异基因造血干细胞移植治疗成人白血病35例

目的 分析总结异基因造血干细胞移植治疗急性和慢性白血病的疗效、并发症以及不良反应。方法 采用同胞异基因骨髓移植、同胞异基因外周血造血干细胞移植以及无血缘关系骨髓移植对35例缓解期或复发难治性成人白血病进行了移植。结果 平均随访26月,10例急性白血病有5例仍无病存活,25例慢性粒细胞性白血病仍无病存活21例（84％）。主要并发症：急性GVHD11例,慢性GVHD15例,CMV感染间质性肺炎6例,其中重症感染者3例,肝静脉闭塞病（HVOD）7例,严重感染败血症9例,白血病复发3例。结论 异基因造血干细胞移植是治疗成人急、慢性白血病的有效方法,相当部分患者可以通过移植获得治愈。     

HLA单倍体外周血联合骨髓干细胞移植治疗急性混合细胞白血病的临床观察

目的 探索急性混合细胞白血病人类白细胞抗原(HLA)单倍体造血干细胞移植治疗方法及疗效观察.方法 对4例急性混合细胞白血病患者进行HLA单倍体外周血造血干细胞联合骨髓移植治疗,观察移植疗效及相关并发症.结果 所有患者均成功重建造血.中性粒细胞及血小板恢复中位时间分别为16.5d(14～21d)、16.5d(15～30d).1例PR患者移植后完全缓解,其余3例持续缓解.2例移植过程中发生急性GVHD,未观察到慢性GVHD的发生.1例患者在移植过程中发生单一的APTT延长.中位随访时间181d(129～337d),1例于移植后190d死于真菌感染,1例CR2和1例PR分别于移植后183d和129d病情复发,另1例无病存活337d.结论 HLA单倍体外周血造血干细胞联合骨髓移植治疗急性混合细胞白血病切实可行,但需积累更多的资料以进一步观察疗效.     

减低预处理剂量的异基因造血干细胞移植治疗难治性急性白血病

目的 探讨减低预处理剂量的异基因造血干细胞移植在难治性急性白血病治疗中的安全性和疗效.方法 6例难治性急性白血病,其中5例耐药复发,1例继发性白血病,经常规化疗2～11个疗程未能达到完全缓解.预处理方案为减低预处理剂量的BuCy方案.结果 除1例死于肠道Ⅳ度急性GVHD外,其余5例均获得造血重建,各脏器预处理相关毒性（RRT）大多数为Ⅰ～Ⅱ级,未发生严重预处理相关并发症.移植后11～24 d均有经DNA检测证实的完全供者嵌合.发生急性GVHD 4例,2例为Ⅳ度肠道GVHD,分别于＋18 d和＋64d死亡.1例为Ⅰ度皮肤GVHD治愈,1例先后出现Ⅳ度皮肤aGVHD和肝脏cGVHD经治疗得到良好控制,无白血病生存.3例移植后发生髓外软组织肿瘤（EMD）,采用联合化疗＋放疗、供者淋巴细胞输注（DLI）,2例进行了二次移植,2例无病生存,1例带瘤生存.结论 减低预处理剂量的BuCy方案治疗难治复发性急性白血病,有较好的耐受性,可取得完全型供者细胞植入及血液学缓解,但有可能增加髓外复发的风险.     

异基因外周血造血干细胞和骨髓混合移植治疗白血病12例

目的探讨异基因外周血造血干细胞和骨髓混合移植治疗白血病的疗效。方法 12例白血病患者,人白细胞抗原（HLA）配型全相合11例,2个位点不相合1例,采用粒细胞集落刺激因子（G-CSF）动员的外周血造血干细胞和骨髓联合移植,环孢素A联合甲氨蝶呤加/不加吗替麦考酚酯方案预防移植物抗宿主病（GVHD）。结果 12例患者均获得异体植活,中性粒细胞（ANC）〉0.5×109L-1,血小板（BPC）〉20×109L-1的中位时间分别为移植后的11 d（10-15 d）和14.5 d（11-43 d）。有3例发生了Ⅰ度急性GVHD,1例发生了Ⅱ度急性GVHD。在可评估的7例患者中有1例出现了局限的慢性GVHD。有3例患者因白血病复发而死亡,另1例因植活后感染死亡,其余8例中位随访时间13个月（2-29个月）,均无病生存。结论外周血造血干细胞和骨髓混合移植对HLA配型全相合和部分相合患者是安全有效的移植方法。     

异基因外周血干细胞与异基因骨髓移植治疗白血病疗效的比较

[目的]比较异基因外周血干细胞移植(allo—PBSCT)和异基因骨髓移植(allo-BMT)治疗白血病的临床疗效。[方法]allo—PBSCT治疗15例,BMT治疗17例。预处理方案:环磷酰胺(Cy)60 mg/(kg·d)×2 d+单次全身照射7.5~8.0 Gv;或白消安(Bu)4 mg/(kg·d)×4 d+Cy 60 mg/(kg·d)×2 d。[结果] 32例均植活,中性粒细胞恢复至>0.5×109/L和血小板>20×109/L的中位时间allo-PBSCT组分别14 d和15 d,allo—BMT组分别为20 d和23 d(P<0.05)。allo-PBSCT组移植相关死亡3例(20％),复发3例(20％),9例无病生存,2年无病生存率为64％±10％;allo-BMT组相关死亡4例(24％),复发3例(18％),10例无病生存,2年无病生存率为59％±10％;两组比较,差异无显著性(P>0.05)。allo-PBSCT组有5例(33％),BMT6例(35％)出现急性移植物抗宿主病。allo-PBSCT组发生慢性移植物抗宿主病6例(40％),明显高于allo—BMT组2例(12％),P<0.05。[结论]allo-PBSCT疗效与allo—BMT相当,但allo-PBSCT慢性移植物抗宿主病发生率高。     

异基因骨髓移植与异基因外周血造血干细胞移植治疗慢性髓系白血病的疗效比较

目的比较HLA相合同胞异基因骨髓移植(allo-BMT)与异基因外周血造血干细胞移植(allo-PB-SCT)治疗慢性髓系白血病(CML)的临床疗效。方法allo-BMT 24例,allo-PBSCT 29例。预处理采用全身照射加环磷酰胺(TBI/Cy)或白消安加环磷酰胺(Bu/Cy)为主的方案。结果BMT组造血重建23例(95.8%),PBSCT组29例;PBSCT组外周血象恢复至中性粒细胞(ANC)>0.5×109/L、WBC>1×109/L、PLT>20×109/L的速度快于BMT组(P均<0.01)。BMT组急性移植物抗宿主病(aGVHD)15例(62.5%),PBSCT组21例(72.4%),2组比较差异无显著性(P>0.05);BMT组慢性GVHD(cGVHD)4例(18.2%),PBSCT组14例(53.8%),PBSCT组高于BMT组(P<0.05);BMT组移植相关死亡(TRM)3例(12.5%),复发4例(16.7%),5年无病生存率(DFS)(76.6±11.8)%,而PBSCT组TRM 7例(24.1%),复发1例(3.4%),5年DFS(75.5±8.1)%,2组比较差异均无显著性(P均>0.05)。结论allo-BMT和allo-PBSCT治疗CML疗效相当,allo-PBSCT组造血重建迅速,但cGVHD发生率高。     

自体造血干细胞移植治疗白血病和淋巴瘤的临床观察

目的 探讨自体骨髓移植（ABMT）、自体外周造血干细胞移植（APBSCF）治疗急性白血病和恶性淋巴瘤的临床疗效。方法 应用ABMT和APBSCT治疗11例急性白血病和6例恶性淋巴瘤,全部患者随访0.6～14年。结果17例患者移植后全部造血重建,无一例患者发生移植相关死亡。ABMT和APBSCT后中性粒细胞恢复>0.5×109/L中位时间分别为16（13～20）d和11（9～14）d,血小板恢复>20×109/L中位时间分别为14（11～16）d和10（8～13）d,移植后无病生存期中位时间为3.8（0.2～14）年,5例急性白血病患者至今已无病生存分别达5,5,6,6,10年,1例淋巴瘤患者带瘤生存已10年（起病至今14年）,4例患者在移植后超过1年后复发。结论ABMT与APBSCT是提高急性白血病和淋巴瘤临床疗效的一种安全和有效的手段。     

HLA配型不合情况下造血干细胞移植的新方法

目的:采用新方法进行非体外去除T细胞的人类白细胞抗原(human leukocyte antigen, HLA)配型不合造血干细胞移植.方法:58例血液恶性肿瘤患者,33例为高危或难治复发白血病,接受了至少一个HLA位点不合的家庭供者造血干细胞移植.移植物为经粒细胞集落刺激因子(granulocyte clony-stimulating factor, G-CSF)动员的骨髓以及外周血造血干细胞,而无需体外去除T细胞.移植物抗宿主病(graft-versus-host-disease, GVHD)预防采用环孢菌素A 霉酚酸酯 短程甲氨喋呤方案.结果:所有患者均获得持久、完全供者植入.58例患者中发生Ⅱ度及以上急性GVHD 22例(37.9%),其中Ⅲ度和Ⅳ度急性GVHD分别为2例和1例,其严重程度与HLA不合程度无相关;42例可评估患者中,慢性GVHD为26例(61.9%),广泛型和局限型分别为11例和15例.复发9例,除1例外均为复发、难治白血病患者.死亡14例,其中7例死于疾病复发,另7例死于移植相关合并症,其中严重感染和间质性肺炎各2例,巨细胞病毒性脑炎、病毒型肝炎和急性GVHD死亡各1例.中位随访10月(2～37.5月),58例患者中42例无病存活(disease-free survival, DFS),高危患者2年DFS明显低于标危患者,分别为63.2%和77.6%(P= 0.04).DFS与供受者间HLA配型不合程度、急性GVHD严重程度及回输干细胞数量无关.结论:(1)无需体外去除T细胞的新方法可克服HLA屏障、安全有效地用于HLA不合的移植;(2)G-CSF动员的外周血干细胞可安全用于HLA不合的造血干细胞移植.     

AM L行异基因造血干细胞移植后复发应用 FLAG方案联合G-DLI的疗效研究

目的：观察急性髓系白血病（AML）行异基因造血干细胞移植（allo‐HSCT）后血液学复发,应用FLAG方案联合粒细胞集落刺激因子动员的供者淋巴细胞输注（G‐DLI）治疗的临床疗效。方法对于接受异基因外周血造血干细胞移植（allo‐PB‐SCT）后复发的患者,给予FLAG方案化疗后在白细胞降至最低点时给予G‐DLI ,观察白血病缓解及生存情况,并通过 PubMed等检索进行文献复习。结果3例移植术后复发接受FLAG方案联合G‐DLI治疗者均再次获得完全缓解（CR）。1例G‐DLI后无病存活（DFS）13个月,后出现中枢复发,但骨髓一直处于缓解状态,23个月后因多脏器功能衰竭死亡,总生存（OS）为23个月。G‐DLI后发生皮肤Ⅱ度急性高移植物抗宿主病（GVHD）及肝脏Ⅰ度急性GVHD ,经处理后控制,未发生慢性GVHD。1例G‐DLI后12个月再次骨髓复发,放弃治疗于1个月后死亡,DFS及OS分别为12、13个月。G‐DLI后发生局限性皮肤慢性GVHD ,给予小剂量免疫抑制剂后得到控制。1例G‐DLI后无病存活至今,DFS为16个月。G‐DLI后发生局限性皮肤慢性GVHD ,给予小剂量免疫抑制剂后得到控制。结论 FLAG方案联合G‐DLI可能是AML行allo‐HSCT术后复发的有效治疗方式之一。     

无血缘关系供者异基因外周血干细胞移植治疗急、慢性白血病7例

目的 观察无血缘关系供者外周血干细胞移植治疗急、慢性白血病的疗效.方法 2005年1月～2006年10月本科行无血缘关系供者造血干细胞移植治疗急、慢性白血病患者7例,所有供受者之间HLA高分辨配型全相合.预处理方案: CY TBI方案4例、BU/CY方案3例.采用环孢菌素A加骁悉加MTX加ATG(即复宁)预防性控制移植物抗宿主病.结果 移植 9～ 22d(中位时间 13.2d),中性粒细胞》0.5×109/L; 14～ 27d(中位时间 17.5d),血小板》20×109/L.2例于移植 38d和 56d发生Ⅱ度急性移植物抗宿主病,予甲强龙治疗后控制,4例发生慢性移植物抗宿主病,局限型2例,广泛型2例;无1例发生VOD及巨细胞病毒感染;移植相关不良反应CY TBI方案与BU/CY方案未见差异;随访5～27个月,6例患者无病生存,1例死于本病复发;3例慢性粒细胞白血病bcr/abl融合基因检测转阴.结论 无血缘关系供者外周血干细胞移植是一种有效的血液肿瘤治疗方法.     

Allogeneic bone marrow transplantation for chronic myeloid leukemia: a single center experience

BACKGROUND: Bone marrow transplantation (BMT) is the therapy of choice for patients with chronic myeloid leukemia (CML) who have a human leukocyte antigen (HLA)-identical donor and are under 50 years of age. METHODS: Here, 45 patients with CML were treated with busulfan (Bu) 16 mg/kg and cyclophosphamide (Cy) 120 mg/kg before allogeneic BMT from an HLA-identical sibling 27 (60%) or a 1-antigen mismatch donor 18 (40%). Eighteen patients (40%) were in the early chronic phase (CP) and 27 (60%) in late CP. We used cyclosporin-A (CsA) in 20 patients and cyclosporin-A-methotrexate (CsA-MTX) in 25 for graft-vs.-host disease (GVHD) prophylaxis. RESULTS: We observed a high incidence of acute and chronic GVHD (69% and 67%, respectively). A multivariate analysis identified differences in the sex of the donor and the recipient (p = 0.03) and grade III-IV acute GVHD (p = 0.0001) as significant adverse influences on disease-free survival. Age, sex, chronic GVHD, disease phase, one antigen-mismatch and use of CsA or CsA-MTX had no statistical significance. The 3-year probabilities of relapse, disease-free survival, and overall survival were 11%, 55%, and 60%, respectively. Transplant-related mortality occurred in 31% of the cases. The high frequency of GVHD is explained by HLA determination by serological typing, differences in sex between the donor and recipient, and a high proportion (40%) of 1 antigen-mismatch donors. CONCLUSIONS: BMT is a procedure feasible for patients with CML in early and late chronic phase and even in those with an HLA non-identical donor. Strategies directed to decrease acute GVHD could improve the outcome of these patients.     

清髓性异基因造血干细胞移植治疗成人急性淋巴细胞白血病非血缘脐血与血缘相关移植的比较——单中心临床研究

目的 评估并比较异基因造血干细胞移植清髓方案治疗成人急性淋巴细胞白血病(ALL)的疗效及安全性.方法 异基因造血干细胞移植治疗37例成人急性淋巴细胞白血病患者:其中17例行非血缘脐血移植(UCBT)患者中位年龄25(14～37)岁、中位体质量55(31～84)kg、男性占82%,UCBT组中高危难治患者共15例(88%...     

Transformation of myelodysplastic syndromes into acute myeloid leukemias

Background Myelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML).Methods Leukemic transformation in 151 patients with MDS was dynamically followed up. The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed.Results During the course of this study, over the past eight years and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia, with a median interval of 5 (1-23) months. There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups. Transformation occurred either gradually or rapidly. There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy. All of the 21 patients with leukemia suffered from MDS-AML, and most of them were M2, M4, or M5. Two (9.52%) MDS-AML patients developed extramedullary infiltration. Leukopenia was found in 47.62% of these patients. Two thirds of these patients, whose bone marrows were generally hypercellular, suffered from neutropenia. After developing AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD33 ［(49.83±24.50)%］, CD13 ［(36.38±33.84)%］, monocytic antigen CD14 ［(38.50±24.60)%］, and stem cell marker CD34 ［(34.67±30.59)%］, were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation. In some cases, lymphoid antigens, such as CD5, CD7, CD9, and CD19, coexisted with myeloid antigens. A low complete remission rate (31.25%) and a short survival time, with median survival of 6 (1-28) months, were found in patients with MDS-AML treated by induction chemotherapy.Conclusions MDS has a high risk of developing into AML, either gradually or rapidly. Patients with MDS-AML have specific biological characteristics and a worse prognosis.     

自体造血干细胞移植治疗恶性血液病

目的　评价自体造血干细胞移植 (AHSCT)治疗恶性血液病的疗效。　方法　用 AHSCT治疗白血病及恶性淋巴瘤患者共 5 8例 ,年龄 31.9± 10 .5 (14～ 5 8)岁。其中急性非淋巴细胞白血病 (ANL L ) 30例 (CR1 2 4例 ,CR2 5例 ,CR31例 ) ,急性淋巴细胞白血病 (AL L ) 18例 (CR1 13例 ,CR2 3例 ,CR32例 ) ,慢性粒细胞白血病 (CML ) 3例 (均获血液学缓解 ) ,恶性淋巴瘤 7例 (CR4例 ,PR3例 )。预处理化疗方案选用以下药物中任意两种或三种联合 :阿糖胞苷 3～ 4g/ m2 ,环磷酰胺 4～ 6 g/ m2 ,鬼臼乙叉苷 (VP- 16 ) 0 .5～ 1.0 g/ m2 。除 5例联合全身骨髓照射 (剂量为7～ 8Gy) ,其余均单用化疗。　结果　所有患者移植后均重建造血 ,移植相关死亡 1例 (1.72 % )。ANL L、AL L CR1期移植者 3年无病生存率分别为 5 2 .4%± 4.2 %和 46 .1%± 3.5 % ,复发率分别为 37.7%± 4.5 %和 40 .5 %±6 .7%。 10例 CML 和恶性淋巴瘤患者中 ,除 1例 期恶性淋巴瘤患者复发 ,余均获持续完全缓解。　结论　为降低白血病和恶性淋巴瘤的复发率 ,提高患者的无病生存期 ,无造血干细胞供者的 CR1 期白血病及恶性淋巴瘤患者应积极行 AHSCT。     

难治复发急性白血病患者造血干细胞移植后感染相关死亡的分析

摘要：目的探讨难治复发急性白血病患者接受异基因造血干细胞移植（allo-HSCT）后感染相关死亡（IRM）的特点。方法回顾
分析127例接受allo-HSCT的难治复发急性白血病患者的临床资料,统计感染相关死亡情况并分析危险因素。结果观察期内
67 例死亡。5 年总生存率为（35.2±5.3）%,无病生存率为（30.8±5.6）%。28.3%（36/127）患者发生感染相关死亡。Ⅱ~Ⅳ°
aGVHD (P=0.049, OR=3.017)和移植后IFI（P=0.032, OR=3.223）是IRM的独立危险因素。结论感染作为移植相关死亡的主
要原因,相对于标危患者,在难治复发患者中占更高的比例。更多的关注严重GVHD后感染的预防和治疗力度是目前减少IRM
的主要措施。
     

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.     

Bone marrow transplantation for childhood acute lymphoblastic leukaemia after marrow relapse

Children with acute lymphoblastic leukaemia in whom relapse in bone marrow occurs have a poor outlook when treated with chemotherapy alone. Twenty-seven patients with childhood acute lymphoblastic leukaemia were treated for marrow relapse with high-dose chemotherapy with or without total body irradiation followed by bone marrow transplantation (BMT). Twenty patients received allogeneic marrow from partially or completely matched histocompatible donors. In this group, nine patients (45%) were free of disease with a median follow-up of 57 months (range, 22 to 126 months) after transplantation, four (20%) died from interstitial pneumonitis and seven (35%) died after a further relapse. Seven patients received autologous marrow collected while they were in remission. In this group, one patient died from infection and six died after a further relapse. We conclude that allogeneic BMT is more effective than autologous transplantation and results in long-term disease-free survival in a significant number of patients. New methods are needed to eradicate residual disease in the patient and to purge marrow ex vivo.     

沙利度胺综合治疗骨髓增生异常综合征24例

目的探讨沙利度胺综合治疗骨髓增生异常综合征(MDS)的疗效。方法根据FAB分型将46例MDS患者分为低危组和高危组,低危组24例包括难治性贫血(RA)和伴环状铁粒幼红细胞的难治性贫血(RAS),采用沙利度胺加司坦唑醇治疗;高危组22例包括未成熟红细胞过多的难治性贫血(RAEB)和伴过度性未成熟红细胞红细胞的难治性贫血(RAEBT)的用沙利度胺加高三尖杉酯碱化疗。根据国内MDS疗效标准判断疗效。结果低危组总有效率79.15%,缓解率54.17%;高危组总有效率63.64%,缓解率45.45%。两组比较无显著差异(P>0.05)。结论沙利度胺对MDS有肯定疗效,可有效延长生存期,改善生存质量。     

Bone marrow Th2 cytokine expression as predictor for relapse in childhood acute lymphoblastic leukemia (ALL)

The immunological environment of leukemic blasts in the bone marrow might play a decisive role in determining an individual's risk for relapse. In order to identify potential predictors of relapse and to elucidate the mechanisms of immune control of leukemic blasts we examined the expression of cytokines, costimulatory molecules and members of the TNF family in leukemic marrow samples in a prospective study. Samples from 49 consecutive pediatric patients with B cell precursor acute lymphocytic leukemia (BCP ALL) were analyzed by semiquantitative RT-PCR. We identified interleukin (IL)-10 expression as a significant adverse prognostic indicator in childhood BCP-ALL. The event free survival (EFS) of patients expressing IL-10 mRNA in high quantity was significantly lower compared with patients expressing low IL-10 mRNA. Taqman RT-PCR of sorted cell populations showed that IL-10 mRNA was synthetized almost exclusively by NK or T cells. In addition, we found an increased expression of IL-1, IL-4, CD86 and VEGF mRNA in patients with late relapses. Possibly, ALL cells mediate a Th2 shift through increased expression of CD86 and thereby influence the individual relapse risk. These findings emphasize the role of the immune system for the outcome of childhood ALL.