FBT预处理方案异基因外周血造血干细胞移植治疗难治／复发急性非淋巴细胞白血病

目的探讨以氟达拉滨＋白舒非＋噻替哌作为预处理方案（FBT预处理方案），进行异基因外周血造血干细胞移植治疗难治／复发急性非淋巴细胞白血病的疗效及可行性。方法以FBT方案作为预处理方案，以环孢素A＋骁悉预防移植物抗宿主病（GVHD），对7例难治／复发急性非淋巴细胞白血病患者进行HLA全相合异基因外周血造血干细胞移植。结果中位随访时间31个月，2例复发，5例患者无病存活。结论FBT预处理方案复发率低，毒副作用轻，相关并发症少，患者耐受性好，对于难治／复发急性非淋巴细胞白血病患者而言，是一种值得进一步探讨的临床治疗方案。     

混合骨髓移植治疗急性白血病11例疗效观察

目的 探讨应用混合骨髓移植（MBMT）治疗急性白血病的疗效。方法 采用化疗加全身照射方案预处理后，回输自体骨髓及1／6HLA半相合的同胞兄妹骨髓。重建造血及免疫功能，诱导移植物抗白血病（GVL）作用，治疗11例急性白血病患者。结果 除2例移植早期死亡外，所有病例均获得造血功能重建及出现皮肤型慢性-过性移植物抗宿主病（GVHD）。4例长期无病存活。占36．4％。结论 MBMT治疗急性白血病疗效满意。     

双次自体造血干细胞移植治疗恶性血液病

目的 探讨双次自体造血千细胞移植（DAHSCT）治疗恶性血液病的疗效、造血重建及生存情况。方法 对6例恶性血液病患者，其中急性白血病3例，多发性骨髓瘤（MM）3例，第一次预处理方案白血病组为CY＋TBI，MM组为HDM（马法兰200mg／m^2）；第二次预处理方案白血病组为MEC（马法兰140mg／m^2，VP-16，CY120mg／kg），MM组仍为HDM。结果 6／6例患者均获造血重建（9～20d），5例至今仍无进展存活（PFS）14—26m，1例MM除出现慢性肾功能不全以外，其他病人病情稳定。结论 DAHSCT意者相关死亡率低，无病生存率较高，以此方案行双次自体千细胞移植是治疗恶性血液病的有效方法。     

自体骨髓移植治疗急性白血病疗效探讨(附35例报告)

目的评价自体骨髓移植(ABMT)治疗急性白血病的疗效。方法自1999-10~2004-10,用ABMT治疗急性白血病(CR1期)35例,中位年龄32.5(9~55)岁。其中急性非淋巴细胞白血病(ANLL)26例,急性淋巴细胞白血病(ALL)9例。预处理方案为马法兰(Mel)140~180mg/m2+环磷酰胺(CTX)120mg/kg+阿糖胞苷(Ara-C)3g/m2。结果所有患者移植后均重建造血,中位随诊时间756(186~1905)d,ANLL、ALL移植者3年无病生存率分别为(65.4±8.9)%和(33.3±13.6)%,复发率(30.6±9.2)%和(60.7±25.5)%。结论为降低急性白血病复发率和提高无病生存率,无异基因造血干细胞移植条件的患者适合接受ABMT。     

骨髓非清除性造血干细胞移植后供者干细胞输注治疗非肿瘤性血液病的探讨

目的探讨非清髓性移植(NST)治疗移植排斥高风险的非肿瘤性血液病的植入效果、并发症。方法对2例重型再障(SAA)和1例重型β-地中海贫血(TM)患者实施NST。2例SAA患者采用G-CSF动员的骨髓联合外周血移植,预处理方案:抗淋巴细胞球蛋白联合减低剂量的环磷酰胺;TM患者实施外周血干细胞移植,预处理方案:抗胸腺细胞球蛋白、氟达拉滨联合减低剂量的马利兰。移植物抗宿主病(GVHD)预防:环孢素A联合甲基强的松龙;于+78d、+99d和+44d行供者干细胞输注(DSI)。结果移植后均形成混合性嵌合体,3例白细胞最低值:0.26×109/L、0.50×109/L、1.26×109/L;中性粒细胞绝对值>0.5×109/L和P lt>20×109/L的时间分别为+12d、+3d、0d和+1d、+5d、0d;3例经过DSI,造血和嵌合体有改善。均无感染、GVHD发生。结论NST后行DSI治疗排斥高风险非肿瘤性血液病,可以获得造血干细胞成功植入,减少并发症。     

异基因造血干细胞移植治疗恶性组织细胞病

目的 探讨异基因造血干细胞移植(Allo-HSCT)治疗恶性组织细胞病(MH)的方法和疗效. 方法 对1例MH患者进行Allo-HSCT,采用改良马利兰/环磷酰胺(Bu/Cy)预处理方案进行亲缘HLA全相合的外周血干细胞移植,移植物抗宿主病(GVHD)的预防采用环孢素A联合短疔程甲氨蝶呤的方案. 结果 患者移植后造血功能恢复顺利,中性粒细胞绝对数＞0.5×109/L时间为+20 d,Pt＞20×109/L时间为+27 d.患者+30 d行骨髓短串联重复序列(STR)-PCR检测显示为完全供者的基因型,移植后2个月发生Ⅱ度急性GVHD,加用泼尼松后病情得到控制,未发生慢性GVHD,随访至移植后8个月,造血功能恢复良好,病情处于持续完全缓解状态,仍在继续随访中. 结论 对符合传统意义上或WHO重新定义的MH患者,Allo-HSCT是一种有效的根治方法.     

HLA单倍型相合外周血造血干细胞移植治疗重型地中海贫血

目的 探索单倍型相合外周血造血干细胞移植(PBHSCT)治疗重型地中海贫血的可行性.方法 以氟达拉滨+白舒非+环磷酰胺+ATG+低剂量TBI作为预处理方案,以环孢素A+骁悉+甲氨蝶呤预防GVHD,对5例重型地贫患儿进行单倍型相合PBHSCT.结果中位随访24月,5例患者全部存活,其中4例无病存活.结论 单倍型相合PBHSCT是治疗重型地中海贫血的有效方法.     

谷氨酰胺双肽对造血干细胞移植后患者血清Th1/Th2类细胞因子水平的影响

目的研究谷氨酰胺双肽对造血干细胞移植患者血清Th1／Th2细胞因子水平的影响，及对移植后急性移植物抗宿主病（GVHD）的预防作用。方法将20例接受异基因造血干细胞移植患者随机分为两组，谷氨酰胺组10例，对照组10例。从移植后当天至第20天，谷氨酰胺组患者除接受标准胃肠外营养支持外，每天给予N（2）-L-丙氨酰-L-谷氨酰胺200ml；对照组采用不含谷氨酰胺的标准化胃肠外营养支持。两组均采用改良白消安加环磷酰胺（BuCy2）预处理方案，采用环孢霉素加霉酚酸酯预防移植物抗宿主病（GVHD），分别干预处理当天，移植后第7、14、21、28和42天收集患者姐清标本，采用酶联免疫吸附实验（ELISA）分别检测肿瘤坏死因子α（TNF-α）、干扰素1（INF-γ）、白介索2（IL-2）、IL-4、IL-10的水平，同时监测两组GVHD发生率及严重程度。结果谷氨酰胺组TNF-α、INF-γ和IL-2水平较对照组低，其中TNF-α、INF-γ与对照组差异有显著意义（P〈0．05）；谷氨酰胺组IL-4和IL-10水平略高于对照组，但仅移植后第42天差异有显著意义（P〈0．05）。GVHD发生两组无明显差异。结论符氨酰胺能使造血干细胞移植患者的Th1／Th2细胞因子向有利于预防GVHD的方向偏移。     

自体造血干细胞移植治疗难治性系统性红斑狼疮的疗效分析

目的 探讨自体外周血造血干细胞移植（APBSCT）治疗难治性系统性红斑狼疮（SLE）的初步疗效和安全性.方法 对5例难治性SLE进行自体外周血造血干细胞移植,预处理方案为环磷酰胺（CTX）40 mg/（kg·d）静脉点滴连用2 d（-4,-3）,抗胸腺细胞球蛋白（ATG）2.5 mg/（kg·d）静脉点滴连用5 d（-6,-5,-4,-3,-2）.同时碱化和水化尿液,保护心、肝、肾功能.结果 5例患者均获得造血重建,中性粒细胞绝对计数〉0.5×10^9/L,血小板〉20×10^9/L的中位数时间分别是9 d,10 d.所有患者在移植后40 d左右颜面部红斑等症状消失,大部分患者自身抗体转阴或抗体滴度减低,5例均出现移植后感染,3例患者出现程度不同的心血管并发症,无移植相关性死亡,随访至移植后1年,2例患者移植后2月激素完全撤退,3例泼尼松用量〈10 mg/d.结论 APBSCT是难治性SLE的有效方法之一,造血重建恢复迅速,且相对安全,但由于例数较少及观察时间有限,远期疗效有待观察.     

自体外周血造血干细胞移植在小儿恶性血液肿瘤的应用研究

目的　对 2 6例自体外周血干细胞移植 (APBSCT)治疗的小儿恶性血液肿瘤患儿有关材料进行总结分析。方法　自1989-0 1～ 2 0 0 3 -0 62 6例恶性血液肿瘤患儿 (急性淋巴细胞白血病 11例、急性髓系白血病 3例、恶性淋巴瘤 7例、神经母细胞瘤 5例 ) ,男 17例 ,女 9例 ,年龄 3 5～ 12 (平均 7 4)岁 ,在其完全缓解 ( 2 4例 ) ,部分缓解 ( 2例 )后进行了APBSCT治疗。移植时病程中位时间 12月 ( 6-64 )。 18例用化疗加rhGM -CSF或rhG -CSF动员 ,8例采用常规化疗方案作为动员剂。预处理方案中 19例基本方案为全身放疗 (TBI)加环磷酰胺 (CTX)。 7例未用TBI ,仅以马法兰为主做为预处理方案 (马法兰 +卡铂 +足叶乙甙 4例 ,白消胺 +马法兰 3例 )。结果　移植后白细胞 >0 5× 10 9/L、>1 0× 10 9/L、血小板 >2 0× 10 9/L的中位时间分别为 12 ( 8～ 2 0 )d、17d( 10～ 2 8)、2 1( 7～ 78)d。中位随访时间 7 3年 ( 1月至 14年 )。至今无病生存 70 %( 18/2 6) ,死亡 3 0 %( 8/2 6) ,其中移植相关死亡 2例 ( 7 7%)。结论　化疗联合G -CSF是一高效、低毒的动员方案 ;APBSCT是治疗小儿血液系统肿瘤 ,改善其预后的重要手段之一。     

异基因外周造血干细胞移植与免疫抑制治疗重型再生障碍性贫血的临床比较

目的 比较异基因外周造血干细胞移植(Allo-PBSCT)与免疫抑制治疗(IST)重型再生障碍性贫血(SAA)的疗效与并发症.方法 25例SAA患者接受了两种方法治疗:PBSCT组12例接受了同胞HLA全相合的PBSCT,预处理方案为:环磷酰胺(Cy)联合兔抗人胸腺免疫球蛋白(ATG);IST组13例治疗方案为:ATG/环孢素A(CsA).比较两种治疗方法的近期疗效、远期疗效与并发症.结果 PBSCT组的中性粒细胞计数、Pt和Hb的恢复时间[分别为(13.5±2.3)、(23.5±4.1)、(82.7±6.1)d]快于IST组[分别为(32.6±3.5)、(73.8±6.2)、(296.4±12.5)d](P<0.05),但1年的近期疗效比较差异无统计学意义(P>0.05).两组3年生存率和总生存率比较差异均无统计学意义(P>0.05),总复发率比较差异有统计学意义(P<0.05).结论 Allo-PBSCT和IST都是治疗SAA的有效手段,但Allo-PBSCT具有造血重建快、复发率低、并发症并没有增加等特点,临床上可作为优先选择.     

Second allogeneic peripheral blood stem cell transplants with reduced-intensity conditioning

In two institutions in México, twelve patients were given a second allogeneic stem cell transplantation, using the "Mexican" non-myeloablative preparative regimen. Eight had a malignant condition (six acute leukemias, one myelofibrosis and one myelodysplasia), eleven individuals were allografted twice from the same donor and in one case, cells from two different umbilical cords were used. The median time to conduct the second allograft after the first one was 6 months (range 1-41). The five patients who failed to engraft after the first transplant failed also to engraft after the second one; all of them had been heavily transfused. Only three patients were successfully rescued with the second transplant, two with acute leukemia and one with aplastic anemia. Seven patients are alive 10-41 months (median 35) after the second transplant, but only three (25%) remain disease-free. The 52-month overall survival (SV) of the patients is 58%, whereas the median overall SV has not been reached, being above 52 months. Conducting a second allograft may be useful to rescue some individuals relapsing after a first hematopoietic allotransplant.     

Allogenic hematopoietic stem cell transplantation in acquired aplastic anemia: first experience of the National Center for Bone Marrow Grafting

Bone marrow transplantation from HLA-identical sibling offers cure and leads to restoration of normal hematopoiesis and long-term survival in 60-80% of recipients. From february 1998 to october 1999, seven patients with aplastic anemia (2 very severe aplastic anemia and 5 severe aplastic anemia), with a median age of 22 years (14-39), received a transplant from an HLA-identical sibling donor. All patients had sustained engraftment. Only one patient developed grade IV acute graft-versus-host disease. One patient died in the 22th day of systemic mycobacterial infection and one in the 79th day of acute graft-versus-host disease. The remaining 5 patients are alive and have a complete hematological recovery, with a median follow-up of 6 months (1,5-12). There are at least two reasons for the improved survival of patients with aplastic anemia who where treated by HLA-indentical bone marrow transplantation. One is the decreased incidence of graft rejection that has resulted from the more judicious use of transfusions before bone marrow transplantation, and improvements in the immunosuppressive qualities of the conditioning programs. Another reason for improved survival is the decrease in the incidence and severity of acute graft-versus-host disease.     

Hematopoietic stem-cell transplantation in aplastic anemia

Severe aplastic anemia is a rare syndrome characterized by bone marrow failure with cytopenias and hypocellular bone marrow biopsy (usually 10-15%), without blasts or myelodysplasia. The first choice treatment for these patients is allogeneic bone marrow transplantation from a sibling matched for HLA-A, HLA-B and HLA-DR. Unfortunately only 30% of patients have an HLA-matched sibling (a 25% chance per sibling). The alternative treatment for severe aplastic anemia for the rest of the patients (70%) is immunosuppression with antithymocyte globuline and cyclosporine. The evolution of bone marrow transplantation since 1970's has been positive in terms of survival and transplant success (initial overall survival 43% vs. 90% lately, and graft rejection of 29% vs. 4%). The favorable outcome of bone marrow transplantation for severe or very severe aplastic anemia is due to: the use of conditioning with antithymocyte globuline and cyclophosphamide, the use of graft-vs.-host disease prophylaxis with short curse methotrexate and cyclosporine and the use of filtrated and irradiated blood products. For those patients without an HLA-matched related donor the first treatment to use is the immunosuppression with antithymocyte globuline and cyclosporine. Another option emerged in the late 80's is the unrelated bone marrow transplantation, with survival hardly half of the HLA-identical related bone marrow transplants. In our country, the first allogeneic bone marrow transplant was done in the Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, in a patient with aplastic anemia, making possible to perform this procedure safely in our country.     

异基因外周血干细胞移植治疗苯中毒性再生障碍性贫血

目的　研究异基因外周血造血干细胞移植治疗苯中毒致重型再生障碍性贫血 (SAA)。方法　用HLA配型全相合的女性供者异基因外周血造血干细胞移植 (Allo PBSCT)治疗 1例苯中毒致SAA男性患者。输入单个核细胞数为 9.4 1× 10 8 kg、CD34 阳性细胞为 12 .4 9× 10 6 kg、粒 -巨噬细胞系祖细胞集落数为 8.2× 10 5 kg。预处理方案由环磷酰胺加全身照射和抗淋巴细胞球蛋白组成 (环磷酰胺总量 12 0mg kg ,全身照射为 8Gy ,抗淋巴细胞球蛋白总量 6 0mg kg)。为防止植入失败 ,移植后第 18天再次输入供者白细胞层 ,其中单个核细胞数为 9.0 2× 10 8 kg、CD34 阳性细胞为 10 .6 2× 10 6 kg、粒 -巨噬细胞系祖细胞集落数为 6 .3× 10 5 kg,并用环孢菌素A和甲氨蝶呤预防移植物抗宿主病。结果　输入单个核细胞后白细胞最低值为 0 ,血小板最低值为 3× 10 9 L ;中性粒细胞于移植后第 2 1天开始大于0 .5× 10 9 L ,血小板于移植后第 2 8天开始大于 5 0× 10 9 L。移植后第 4个月出现皮肤局限性慢性移植物抗宿主病。受者染色体转为 4 6 ,XX ;ABO血型由B型转为O型。结论　此例为国内首例采用Allo PBSCT治疗苯中毒致SAA并获得成功 ,为苯中毒治疗开辟了新的途径。     

Nutrient support in hematopoietic cell transplantation.

High-dose cytoreduction and hematopoietic stem cell infusion form the basis for treatment of hematologic cancers, defects or failure of hematopoiesis, and some solid tumors. As an antitumor therapy, allogeneic hematopoietic cell transplantation (HCT) is superior to autologous HCT by induction of a graft-vs-tumor effect. However, recipients of allografts suffer higher transplant-related mortality owing to graft-vs-host disease (GVHD). Nutrition support research must recognize that HCT is a heterogeneous modality whose short and long-term outcomes are affected by transplant type, preparative regimens, diagnosis, disease stage, age, and nutritional status. The field of HCT will diversify further as lower dose cytoreduction and mixed chimerism grafts allow expansion of the technique to older patients and to other diseases.     

Peripheral blood stem cell transplantation for non-Hodgkin's lymphoma in complete remission

High-dose chemotherapy with PBSCT as consolidation therapy was administered to 15 patients with non-Hodgkin's lymphoma admitted to our department between November 1991 and March 1998. The average number of CD34-positive cells harvested was 3.1 x 10(6)/kg and the median time to a granulocyte count above 500/microliter was 12.8 days. Of the patients, one died from cytomegalovirus pneumomonia after WBC count recovered, 2 relapsed, and 12 patients are still alive and disease-free. The average disease-free survival period was 50.0 months. Stem cell harvesting is relatively simple and hematopoietic recovery is mory rapid with PBSCT than with ABMT. Our findings suggest that PBSCT can be used for consolidation therapy in NHL patients who have achieved complete remission with standard chemotherapy.