异基因干细胞移植治疗恶性淋巴瘤

恶性淋巴瘤是自体干细胞移植（ASCT）的主要适应证,而异基因移植（allo-SCT）的应用相对较少。allo—SCT的复发率（RR）较ASCT低,但移植相关死亡率（TRM）较高,二者的长期总体生存率（OS）无统计学差异。ASCT治疗霍奇金病疗效良好,因此仅在自体干细胞获取困难或严重损伤时考虑allo—SCT。而某些亚型的非霍奇金淋巴瘤ASCT疗效很差,allo-SCT可使部分患者获得长期无病生存,可以优先选择allo-SCT。此外,非清髓性预处理、去T细胞、供者淋巴细胞输注等技术的进展有望控制allo-SCT的TRM,并保留移植物抗淋巴瘤作用,改善患者生存。     

造血干细胞移植在复发难治霍奇金淋巴瘤中的若干问题

对于复发难治性霍奇金淋巴瘤,目前标准的治疗方案为解救化疗有效后给予大剂量化疗+ 自体干细胞移植（HDCT/ASCT）。 常用的解救方案之间没有优劣,如BEAM ,CBV ,IGEV 等。解救化疗后行PET 检查对自体造血干细胞移植有重要的预后价值。降低预处理强度的异基因造血干细胞移植（RIC-alloSCT）可作为ASCT后复发患者一种有效的治疗方法。本文就造血干细胞移植在复发难治性霍奇金淋巴瘤中的若干问题进行综述。     

大剂量化疗联合自体造血干细胞移植治疗淋巴瘤59例回顾性分析

目的:通过分析大剂量化疗(HDT)联合自体造血干细胞移植(ASCT)治疗淋巴瘤的临床体会,探究安全合理的动员和预处理方案,以进一步提高治疗的安全性和疗效.方法:对59例接受HDT联合ASCT治疗的淋巴瘤患者的资料进行回顾分析.结果:59例患者采集到足够数量的造血干细胞,预处理后接受ASCT并成功恢复造血.随访1～88个月(中位数26.3个月),47例患者无病生存1～88个月(中位数28.5个月),10例在移植后2～37个月死于肿瘤复发,1例移植后16个月死于深部霉菌感染.1例移植后9个月死于爆发性肝炎.结论:HDT联合ASCT与常规化疗有机结合可能是治疗淋巴瘤安全、有效的方法.     

异基因造血干细胞移植治疗外周T细胞淋巴瘤现状

外周T细胞淋巴瘤作为一组异质性肿瘤,大多侵袭性强,易出现复发和耐药,预后极差.以化疗和自体造血干细胞移植(ASCT)为基础的治疗,5年无病生存率不足30％.异基因造血干细胞移植(allo-HSCT)治疗外周T细胞淋巴瘤具有移植物抗淋巴瘤效应,治疗复发难治性外周T细胞淋巴瘤的长期无病生存率达35％～50％.allo-HSCT可作为治疗外周T细胞淋巴瘤的有效手段.     

血管免疫母细胞性T细胞淋巴瘤治疗研究进展

血管免疫母细胞性T细胞淋巴瘤（AITL）是一种系统性、侵袭性外周T细胞淋巴瘤,目前仍然缺乏标准治疗方案。联合化疗没有明显改善预后且缓解持续时间短;靶向药物和免疫抑制治疗研究样本小,不能明确疗效;大剂量化疗联合自体造血干细胞移植（HDT—ASCT）和异基因造血干细胞移植（allo-HSCT）虽然都取得了显著疗效,但HDT—ASCT具有高复发率、远期继发肿瘤等诸多风险,allo—HSCT亦因移植相关死亡率较高而有待进一步探讨。文章就近年来AITL的治疗研究进展加以综述。     

造血干细胞移植治疗外周T 细胞淋巴瘤的进展

外周T 细胞淋巴瘤（PTCL）,其免疫表型提示来源于胸腺后（或成熟）T 细胞,包括大组非特异性PTCL。在全球范围内,PTCL约占非霍奇金淋巴瘤（NHL ）的10％,在我国约占20% ～30% ,明显高于西方国家。大多数PTCL侵袭性强,恶性程度高,传统的化疗方法与B 细胞NHL 相比疗效不佳、预后不良,５年生存率低。近年来研究表明造血干细胞移植（HSCT）对PTCL有较好的疗效,优于传统的化疗方法。本文主要总结自体造血干细胞移植（ASCT）、异基因造血干细胞移植（allo-SCT ）和自体外周血干细胞移植联合自体骨髓移植（APBHSCT+ABMT）三种方式及其优劣。ASCT无供受者之间的免疫排斥反应,造血重建快,但其复发率相对较高;allo-SCT 具有移植物抗淋巴瘤作用,但其有较高的治疗相关死亡率;APBHSCT+ABMT对于年龄偏大、造血功能差而难以采集足够外周血干细胞、有潜在出血和感染风险较大PTCL患者意义较大。HSCT的移植方法、移植时机、预处理方案及强度等多种因素对移植疗效均有影响,如何根据不同PTCL患者的具体情况选择不同的移植方式、选择合适的移植时机等问题还值得进一步深入的研究。      

自体干细胞移植支持下的大剂量化疗一线治疗恶性淋巴瘤

背景与目的:目前自体干细胞移植(autologous stem cell transplantation,ASCT)支持下的大剂量化疗(high-dose chemotherapy,HDC)已成为复发或难治性恶性淋巴瘤(malignant lymphoma,ML)的标准治疗方法,但是对于一些选择的ML是否可作为一线治疗方案目前尚不明确.本文旨在通过回顾性分析探讨HDC/ASCT作为一线方案治疗ML的疗效.方法:自2000年9月至2007年6月, 连续收治28例ML患者,中位年龄32岁(8～60岁),其中男性17例,女性11例.组织学类型包括24例非霍奇金淋巴瘤,4例霍奇金淋巴瘤.自体外周血干细胞动员采用化疗药物联合重组人粒细胞集落刺激因子方案.HDC方案采用BEAC(BCNU、CTX、Ara-C 、VP-16)方案.随访日期自干细胞回输之日期开始,末次随访日期为2007年7月30日.结果:28例患者均移植成功,重建造血功能.移植前CR 14例,PR 14例,移植后CR 22例,PR 6例.随访截止日期为2007年7月30日,中位随访时间为28个月(1.5～82个月),移植后4例病情进展,其中2例死亡,3年生存率及无进展生存率分别为89%和76%.大剂量化疗期间不良反应均可耐受,无移植相关死亡.结论:HDC/ASCT作为一线方案治疗ML是安全、可行及有效的治疗方法.     

自体外周血干细胞移植治疗难治复发性恶性淋巴瘤

[目的]探讨自体外周血干细胞移植治疗难治、复发性恶性淋巴瘤的疗效.[方法]3例复发难治恶性淋巴瘤患者(其中霍奇金病2例,非霍奇金淋巴瘤1例)接受自体外周血干细胞移植.[结果]3例患者采集干细胞CD34 细胞数为3.20×106/kg～7.8×106/kg.3例自体外周血干细胞移植后均获造血重建,移植后中性粒细胞上升至＞0.5×109/L的时间为7～14d,血小板上升至＞50×109/L为10～16d.2例HD患者移植后随访18～48个月持续缓解,1例6个月后复发.[结论]自体外周血干细胞移植安全、可靠,对复发、难治恶性淋巴瘤仍有较好的疗效.     

自体造血干细胞移植治疗B细胞非霍奇金淋巴瘤的研究进展

非霍奇金淋巴瘤(non-hodgkin lymphoma,NHL)是一组起源于包括B-细胞、T细胞及NK细胞的异质性淋巴增殖性疾病.欧美国家B细胞淋巴瘤(B-NHL)约占80％ ～85％[1].我国B细胞淋巴瘤发生率约占NHL的61.6％～74.2％[24].B-NHL包括弥漫大B细胞淋巴瘤、套细胞淋巴瘤、滤泡性淋巴瘤等.NHL的治疗包括化疗、放疗、免疫治疗、放射免疫治疗及造血干细胞移植.近10多年来,由于CD20单克隆抗体(单抗)的应用和自体造血干细胞移植(autologous stem cell transplantation,ASCT)作为巩固治疗使得B-NHL的疗效明显提高[5-6].然而,自体造血干细胞移植是作为该病一线巩固还是待疾病复发后作为挽救性治疗仍待进一步明确.     

自体造血干细胞移植治疗霍奇金淋巴瘤38例临床疗效及预后影响因素分析

目的 探讨自体造血干细胞移植（ASCT）治疗霍奇金淋巴瘤（HL）的临床疗效以及影响预后的因素。方法 回顾2007年10月至2021年10月于郑州大学附属肿瘤医院经ASCT治疗的HL38例患者资料,Kaplan-Meier和Cox方法分析移植后疗效以及预后影响因素。结果 38例移植患者均获得造血重建。全组患者移植前后CR率分别为55.3%和81.6%,5年PFS和OS分别为76.1%和79.0%。单因素分析显示B症状、IPS评分、移植前缓解状态、结外受累和预处理方案（均P<0.05）是影响HL患者ASCT预后的因素,多因素分析显示B症状（P<0.05）是影响5年PFS的独立危险因素。结论 ASCT治疗高危、复发难治HL患者的疗效显著,有B症状是影响移植预后的独立危险因素。     

大剂量化疗联合自体造血干细胞移植治疗淋巴瘤的疗效

目的:观察大剂量化疗联合自体造血干细胞移植治疗恶性淋巴瘤的疗效。方法:选择2009年12月－2015年12月于我科住院治疗的恶性淋巴瘤病例30例,均接受大剂量化疗联合自体造血干细胞移植治疗。结果:1例患者造血干细胞回输后因严重肺部感染死亡,其余均成功植入并快速重建造血;随访至2016年3月1日,有22例存活,无病生存19例,9例复发,中位复发时间为4.5(1~15)个月,其中6例复发后3年内死亡,2例治疗后重新评估为CR随访至今未再复发,1例为单一椎体复发至今仍存活。移植相关死亡率为6.7%。结论:大剂量化疗联合自体造血干细胞移植能很快重建造血,是治疗恶性淋巴瘤安全有效的方法。     

Autologous and allogeneic stem cell transplantation in Hodgkin's lymphoma

Newly diagnosed patients who have advanced-stage Hodgkin's lymphoma have an excellent prognosis because most of them can be cured with initial treatment. In contrast, the prognosis for patients relapsing after first-line therapy with either combination chemotherapy or chemotherapy followed by radiotherapy remains poor in many cases. In most of these cases, high-dose chemotherapy and autologous stem cell transplantation (ASCT) is currently considered to be the treatment of choice. However, results of ASCT in primary refractory patients are poor and new therapeutic alternatives should be sought for these patients. Allogeneic stem cell transplantation has been used increasingly in relapsed or refractory Hodgkin's lymphoma patients, with the introduction of reduced-intensity conditioning protocols.     

自体造血干细胞移植治疗中、高度恶性淋巴瘤

背景与目的:自体造血干细胞移植(autologoushemotopoieticstemcelltransplantation,ASCT)支持下的大剂量化疗目前已成为治疗对化疗敏感的淋巴瘤最有效的手段之一。本研究评价自体造血干细胞移植支持下的大剂量化疗加放疗治疗预后差的中、高度恶性淋巴瘤的疗效。方法:1995年11月～2001年5月收集到的13例病例中,非霍奇金淋巴瘤(non-Hodgkinslymphoma,NHL)11例,复发霍奇金淋巴瘤(Hodgkinsdisease,HD)2例。移植前首次完全缓解(firstcompleteremission,CR1)8例,第二次完全缓解(secondcompleteremission,CR2)4例,第二次部分缓解(secondpartialremission,PR2)1例。预处理方案:单纯化疗4例;化疗加受累区放疗6例;全身放疗加化疗3例。2例采用自体骨髓移植,11例行自体外周血干细胞移植。结果:本组病例回输单核细胞(mono-nuclearcell,MNC)和粒-巨细胞系祖细胞(granulocyte-macrophagecolony-formingcells,CFU-GM)的均数(范围)分别为2.55(2.07～3.31)×109/L和1.43(0.6～2.36)×109/L。随访到2001年10月,所有患者造血功能都获得重建。白细胞恢复到≥1.0×109/L和血小板>50×109/L的中位时间(范围)分别为6(7～35)天和8(6～32)天。CR持续时间为4～57个月,中位时间为16个月,1年生存率76.9%,3年生存率46.2%。结论:自体造     

Initial chemotherapy with mitoxantrone, chlorambucil, prednisone impairs the collection of stem cells in patients with indolent lymphomas--results of a randomized comparison by the German Low-Grade Lymphoma Study Group.

Myeloablative radio-chemotherapy with subsequent autologous stem cell transplantation (ASCT) significantly prolongs progression free and probably overall survival in follicular lymphoma (FL) in first remission. The current trial explored prospectively the rate of successful stem cell mobilization in patients with advanced stage FL after initial therapy with either Mitoxantrone, Chlorambucil, Prednisone (MCP) or Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) as part of a prospective randomized comparison of both regimens. ASCT patients received Dexa-BEAM (Dexamethasone, BCNU, Melphalan, Etoposide, Cytarabine) for mobilization of stem cells. Stem cells were collected and a minimum of 2x2.0x106/kg bw CD34+ was required for ASCT. Of 79 evaluable patients, 58 (73%) had follicular lymphoma, 13 (16%) mantle cell lymphoma and 8 (10%) lymphoplasmacytic lymphoma. In the 45 patients assigned to CHOP, stem cell collection was successful in 42 cases (93%, 95% CI 82% to 99%). This high mobilization rate after CHOP could be confirmed in 61 subsequent patients (87%). In contrast, after MCP therapy stem cell collection was successful in only 15 of 34 patients (44%, 95% CI 27% to 62%; P=0.0003). In conclusion, initial therapy with MCP significantly impairs the ability to collect stem cells and should be avoided for first line therapy of younger patients potentially qualifying for high dose consolidation and ASCT in first remission.     

Involved field radiation post autologous stem cell transplantation in lymphoma patients is associated with major haematological toxicities

Irradiation is known to cause temporary to permanent marrow aplasia in cancer patients when administered as a sole therapy or in combination with chemotherapy. Until now, no studies have been carried out evaluating the haematological toxicities of involved field radiation administered post autologous stem cell transplantation (ASCT). We assessed bone marrow (BM) toxicity in 93 patients who received involved field radiation post ASCT (non-Hodgkin’s lymphoma 21, Hodgkin’s disease 7, breast cancer 15, and other solid tumours 50. Severe BM toxicity, with grade IV neutropenia, and/or thrombocytopenia, and/or anaemia necessitating interruption of radiotherapy for more than a week, was observed in 11 patients (malignant iymphoma-8 of which 7 were NHL, and 1 HD, breast cancer-1, Wilm’s tumour-1, Ewing’s sarcoma-1). Patients with malignant lymphoma were at higher risk of developing post ASCT radiation-induced cytopenias than patients with breast cancer or solid tumours, 28% vs 4.5%, respectively (P<0.05). Of the 11 patients, 7 developed bacterial sepsis and 10 were hospitalised. The radiation-induced cytopenia patients necessitated platelets and red blood cell transfusions, interrupting the course of irradiation. Of the patients suffering from non-Hodgkin’s lymphoma, 8/14 (57%) of those who received conventional courses of radiotherapy relapsed compared to 6/7 (86%) of those who received interrupted radiotherapy (P < 0.05). The most appropriate timing for radiation in malignant lymphoma patients who are scheduled for ASCT, as well as the protective role of haematopoietic growth factors like erythropoietin and Granulocyte (G) or Granulocyte-Monocyte (GM), colony stimulating factors (CSF) and others, are discussed. Keywords: ABMT; radiation; neutropenia; thrombocytopenia; sepsis; transfusion; relapse; haematopoietic growth factors (HGF)     

High dose therapy and autologous stem cell transplantation for human immunodeficiency virus-associated non-Hodgkin lymphoma in the era of highly active antiretroviral therapy

BACKGROUND: The advent of highly active antiretroviral therapy (HAART) has allowed the exploration of more dose-intensive therapy such as autologous stem cell transplantation (ASCT) in selected patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL). METHODS: The authors report on the use of myeloablative chemotherapy with ASCT in two HIV positive patients with NHL. The first patient underwent ASCT at the time of first disease remission for poor risk, diffuse, large cell NHL and the second patient had multiply recurrent, chemosensitive Burkitt lymphoma. ASCT was performed in both patients using a transplant conditioning regimen of high dose cyclophosphamide, carmustine, and etoposide (CBV). RESULTS: The target dose of >/= 5 x 10(6)/kg CD34 positive peripheral blood stem cells (PBSC) utilized for ASCT was collected using granulocyte-colony stimulating factor (G-CSF) after chemotherapy for mobilization while both patients were receiving concomitant HAART for HIV infection. HAART was continued during CBV conditioning. Prompt hematopoietic recovery was observed after ASCT. Both patients remained in clinical disease remission from their lymphoma at 28 months and 20 months after transplant, respectively. CONCLUSIONS: ASCT is feasible in patients with HIV-associated NHL. Adequate numbers of CD34 positive PBSC can be procured from patients receiving HAART and chemotherapy for NHL. Selected patients with HIV-related lymphoma can tolerate the high dose CBV myeloablative chemotherapy regimen without increased acute regimen-related toxicity. Reinfusion of G-CSF-mobilized PBSC can lead to rapid recovery of hematologic function and sustained engraftment after ASCT. Given the poor prognosis of patients with HIV-associated NHL treated with conventional chemotherapy, further investigation of this approach should be considered.     

The Role of Autologous Transplantation in Hodgkin Lymphoma

Between 80% and 90% of Hodgkin lymphoma (HL) patients can be cured with up-to-date combined-modality treatments, but patients with disease refractory to first-line therapy and those who relapse after first-line therapy still have a relatively poor prognosis. Dose intensification with stem cell support has been evaluated both to avoid relapses and to cure patients with refractory or relapsed disease. In this review, we focus on the use of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in first-line, second-line, and third-line therapy for HL patients. The relevance of salvage therapy before high-dose chemotherapy is discussed, as well as the role of sequential high dose chemotherapy. We also review current evidence for tandem transplantation in high-risk HL patients and ASCT in elderly patients. Finally, we discuss current concepts of ASCT for HL patients and the use of functional imaging and consolidation therapy.     

A novel potent Fas agonist for selective depletion of tumor cells in hematopoietic transplants

There remains a clear need for effective tumor cell purging in autologous stem cell transplantation (ASCT) where residual malignant cells within the autograft contribute to disease relapse. Here we propose the use of a novel Fas agonist with potent pro-apoptotic activity, termed MegaFasL, as an effective ex-vivo purging agent. MegaFasL selectively kills hematological cancer cells from lymphomas and leukemias and prevents tumor development at concentrations that do not reduce the functional capacity of human hematopoietic stem/progenitor cells both in in vitro and in in vivo transplantation models. These findings highlight the potential use of MegaFasL as an ex-vivo purging agent in ASCT.