Twelve Cases of Malignant Hematopathy Treated by Combined Therapy of Hematopoietic Stem Cell Transplantation and Chinese Herbal Medicine

Ｉｎｒｅｃｅｎｔｙｅａｒｓｔｈｅｈｅｍａｔｏｐｏｉｅｔｉｃｓｔｅｍｃｅｌｌｔｒａｎｓｐｌａｎｔａｔｉｏｎ（ＨＳＣＴ）ｄｅｖｅｌｏｐｅｄｒａｐｉｄ ｌｙ， ｐａｒｔｉｃｕｌａｒｌｙｔｈｅａｕｔｏ ｐｅｒｉｐｈｅｒａｌｂｌｏｏｄｈｅｍａｔｏｐｏｉｅｔｉｃｓｔｅｍ     

异基因外周血造血干细胞移植后巨细胞病毒间质性肺炎

目的：探讨异基因外周血造血干细胞移植(Allo-PBSCT)后间质性肺炎（IP）的病因,危险因素及防治方法。方法;将Allo-PBSCT患者分为更昔洛韦（GCV）预防组18例和对照组（未预防组）22例,比较两组巨细胞病毒南性肺炎（CMV－IP）的发生率。结果：对照组Allo-PBSCT患者中并发CMV－IP5例,预防组无1例发生CMV－IP。发生CMV－IP的高危因素为女性供者,合并移植物抗宿主病（GVHD）。4例治愈,1例治疗无效死亡。结论：Allo-PBSCT后CMV感染是IP的主要病因,IP的发生与GVHD严重程度及妇性供者密切相关,GCV能有效预防和治疗CMV－IP。     

异基因外周血干细胞的动员,检测及临床移植的应用研究

目的：探讨异基因外周血干细胞移植（ａｌｌｏ－ＰＢＳＣＴ）供者经Ｇ－ＣＳＦ或Ｇ－ＣＳＦ＋ＧＭ－ＣＳＦ动员后,采集的外周血干细胞（ＰＢＳＣ）移植物中的幼稚粒细胞与单个核细胞（ＭＮＣ）、ＣＤ３４＾＋细胞及ＣＦＵ－ＧＭ之间的相关性和移植的剂量标准及临床应用效果。方法：对１１例ａｌｌｏ－ＰＢＳＣＴ供者用Ｇ－ＣＳＦ（９例）或Ｇ－ＣＳＦ＋ＧＭ－ＣＳＦ（２例）进行动员,于动员前及动员后,分别对外周血及ＭＮＣ惧物中的幼稚粒细胞、ＣＤ３４＾＋细胞及ＣＦＵ－ＧＭ进行检测计数,预处理方法主要用大剂量环磷酰胺（ＣＴＸ）＋全身照射（ＴＢＩ）。结果：动员后外周血中的幼稚粒细胞与ＣＤ３４＾＋细胞及ＣＦＵ－ＧＭ同步增加,外周血ＭＮＣ中的幼稚粒细胞数与ＣＤ３４＾＋细胞数及ＣＦＵ－ＧＭ有较好的相关性。１１例患者全部植活和恢复造血功能,并为染色体核型     

Allogeneic peripheral blood stem cell transplantation in the treatment

Objective To investigate the efficacy of allogeneic peripheral blood stem cell transplantation (PBSCT) in the treatment of severe aplastic anemia (SAA) and severe infection. Methods A patient with SAA and pseudomonas aeruginosa septicemia was treated with PBSCT from an HLA-identical sibling with cyclophosphamide (CY) and total body irradiation (TBI) for conditioning. The patient was infused with 20.3×108/kg mononuclear cells including 61.0×106/kg CD34+cells following the conditioning regimen. Results Twenty days after PBSCT, the absolute neutrophil count (ANC) of 1.0×109/L was achieved, with platelet count >50×109/L. The donor origin of engraftment was confirmed by polymerase chain reaction (PCR) analysis of short tandem repeats at the end of the first, sixth and twelfth month. The patient’s body temperature dropped to normal level when her ANC reached 0.5×109/L on day 10, and the bacterial culture of blood sample became negative subsequently. Symptoms and signs of acute or chronic graft versus host disease (GVHD) were not observed in 30 months after PBSCT. Conclusions Hematopoiesis was reconstituted shortly after PBSCT. The combination of CY and TBI and the infusion of sufficient peripheral blood stem cells may contribute to the successful engraftment. PBSCT may be considered as the first choice when hematopoietic stem cell transplantation is needed for SAA patients complicated with severe infection.     

Allogeneic peripheral blood stem cell transplantation in the treatment of severe aplastic anemia and severe infection

Severeaplasticanemia (SAA)ischaracterizedbyafailureofbloodcellproductionresultinginseverepancytopeniawithamarkedlyhypocellularbonemarrow Bonemarrowtransplantation (BMT)isoneofthecurativeapproachesinpatientswithSAA Peripheralbloodstemcelltransplantation(PBSCT )hasbeenmainlyusedinthetreatmentofmalignanttumors Recently ,successfulsyngeneicandallogeneicPBSCTinpatientswithSAAwasreported ,1 3 　andsomewasasasalvagetreatmentinpatientswithSAAwhofailedtoBMT 4,5Wesuccessfullycompletedanallo…     

抗人T淋巴细胞兔免疫球蛋白预防异基因造血干细胞移植中急性移植物抗宿主病的临床研究

目的探讨异基因造血干细胞移植中抗人T淋巴细胞兔免疫球蛋白（ATG）联合环孢霉素A（CsA）、霉酚酸酯（MMF）、甲氨蝶呤（MTX）对促进移植植入和预防急性移植物抗宿主病（aGVHD）的作用。方法15例恶性血液病及5例重型再生障碍性贫血（SAA）患者实施血缘相关供者异基因造血干细胞移植,其中8例为人类白细胞抗原（HLA）配型全相合,12例HLA配型为单倍体相合。在移植前5d至前2d应用ATG 10．0mg／kg。供者应用重组人粒细胞集落刺激因子（rhG—CSF）5μg／（kg·d）,连续应用5d后采集外周血干细胞,单个核细胞（MNC）计数中位数为5．3×10^8／kg,CD34^＋细胞计数中位数为6．0×10^6／kg。结果移植后所有受者均获得造血重建,中性粒细胞（ANC）≥0．5×10^9／L和血小板（Plt）≥20×10^9／L中位时间分别为12d和14d。出现aGVHD7例,其中Ⅰ度皮肤aGVHD 3例;Ⅱ度肠道aGVHD 2例;Ⅲ度及Ⅳ度肠道aGVHD各1例。结论ATG在促进造血干细胞的植入,预防aGVHD的发生和降低其严重程度方面具有明显的效果。     

Association of CD 34 positive cell dose with engraftment kinetics in autologous peripheral blood stem cell transplant patients of multiple myeloma

BackgroundTreatment with high-dose chemotherapy and stem cell transplantation has prolonged survival in patients of multiple myeloma (MM). A dose-response relationship between number of CD34+ cells infused and leukocyte and platelet recovery, exists. Patients receiving dose of <2.0 × 10⁶ CD34+ cells/kg have delayed engraftment. The level of optimal cutoff for accelerated engraftment is yet to be validated. Hence, this study was undertaken to study the association of CD 34+ cell dose with engraftment kinetics in patients of MM who underwent autolgous peripheral blood stem cell transplant (PBSCT).MethodsWe retrospectively analyzed 19 patients of MM who underwent PBSCT at our center between December 2016 to December 2018. Complete blood counts were carried out daily after transplantation to record neutrophil and platelet engraftment.ResultsBased on the CD34+ cell dose given : <5 × 10⁶/kg (category 1), 5−10 × 10⁶/kg (category 2), >5 × 10⁶/kg (category 3), the mean (SD) neutrophil engraftment time was 11.3 (0.5) days, 10.6 (0.9) days, and 10.2 (1.3) days respectively. Platelet engraftment time was 12.4 (2.60) days, 10.6 (1.14) days, and 11.2 (1.64) days for category 1, 2, and 3 patients, respectively. Correlation co-efficient between CD 34+cell dose and days for neutrophil and platelet engraftment was found to be −0.24 and −0.20, respectively. Time for neutrophil engraftment was found to be significantly associated with CD34+ cell dose category.ConclusionCD 34+ cell dose appears as the strongest predictor of leukocyte and platelet engraftment. CD 34+ cell dose of >5.0 × 10⁶ cells/kg leads to an accelerated neutrophil and platelet engraftment in patients of MM.     

异基因造血干细胞移植后血小板植入失败行供者外周血造血干细胞输注治疗

目的对异基因造血干细胞移植（allo—HSCT）后血小板植入失败行供者外周血造血干细胞输注（GPBSCI）治疗的安全性、有效性进行初步评估。方法采用回顾性分析方法,针对2003年4月—2006年6月于北京大学血液病研究所行allo—HSCT的15例患者行16例次GPBSCI治疗的临床资料进行分析。结果15例患者中位年龄为33岁（14～48岁）,男性9例,女性6例,均为急慢性白血病患者,接受人类白细胞抗原（HLA）配型相合或不相合骨髓或骨髓联合外周血干细胞移植,回输骨髓单个核细胞（MNC）计数平均为（4．21±1．91）×10^8／kg[（1．50～7．46）×10^8／kg],回输外周血干细胞MNC计数平均为（3．27±1．40）×10^8／kg[（1．13—5．90）×10^8／kg],CD34^＋计数平均为（2．13±1．69）×10^6／kg[（0．24～5．67）×10^6／kg]。所有患者获得粒细胞植入,8例因原发性血小板植入失败,余8例因继发性血小板植入失败而实施GPBSCI治疗。回输中位时间为移植后＋113d（43～384d）。回输MNC计数平均为（3．09±1．54）×10^8／ks[（1．35～5．99）×10^8／kg]。仅1例患者在回输后出现急性移植物抗宿主病（aGVHD）表现。3例显著有效,6例有效,1例进步,6例无效。有效率为56．3％。其中移植后100d内进行2次回输疗效更好。结论对于allo—HSCT患者血小板植入失败,采取供者外周血造血干细胞2次回输,相关不良反应小,对促进受者造血恢复能够发挥一定的疗效。     

Monitoring the source of mesenchymal stem cells in patients after transplantation of mismatched-sex hematopoietic stem cells plus third-party cells

Background In bone marrow transplant patients, the microenvironment in bone marrow is damaged after chemotherapy or radiotherapy. Subsequent to allogenic hematopoietic stem cell transplantation in patients with clinically successful engraftments, the source of mesenchymal stem cells （MSCs） remains controversial. To further verify the stimulatory effect of the simultaneous transplantation of cells from second donors on engraftment success for hematopoietic stem cell transplantation in support of donor MSCs engraftments, the aim of this study is to monitor the dynamics of the engraftment of bone marrow-derived MSCs in patients after transplantation with mismatched-sex hematopoietic stem and third-party cells. Methods In this study, the hematopoietic stem cells from 32 clinical donors of different sexes that resulted in successful engraftments were selected for transplantation and were classified into three groups for research purposes： group A consisted of 14 cases of transplantation with bone marrow and recruited peripheral hematopoietic stem cell transplantation, group B contained 8 cases of simultaneous re-transfusion of MSCs from the second donor, and group C contained 10 cases of simultaneous re-transfusion of umbilical blood from the second donor. The bone marrow from 32 patients with successful engraftments of hematopoietic transplantation were selected and sub-cultured with MSCs. Flow cytometry （FCM） was used to measure the expression of surface antigens on MSCs. Denaturing high-performance liquid chromatography （DHPLC） in combination with polymerase chain reaction amplification of short tandem repeats （STR- PCR） was used to measure the engraftment status of fifth-generation MSCs in patients. Fluorescence in situ hybridization （FISH） revealed the sex origin of the fifth-generation MSCs in 32 patients. Dynamic examinations were performed on patients receiving donor transplantations. Results The progenies of fifth-generation MSCs were successfully cultured in 32 cases. The results of FCM demonstrated that the expression levels of CD14＋ and CD45＋ cells were lower than 0.04% in the fifth-generation MSCs. The analysis using DHPLC and FISH showed similar results. One patient from group B also received a temporary transplantation of MSCs from the donor. The MSCs in the remaining 31 patients all originated from the patients themselves. Conclusions After transplantation, the MSCs present in patients originated from the host. In patients transplanted with MSCs from a second donor, the phenomenon of temporary chimerization of MSCs was observed.     

粒细胞集落刺激因子动员的异基因骨髓与外周血干细胞混合移植治疗血液系统恶性疾病

目的　探讨粒细胞集落刺激因子 (G CSF)动员的异基因骨髓与外周血干细胞混合移植治疗血液系统疾病的可行性与疗效。方法　供者给予G CSF连续 4～ 6天皮下注射 ,注射后第 3天从髂后上嵴抽取G CSF动员的骨髓血 ,第 4天开始取外周血干细胞。并立即输给受者——— 14例血液系统恶性疾病患者 (恶性肿瘤 10例 ,重症再生障碍性贫血 4例 )接受了G CSF动员的异基因骨髓与外周血干细胞混合移植 ,分析其植活率、植活速度以及急性、慢性移植物抗宿主病 (aGVHD ,cGVHD)的发生率。结果　 14例患者均获得异体植活 ,白细胞数恢复至≥ 1× 10 9/L ,血小板≥ 2 0× 10 9/L的中位时间分别为移植后的 14d(12～ 18d)和 13d (11～ 6 5d)。有 4例发生了Ⅰ度aGVHD ,3例发生了Ⅱ度aGVHD ,但无一例重度aGVHD发生。在可评估的 9例患者中有 3例出现了广泛的cGVHD。有 2例患者因白血病复发而死亡 ,另 1例因植活不良 ,再次输注供者外周血干细胞 (PBSC)后出现IV度aGVHD死亡 ,其余 11例中位随访时间 4 5 5d(84～ 715d) ,均无病生存。结论　G CSF动员的异基因骨髓与外周血干细胞混合移植可以用于血液系统恶性疾病的治疗 ,能保证持久、稳定的植活 ,植活速度快 ,急、慢性GVHD的发生率与异基因骨髓移植相比并没有增加。     

可变数串联重复序列检测异基因外周血造血干细胞移植后植？…

目的 从血型、染色体核型、ＤＮＡ可变数串联重复序列（ＶＮＴＲ）几个方面进行对比研究以更好地评估异基因移植后的植入状态及其与疾病复发的关系。方法 采用聚合酶链反应（ＰＣＲ）方法扩增Ｄ１７Ｓ３０、Ｄ１Ｓ８０、ＡｐｏＢ３个不同位点的多态性,对１５例白血病患者异基因外周血造血干细胞移植（ａｌｌｏ－ＰＢＳＣＴ）后的嵌合状态进行检测,对其中７例异性间移植和３例血型不合移植又分别进行了染色体核型分析和全套血型分     

异基因造血干细胞移植治疗骨髓增生异常综合征临床疗效分析

回顾性分析异基因造血干细胞移植(Allo-HSCT)治疗骨髓增生异常综合征(MDS)的适应证、治疗时机、移植物的选择、移植预处理方案的选择和移植疗效。22例患者中21例获得造血重建,1例非血缘脐血移植(UCBT)未获得植入的成人患者,于非血缘脐血移植(UCBT)后38 d进行母亲HLA4/6相合的外周血联合骨髓造血干细胞移植解救治疗获得植入。22例中死亡3例,无1例复发。MDS患者何时进行Allo-HSCT需依据国际预后积分系统(IPSS)对患者分组,评分属于高危组的患者宜在疾病确诊后尽早进行移植,而低危组的患者可在其他药物治疗效果不佳的时候进行;不仅可选择血缘关系的骨髓移植(BMT)和外周血造血干细胞移植(PBSCT),也可进行非血缘人类白细胞共同抗原(HLA)不全相合的UCBT;移植预处理如采用减低强度的方案(RIC)并不影响移植效果。     

HLA配型对慢性粒细胞白血病异基因造血干细胞移植效果的分析

目的分析HLA相合程度对慢性粒细胞白血病(CML)异基因造血干细胞移植的影响。方法 121例CML患者包括:慢性期90例、加速期8例、急变期23例。85例接受相关、36例无关移植。HLA全相合91例、部分相合30例。预处理方案:37例患者用含全身放疗+环磷酰胺、84例改良Bucy(白消安+环磷酰胺+阿糖胞苷)方案,移植物抗宿主病(GVHD)预防:HLA全相合相关移植用环孢素A+甲氨蝶呤(CsA+MTX),无关及相关HLA位点不合移植者采用CsA+MTX+抗胸腺细胞球蛋白或霉酚酸酯。COX模型分析影响长生存的因素。结果 121例患者除4例死于预处理相关毒性外、其余117例病人均获造血重建;HLA全相合与不相合移植者Ⅱ~Ⅳ°急性GVHD发生率分别为26.1%和53.3%(P=0.006),3年累计慢性GVHD发生率在全相合与不相合者分别为47.4%和49.6%(P=0.947);非复发移植相关死亡(TRM)率在HLA相合与不相合者分别为16.5%和40.0%(P=0.007);5年累积白血病复发率为16.7%、其中HLA相合与不相合者复发率分别为15.3%和22.7%(P=0.396);5年累积总生存(OS)和无病生存(DFS)率分别为70.6%和63.8%,其中OS和DFS在相合者为78.2%和70.3%、不相合者为47.6%和43.3%。多因素分析显示:HLA不合为Ⅱ~Ⅳ°急性GVHD的危险因素,Ⅱ~Ⅳ°急性GVHD为TRM发生的危险因素,HLA不合、急性GVHD、疾病分期为影响生存的危险因素。结论 HLA不相合移植TRM高于相合移植,从而导致OS显著低于HLA全相合移植,长期生存与供受来源无关。     

异基因造血干细胞移植治疗伊马替尼耐药Ph染色体阳性白血病

目的 探讨造血干细胞移植(HSCT)作为甲磺酸伊马替尼(IM)耐药的费城染色体阳性(Ph+)白血病挽救性治疗的疗效.方法 回顾性分析2002年7月至2006年8月北京大学人民医院血液病研究所住院的14例IM耐药Ph(+)白血病患者行异基因(allo)-HSCT的效果,其中复发/难治急性淋巴细胞白血病(ALL)3例,慢性髓性白血病加速期(CML-AP)1例,慢性髓性白血病急变期(Bc)10例;7例行HLA配型完全相合同胞间移植,7例行HLA配型不相合亲缘移植;采用重组人粒细胞集落刺激因子(rhG-CSF)动员的骨髓(BM)加外周血干细胞(PBSC)混合移植8例,单用PBSC移植6例;10例患者给予预防或治疗性rhG-CSF动员后的供者淋巴细胞输注(DLI).结果 所有病例均达到完全供者型造血重建,移植后中性粒细胞和血小板植活的中位时间分别为16 d和13 d;发生Ⅱ度急性移植物抗宿主病(aGVHD)7例,Ⅲ度aGVHD 2例,局限型慢性移植物抗宿主病(cGVHD)4例,广泛型cGVHD 6例;血液学复发9例;无早期移植相关死亡.结论 联合应用多种方法预防白血病复发,HSCT可作为IM耐药Ph(+)白血病患者重要的挽救治疗选择.     

MMC方案预处理后异基因外周血造血干细胞移植治疗慢性粒细？…

为进一步探讨慢性粒细胞白血病的治疗，对３例ＣＭＬ患者采用ＨＬＡ相合同胞史妹异基因外周血干细胞移植治疗，预处理方案为马法兰（Ｍ）１７０ｍｇ／ｍ＾２＊１，甲环亚硝脲（Ｍ）４００ｍｇ／ｍ＾２＊１，环磷酰胺（Ｃ）６０ｍｇ／ｋｇ＊２。     

全不相合与全相合骨髓细胞在致敏模型的归巢与植入

【目的】 探讨全不相合与全相合供者骨髓细胞在致敏模型的归巢与植入情况。【方法】 以异基因脾细胞输注致敏的BALB/c小鼠作为移植受者,致敏模型经8 Gy 60Co照射后分别经尾静脉移植1 × 107 C57BL/6或BALB/c供者的骨髓细胞。予CFSE标记供者骨髓细胞,并分别在移植后不同时间点(2、12及48 h),通过病理切片及组织细胞悬液动态示踪供者细胞在致敏受者各组织的分布。移植后记录各组的生存情况,每周监测造血重建与骨髓恢复情况。【结果】 归巢实验表明C57BL/6骨髓细胞在致敏受者股骨的分布随时间推移先增加而后减少,在脾脏的分布随时间推移呈进行性减少。BALB/c骨髓细胞在致敏模型股骨及脾脏的分布均随时间推移而增加。接受C57BL/6骨髓细胞的致敏模型于移植第12 ~ 15天内全部死亡,血象及骨髓象呈进行性下降;而接受BALB/c骨髓细胞的能长期存活,血象及骨髓象能迅速恢复。【结论】 全不相合的供者骨髓细胞在致敏模型中完全被排斥,而全相合供者的骨髓细胞能在致敏模型中能进行有效的归巢与植入。     

外周血干细胞移植治疗血液肿瘤283例临床观察

目的 观察外周血干细胞移植(PBSCT)治疗血液肿瘤临床疗效.方法 自2001年3月～2007年4月,对283例血液肿瘤患者施行外周血干细胞移植,其中自体移植231例,异基因移植52例,观察其临床疗效和并发症.结果 除1例ALL外,230例患者行自体外周血干细胞移植后造血功能均快速重建.异基因移植中急性移植物抗宿主病发生率23.1%,慢性移植物抗宿主病发生率21.2%,其中局限型占15.4%;9例患者于移植后1 ～16个月分别死于移植物抗宿主病、感染和疾病复发或进展,35例患者已无病存活3～46个月.结论 外周血干细胞移植是治疗血液肿瘤的有效方法,依据患者疾病诊断、年龄、身体状况、供者情况选择移植方式.     

供者调控T细胞对异基因造血干细胞移植后造血与免疫重建、移植物抗宿主病发生及生存的影响

目的 研接受不同数量供者CD4 CD25 调控T细胞(TReg)移植对异基因造血干细胞移植(allo-HSCT)患者移植物抗宿主病(GVHD)的发生和造血与免疫重建的影响.方法 对30例接受allo-HSCT患者采用流式细胞仪测定移植物中的TReg值和移植后患者不同时间点外周血T淋巴细胞亚群及TReg.按移植供者TReg绝对数是否大于或等于10.0×10/kg为标准分为高TReg移植组和低TReg移植组,比较两组患者移植后造血与免疫重建、TReg重建、GVHD发生及无病生存率有无差异.结果 高TReg组的白细胞(WBC)和血小板(PLT)重建时间分别为 (8.62±2.29)d和 (12.69±5.74)d,低TReg组分别为 (8.88±2.71)d和 (15.18±6.71)d(P值分别为0.778和0.613),两组间WBC和PLT重建时间无显著性差异.高TReg组患者移植后 15 dCD4 CD3 ,CD45RO CD4 T细胞重建, 30dCD3 、CD4 CD3 T细胞重建明显快于低TReg组患者(P值分别为0.039、0.024、0.014、0.020).高TReg组患者移植后 15 dCD4 CD25 TReg重建, 180 d与低TReg组相比明显加快(P值分别为0.013、0.005).高TReg组和低TReg组患者急性GVHD发生率分别为61.54%(8/13)和94.12%(16/17),两组统计有显著性差异(P=0.027),移植的供者TReg数与急性GVHD的发生程度呈负相关(rs=0.393,P=0.032).高与低TReg组无病生存率分别为(60.40±16.10)%和(72.00±2.00)%,无显著性差异(P=0.818).结论 供者TReg能促进allo-HSCT后免疫重建及CD4 CD25 TReg重建,降低移植后急性GVHD的发生率.     

造血干细胞移植治疗恶性血液病、实体瘤回顾分析

目的 探讨不同预处理方案以及不同移植方法治疗恶性血液病、实体瘤的疗效,对其移植效果及移植风险进行评价.方法 回顾分析非净化自体骨髓移植（auto-HSCT）31例,外周血干细胞加自体骨髓活化移植（PBSCT＋ABM）26例,清髓性异基因骨髓移植（allo-HSCH）18例,非清髓性异基因骨髓/外周血移植（allo-NSCT）43例,脐带血干细胞移植（CBT）7例的临床资料.PBSCT＋ABM、auto-HSCH和allo-HSCH均采用MAC方案预处理.PBSCT＋ABM系采用自身外周血干细胞及体外活化自体骨髓液750 ml回输;allo-HSCT采集供者骨髓液于移植0 d回输;allo-NSCT是采用低强度的FAAC或MAAC两种方案预处理,移植后根据嵌合体形成的情况,以递增方式将供体淋巴细胞输注（DLI）给患者.allo-CBT患儿,2例采用脐血库的干细胞,HLA配型4个以上的位点相合,5例采用同胞的脐带血干细胞,预处理采用CTX/ATG,移植的程序与上述一致.异基因移植患者常规使用免疫抑制剂（环胞霉素、氨甲蝶呤/骁悉）,并根据白细胞、血小板、骨髓恢复,ABO血型分析,STR测定嵌合体形成等情况作为植活的证据.aGVHD按Glucksberg标准分析,cGVHD根据Shulman标准分析.结果 125例患者中除有1例慢性髓性白血病（CML）NSCT移植后40 d时植入失败死于骨髓衰竭,1例急性髓性白血病（AML）NSCT在造血恢复前死于脑出血外,其余123例都预期恢复造血.异基因移植aGVHD发生率9.69%,cGVHD发生率22.23%.auto-HSCT31例,截止资料分析时生存8例（25.80%）.PBSCT＋ABM 26例,生存15例（57.69%），allo-HSCT 18例,生存11例（61.11%）,NSCT43例,生存19例（45%）.CBT7例生存2例.结论 异基因造血干细胞移植是一种根治性的治疗手段,尤其非清髓性预处理的异基因造血干细胞移植方法不仅扩大了移植的应用范围及适应证,而且提高了移植的安全性并降低了移植费用.     

Modified conditioning regimen busulfan-cyclophosphamide followed by allogeneic stem cell transplantation in patients with multiple myeloma

Background Allogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma. The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment modality. The challenge for clinical investigators is to reduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem cell transplantion for multiple myeloma. In this study the toxicity and efficacy of modified myeloablative conditioning regimen followed by allogeneic stem cell transplantation was investigated in patients with multiple myeloma. Methods The conditioning regimen consisted of hydroxyurea, cytarabine, busulfan, cyclophosphamide, and semustine. Ten patients underwent allogeneic transplantation among them hydroxyurea （40 mg/kg） was administered twice on day -10 and cytarabine （2 g/ms） was given on day -9, busulfan was administered orally in four divided doses daily for 3 days （days -8 to -6）. The dose of busulfan was 12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1 hour on days -5 and -4 （1.8 g/m^2）, and with semustine （Me-CCNU） 250 mg/m^2 on day -3. Results Chimerism data were available on all patients and all patients achieved full donor chimerism without graft failure. Six patients had not acute graft-versus-host disease （GVHD, 36.4%; 95% CI： 13.9%-38.6%）. Two patients （18.2%） developed grade Ⅰ acute GVHD （95% CI： 10.9%-35.9%） and grade Ⅱ acute GVHD occurred in one patient （9.1%; 95% Cl. 8.4%-32.3%）. Severe grade IVa GVHD was seen in one patient, who died from acute GVHD. The incidence of chronic GVHD was 22.2% （95% Cl： 11.7%-36.7%）, among them one died of severe grade IV GVHD and one developed multiorgan failure on day ＋170; the treatment-related mortality was 22.0% （95% Cl： 10.3%-34.1%）. The overall 4-year survival rate was 67.8% （95% Cl： 16.3%-46.7%）. The estimated 4-year progression-free survival rate was 58.5% （95% CI： 13.7%-41.8%）. The 4-year complete remission was 72.7% （95% CI： 27.8%-49.6%）. One patient relapsed after 4 months and achived the complete remission after receiving the donor lymphocyte infusion. Conclusions Modified conditioning regimen busulfan-cyclophosphamide with peripheral blood stem cells＋bone marrow cells transplantation result in a low incidence of severe GVHD with a relatively low treatment-related mortality, high complete remission rates and a long-term survival.