Autologous stem cell transplantation for the treatment of neuroblastoma in Korea

Autologous stem cell transplantation (ASCT) for the treatment of high-risk neuroblastoma (NBL) is an accepted method for restoring bone marrow depression after high dose chemotherapy. We retrospectively analyzed eighty eight cases of NBL that underwent ASCT following marrow ablative therapy at 12 transplant centers of the Korean Society of Pediatric Hematology-Oncology between January 1996 and September 2000. Seventy nine children were of stage IV NBL and 9 were of stage III with N-myc amplification. Various cytoreductive regimens were used. However, the main regimen was 'CEM' consisting of carboplatin, etoposide and melphalan, and this was used in 66 patients. Total body irradiation was also added in 36 patients for myeloablation. To reduce tumor cell contamination, stem cell infusions after CD34+ cell selection were performed in 16 patients. Post-transplantation therapies included the second transplantation in 18 patients, interleukin2 therapy in 45, 13-cis retinoic acid in 40, 131-meta-iodobenzylguanidine in 4, conventional chemotherapy in 11, and local radiotherapy in 8. Twenty two patients died, sixty six patients are surviving 1 to 46 months after ASCT (median followup duration, 14.5 months). Although the follow-up period was short and the number of patients small, we believe that ASCT might improve the survival rate in high-risk NBL.     

Autologous stem cell transplantation in treatment of aggressive non-Hodgkin's lymphoma

There is no doubt that autologous stem cell transplantation is useful for patients with relapsed aggressive non-Hodgkin s lymphoma if they are responsive to the chemotherapy given before the transplantation. A small subset of patients with primary refractory disease still profits from this high dose chemotherapy regimen, but only if chemosensitive and if presenting with favorable risk factors at the moment of transplant eligibility. Autologous stem cell transplantation as upfront first line therapy for patients with aggressive non-Hodgkin s lymphoma does not contribute to a better outcome, most certainly not if it concerns patients with a favorable risk profile. There is still some doubt whether there is any place for autologous stem cell transplantation as first line therapy for patients with an unfavorable risk profile. Most randomized studies do not show an advantage, but more data are needed to definitely assess the place for this therapy option.     

自体分选造血干细胞和异体脐带间充质干细胞移植治疗神经系统变性疾病

背景：将自体分选造血干细胞和异体脐带间充质干细胞技术应用于临床,试图寻找一种新的治疗神经系统变性疾病的可行方法。 目的：探讨自体分选CD34⁺造血干细胞和异体脐带间充质干细胞治疗神经系统变性病的可行性。 方法：入选神经系统变性病患者21例,其中运动神经元病15例,脊髓小脑共济失调6例。取4 mL的脐带间充质干细胞或自体分选干细胞液经腰穿注射到患者蛛网膜下腔,每次注射的细胞数1.0×10⁷。于干细胞治疗后3个月进行评分。 结果与结论：15例运动神经元病患者,治疗总有效率为80%,治疗前后的脊髓侧索硬化功能分级量表和自我评估问卷评分差异有显著性意义(P < 0.05);6例脊髓小脑共济失调患者,按ICARS评分,4例病情等级下降,治疗总有效率为77%。21例中4例有轻度低颅压性头痛(腰穿后),14例采用脐带间充质干细胞治疗的患者中2例在治疗后2 h出现短暂发热,其余患者治疗后未见明显不良反应。结果初步表明自体分选造血干细胞和异体脐带间充质干细胞治疗神经系统变性病临床疗效肯定,安全可行。     

Stem cell transplantation in rheumatoid arthritis

The therapeutic potential of high dose cytotoxic therapy and stem cell transplantation (SCT) in severe rheumatoid arthritis (RA) was originally supported by animal studies and serendipitous clinical cases where allogeneic and autologous procedures were shown to ameliorate and potentially cure the disease. Phase I and Phase II clinical studies established the feasibility, safety and efficacy of autologous stem cell mobilisation and transplantation. Although it was clear that the effects of high dose chemotherapy and autologous SCT could safely achieve profound responses, sustained control of disease usually required the reintroduction of disease modifying agents. Responses were improved with dose escalation of the conditioning regimen, and also with post-SCT therapy, such as rituximab, but were not observed with graft manipulation. Phase III studies were attempted, but recruitment was compromised by the increasingly widespread use of biological anti-rheumatic agents. Autologous SCT is now only reasonably considered in relatively rare patients whose disease has resisted conventional and biological treatments, and small numbers of cases continue to be registered with the EBMT. Occasional patients treated with allogeneic and syngeneic SCT continue to stimulate academic interest, particularly as some appear to be cured, but significant logistical and toxicity issues mean that routine and widespread application is unrealistic. In summary, SCT continues to have a limited therapeutic potential in rare patients with RA refractory to modern therapy and sufficient fitness for the procedure. From a scientific perspective, ablation of the dysfunctional rheumatoid immune system and its reconstruction with SCT has provided useful insights into the pathophysiology of RA.     

Stem cell transplantation in rheumatoid arthritis

The therapeutic potential of high dose cytotoxic therapy and stem cell transplantation (SCT) in severe rheumatoid arthritis (RA) was originally supported by animal studies and serendipitous clinical cases where allogeneic and autologous procedures were shown to ameliorate and potentially cure the disease. Phase I and Phase II clinical studies established the feasibility, safety and efficacy of autologous stem cell mobilisation and transplantation. Although it was clear that the effects of high dose chemotherapy and autologous SCT could safely achieve profound responses, sustained control of disease usually required the reintroduction of disease modifying agents. Responses were improved with dose escalation of the conditioning regimen, and also with post-SCT therapy, such as rituximab, but were not observed with graft manipulation. Phase III studies were attempted, but recruitment was compromised by the increasingly widespread use of biological anti-rheumatic agents. Autologous SCT is now only reasonably considered in relatively rare patients whose disease has resisted conventional and biological treatments, and small numbers of cases continue to be registered with the EBMT. Occasional patients treated with allogeneic and syngeneic SCT continue to stimulate academic interest, particularly as some appear to be cured, but significant logistical and toxicity issues mean that routine and widespread application is unrealistic. In summary, SCT continues to have a limited therapeutic potential in rare patients with RA refractory to modern therapy and sufficient fitness for the procedure. From a scientific perspective, ablation of the dysfunctional rheumatoid immune system and its reconstruction with SCT has provided useful insights into the pathophysiology of RA.     

Autologous stem cell transplantation for systemic sclerosis

Systemic sclerosis (SSc) is a generalised autoimmune disease, of yet unknown origin, with two major clinical subsets: the limited (lcSSc) and the diffuse cutaneous (dcSSc) forms, which can be distinguished by the extent of skin involvement, the autoantibody profile and the pattern of organ involvement. With an incidence of 1/10(5), SSc affects around 250,000 people in Europe and is responsible for significant morbidity with a 5-year mortality rate of at least 30% of all patients. In patients with rapidly progressive dcSSc, the 5-year mortality is estimated to be 40-50%. Hematopoietic stem cell transplantation (HSCT), mostly autologous but also allogeneic in some specific cases, has been employed worldwide since 1996 as a new therapeutic strategy in patients with a poor prognosis. In 2007, 150 HSCT procedures have been reported in the EBMT data base. We review herein both the short and the long-term reports from the various European and North American phase I-II studies, which have shown that autologous HSCT in selected patients with severe dcSSc results in sustained improvement of skin thickening and stabilisation of organ function up to seven years after transplantation. Based on these promising results, ongoing phase III trials have been designed in parallel, both in Europe (ASTIS) and in North America (SCOTT) aiming to analyse the respective benefits from autologous HSCT respectively without or with high dose irradiation. This review reports the current data concerning the effects of HSCT on survival, skin, and major organ function in patients with severe dcSSc.     

Autologous stem cell transplantation for systemic sclerosis

Systemic sclerosis (SSc) is a generalised autoimmune disease, of yet unknown origin, with two major clinical subsets: the limited (lcSSc) and the diffuse cutaneous (dcSSc) forms, which can be distinguished by the extent of skin involvement, the autoantibody profile and the pattern of organ involvement. With an incidence of 1/10⁵, SSc affects around 250,000 people in Europe and is responsible for significant morbidity with a 5-year mortality rate of at least 30% of all patients. In patients with rapidly progressive dcSSc, the 5-year mortality is estimated to be 40–50%. Hematopoietic stem cell transplantation (HSCT), mostly autologous but also allogeneic in some specific cases, has been employed worldwide since 1996 as a new therapeutic strategy in patients with a poor prognosis. In 2007, 150 HSCT procedures have been reported in the EBMT data base. We review herein both the short and the long-term reports from the various European and North American phase I–II studies, which have shown that autologous HSCT in selected patients with severe dcSSc results in sustained improvement of skin thickening and stabilisation of organ function up to seven years after transplantation. Based on these promising results, ongoing phase III trials have been designed in parrallel, both in Europe (ASTIS) and in North America (SCOTT) aiming to analyse the respective benefits from autologous HSCT respectively without or with high dose irradiation. This review reports the current data concerning the effects of HSCT on survival, skin, and major organ function in patients with severe dcSSc.     

自体外周血干细胞移植治疗周围神经损伤

背景：关于神经干细胞对周围神经损伤的治疗已有多篇报道,但外周血干细胞对周围神经损伤治疗鲜有报道。 目的：探讨自体外周血干细胞移植治疗周围神经损伤使失神经骨骼肌重获神经再支配的临床应用。 方法：应用外周血干细胞治疗周围神经损伤6例,同时与周围神经损伤单纯行神经断端吻合或神经移植10例比较。2组患者术后常规肌注鼠神经生长因子一两个疗程,同时给予针灸、理疗、经皮电刺激治疗及功能康复训练。 结果与结论：两组患者随访均超过6个月。干细胞移植组运动神经传导速度和感觉神经传导速度的恢复率要明显高于单纯神经吻合组。提示周围神经损伤后给予修复局部用外周血干细胞移植能够使远端失神经骨骼肌早期重新获得神经再支配。     

间充质干细胞治疗类风湿性关节炎的研究与应用

背景：目前的研究发现来源于骨髓或脂肪组织的间充质干细胞具有免疫抑制及抗炎的特性,使得其在治疗类风湿性关节炎等自身免疫性疾病方面具有广阔的应用前景。 目的：综述间充质干细胞的生物学特性、特别是免疫抑制及抗炎作用机制及其在治疗类风湿性关节炎方面的研究进展。 方法：检索2005/2011西文生物医学期刊文献数据及CNKI 数据库有关类风湿性关节炎研究、骨髓间充质干细胞生物学特性及其免疫抑制作用、在类风湿性关节炎方面的应用方面的文献,英文检索词为“marrow stem cells,rheumatoid arthritis,immunosuppressive”,中文检索词为“间充质干细胞,类风湿性关节炎,免疫抑制”,纳入近年来起重大影响以及开启和引领新方向的重要研究成果,排除重复性研究,纳入24篇文章进行综述。 结果与结论：间充质干细胞在维持关节组织的内环境稳态,如调控炎症反应及免疫应答、抗纤维化及组织再生方面具有重要的作用,而间充质干细胞在治疗类风湿性关节炎方面疗效的稳定性及安全性方面仍需进一步的研究。     

Autologous stem cell transplantation in acute lymphocytic leukemia.

Autologous stem cell transplantation (ASCT) as well as allogeneic stem cell transplantation and conventional chemotherapy (CT) are less effective at treating acute lymphocytic leukemia (ALL) than acute myelocytic leukemia (AML). Chemoresistance and late relapses are hallmarks of ALL. In this context, the question of whether ASCT is superior to CT remains unanswered. In vitro marrow purging using monoclonal antibodies is not routinely used. This review summarizes the results of ASCT for adult and childhood ALL. Statistics from the European Group for Blood and Marrow Transplantation reveal a transplant-related mortality at 5 years of 11% +/- 1%, a relapse incidence of 60% +/- 2%, and a leukemia-free survival (LFS) and overall survival (OS) of 36% +/- 2% and 42% +/- 2%, respectively in 1,366 adults autografted in first remission (CR1). In 269 children, the LFS and OS were 50% +/- 3% and 54% +/- 3%, respectively. There was no evidence in favor of purging the autograft in vitro. In contrast, multicentric and single-institution studies have found better results in adults autografted in CR1, with LFS at 5 years from 46% to 64%, possible efficacy of marrow in vitro purging with mafosfamide (LFS 52%), and improvement in outcome with additional measures post-ASCT, such as maintenance chemotherapy (LFS 57%). Further, as already observed for AML, analyses by risk groups suggest that ASCT may essentially benefit good- but not poor-risk patients. For patients with the Ph1/bcr-abl translocation, the role of STI571 anti-tyrosine kinase for in vivo purging before stem cell harvesting is being investigated.     

Autologous hematopoietic stem cell transplantation for Crohn's disease

The feasibility and early experience of hematopoietic stem cell transplantation for severe Crohn's disease (CD) are discussed. The natural history, therapy, and evidence for autoimmunity of CD are outlined and related to this new therapy in terms of morbidity and mortality.     

自体干细胞移植治疗严重下肢缺血

背景：严重下肢缺血是周围血管疾病中难于治疗的疾病,自体干细胞移植方法的运用可以为该病的治疗带来一定的希望。 目的：总结自体干细胞移植治疗严重下肢缺血的发展近况,探讨其机制及存在的问题。 方法：以“干细胞,移植,严重下肢缺血”,“stem cell,transplant,critical limb ischemia”为检索词,检索时间1990年1月至2013年3月,检索数据库：万方数据库、中国知网和Pubmed数据库,纳入与自体干细胞移植治疗严重下肢缺血疾病方面的相关研究,排除与研究无关和重复文献,保留47篇文献进行综述。 结果和结论：对于严重下肢缺血的自体干细胞移植治疗,干细胞类型、数量、分离方式,是否有细胞因子的刺激都可能影响治疗效果,自体干细胞移植治疗严重下肢缺血是一全新治疗手段,疗效显著,但是自体干细胞如何长期维持治疗效果其机制尚不清楚,尚需进一步研究和探讨。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

Autologous stem cell transplantation for small cell lung cancer.

Small cell lung cancer usually responds to radiation and chemotherapy, but cures are infrequent. Autotransplantation attempts to increase cures by intensifying the effects of chemotherapy. We studied 103 patients receiving high-dose chemotherapy with autologous hematopoietic stem cell transplantation (SCT) for small cell lung cancer in 1989-1997 at 22 centers participating in the Autologous Blood and Marrow Transplant Registry. Median age at transplantation was 50 years (range, 30-74 years). Fifty-five percent of patients were men. Forty-seven percent of patients underwent transplantation in 1989-1993 and 53% in 1994-1997. Most patients received peripheral blood stem cells alone (39%) or with bone marrow (44%); 18% received bone marrow alone. The 2 most common preparative regimens were cyclophosphamide/carmustine/cisplatin (CBP) (60%) and ifosfamide/carboplatin/etoposide (ICE) (28%). Median time from diagnosis to transplantation was 6 months (range, 1-34 months). Most patients underwent transplantation after partial response (66%) or complete response (27%) to combination therapy. The 100-day mortality was 11% (95% confidence interval [CI], 6%-18%). Three-year probabilities of survival and progression-free survival (PFS) were 33% (95% CI, 24%-44%) and 26% (95% CI, 17%-36%), respectively, for all patients. Factors negatively associated with outcome in multivariate analysis were age greater than 50 years, extensive-stage disease at presentation, and preparative regimens other than CBP or ICE. Three-year survival and PFS rates were higher in patients with limited versus extensive disease, 43% versus 10% (P < .001) and 35% versus 4% (P < .001), respectively. Patients older than 50 years had nearly twice the risk of death or progression as younger patients (relative risk, 1.7; 95% CI, 1.1-2.8). Autologous SCT produces long-term survival in some patients with small cell lung cancer; SCT outcomes appear better in young patients with limited-stage disease. Transplantation for patients with extensive disease does not appear to produce substantial benefit.     

Autologous hematopoietic stem cell transplantation for mantle cell lymphoma.

This study evaluated the outcomes of patients who underwent high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (autoHSCT) for mantle cell non-Hodgkin's lymphoma and the effect of clinical and treatment characteristics. The clinical outcome and prognostic factors in 40 patients who underwent HDC and autoHSCT for mantle cell lymphoma between June 1991 and August 1998 were analyzed. With a median follow-up of 24 months for the surviving patients (range, 4-68 months), the 2-year overall survival was 65% and the 2-year event-free survival (EFS) was 36%. In univariate analysis, characteristics predictive of a poor EFS were blastic morphology (P = .019) and the patient having received 3 or more prior chemotherapy regimens (P = .004). In a multivariate analysis, the only factor associated with a poor EFS was the number of prior chemotherapy regimens. Those patients who received 3 or more prior therapies had a 2-year EFS of 0%, and those who received <3 therapies had a 2-year EFS of 45% (P = .004). Patients with mantle cell lymphoma can obtain prolonged EFS with HDC and autoHSCT; however, this strategy for prolonged EFS appears to work optimally in patients who are less heavily pretreated. Whether this therapy will increase the overall survival or EFS in patients receiving transplants in first complete remission will need to be tested in prospective randomized clinical trials.     

自体造血干细胞移植治疗外周T细胞淋巴瘤

背景：外周T细胞淋巴瘤亚洲地区发病率高,具有侵袭性,预后普遍较差,目前尚无标准治疗策略。 目的：评价自体造血干细胞移植治疗外周T细胞淋巴瘤的疗效及毒副反应。 方法：回顾性分析2003年3月至2014年4月行自体造血干细胞移植治疗外周T细胞淋巴瘤35例,包括结外NK/T细胞淋巴瘤鼻型22例,血管免疫母细胞T细胞淋巴瘤1例,外周T细胞淋巴瘤(非特殊型)8例,间变性大T细胞淋巴瘤 ALK(+)3例,ALK(-)1例;所有病例均按WHO 2001年和WHO 2008年分类进行病理分型,均采用VAEMMC+全射照射预处理方案。 结果与结论：随访中位时间54个月(9-120个月),28例患者(80%)存活,其中无病存活25例(71%),8例(23%)复发,其中7例死亡,1例尚在治疗中。近期毒性主要为骨髓造血受抑,无明显远期并发症。结果表明自体造血干细胞移植治疗外周T细胞淋巴瘤安全有效,早期(第1次完全缓解)行移植疗效佳。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

Autologous blood-derived stem cell transplantation in the treatment of hematopoietic malignant diseases (Part II)]

Autologous transplantation of circulating stem cells is potentially capable of creating a chance of normal hematopoietic reconstitution in the patients in which both allogeneic and autologous bone marrow transplantation was impossible. The authors have reviewed the possibilities for collection of adequate and sufficient numbers of peripheral blood stem cells as well as up-to-date results of their autografting especially in relation to hematopoietic malignant diseases. The advantages resulting from autologous transplantation of circulating stem cells depends on: 1. The lack of risk of GvH--disease. 2. early and rapid hematopoietic and lymphoid recovery, 3. probably, the low risk of graft contamination by tumor cells in early remission.     

Autologous blood-derived stem cell transplantation in the treatment of proliferative disorders of the hematopoietic system (I)]

Peripheral blood can be an alternative source of hematopoietic stem cells which after autografting are capable of sustaining or completely recovering of lymphopoiesis without the necessity of bone marrow harvesting. Theoretical assumptions conditioning the clinical application of circulating stem cells autotransplantation have been described. The results of experimental studies performed in animals and humans have allowed for closer characterization of these cells. However, the physiological significance of their presence in the peripheral blood still remains unknown.