换免疫抑制剂的种类;手术切除肿瘤,辅以化疗和放疗。后者转归较佳。讨论要重视肾移植后病人发生肿瘤的问题。肾移植后个体化监测及治疗对术后并发恶性肿瘤患者有较大的帮助。     

LIVER TRANSPLANTATION FOR HEPATIC CANCER

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