造血干细胞移植在儿童白血病治疗中的应用

 白血病是儿童时期最常见的恶性肿瘤,约占该时期所有恶性肿瘤的35 %,对于传统化疗难以治愈的高危急性白血病和慢性粒细胞白血病,造血干细胞移植（HSCT）是主要的治疗手段。目前国际上推荐首选HLA匹配相关供者（MRD）的HSCT。由于80 %的儿童白血病患者缺少这种供者,自体造血干细胞移植（auto-HSCT）也被选择性地应用于急性淋巴细胞白血病（ALL）和急性髓系白血病（AML）的治疗。据统计有30 %～40 %的患者接受了匹配的无关供者（MUD）的HSCT治疗。近年来,无关脐血移植（UDCBT）和HLA不相匹配的相关供者HSCT呈上升趋势。就近年来该方面的进展作一综述。     

骨髓间充质干细胞在造血干细胞移植中的应用研究

造血干细胞移植(HSCT)后，干细胞的成活、分化、增殖及造血功能的恢复，影响治疗的效果，移植过程中难免会遇到诸多问题。如造血微环境的破坏，干细胞归巢问题及移植后的移植物抗宿主反应(GVHR)均影响移植成败。近年研究发现骨髓间充质干细胞(MSC)为造血微环境的重要组成成分，可分泌多种细胞因子，能够促进造血，加速干细胞归巢，还能参与免疫反应，降低T淋巴细胞反应。而MSC的这些特性恰好可以减少HSC中的以上问题。因此，国内外已将HSC与MSC共移植治疗恶性肿瘤应用于临床，并取得了良好的临床效果。     

造血干细胞移植在乳腺癌治疗中的作用

近 2 0余年来乳腺癌发病率一直位居女性肿瘤之首 ,并以 2 %的速度在全球递增。1 998年全球乳腺癌死亡数为 31 .4万 ,占当年发病数的 30 .5 % ,死亡率为 1 2 .9/1 0万 [1]。在美国 ,乳腺癌发病率占女性恶性肿瘤的 2 6%。我国乳腺癌发病率在世界上虽较低 ,但近年来也有明显上升趋势。 2 0世纪 80年代末我国乳腺癌新发病数仅为 3万例左右 ,但 90年代初则猛增至 6.7万例 ,减去人口增长因素 ,年均增长达3%～ 4% ,高于全球 1 %～ 2 % [2 ]。近半个世纪来 ,乳腺癌治疗发生了划时代的重大变化 ,造血干细胞移植 ( hematopoietic stem cell transplant…     

间充质干细胞在造血干细胞移植中的应用

 间充质干细胞是一种能够从各种人成体组织分离出来的非造血多能干细胞,近年来,许多研究表明间充质干细胞具有免疫调节能力及促进组织重建等功能。就其在造血干细胞移植中的应用,如急慢性移植物抗宿主病（GVHD）、GVHD造成的移植失败、纯红细胞再生障碍性贫血及免疫性血小板减少性紫癜、出血性膀胱炎作以综述。     

骨髓间充质干细胞在造血干细胞移植中的应用研究

造血干细胞移植(HSCT)后,干细胞的成活、分化、增殖及造血功能的恢复,影响治疗的效果,移植过程中难免会遇到诸多问题。如造血微环境的破坏,干细胞归巢问题及移植后的移植物抗宿主反应(GVHR)均影响移植成败。近年研究发现骨髓间充质干细胞(MSC)为造血微环境的重要组成成分,可分泌多种细胞因子,能够促进造血,加速干细胞归巢,还能参与免疫反应,降低T淋巴细胞反应。而MSC的这些特性恰好可以减少HSC中的以上问题。因此,国内外已将HSC与MSC共移植治疗恶性肿瘤应用于临床,并取得了良好的临床效果。     

自体造血干细胞移植在恶性淋巴瘤中的应用进展

 近年来,自体造血干细胞移植（ASCT）在多种恶性血液病中被成功应用,使之成为治疗恶性淋巴瘤的又一有效手段。就ASCT治疗恶性淋巴瘤的疗效、预处理方案、干细胞采集净化、移植后治疗等方面作简要综述。     

自体血造血干细胞的移植

自1985年首例成功地进行了自体外周血造血干细胞移植(ABSCT)后，此种移植造血干细胞的新方法在世界范围内增长很快，因为其显示有某些优点：造血恢复的快；移植后住院时间短；费用低廉。外周血造血干细胞移植的指征现在也较好的定下来了，虽然由于缺乏对照的研究，限制了其临床资料的应用。尽管有些方面尚不能最后肯定．如周围血造血干细胞的本质，其长期植活的能力，外周血造血干细胞植入(PBSC)定量的检测，或谓它比采集骨髓中含有较少的恶性细胞。近来实骑研究了用造血刺激因子来动员外周血造血干细胞现在也在实验中。     

造血干细胞移植在原发性骨髓纤维化治疗中的应用

药物及对症支持治疗仍然是原发性骨髓纤维化(PMF)的主要治疗方法,但是其仅能改善患者症状而无法改变PMF的自然病程,而造血干细胞移植是目前治愈PMF唯一有效的手段.然而,严重的移植相关并发症限制了其在PMF患者中的广泛开展.文章就PMF患者造血干细胞移植过程中供者的选择、预处理方式、影响移植成功的因素等作一综述.     

造血干细胞移植在非霍奇金淋巴瘤治疗中的应用

造血干细胞移植联合大剂量化疗能明显改善非霍奇金淋巴瘤的预后。本文综述了近年来自体，异基因骨髓和周围血造血干细胞移植在ＮＨＬ治疗中应用的研究进展。     

造血干细胞移植治疗恶性血液病临床研究

 目的 探讨造血干细胞移植（HSCT）治疗恶性血液病的临床疗效及并发症的防治。方法51例急慢性白血病、恶性淋巴瘤、多发性骨髓瘤患者中,36例选择自体造血干细胞移植（auto-HSCT）,15例接受异基因造血干细胞移植（allo-HSCT）,包括HLA不全相合3例及非血缘关系移植4例,混合移植2例;预处理自体移植主要选用CBV,BEAC方案,异基因移植采用BU／CY2及改良的BU／CY方案;移植物抗宿主病（GVHD）的预防采用CsA+MTX或CsA+MTX＋MMF方案。结果 51例患者中49例获得造血重建,在auto-HSCT和allo-HSCT后WBC≥1.0×109／L的中位时间分别为13 d和17 d,血小板≥20×109／L的中位时间分别为21和25 d;40 ％出现aGVHD,26.7 ％出现cGVHD;3.9 %出现HVOD;出血性膀胱炎发生率5.9 ％;CMV感染发生率33.3 ％;62.7 ％出现黏膜炎;54.9 ％出现不同部位的感染;移植相关死亡率3.5 %,随访3～95个月,移植后复发11例,其中auto-HSCT 9例,allo-HSCT 2例。结论 HSCT是目前治疗恶性血液病的最佳方法,但移植期间需要进一步探索如何减少其相关并发症,以提高血液肿瘤的治愈率及延长患者的无病生存时间。     

Pre-transplant depression as risk factor for survival of patients undergoing allogeneic haematopoietic stem cell transplantation

Introduction: Depression is discussed as a possible risk factor for survival in cancer patients. We explored this relationship for patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT). Patients and methods: The depression subscale of the Hospital Anxiety and Depression Scale (HADS) served as a measure for depression. One hundred and thirty‐eight patients (mean age 41 years; different diagnoses) participating in a psycho‐oncology study filled in the HADS after admission for allogeneic HSCT. They were followed‐up for at least two years; 72 patients died during follow‐up. Results: Depression scores were not correlated with medical and psychosocial objective factors with the exception of having under‐aged children. Controlling for medical factors that showed up as predictors for survival in our sample (patient's age at HSCT, having had a transplant before, risk for treatment failure) the HADS depression score (range 0–21) emerged as an independent predictor (Cox regression): hazard ratio = 1.087, 95% CI = 1.018–1.161. Conclusion: Depression is probably not a simple indicator of a worse health status. Further research is needed to decide if depression must be considered as an independent risk factor for survival when diagnosed in the pre‐transplant period. Copyright © 2007 John Wiley & Sons, Ltd.     

Safety and feasibility of physical therapy in cytopenic patients during allogeneic haematopoietic stem cell transplantation

This study aimed to investigate the safety and feasibility of physical therapy in cytopenic patients undergoing allogeneic haematopoietic stem cell transplantation (allo‐HSCT), and to investigate the effect of physical therapy on physiological functions and quality of life (QOL) in allo‐HSCT patients. The study cohort included 321 patients who underwent allo‐HSCT. To investigate the safety and feasibility of physical therapy during cytopenia, patients were assigned to the physical therapy group (n = 227) or the control group (n = 94). To determine the effects of physical therapy, patients were divided according to the frequency with which they underwent physical therapy (n = 51 per group). Handgrip strength, knee extensor strength and a 6‐min walk test were used as measures of physiological function. Short‐Form 36 was used to assess QOL. The physical therapy group had higher rate of achieving engraftment and lower death rate than the control group (P < 0.05). After HSCT, the high‐frequency physical therapy group showed significantly less decline than the low‐frequency physical therapy group with respect to physical functioning of QOL (P < 0.01). Physical therapy is quite beneficial and can be performed safely and feasibly in cytopenic patients during allo‐HSCT.     

Hematopoietic stem cell transplantation in mantle cell lymphoma.

BACKGROUND: Patients with mantle cell lymphoma (MCL) have in general, lower response rates and overall survival (OS) than those with other B-cell non-Hodgkin's lymphomas. The role of hematopoietic stem cell transplantation (HSCT) in MCL is unclear. Hence we decided to study the clinical course of patients who received autologous and allogeneic HSCT for MCL. METHODS: Ninety-seven patients, (80 patients-autologous; 17 patients-allogeneic) who received a HSCT for mantle cell lymphoma were included in the study. RESULTS: The complete response rates at day 100 between the two groups were similar (73% vs. 62%). Day-100 mortality was higher in the allogeneic HSCT group (19% vs. 0%) (P < 0.01). The estimated 5-year relapse rates, 5-year event-free survival (EFS) and 5-year OS among the allogeneic HSCT patients were 21%, 44% and 49%, respectively, similar to 56%, 39% and 47% in the autologous group. Ten patients received HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone + high-dose methotrexate and cytarabine) +/- rituximab prior to transplant. There have been no relapses or deaths amongst these patients at a median follow-up of 16 months. CONCLUSIONS: Patients treated with allogeneic HSCT had a lower relapse rate, but similar EFS and OS to autologous HSCT. Treatment of MCL with HyperCVAD +/- rituximab followed by HSCT seems promising.     

Immune recovery after conventional and non-myeloablative allogeneic stem cell transplantation

The immune recovery of 66 patients undergoing allogeneic stem cell transplantation with either conventional or non-myeloablative conditioning regimen was studied. Infections post-transplant were enumerated and quantitative immunoglobuilins (IgG, IgA, IgM) and lymphocyte sub-sets 3, 6 and 12 months post-transplant were measured. A significant difference was found in the immunologic recovery of non-myeloablative and conventional ASCT in the patient population. The T-helper cell reconstitution was significantly faster after NMA than conventional transplantation and the recovery of B cells was faster after conventional transplantation. Regarding immunoglobulin levels, a faster recovery of IgM levels after NMA-ASCT and a delayed recovery of IgA levels was observed in both groups. These were accompanied by a significant difference in the frequency and severity of infectious episodes.     

异基因外周血干细胞移植后外周血出现幼稚粒细胞与白血病复发的关系

目的了解异基因外周血干细胞移植（allo-PBSCT）后白血病复发与外周血幼稚粒细胞的关系。方法97例白血病患者经allo-PBSCT治疗,于14、30、60、90、120、180d及1年以后骨髓随访时同时观察外周血幼稚粒细胞出现情况,分析与白血病复发的关系。结果97例中,15例发生白血病复发。在30d及其以后外周出现幼稚粒细胞的57例中,复发14例,复发率24．6％,而30d及其以后外周血未出现幼稚粒细胞者的40例中仅有1例复发,复发率2．5％（P〈0．05）。复发与不复发者移植物抗宿主病（GVHD）差异无统计学薏：义（P〉0．05）。结论白血病复发与移植后外周血幼稚粒细胞有关．复发后治疗难度大,预后差。     

Adenovirus infection after allogeneic stem cell transplantation

Adenovirus infection after allogeneic hematopoietic stem cell transplantation (HSCT) is an emerging pathogen causing relevant morbidity and mortality, with preponderance in children. During the last years, basic research on the biology of the virus and host immune response ameliorated the diagnostic, surveillance, and therapeutic strategies. Risk factors for infection commonly have an impact on T-cell reconstitution, such as T-cell depleted graft, unrelated or HLA-mismatched donor transplantation, and GvHD. Weekly surveillance by PCR in stool and blood till day 100 or longer post-HSCT and pre-emptive therapy with cidofovir are the mainstay of the current approach to adenoviral infections post-HSCT. Since a sufficient host T-cell response is essential to clear the virus, diagnostic procedures for detection of virus-specific T-cells have recently been developed to assess the risk of the infection. Furthermore, adoptive immunotherapy is a new treatment option for patients with absent specific T-cell response and present systemic adenoviral infection.     

Sustained molecular remission by non-myeloablative stem cell transplantation after autologous hematopoietic stem cell transplantation in a patient with multiple myeloma

Multiple myeloma (MM) is refractory to conventional chemotherapy. To achieve a sustained complete remission, we performed planned non-myeloablative allogeneic stem cell transplantation (NST) after autologous hematopoietic stem cell transplantation (HSCT) in a patient with stage III MM. Autologous HSCT was performed using high-dose melphalan after conventional chemotherapy, followed by NST from an HLA-identical sibling using low-dose total body irradiation (200 cGy) for conditioning. Cyclosporine and mycophenolate mofetil were used for graft-vs-host disease (GVHD) prophylaxis. Acute GVHD was transiently seen in the skin and intestine, while, in addition, mild chronic GVHD was seen in the oral mucosa and skin. Complete donor chimerism was achieved and the disappearance of tumor-derived monoclonal B cells was confirmed based on an analysis of immunoglobulin light chain messenger signals on day 156 when chronic GVHD occurred. The clinical course in this case strongly suggested the existence of a graft-vs-myeloma effect.     

Five‐year follow‐up of survival and relapse in patients who received cryotherapy during high‐dose chemotherapy for stem cell transplantation shows no safety concerns

SVANBERG A., ÖHRN K. & BIRGEGÅRD G. (2012) European Journal of Cancer Care Five‐year follow‐up of survival and relapse in patients who received cryotherapy during high‐dose chemotherapy for stem cell transplantation shows no safety concerns We have previously published a randomised controlled study of the efficacy of cryotherapy in preventing acute oral mucositis after high‐dose chemotherapy for stem cell transplantation. The present study is a 5‐year follow‐up safety study of survival in these patients. In the previously published study oral cryotherapy (cooling of the oral cavity) during high‐dose chemotherapy significantly reduced mucositis grade and opiate use in the treated group. All patients were followed up for at least 5 years with regard to relapse and death rates. Baseline data, transplant complications and mucositis data were compared. Significantly more patients (25/39) who received oral cryotherapy were alive after 5 years compared to 15/39 in the control group (P= 0.025). Relapse rates were similar. The only baseline difference was a lower proportion of patients in complete remission at transplantation in the control group (6 vs. 13, P= 0.047). This 5‐year follow‐up study gave no support for safety concerns with cryotherapy.     

树突状细胞在造血干细胞移植后重建及与临床结果的相关性

 异基因造血干细胞移植后,供体树突状细胞（DCs）在受者体内逐步重建。DC1、DC2在宿主体内重建速度各异。一些内源或外源性因素影响DCs重建。异基因和自体造血干细胞移植各有自己的DCs重建规律,并与移植后临床结果如移植物抗宿主病、移植后感染、移植物抗白血病效应具有相关性。