专栏寄语

高剂量治疗联合自体造血干细胞移植(high-dose therapy/autologous hematopoietic stem cell transplantation,HDT/AHSCT)是治疗恶性肿瘤的一项重要手段。1978年,美国国家癌症研究所的Appelbaum等首次报道了高剂量治疗(high-dose therapy,HDT)联合自体骨髓移植治疗Burkitt’s淋巴瘤,可使部分既往常规化疗效果不佳的患者获得治愈,从而激发了HDT/AHSCT在恶性实体瘤治疗中的广泛研究与应用。我国自1989年中国医学科     

大剂量化疗联合自体造血干细胞移植治疗外周T细胞淋巴瘤的回顾性研究

目的 :探讨大剂量化疗联合自体造血干细胞移植(high-dose therapy/autologous hematopoietic stem cell transplantation,HDT/AHSCT)在外周T细胞淋巴瘤(peripheral T-cell lymphoma,PTCL)治疗中的价值。方法:对50例接受HDT/AHSCT治疗的PTCL患者的病历资料进行回顾性分析,并进行随访。结果 :50例患者均未发生HDT/AHSCT相关死亡。中位随访时间为13个月(1~136个月),2年无进展生存率为59.0%,2年总生存率为65.0%。单因素分析结果显示,移植前达完全缓解(complete remission,CR)患者的2年无进展生存率和总生存率均明显优于非CR患者(2年无进展生存率:72.8%vs 41.9%,P=0.003;2年总生存率:88.2%vs41.9%,P=0.002),一线治疗敏感患者接受HDT/AHSCT的预后优于二线治疗敏感患者(2年无进展生存率:76.8%vs 30.8%,P=0.001;2年总生存率:81.1%vs 46.2%,P=0.015)。此外,移植前的红细胞沉降率是2年无进展生存率和2年总生存率的影响因素(P=0.004,P=0.018),移植前血清乳酸脱氢酶水平是2年无进展生存率的影响因素(P=0.044)。多因素分析结果显示,仅移植前达CR是2年总生存率的独立影响因素[相对风险=4.879(95%可信区间:1.583~15.034),P=0.006];未发现与2年无进展生存率相关的独立影响因素。亚组分析显示,一线治疗达CR的血管免疫母细胞性T细胞淋巴瘤及晚期自然杀伤细胞/T细胞淋巴瘤患者接受HDT/AHSCT可有生存获益。结论 :HDT/AHSCT作为PTCL患者一线巩固治疗或挽救治疗的安全性较高,并且可以部分改善PTCL患者的预后。今后有待开展前瞻性随机对照研究以验证HDT/AHSCT在不同病理亚型及移植前状态下的应用价值。     

单纯Hyper-CVAD方案或联合自体造血干细胞移植一线治疗淋巴母细胞淋巴瘤的疗效分析*

目的：探讨单纯Hyper-CVAD 方案与Hyper-CVAD 方案联合自体造血干细胞移植一线巩固治疗淋巴母细胞淋巴瘤（lymphoblastic lymphoma ,LL）的疗效。方法：回顾性分析26例青少年和成人初治采用改良Hyper-CVAD 方案的LL患者资料。其中,22例不伴骨髓受侵的患者中,11例接受单纯改良Hyper-CVAD 方案治疗,另外11例接受改良Hyper-CVAD 方案联合HDT/AHSCT 巩固治疗。结果：全组61.5%（16/26）的患者初治达完全缓解（complete remission ,CR）或不确定的CR（unconfirmedCR,CRu ）,中位随访29.5 个月,5 年的总生存（overall survival,OS）率和无进展生存（progress-free survival ,PFS）率分别为66.8% 和50.2% 。22例无骨髓受侵的患者中,单纯Hyper-CVAD 组与联合HDT/AHSCT组的5 年OS率分别为60.0% 和70.7%（P=0.438）,5 年PFS 率分别为43.6% 和62.3%（P=0.209）,均无统计学差异。单因素预后分析结果显示,初治缓解后1 年内疾病进展或复发与预后不良相关（P=0.012）。 结论：改良Hyper-CVAD 方案是青少年和成人LL一线有效的治疗方案。对于无骨髓侵犯的患者,单纯改良HyperCVAD 已能取得较好疗效,联合HDT/AHSCT巩固治疗未能进一步改善预后。     

淋巴瘤自体造血干细胞移植的临床实践优化探索与未来展望

自体造血干细胞移植(autologous hematopoietic stem cell transplantation,AHSCT)是高度侵袭性和复发/难治性淋巴瘤的有效治疗手段之一,可为患者带来生存获益.近年来,小分子靶向药物、单克隆抗体、细胞治疗和免疫治疗等新药给淋巴瘤患者提供了更多的选择,但AHSCT在淋巴瘤治...     

自体造血干细胞移植治疗恶性淋巴瘤的研究进展

自体造血干细胞移植(AHSCT)是治疗恶性淋巴瘤(ML)的重要方法,其治疗过程较为复杂,疗效也受诸多因素影响.近年来AHSCT在ML的治疗中应用更加广泛,寻找有效的预后因素以进一步区分可能从AHSCT中获益的患者以及制订合理的移植方案是临床医生关注的重要问题.文章就AHSCT治疗ML的研究进展作一综述.     

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.     

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治疗恶性淋巴瘤

目的观察白体造血干细胞移植（AHSCT）治疗恶性淋巴瘤的疗效。方法自1998年1月至2003年2月,用AHSCT治疗恶性淋巴瘤15例。外周血千细胞动员均采用CHOP方案＋VP16＋粒细胞集落刺激因子（G—CSF300μg／d,5～7d）。预处理方案为CBV或改良CHOP方案。结果全部患者均获得缓解,随诊至2003年12月,3年无瘤生存率为86．1％,无移植相关死亡。结论AHSCT联合大剂量化疗对中高度、中晚期恶性淋巴瘤疗效佳,能够提高生存率并优于常规化疗。     

Ki-67、p53、bcl-2的表达与恶性淋巴瘤自体造血干细胞移植预后的相关性

 目的　研究bcl-2、p53、Ki-67在恶性淋巴瘤组织中的表达以及与自体造血干细胞移植（AHSCT）预后的相关关系。方法　采用免疫组织化学IHC法检测33例行AHSCT治疗的患者淋巴瘤组织切片中Ki-67、p53、bcl-2的表达。并分析Ki-67、p53、bcl-2的表达与预后的相关性。生存率统计采用Kaplan-Meier生存曲线,Log-Rank检验,多因素分析采用COX风险回归模型。结果　p53 的表达与33例AHSCT患者预后无关,bcl-2阳性表达组和阴性表达组移植后3年无瘤生存率（DFS）分别为35.71 %和88.89 %（P＜0.05）;Ki-67阳性表达组和阴性表达组3年DFS分别为43.75 %和85.71 %（P <0.05）,提示bcl-2和Ki-67的表达与AHSCT的预后相关。COX多因素分析显示,Ki-67和bcl-2是影响淋巴瘤患者AHSCT后无瘤生存的相关因素（P＝0.0437）。结论　bcl-2、Ki-67蛋白阳性表达的淋巴瘤患者,AHSCT后易复发,可作为移植后预后判断的指标之一。Ki-67和bcl-2是影响淋巴瘤患者AHSCT无瘤生存的独立相关因素。     

T淋巴母细胞淋巴瘤自体干细胞移植后的长期随访观察

目的评价自体造血干细胞移植（autologous hematopoietic stem cell transplantation,AHSCT）治疗复发难治T淋巴母细胞淋巴瘤（TLBL）的临床疗效及安全性。方法本文回顾性分析AHSCT治疗后长期随访的TLBL16例,预处理方案主要为BEAM和BEAC。结果 15例患者可评价疗效,1例失访。中位随访37个月（12~132个月）,中位无进展生存时间（PFS）34.5个月。预计中位总生存时间49月。1、3、5年总生存率分别为60%、53%、32%。初治患者一线治疗有效者,接受AHSCT者预计中位总生存时间为108个月,5年总生存率、无进展生存率分别为62%、63%;复发患者挽救治疗后接受AHSCT者,中位总生存时间为22.8个月,5年总生存率、无进展生存率分别为33%、22%。初始治疗未达CR/PR的难治患者,中位生存仅21个月,5年生存率和无进展生存率分别为20%和29%。结论 AHSCT常规化疗治疗TLBL安全、有效,可提高复发难治的T淋巴母细胞淋巴瘤的远期生存,延长初治TLBL患者的无进展生存期,但复发率仍偏高,值得开展大规模临床试验进一步深入研究。     

High-dose therapy/autologous hematopoietic stem cell transplantation in relapsed or refractory marginal zone non-Hodgkin lymphoma

The optimal therapy for patients who have relapsed or refractory marginal zone lymphoma has not been defined. We analyzed the clinical outcomes of 14 patients who had relapsed or refractory marginal zone lymphomas and underwent high-dose therapy/autologous hematopoietic stem cell transplantation (HDT/AHSCT) at the University of Nebraska from August 1992 to August 2008. The median age of patients was 48 years (range, 29 to 62 years). All patients had relapsed or refractory disease. There were three treatment-related deaths within 100 days of transplantation. With a median follow-up of 138 months, the median duration of failure-free survival is 108 months, and the median duration overall survival is 120 months. Only two patients have relapsed. Secondary malignancies were seen in three patients (myelodysplastic syndrome, n = 2; gastric carcinoma. n = 1). We conclude that HDT/AHSCT is feasible in patients who have relapsed/refractory marginal zone lymphomas. Approximately one- third of patients can achieve long-term disease-free survival.     

自体造血干细胞移植联合利妥昔单抗治疗CD+20B细胞淋巴瘤

 采用自体造血干细胞移植（AHSCT）治疗中,高危侵袭性淋巴瘤已获得了较好疗效,但仍有部分移植患者因复发而死亡。复发的根源主要为微小残留病变,包括体内残留的肿瘤细胞和移植物中的肿瘤细胞污染。利妥昔单抗可靶向性清除CD+20 B细胞,因此,对CD+20 B细胞淋巴瘤患者,移植前后应用利妥昔单抗可起到体内净化和清除残留病灶作用,AHSCT联合利妥昔单抗有望进一步提高CD+20 B细胞淋巴瘤的疗效。     

自体造血干细胞移植治疗恶性血液病61例疗效分析

 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　中南大学湘雅医院自1994年4月至2008年8月对61例恶性血液病患者进行了61次AHSCT治疗,移植时急性非淋巴细胞白血病（ANLL）30例,非霍奇金淋巴瘤（NHL）25例,霍奇金淋巴瘤（HL）3例,浆细胞瘤3例。ANLL采用预处理方案为MAC方案：美法仑（Mel）160 mg／m2×1次,阿糖胞苷（Ara-C）2.0／2.5 g×2次,环磷酰胺（Cy）1.8 g／m2×2次;淋巴瘤以及浆细胞瘤采用预处理方案：全身放疗（TBI）+Cy,单次照射8～10 Gy,剂量率5 cGy／min,Cy 1.8 g／m2×2次。或在以上方案基础上进行修改。结果　所有患者重建造血,1例患者移植过程中心功能衰竭死亡,移植相关死亡率为1.6 %。60例患者长期随访,1例患者失访。移植组中位随访期为52（2～211）个月,复发13例（21.3 %）,复发中位时间为18（2～77）个月。死亡14例（23.0 %）,现生存47例（77.0 %）,中位生存时间为66（15～211）个月。5年无病生存率（DFS）为[（77.5±5.5）%,比同期单纯接受化疗者的（31.6±7.3）%]明显增高,差异有统计学意义（P＜0.01）。结论　AHSCT移植患者移植相关死亡率低,无病生存率较高,可作为恶性血液病治疗的重要方法。     

Clinical value of serum HMGB1 in diagnosis and prognosis of laryngeal squamous cell carcinoma

Autologous hematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsed and recurrent follicular lymphoma (R/R FL); however, its value in the rituximab era remains to be elucidated. To evaluate the safety and clinical outcome of AHSCT for relapsed FL, we present a retrospective series of AHSCT for 30 FL patients (17 male and 13 female) at median age of 49 years. Patients were transplanted in second or subsequent complete or partial response after at least one therapeutic line including chemotherapy and rituximab. Overall, seven patients achieved second or higher complete response (CR) at AHSCT, whereas 23 were transplanted in partial response. Median overall survival (OS) was not reached, whereas progression-free survival (PFS) was 4.8 years. The estimated 10-year OS and PFS were found to be 60 and 33 %, respectively. There was no significant difference in OS and PFS in terms of FLIPI score and disease status at transplant. Median follow-ups from diagnosis and from AHSCT were 4.9 years (range 1.5–18.4 years) and 1.7 years (range 0.03–16.5 years), respectively. Fifteen patients relapsed, and 11 out of them (73 %) died of disease recurrence and chemoresistance. At the last contact, 19 patients are alive: 12 are in CR, whereas seven patients receive salvage regimens due to active lymphoma. AHSCT for relapsed FL patients who were pretreated with rituximab remains a safe procedure with low transplant-related mortality and long-term progression-free survival in about one-third of transplanted patients.     

Non-Hodgkin's lymphoma protocols in the treatment of patients with Burkitt's lymphoma and lymphoblastic lymphoma: a report on 58 patients

Lymphoblastic lymphoma (LBL) and Burkitt's lymphoma belong to the very aggressive lymphomas requiring intensive therapy. We retrospectively analyzed 29 patients with Burkitt's lymphoma and 29 patients with LBL who received induction therapy with a CHOP-like lymphoma protocol. Patients with Burkitt's lymphoma (with a median age of 54.5 years) have a CR rate of 72% and a lymphoma free long-time survival of 55%. The International Prognostic Index was the most valuable prognostic factor for survival. Patients with LBL with a median age of 45 years had a CR rate of 55% and a lymphoma-free survival of 38%. Stage was the most predictive prognostic factor. Our data suggest that for older patients (>50) treatment with lymphoma protocols may yield response rates that are comparable to the results of patients with disseminated diffuse large cell lymphoma. Younger patients with risk factors should be treated with more intensive therapy like ALL-protocols. The role of auto-transplantation after high dose therapy (HDT) however as part of primary treatment still needs to be evaluated in clinical trials. One of four patients with LBL who received HDT and one of four patients with Burkitt's lymphoma who received HDT achieved long-term remission.     

Hochdosistherapie bei malignen Lymphomen

High-dose therapy (HDT) and autologous transplantation of hematopoietic stem cells are important in the treatment of patients with lymphoma. Data from the European Group for Blood and Marrow Transplantation (EBMT) document increasing numbers of autologous and allogeneic transplants for most lymphoma subtypes. Recent developments in conventional therapy, in particular the ever-increasing use of the monoclonal anti-CD20 antibody rituximab well as the incremental use of reduced-intensity conditioning prior to allogeneic transplantation call for a re-evaluation of HDT and stem cell transplantation to allow the role of these modalities to be freshly defined in 2006.     

Shortened first-line high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma.

PURPOSE: Randomized trial LNH93-3 was conducted on patients who had poor-prognosis aggressive lymphoma and were younger than 60 years with two to three factors of the age-adjusted International Prognostic Index to evaluate the benefit of early high-dose therapy (HDT) with autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: Patients were randomized between doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) chemotherapy followed by sequential consolidation and an experimental shortened treatment consisting of three cycles with escalated doses of cyclophosphamide, epirubicin, vindesine, bleomycin, and prednisone and collection of peripheral-blood stem cells. On day 60, HDT was administered with 1,3-bis(2-chloroethyl)-1-nitrosourea, etoposide, cytarabine, and melphalan followed by ASCT. RESULTS: Eligible patients (n = 370) with aggressive lymphoma were analyzed. For ACVBP (181 patients) and HDT (189 patients), respective complete remission rates were 64% and 63%. With a median follow-up of 60 months, 5-year overall survival and event-free survival for ACVBP and HDT were 60% +/- 8% and 46% +/- 8% (P =.007) and 52 +/- 8% and 39 +/- 8% (P =.01), respectively. Survival was independently affected by age greater than 40 years (P =.0003), T-cell phenotype (P =.009), bone marrow involvement (P =.003), and HDT treatment group (P =.04). CONCLUSION: Early HDT with ASCT in high-risk patients was inferior to the ACVBP chemotherapy regimen. These results indicate that the received dose-intensity before HDT was too low when compared with ACVBP and HDT and was given too early.