流式细胞术在实体肿瘤临床中的应用

流式细胞仪在实体肿瘤中广泛应用。应用流式细胞仪可检测实体瘤患者的外周血中各种淋巴细胞、表面细胞因子受体及细胞内细胞因子的表达，监测放化疗前后免疫功能的变化、对造血功能的影响，检测多药耐药基因表达产物及在造血干细胞移植中的应用等。     

自体外周血干细胞移植在治疗鼻咽癌中的应用

鼻咽癌（NPC）目前的治疗方法主要是放化疗联合,以放疗为主。NPC局部失控、复发和远处转移是治疗失败的主要原因。近年来,自体外周血干细胞移植（APBSCT）治疗实体瘤的应用逐渐增多并呈现出常规治疗无法达到的良好效果。造血干细胞移植支持下行高剂量放化疗是其主要治疗原理。对放化疗敏感但常规剂量治疗效果不理想的恶性肿瘤是自体外周血干细胞移植的适应证。NPC对放化疗敏感,国内外有关学者用APBSCT治疗NPC呈现出较好的临床效果。     

超大剂量化疗在治疗卵巢癌中的应用

目前 ,卵巢癌仍然是妇科恶性肿瘤中死亡率最高的肿瘤 ,耐药和复发是治疗失败的主要原因 ,妇科肿瘤学者在不断地寻求新的治疗方法 ,以改善卵巢癌患者的生存率。在造血干细胞移植的支持下 ,超大剂量化疗治疗血液系统疾病和淋巴瘤、乳腺癌等实体瘤已经取得了较好的疗效 ,对卵巢癌的治疗也显示出了较好的应用前景。一、超大剂量化疗和造血干细胞移植临床实践证明 ,增加化疗药物剂量可显著提高对肿瘤细胞的杀伤作用。但化疗药物对正常骨髓细胞的抑制作用严重限制了其剂量的增加 ,并影响到实体瘤的治疗效果。造血干细胞移植是在患者接受化疗之前 ,…     

异基因造血干细胞移植后慢性移植物抗宿主病1例

异基因造血干细胞移植是目前治疗造血系统恶性肿瘤和实体瘤的重要手段.随着移植技术的进步,患者移植后存活率提高,生存时间明显延长,但移植后相关并发症会严重影响其治疗效果.     

大剂量化疗合并自体造血干细胞移植治疗晚期实体瘤进展

大剂量化疗合并自体造血干细胞移植治疗晚期实体瘤进展苏州医学院附属一院（苏州市２１５００６）张军宁综述许昌韶审校早在１９５８年，Ｋｕｒｎｉｃｋ等（１）首先提出自体骨髓移植治疗放化疗所致骨髓再生障碍的设想，直至１９７８年，Ｂｌｏｏｄ杂志才首先报道了大剂量...     

自体造血干细胞移植治疗复发难治非霍奇金淋巴瘤

目的探讨高剂量放化疗联合自体造血干细胞移植治疗复发、耐药侵袭性和高度侵袭性非霍奇金淋巴瘤(NHL)的疗效和安全性。方法23例复发和11例耐药的NHL患者接受了解救化疗和自体造血干细胞采集,采集后进行了自体造血干细胞支持下的高剂量放化疗。结果采集到的全部患者干细胞数均达到了移植要求,CD34+细胞中位数为6.06×106/kg。接受移植的患者经高剂量放化疗治疗后全部出现Ⅳ度骨髓抑制,出现1例移植相关死亡。移植后23例完全缓解,6例部分缓解,5例进展。缓解的患者中,10例复发,中位疾病进展时间(TTP)为7.9个月,复发患者中7例死亡。1例发生第二肿瘤。5年总生存率为60.5%,5年无复发总生存率为58.2%。结论高剂量放化疗联合自体造血干细胞移植治疗复发耐药的侵袭和高度侵袭性NHL疗效高、安全性好,但对于预后差的患者尚需探讨新的方法。     

自体造血干细胞移植治疗恶性实体瘤的新进展

近年来自体造血干细胞移植（ＡＳＣＴ）在实体瘤的治疗上积累了一定的经验,针对实体瘤ＡＳＣＴ的疗效、适应症及其在综合治疗中的位置等需要回答的问题进行了相应的研究,得出了一些新的结果。１非霍奇金淋巴瘤（ＮＨＬ）１．１复发耐药者ＤＨＡＰ、ＶＩＭ等常规的解救方...     

体外液体培养联合天然抑癌物净化后自体骨髓移植治疗晚期淋巴瘤

大剂量化疗和放化疗后自体骨髓移植(ＡＢＭＴ)已广泛应用于某些实体瘤的治疗,尤其是淋巴瘤,取得较满意的疗效[1]。尽管自体骨髓回输提供了足够的造血干细胞,但因骨髓中存在的肿瘤细胞是移植后复发的重要原因之一,有报道骨髓穿刺、活检侵犯骨髓者达15%～63%,用多聚酶链反应...     

厌氧菌在肿瘤基因治疗中的研究进展

实体瘤乏氧代谢区的存在,降低了放化疗的治疗效果,成为肿瘤治疗中难以逾越的障碍.基因治疗是肿瘤治疗中最有前途的方法,但目前所使用的基因转移载体的靶向性较差,而厌氧菌具有趋低氧的特点,对实体瘤组织具有良好的靶向性,成为肿瘤基因治疗的转移载体.     

克隆性造血对肿瘤体细胞突变检测的影响

克隆性造血（clonal hematopoiesis,CH）突变是造血干细胞（hematopoietic stem cell,HSC）携带的突变,是年龄和外在环境（吸烟、放化疗等）共同作用的结果。随着肿瘤基因研究的进展,基因检测已成为实体瘤患者全病程管理中一个重要的环节。目前CH在实体瘤中的价值越来越受到关注。将围绕CH的检出,详细阐述实体瘤患者组织样本及循环肿瘤DNA （circulating tumor DNA,ctDNA）样本中CH的检测方法,探讨CH对肿瘤体细胞突变检测的影响和挑战。     

造血干细胞移植在神经母细胞瘤治疗中的应用

高危神经母细胞瘤（neuroblastoma，NB）恶性程度高且预后差，需要综合治疗。造血干细胞移植（hematopoietic stem cell transplantation，HSCT）是诱导缓解后巩固治疗中的重要组成部分，目前以自体造血干细胞移植（autologous HSCT，AHSCT）为主，取得较好的客观缓解，也有复发/难治性患儿接受异基因造血干细胞移植（allogeneic HSCT，allo-HSCT）。作为超大剂量化疗下的支持治疗，双次HSCT比单次HSCT更能改善患儿无事件生存。HSCT预处理方案以白消安/马法兰（Bu/Mel）和卡铂/依托泊苷/马法兰（CEM）为主。Bu/Mel在无事件生存率上优于CEM方案。尽管免疫治疗明显改善了高危患儿的生存期，但是HSCT目前仍在一线综合治疗中处于重要地位。本文拟就HSCT在NB中的应用进行综述。      

Allogeneic stem cell transplantation for myelodysplastic syndromes: critical for cure?

Allogeneic stem cell transplantation (SCT) is the treatment of choice for young patients (age ≤ 55 years) with myelodysplastic syndromes (MDS) characterized by poor-risk or intermediate-risk cytogenetics, who have a histocompatible related or unrelated donor. For patients who lack an human leukocyte antigen-compatible donor, autologous SCT, or chemotherapy may be good alternatives for those with MDS and with good-risk cytogenetic characteristics. Iron toxicity is an underestimated cause of hematopoietic stem cell transplantation (HSCT) treatment-related mortality. The pathogenesis, diagnosis, and monitoring of iron-induced organ damage are currently topics of investigation. Prospective studies on the prevention or treatment of iron toxicity before HSCT and/or after HSCT are necessary.     

Reduced-intensity hematopoietic stem cell transplantation (RIST) for solid malignancies

Reduced intensity stem cell transplantation (RIST) is a new approach of stem cell transplantation, which has shown promising features as reported in multiple phase I and II studies. Elderly patients, who are not eligible for conventional myeloablative hematopoietic stem cell transplantation (HSCT), are now treatable with RIST. It has also reduced regimen-related toxicity and provided better prognosis in short-term follow-up than conventional HSCT. Among solid tumors, metastatic renal cell carcinoma was found to respond well to RIST. Clinical studies are currently being conducted to evaluate the efficacy of RIST in other types of solid tumors. However, the mechanism of graft-versus-host disease (GVHD) and graft-versus-tumor (GVT) effects remains unclear. More knowledge on the mechanism is crucial to enhance the antitumor effect and to improve the prognosis further.     

Combination of anti‐CD4 antibody treatment and donor lymphocyte infusion ameliorates graft‐versus‐host disease while preserving graft‐versus‐tumor effects in murine allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is not only a well‐established immunotherapy for hematologic malignancies, but is potentially useful for treating solid tumors refractory to available therapies. However, application of allo‐HSCT to solid tumors is limited, despite the beneficial antitumor effects, by the risk of graft‐versus‐host disease (GVHD). CD4⁺ T cells have been implicated in several aspects of GVHD, and suppress antitumor CD8⁺ T‐cell responses. In the present study, we investigated clinically applicable allo‐HSCT protocols designed to maximize antitumor effects while reducing the risk of GVHD. We used a mouse model of allo‐HSCT with s.c. tumors. We found that myeloablative conditioning was associated with better inhibition of tumor growth but with severe acute GVHD. Early treatment with anti‐CD4 mAb substantially ameliorated GVHD while preserving antitumor effects, leading to improved survival in myeloablative allo‐HSCT. Late treatment with anti‐CD4 mAb also ameliorated GVHD to some extent. Donor lymphocyte infusion in GVHD mice treated with anti‐CD4 mAb further suppressed tumor growth without exacerbating GVHD. Collectively, our results suggest that myeloablative allo‐HSCT followed by anti‐CD4 mAb treatment and donor lymphocyte infusion could be a potent and safe immunotherapy for patients with cancers refractory to available therapies.     

Allogeneic blood stem cell transplantation after a reduced-intensity,preparative regimen: a pilot study in patients with refractory malignancies

BACKGROUND: The immune-mediated graft-versus-tumor (GVT) effect plays a therapeutic role in the treatment of patients with hematologic malignancies who undergo allogeneic hematopoietic stem cell transplantation (HSCT). More recently, it was reported that a GVT effect also occurred in patients who underwent transplantation for metastatic renal carcinoma. The authors carried out a pilot trial of allogeneic transplantation after a reduced-intensity, preparative regimen in patients with refractory malignancies, including solid tumors. The objectives of the current study were to evaluate the feasibility of this approach in terms of toxicity and engraftment and to document evidence of GVT effects. METHODS: Seventeen patients with Stage IV malignancies (7 patients with renal cell carcinoma, 3 patients with sarcoma, 2 patients with breast carcinoma, 2 patients with Hodgkin disease, 1 patient with ovarian carcinoma, 1 patient with melanoma, and 1 patient with both melanoma and renal cell carcinoma) that were not amenable to further conventional treatment were enrolled. The median patient age was 43 years (range, 10-60 years). The Eastern Cooperative Oncology Group performance status (PS) was 0-1 in 11 patients and 2-3 in 6 patients. Preparative treatment consisted of reduced-intensity chemotherapy with fludarabine (30 mg/m(2) per day for 4 consecutive days) and cyclophosphamide (30 mg/Kg per day for 2 consecutive days) prior to allogeneic HSCT from a human leukocyte antigen-identical sibling. The median number of CD34+ cells infused was 6.06 x 10(6)/kg (range, 1.5-14.0 x 10(6)/kg). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin-A and short-term methotrexate. RESULTS: Patients who had a PS of 2-3 prior to undergoing HSCT experienced Grade 4 hematologic toxicities and Grade > or = 3 organ toxicities and died of either treatment-related complications or disease progression within 100 days from transplantation. By contrast, 10 of 11 patients who had a PS of 0-1 prior to undergoing HSCT experienced only short-lasting, Grade < or = 3 neutropenia and thrombocytopenia and no organ toxicity; 1 of 10 patients died of graft failure on Day +29 after undergoing HSCT. By Day +90, 100% donor chimerism was documented in all patients with a past history of heavy chemotherapy, whereas mixed donor chimerism was observed in the 4 patients with a past history of only 1 line of chemotherapy and/or immunotherapy prior to entering the HSCT program. Grade 2-3 acute GVHD occurred in 5 patients. Among patients with a follow-up > 100 days, 2 complete responses and 3 transitory partial responses were recorded. CONCLUSIONS: With this conditioning regimen, full donor chimerism was achieved rapidly only in patients who had received previous intensive chemotherapy. In a proportion of patients with refractory malignancies, allogeneic transplantation resulted in tumor regression. This novel therapeutic strategy may provide little benefit in patients with poor PS and rapidly progressing disease.     

Allogeneic hematopoietic stem cell transplantation for lymphoma

For patients with relapsed or refractory Hodgkin's or non-Hodgkin's lymphomas, allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment option when autologous HSCT fails to achieve durable remission or is deemed inappropriate. Allogeneic HSCT can result in long-term survival even in patients with refractory lymphomas. The efficacy of allogeneic HSCT is attributed, at least in part, to an immune-mediated graft-versus-lymphoma (GVL) effect that can also be associated with significant toxicity resulting from graft-versus-host disease. However, clinical evidence of a potent GVL effect is inconsistent. Reduced-intensity conditioning before allogeneic HSCT can facilitate the use of this treatment in older patients and those at high risk. The decrease in toxicity with reduced-intensity regimens may be associated with a loss of antitumor effects. Patients with lymphoma should be selected for allogeneic HSCT on the basis of characteristics that strongly influence transplant outcomes, including histology, chemosensitivity, and donor source.     

单倍型造血干细胞移植治疗不同肿瘤负荷恶性血液病的效果及预后分析

目的 探讨单倍型造血干细胞移植治疗移植前处于不同肿瘤负荷的血液恶性肿瘤的安全性及影响生存的危险因素.方法 回顾性分析2007年1月至2013年5月70例接受单倍型造血干细胞移植的血液恶性肿瘤患者临床资料,根据移植前肿瘤残留的情况分成低肿瘤负荷组、中肿瘤负荷组、高肿瘤负荷组,分析移植前肿瘤残留对生存的影响.同时分析这些患者的预处理方案、移植相关并发症及复发等情况.结果 随访截至2014年1月1日,中位随访34.05个月（7.4～83.6个月）.全部患者均获得植入,Ⅱ～Ⅳ度急性移植物抗宿主病（GVHD）发生率47.14％（33/70）,其中Ⅲ～Ⅳ度急性GVHD发生率21.4％（15/70）.慢性广泛型GVHD发生率20.0％（14/70）.至随访期结束总生存率68.6％,移植相关死亡率12.8％,复发死亡率18.6％.低肿瘤负荷组、中肿瘤负荷组、高肿瘤负荷组2年生存率分别为91.7％、72.7％、33.3％,移植前肿瘤残留是影响生存的高危因素（移植前中、高肿瘤负荷组2年生存率比较,P=0.016）.结论 单倍型造血干细胞移植在血液恶性肿瘤的治疗中是安全有效的,移植前肿瘤残留为影响患者总生存及导致复发的重要原因,对预后不良的血液恶性肿瘤患者,应该在缓解后尽早接受造血干细胞移植来减少移植后的复发,提高总生存.     

供体来源嵌合抗原受体T细胞治疗血液系统恶性肿瘤移植后复发的研究进展

异基因造血干细胞移植(allo-HSCT)是治疗血液系统恶性肿瘤的重要手段,而移植后复发是allo-HSCT主要的并发症,也是目前患者移植后总生存(OS)率降低的主要原因.嵌合抗原受体T细胞(CAR-T)免疫疗法是一种疗效显著的针对恶性血液系统肿瘤的新兴治疗方法,而且随着研究的进展,CAR-T的安全性和有效性也在不断提高.研究发现移植后复发患者通过供体来源的CAR-T能够显著提高OS率,控制疾病的复发和进展.现综述近年来将供体来源CAR-T用于allo-HSCT后患者治疗的相关研究,并总结该治疗方法存在的问题及解决措施.     

食管癌根治性放疗后局部复发再程三维适形放疗临床分析

目的 研究食管癌根治性放疗后局部复发行再程三维适形放疗(3DCRT)的安全性、疗效及影响生存预后因素.方法 回顾性分析2010年1月至2014年4月本院收治的46例食管癌根治性放疗后局部复发行3DCRT再程治疗患者的治疗效果,并应用Log-rank进行单因素预后分析,用Cox比例风险模型进行预后的多因素分析.结果 6例患者未完成放疗,40例患者顺利完成放疗,3DCRT总有效率为80.0％ (32/40).1、2年生存率分别为47.5％ (19/40)、20.0％ (8/40).再程放疗中出现2+3级的放射性消化道反应19例(47.5％)、放射性肺炎14例(35.0％)、造血系统毒性反应6例(15.0％)、心脏毒性4例(10.0％),全组均未出现4度以上放射性损伤及治疗相关性死亡.单因素分析显示年龄(x2=8.432,P=0.015)、放疗间隔时间(x2=7.006,P=0.008)、放疗剂量(x2=18.718,P=0.000)、大体肿瘤体积(GTV) (x2=10.121,P=0.006)、辅助化疗(x2=5.014,P=0.025)、肿瘤长度(x2=7.391,P=0.025)、野内复发(x2 =9.933,P=0.002)、肿瘤控制情况(x2=14.665,P=0.001)与预后密切相关;病变部位有影响总生存的趋势(x2=5.493,P=0.064);多因素分析显示年龄(x22=4.759,P=0.029)、放疗间隔时间(x2 =4.139,P=0.041)、GTV (x2=4.799,P=0.024)、肿瘤控制情况(x2=4.501,P=0.030)是影响总生存时间的重要因素.结论 对于食管癌根治性放疗后局部复发患者,3DCRT再程放疗虽然毒性反应大,但其可提高近期疗效.年龄、放疗间隔时间、GTV、肿瘤控制情况是再程放疗的预后因素.     

Oral malignancies following HSCT: graft versus host disease and other risk factors

Allogenic hematopoietic stem cell transplantation (HSCT), a procedure that is widely used in the treatment of a large number of malignant and non-malignant hematological diseases, is still associated with a wide range of complications, one of the most important of which is graft versus host disease (GVHD). The patients undergoing allogenic HSCT are also at high risk of developing secondary neoplasms, particularly leukemias and lymphomas. Solid tumors are less frequent, and the incidence appears to increase over time; the most frequent solid tumors are squamous cell carcinomas. We found that almost all studies of solid cancers occurring after transplantation are based on relatively small numbers of cases which have been monitored for short periods, and little information is available on individual cancers. In particular, reports of oral cancers in HSCT are very few. Potential risk factors associated with the development of secondary solid cancers after HSCT have been well described. They include graft versus host disease (GVHD), preoperative regimens, with either radio-chemotherapy or chemotherapy alone, conditioning regimes, immunosuppressive GVHD prophylaxis, viral infection and chronic stimulation as a result of viral antigens, antigenic stimulation from histocompatibility differences between recipient and donor, primary diagnosis, interaction of any of these factors with genetic predisposition, and other factors such as sex and age. All patients treated with HSCT should therefore be closely followed over the long term with the aim of identifying the onset of secondary tumors as early as possible.