自体造血干细胞移植治疗淋巴瘤的进展

背景：自体造血干细胞移植是治疗淋巴瘤的积极有效方案。 目的：综述自体造血干细胞移植治疗淋巴瘤的研究进展。 方法：应用计算机检索2000-01/2011-08 PudMed、CNKI数据库、万方数据库、维普数据库及中华医学会数字期刊数据库及Google网络数据库自体造血干细胞移植治疗淋巴瘤的相关文章,检索词为“autologous hematopoietic stem cell transplantation,lymphoma,自体造血干细胞移植,淋巴瘤”。共检索到文献371篇,最终纳入符合标准的文献31篇。 结果与结论：自体造血干细胞移植自20世纪80年代兴起以来,成千上万的淋巴瘤患者获益。其移植前的治疗从最初以单纯大剂量放化疗作为预处理方案发展到联合利妥昔单抗甚至联合同位素标记的单抗作为预处理方案;利妥昔单抗也从仅作为预处理前的净化用药发展到利妥昔单抗在移植前后长期序贯用药。但是无论移植前后的治疗如何进展改变,自体造血干细胞移植为患者备份造血系统,促进患者在接受大剂量的预处理后造血系统功能快速恢复的本质作用始终没有发生改变。随着研究的进一步发展,自体造血干细胞移植将成为淋巴瘤治疗的重要方案。     

自体造血干细胞移植联合异体细胞因子诱导的杀伤细胞及白细胞介素2治疗高危急性髓系白血病2例*

背景：自体造血干细胞移植治疗高危急性髓系白血病的复发率极高,如何降低移植后复发率至今仍是难点。 目的：观察自体造血干细胞移植联合异体细胞因子活化杀伤(CIK)细胞及白细胞介素2治疗高危急性髓系白血病的临床效果。 方法：2例高危急性髓系白血病患者,经诱导化疗及巩固强化治疗后,在第1次缓解期行自体造血干细胞移植, 移植后1个月给予三四疗程异体CIK细胞输注,每隔半年1个疗程,每疗程分5次输注异体CIK细胞,每隔1日输注1次。每次输注CIK细胞前半小时内给予皮下注射白细胞介素2,第1次输注后隔日皮下注射白细胞介素2,半年后减为隔2日1次,1年后减为隔3日1次,1年半后减为1次/周,维持半年后结束,预防白血病复发。 结果与结论：2例患者自体造血干细胞移植后输注异体CIK细胞及皮下注射白细胞介素2无发热、寒战、皮疹等不良反应,无骨髓抑制及移植物抗宿主反应,治疗安全。2例患者持续缓解时间分别为20个月及2年,目前仍无复发。首次得出对于无合适供者的高危急性髓系白血病患者,在缓解后可行自体造血干细胞移植联合异体CIK细胞及白细胞介素2治疗,有机会获得长期无病生存。       

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：     

白细胞介素—11对小鼠骨髓造血的影响

白细胞介素－１１（ＩＬ－１１）是一种新的造血生长因子，于１９９０年基因克隆成功。本文对ＩＬ－１１的造血调节作用进行了初步的研究，探讨了ＩＬ－１１及其与其它造血因子协同对小鼠骨髓造血祖细胞增殖的促进作用。结果表明，ＩＬ－１１单独对骨髓集落的形成无显著的促进作用，但与多系集落刺激因子ＩＬ－３一起则具有很强的协同作用，能明显促进小鼠骨髓Ｍｅｇ－ＣＦＵ和Ｍｉｘ－ＣＦＵ的形成。     

自体造血干细胞移植在白血病的应用

自体造血干细胞移植（Auto—HSCT）是将患者的自身造血干细胞采集出来,进行或不进行特殊处理后再回输到经过超大剂量放疗和（或）化疗处理后的患者体内,使其造血和免疫功能得以恢复重建。依据移植中回输的造血干细胞来源,可分为自体骨髓移植（ABMT）、自体外周血造血干细胞移植（APBSCT）和自体脐带血移植（ACBT）。     

造血干细胞移植后免疫状态的研究进展

造血干细胞移植后面临的重要问题是移植后感染和肿瘤复发，移植后免疫重建迟于造血重建，甚至两年后免疫功能仍有缺陷，因此移植后免疫状态的研究对于指导免疫重建、防治感染及免疫治疗等有重要意义。本文就移植后免疫细胞的数量、功能变化及其机制作一综述。     

自体造血干细胞移植规范

前 言 本文件按照 GB/T 1.1-2020《标准化工作导则 第 1 部分:标准化文件的结构和起草规则》的规定起草. 本文件由中国医药生物技术协会提出并归口. 本文件起草单位:中国医药生物技术协会、天津市血液与再生医学学会、国家血液系统疾病临床医学研究中心、中国医学科学院血液病医院(中国医学科学院血液学研究所)、实验...     

自体造血干细胞移植治疗多发性硬化的疗效及免疫学改变

目的研究自体造血干细胞移植(ASCT)治疗进展型多发性硬化(MS)临床应用的可行性及免疫学改变。方法对10例处于继发进展期的MS患者进行了ASCT。移植后依据扩展疾病状态(EDSS)评分、发作次数、核磁共振(MRI)检查及免疫抑制药物的需求指标评定疗效。用流式细胞仪方法动态检测移植前后MS患者T淋巴细胞亚群、CD4 CD25 细胞及Th2细胞的改变。结果移植相关死亡率为零。随访观察9~26个月(平均17.9个月),至随访截止时有1例患者出现复发;4例患者处于疾病无进展状态;5例患者病情明显好转。除1例复发者外,全部患者在ASCT后不需要免疫抑制剂治疗。移植前、后相同观察期内发作次数由24次减至1次。移植后6个月MRI检查病灶由移植前的92处减少至6处。移植后1a(n=6)CD3 细胞、CD8 细胞及CD4 CD25 细胞的恢复高于移植前水平;CD4 细胞及CD3 CD4-CD8-细胞的恢复未达到移植前水平。结论ASCT治疗进展型MS患者是安全、有效的;移植后CD4 细胞及CD4-CD8-细胞的恢复较慢,CD4 CD25 细胞的恢复高于移植前水平。     

重组人白细胞介素2对骨髓造血祖细胞体外增殖的影响

重组人白细胞介素２对骨髓造血祖细胞体外增殖的影响郝思国邹正辉①杨吉成②虞斐①盛伟华②王苏③沈美凤①（安徽医科大学附一院，合肥２３００２２）①苏州医学院附二院，苏州２１５００４②苏州医学院，苏州２１５００７③辽宁省人民医院血液科，沈阳１１０００３作者简...     

白细胞介素2受体与淋巴瘤的发病机制

白细胞介素 2 (ＩＬ 2 )过去称为Ｔ细胞生长因子 ,是与Ｔ淋巴细胞从细胞周期Ｇ1到Ｓ期进展有关的细胞因子 ,主要由ＣＤ4 +Ｔ细胞产生 ,可作用于产生它的同一细胞及其附近的Ｔ淋巴细胞 (包括ＣＤ4 +和ＣＤ8+细胞 )。ＩＬ 2还可刺激ＮＫ细胞生长并增强它的溶细胞功能 ,能诱导细胞生长和分化。由于Ｔ淋巴细胞的功能主要不是靠它本身直接发挥 ,而是靠各种淋巴因子的扩大效应来体现 ,所以后者在机体免疫中发挥重要作用 ,而ＩＬ 2在细胞上的作用是通过ＩＬ 2受体 (ＩＬ 2Ｒ)介导的。许多研究表明 ,与免疫功能紊乱有关的疾病 ,包括恶性肿瘤 ,可出现…     

Long-term follow-up after autologous hematopoietic stem cell transplantation for low-grade non-Hodgkin lymphoma.

Autologous hematopoietic stem cell transplantation (AHSCT) in low-grade non-Hodgkin lymphoma (NHL) can result in a prolonged remission, although most patients eventually relapse and die of their disease. We report long-term outcomes of AHSCT for patients with relapsed low-grade NHL. Between May 1983 and 2001, 67 patients with relapsed or refractory stage III and IV low-grade NHL received an AHSCT at the University of Minnesota at a median of 2.3 years (range, 0.4-15.2 years) after diagnosis. At transplantation, 62 patients (92%) were in complete remission (CR) (6%) or partial remission (PR) (86%); 5 (8%) had resistant disease; and 9 (14%) had transformed to a higher-grade NHL. After AHSCT, 32 (49%) of 65 evaluable patients achieved CR, and 26 (40%) achieved PR. Overall survival (OS) was 50% (95% confidence interval [CI], 38%-62%) at 4 years and 33% (95% CI, 20%-46%) at both 10 and 18 years, whereas progression-free survival (PFS) was 28% (95% CI, 17%-39%) at 4 years, 18% (95% CI, 8%-28%) at 10 years, and 14% (95% CI, 4%-25%) at 18 years. Transplant-related mortality in the first 100 days was 3% (95% CI, 0%-7%). Relapse occurred in 62% (95% CI, 48%-75%) at 4 years and 72% (95% CI, 56%-87%) at 10 years. Eleven patients (16%) developed myelodysplastic syndrome/acute myeloid leukemia 1 to 8 years after AHSCT, and 3 (5%) developed solid tumors. In multiple regression analysis, the International Prognostic Index (IPI) score at transplantation was the most significant predictor for both OS and PFS. The median OS has not been reached in patients with an IPI score of 0 or 1 at transplantation (20 of 35 survive 2 to 18 years after AHSCT), whereas it was 2.3 and 1.6 years for IPI scores of 2 and 3, respectively ( P = .002). A good response (CR/PR) to AHSCT (relative risk [RR], 0.4; 95% CI, 0.2-0.9; P = .04) and age <50 years (RR, 0.5; 95% CI, 0.2-0.8; P = .01) were also independently significant predictors of good OS and PFS. We present mature follow-up data (median follow-up, 8 years; range, 2-18 years) of patients undergoing AHSCT for relapsed low-grade NHL and demonstrate extended OS and PFS. Very long-term remissions were seen in nearly 20% of patients. AHSCT remains promising, especially for patients with sensitive relapse and lower IPI scores. Recurrent lymphoma after AHSCT remains the major problem, and prolonged survival is further tempered by a significant risk of post-transplantation second malignancies, including myelodysplastic syndrome/acute myeloid leukemia and solid tumors.     

Autoimmune disease after autologous hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for refractory autoimmune diseases. The safety and long-term outcome have been also acceptable. Infectious diseases under immune suppressive state after autologous HSCT are common transplantation related complications whereas autoimmune diseases are uncommon. Organ specific autoimmune diseases, such as immune mediated thrombocytopenia and thyroid dysfunction, are the most common after autologous HSCT. Systemic autoimmune diseases can also develop after autologous HSCT in patients with hematological disorders with genetic predisposition to autoimmune diseases. Although the mechanism of autoimmunity after HSCT is not well-known, long-term follow-up is essential in patients with autoimmune diseases treated with autologous HSCT.     

Complications of autologous hematopoietic stem cell transplantation

Myeloablative therapy followed by autologous hematopoietic stem cell (HSC) transplantation is a therapeutic option proposed for a variety of hematological and non-hematological diseases. However, although mortality due to this procedure is steadily decreasing, patients are still exposed to the risk of a number of complications negatively affecting their expectancy or quality of life. Adverse events due to HSC harvesting are rare and generally reversible. The early post-transplant complications include infections, mucositis, hepatic veno-occlusive disease and various acute organ toxicities. Immune derangement is a leading cause of most late events, such as viral or fungal infections, auto-immune manifestations and secondary neoplasms, of which secondary AML/MDS are the most commonly reported. In line with the favoured pathogenetic explanation, neoplastic clones previously established during conventional treatment are harvested and reinfused at the time of autografting. Other late effects are single organ dysfunction due to the underlying disease and treatment toxicities combined with infectious and post-infectious phenomena. The lungs, heart, CNS and reproductive system are the most investigated targets, but no clinical patterns have been identified as specific for autografting.     

Preemptive cellular immunotherapy after T-cell-depleted allogeneic hematopoietic stem cell transplantation.

GVHD is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is due to donor lymphocytes that are cotransplanted with donor stem cells. These donor lymphocytes are primed by histocompatibility differences between donors and recipients and activated by a cytokine storm caused by the conditioning regimen. The most efficient method for prevention of GVHD consists of T-cell depletion (TCD) of the graft. However, TCD usually leads to an increased risk of leukemia relapse because of the loss of the graft-versus-leukemia (GVL) effect. Several groups have studied the feasibility of preemptive donor lymphocyte infusion (DLI) to lessen the impact of TCD on leukemia relapse. Preemptive DLI is given several weeks to months after the transplantation, ie, after the cytokine storm and after the patient has recovered from conditioning-regimen-related toxicities. After briefly discussing various techniques of TCD of the graft and the efficacy of DLI, this article reviews the first clinical studies evaluating a strategy of TCD of the graft followed by preemptive DLI.     

Augmentation of virus-specific immunity after hematopoietic stem cell transplantation by adoptive T-cell therapy

Adoptive transfer of virus-specific T cells offers the potential for accelerating reconstitution of antigen-specific immunity after allogeneic hematopoietic stem cell transplantation. However, the logistics of producing virus-specific T cells and the risk of inducing graft-versus-host disease has limited their application. We developed a relatively simple system employing cytomegalovirus lysate-pulsed, monocyte-derived dendritic cells as stimulator cells, requiring only a single blood draw from the donor. We treated 16 patients with these T-cell lines, administered after the detection of human cytomegalovirus (HCMV) DNA by polymerase chain reaction. Massive in vivo expansions of HCMV-specific cytotoxic T lymphocytes (3-5 log) were observed within days of adoptive transfer. In eight cases viral titers were decreasing within 5 days and antiviral drug therapy was not required. The T-cell receptor CDR3 lengths of HCMV-specific cytotoxic T lymphocytes expanding in vivo were identical to those of the transferred cells. A low incidence of late CMV reactivation was seen (2/14 assessable patients compared with 45/72 historical controls, p = 0.001) and no significant toxicities were observed. Our findings indicate that application of cell lines generated in relatively short-term in vitro cultures is both feasible and effective in a clinical environment. This simple in vitro methodology should allow widespread application of adoptive transfer of virus-specific T cells.     

Optimistic expectations and survival after hematopoietic stem cell transplantation.

An optimistic attitude is hypothesized to be beneficial when facing a life-threatening medical condition. However, the actual relationship of high expectations for treatment success and medical outcome is controversial. Using a prospective cohort of 313 autologous and allogeneic hematopoietic stem cell transplant patients enrolled July 1996 through November 1999, we tested whether patient-reported expectations before transplantation were associated with survival and quality of life following the procedure. Before transplantation, patients with higher expectations that the transplant procedure would go well had better mental and emotional functioning, but similar physical status and medical condition to patients with less optimistic expectations. In the first 2 months after transplantation, optimistic expectations were associated with better survival (92% v 84%; relative risk for mortality 0.45, 95% confidence interval 0.22-0.92; P=.03) controlling for other physical and mental characteristics. However, by 6 months posttransplantation, survival and quality of life were indistinguishable between patients with initially higher and lower expectations. Our data suggest an association between more optimistic expectations and early survival following hematopoietic stem cell transplantation, but this association is not present by 6 months posttransplantation.     

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.     

Pharmacokinetic-directed high-dose busulfan combined with cyclophosphamide and etoposide results in predictable drug levels and durable long-term survival in lymphoma patients undergoing autologous stem cell transplantation

The clinical advantage of pharmacokinetic (PK)-directed-based dosing on intravenous (i.v.) versus oral busulfan-related toxicity and survival remains unclear. We performed a retrospective cohort study of sequential cohorts of patients comparing PK-directed oral and i.v. busulfan-based conditioning regimens in lymphoma patients undergoing autologous hematopoietic cell transplantation (ASCT). Patients received oral (n = 95), every 6 hours i.v. (IV16, n = 113), or once-daily i.v. (IV4, n = 86) busulfan, cyclophosphamide, and etoposide. PK-directed dosing was performed to achieve a predefined target area under the curve (AUC) of 20,000 μM-min (range: 18,400-21,600 μM-min). PK-directed dose adjustments markedly reduced the number of patients in the oral group with total AUC higher than the targeted AUC range, and reduced the variations of total AUC values in all patient groups. One hundred-day mortality was 2.1%, 3.6%, and 3.5% for oral, IV16, and IV4 cohorts, respectively. Five-year overall survival (OS) was 57% (95% confidence interval [CI] 45%-66%) and 64% (95% CI 53%-73%) for patients who received oral and i.v. busulfan, respectively. Both multivariable and instrumental variable analyses indicated the route of delivery had no significant impact on OS, whereas refractory disease and age ≥55 were significantly associated with poorer OS. In lymphoma patients undergoing ASCT, PK-directed i.v. or oral busulfan-based conditioning regimens have comparable toxicity and OS.