自体造血干细胞移植治疗急性白血病的临床观察

目的：评价自体造血干细胞移植治疗急性白血病的疗效;观察多疗程中大剂量阿糖胞苷（Ara-C）治疗后外周血干细胞采集效果。方法：17例急性白血病患者行自体造血干细胞移植,其中骨髓移植4例,外周血造血干细胞移植13例,在外周血造血干细胞移植的患者中有4例在诱导和巩固治疗中采用中大剂量Ara—C2疗程或2疗程以上,观察不同组患者造血干细胞采集情况及造血重建情况,并监测患者的疗效。结果：外周血干细胞移植的患者采集的中位MNC数和中位CD34^＋细胞数明显高于骨髓组,差异有统计学意义（均P〈0．05）;使用中大剂量Ar〉C2疗程或2疗程以上的患者采集的中位MNC和中位CD34^＋细胞数与未使用的患者比较差异无统计学意义（P〉0．05）;外周血干细胞移植患者中性粒细胞〉0．5×10^9／L和血小板〉20×10^9／L的时间较骨髓移植患者短,差异有统计学意义（P〈0．01）;4例患者在复发状态行自体造血干细胞移植,移植后中位生存期9．5个月,缓解期行自体造血干细胞移植的移植后中位生存期81个月,差异有统计学意义（P〈0．05）;17例患者中位生存期（OS）84个月,中位无白血病生存期（DFS）81个月,患者3年无白血病存活率为（68．25±11．23）％。结论：自体外周血造血干细胞移植比自体骨髓移植造血重建快;2疗程或2疗程以上的中大剂量Ara-C治疗的患者仍能采集到足量的外周造血干细胞;缓解期行自体造血干细胞移植可获得较好的OS和DFS。     

Autologous cell based therapy for treating chronic infarct myocardium

Recent experimental and clinical studies have shown that autologous cell based therapy using skeletal myoblasts or bone marrow-derived stem cells might have beneficial effects in chronic ischemic heart disease. The underlying concept is based on the repopulation of necrotic tissue by either readily contractile myoblasts or by bone marrow-derived stem cells. However, there is a need to resolve a number of issues for determining the better way to perform these treatments and, moreover, for assessing the real beneficial functional effect of each of these cell therapies. In this mini-review, we will discuss (i) the issues of the selection of chronic infarct animal to truly determine the impact of cell therapy on cardiac function recovery, and (ii) the evaluation of the bio-availability and the bio-distribution of transplanted cells. Some new investigational methodologies based on clinical end-points are also proposed.     

Autologous stem cell transplantation for non-Hodgkin's lymphoma

Autologous stem cell transplantation (ASCT) is the only curative option for many patients with relapsed or refractory non-Hodgkin's lymphoma. ASCT achieves long-term survival in up to 50% of patients with chemotherapy-sensitive relapsed diffuse large cell lymphoma (DLCL), and prospective randomized studies have documented the superiority of ASCT over salvage chemotherapy in patients with relapsed DLCL However, the role of ASCT as an upfront therapy for patients with high-risk DLCL remains unclear, and prospective randomized studies have yielded mixed results. In addition, ASCT may not be curative in follicle center or mantle cell lymphoma, although longer follow-up may identify a subset of patients with prolonged survival. Ongoing clinical trials are studying the use of monoclonal antibodies, such as rituximab and iodine 131I-tositumomab, in ASCT regimens to purge tumor cells in vivo and improve long-term outcome in follicle center and mantle cell lymphoma.     

干细胞移植治疗下肢动脉闭塞症

目的探讨闭塞性动脉病再生治疗的临床应用新进展,评价动员后自体外周血干细胞移植治疗下肢动脉闭塞症的临床疗效及部分影响因素。方法血管造影确诊的下肢动脉闭塞症患者12例,经重组人粒细胞集落刺激因子(rhG-CSF)皮下注射150μg/d进行干细胞动员后,第5天用血细胞分离机采集分离干细胞,以3×109细胞/患肢对患肢进行肌肉注射,术后观察3个月至1年,进行各项指标综合评估。结果移植后3个月12例患者疼痛、患肢冷感、间歇性跛行及溃疡明显好转(按移植前后打分结果,P<0.01),选患肢相对恒定位置观测肢体血流图血流波幅[移植前(2.65±1.06)mm、移植后(7.76±0.59)mm,P<0.01]及血管超声血流灌注量[移植前(21.32±0.63)cm/s、移植后(44.55±4.13)cm/s,P<0.01],干细胞移植后血流灌注明显改善,血管造影示新生侧支血管明显增多,12例均未发现并发症和不良反应。结论采用动员后的外周血干细胞移植治疗下肢动脉闭塞症安全、有效,值得推广应用和深入研究。     

Autologous stem cell transplantation for systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is responsive to treatment with immunosuppressives and steroids, but often pursues a relapsing or refractory course resulting in increasing incapacity and reduced survival. Autologous stem cell transplantation (ASCT) following immunoablative chemotherapy is a newer therapy for autoimmune disease of potential use in severe SLE. A retrospective registry survey was carried out by the European Blood and Marrow Transplant and European League Against Rheumatism (EBMT/EULAR) registry. Data was collected from 53 patients with SLE treated by ASCT in 23 centres. Disease duration before ASCT was 59 (2-155) months (median, range), 44 (83%) were female, and median age was 29 (9-52) years. At the time of ASCT a median of seven American College of Rheumatology (ACR) diagnostic criteria for SLE were present (range 2-10) and 33 (62%) had nephritis. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor in 93% of cases. Ex vivo CD34 stem cell selection was performed in 42% of patients. Conditioning regimens employed cyclophosphamide in 84%, anti-thymocyte globulin in 76% and lymphoid irradiation in 22%. The mean duration of follow-up after ASCT was 26 (0-78) months. Remission of disease activity (SLEDAI < 3) was seen in 33/50 (66%; 95%CI 52-80) evaluable patients by six months, of which 10/31 (32%; 95%CI 15-50) subsequently relapsed after six (3-40) months. Relapse was associated with negative anti-double stranded DNA (anti-dsDNA) antibodies before ASCT (P = 0.007). There were 12 deaths after 1.5 (0-48) months, of which seven (12%; 95%CI 3-21) were related to the procedure. Mortality was associated with a longer disease course before ASCT (P = 0.036). In conclusion, this registry study demonstrates the efficacy of ASCT for remission induction of refractory SLE, although mortality appeared high. The safety of this procedure is likely to be improved by patient selection and choice of conditioning regimen. The return of disease activity in one-third of patients might be reduced by long-term immunosuppressive therapy post-ASCT.     

Autologous stem cell transplantation for acute myeloid leukemia

Autologous bone marrow transplant (ABMT) and stem cell transplantation (ASCT) are important treatment modalities for acute myeloid leukemia (AML). The role of ASCT in first remission patients remains controversial. Phase II and phase III studies demonstrate that patients with favorable-risk cytogenetics benefit from ASCT, with reduction in relapse and improvement in leukemia-free survival (LFS). Patients with poor-risk cytogenetics do not appear to benefit significantly from ASCT and should preferentially be treated with allogeneic transplant. The role of ASCT for patients with intermediate risk disease is uncertain. It appears that ASCT in first remission will improve disease-free survival compared to standard chemotherapy. Sufficient patients who relapse after chemotherapy treatment can be salvaged with ASCT in second remission such that the beneficial effect on overall survival is blunted. ASCT produces equivalent results to ABMT but with reduced morbidity. The collection of stem cells during recovery from intensive dose consolidation therapy appears to be an attractive strategy that can increase the percentage of patients who are able to receive their intended transplant. Consolidation therapy prior to stem cell collection and transplant has been shown to decrease the relapse rate and improve outcomes, but the optimal nature of this consolidation therapy is unknown. For patients with AML in second remission, ABMT/ASCT offers a substantial salvage rate, and is particularly effective for patients with acute promyelocytic leukemia.     

Autologous hematopoietic stem cell transplantation for autoimmune diseases

Experimental data and early phase I/II studies suggest that high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) can arrest progression of severe autoimmune diseases. We have evaluated the toxicity and disease response in 473 patients with severe autoimmune disease treated with autologous HSCT between 1995 and 2003, from 110 centers participating in the European Group for Blood and Marrow Transplantation (EBMT) autoimmune disease working party database. Survival, transplant-related mortality, treatment response and disease progression were assessed. In all, 420 patients (89%; 86+/-4% at 3 years, median follow-up 20 months) were alive, 53 (11%) had died from transplant-related mortality (N=31; 7+/-3% at 3 years) or disease progression (N=22; 9+/-4% at 3 years). Of 370 patients, 299 evaluable for response (81%) showed a treatment response, which was sustained in 213 (71% of responders). Response was associated with disease (P<0.001), was better in patients who received cyclophosphamide during mobilization (relative risk (RR)3.28 (1.57-6.83)) and was worse with increasing age (>40 years, RR0.29 (0.11-0.82)). Disease progression was associated with disease (P<0.001) and conditioning intensity (high intensity, RR1; intermediate intensity, RR1.81 (0.96-3.42)); low intensity, RR2.34 (1.074-5.11)). These data from the collective EBMT experience support the hypothesis that autologous HSCT can alter disease progression in severe autoimmune disease.     

Autologous stem cell transplantation for primary systemic amyloidosis

High-dose melphalan with autologous blood stem cell transplantation (SCT) can reverse the disease process in selected patients with primary systemic amyloidosis (AL); however, SCT for AL remains controversial because of the treatment-related mortality in patients with cardiac and multisystem organ involvement. In this review, we briefly discuss recent advances in AL, such as the free light-chain assay and the role of immunoglobulin light-chain variable region germline genes in the disease, and then we discuss the current status of SCT for AL with emphases on patient selection, approaches to stem cell mobilization, and peri-SCT management. It is clear that patients with AL who have advanced amyloid cardiomyopathy or more than 2 major viscera involved with disease are poor candidates for SCT. Therefore, the importance of patient selection cannot be overemphasized, and patients with 1 or 2 involved organs or with early cardiac involvement are usually appropriate candidates for SCT. Because the toxicity of melphalan is dose-related and survival with AL may be age-related, patient age and the extent of organ involvement can provide a basis for patient stratification. We discuss such a risk-adapted approach to melphalan dosing in detail and conclude with a brief overview of current research using SCT to treat patients with AL.     

Autologous stem cell transplantation for chronic lymphocytic leukemia

Autologous stem cell transplantation (ASCT) has been intensively investigated for treatment of patients with chronic lymphocytic leukemia (CLL) during recent years. To assess the potential therapeutic value of ASCT for CLL, the present article aims at answering the following crucial questions: (1) Does ASCT have curative potential? (2) What is the therapeutic potential of ASCT in terms of disease control in relation to toxicity? (3) What is the role of ASCT in the current arsenal of CLL treatment modalities? Evidence from clinical and minimal residual disease (MRD) studies suggests that ASCT has curative potential in only a few patients, if any. Nevertheless, ASCT might be capable of prolonged disease control even in CLL with poor-risk features. Uncontrolled prospective studies have indicated the superiority of ASCT over alkylator and fludarabine monotherapy but not necessarily over purine analogue cyclophosphamide or antibody combinations. A significant risk of secondary neoplasms, in particular myelodysplasias, has to be taken into account. Therefore, ASCT cannot be considered as standard treatment for CLL and should be performed only in the context of clinical trials.     

Autologous hematopoietic stem cell transplantation for autoimmune diseases

Ten years have passed since the first published consensus statement on the use of hematopoietic stem cell transplantation (HSCT) in the treatment of severe autoimmune disease (AD) appeared. During that time, around 700 patients suffering from severe AD have undergone HSCT in the frame of phase I/II clinical trials from over 20 countries including the US. The majority have received an autologous HSCT using one of a limited number of regimens, consistent with the original consensus statement. Long-term drug-free remissions, remission then relapse, no response and treatment-related mortality (TRM) were seen in all the subgroups of AD. An overall TRM of 7% was observed, with marked variation between ADs, i.e. 11% in systemic lupus erythematosus (SLE) and only 1 patient in rheumatoid arthritis (RA). Phase III prospective, comparative randomized trials are running or being planned in multiple sclerosis (MS), systemic sclerosis (SSc), SLE and RA. Basic science programs are also being undertaken to study the immunological mechanisms underlying the clinical events observed.     

Autologous stem cell transplantation for systemic lupus erythematosus

Some patients with severe systemic lupus erythematosus do not respond to conventional immunosuppression or suffer severe side effects from such treatment. In order to explore the concept of immunoablation followed by haematopoietic stem cell transplantation (HSCT) or 'rescue', an international collaboration has occurred over the past seven years. The European Group for Blood and Marrow Transplantation (EBMT) and The European League Against Rheumatism (EULAR) have analysed their collective phase I and II studies and found a remission rate (based on a reduction of the SLEDAI to < 3) in 66%, one-third of whom later relapsed to some degree. The most often used protocol was cyclophosphamide (CY) and G-CSF for mobilization and CY plus anti thymocyte globulin as conditioning. Procedure related mortality was 12% in this sick group of patients with major organ involvement. The North American, mostly single centre experience showed higher rates of remission and one procedure related death. Some relapse was also observed. Phase II studies designed to assess the role of post-HSCT maintenance therapy are being considered by the EBMT/EULAR group.     

多发性骨髓瘤的自体造血干细胞移植治疗

多发性骨髓瘤(multiple myeloma,MM)是一种好发于中老年人的血液系统恶性疾病,由骨髓中的浆细胞单克隆性增生引起。典型临床表现为骨骼系统破坏,如病理性骨折、本-周蛋白尿、贫血以及慢性肾功能不全,并伴随高钙血症、血沉增快及免疫球蛋白电泳出现单克隆免疫球蛋白峰等。MM常规化学治疗(化疗)反应率低,其中位生存期多为2～3年。临床研究证明经自体造血干细胞移植(AHSCT)治疗可     

Autologous stem cell transplantation for HIV-associated lymphoma.

Is peripheral stem cell mobilization followed by autologous stem cell transplantation (ASCT) feasible in patients with human immunodeficiency virus (HIV)- associated lymphoma (HIV-L)? Studies have demonstrated that, in the HIV- negative (HIV(-)) setting, ASCT may improve lymphoma-free survival in high-risk non-Hodgkin lymphoma (NHL) or relapsed Hodgkin disease (HD) and NHL. Given the poor prognosis of HIV-L with conventional chemotherapy, this dose-intensive approach was explored. Nine patients with HIV-HD or NHL mobilized a median of 10.6 x 10(6) CD34(+) cells/kg and engrafted after ASCT. CD4 counts recovered to pretransplantation levels and HIV viral loads were controlled in patients compliant with antiretroviral therapy. Seven of 9 patients remain in remission from their lymphoma at a median of 19 months after transplantation. Thus, patients with HIV-L on antiretroviral therapy can engraft following ASCT. Prolonged lymphoma remissions, without significant compromise of immune function, can be seen, suggesting that ASCT can be used in selected patients with HIV-L.     

Autologous stem cell transplantation in the treatment of adults with acute myeloid leukaemia

Most adult patients under 60 years with acute myeloid leukaemia (AML) who achieve a complete remission after induction chemotherapy will relapse if they do not receive further therapy. Consolidation treatment with autologous stem cell transplantation (SCT) is one option that has been studied extensively. High-dose cytotoxic therapy followed by autologous SCT or intensive cycles of chemotherapy furnish overall approximately similar probabilities of survival when applied in first remission. Here, we present a concise update regarding the place of autologous SCT in the treatment of AML. Particular issues discussed are the value of autologous SCT in different prognostic subsets of AML and the value of autologous mobilised peripheral blood stem cell transplants, which offer a much faster haematopoietic recovery.     

Autologous stem cell transplantation in lymphoma

High-dose therapy (HDT) followed by autologous transplantation of hematopoietic stem cells (ASCT) is frequently performed in patients with lymphoma. For many subentities, reliable results from prospective randomized studies are missing. In Hodgkin's disease (HD), HDT/ASCT is a standard indication for patients with chemosensitive first relapse. Patients with indolent or aggressive B-cell lymphoma may benefit from HDT/ASCT if considered as part of first-line therapy or at the time of relapse. However, new randomized studies comparing HDT/ASCT with optimal chemoimmunotherapy are necessary because the introduction of monoclonal antibodies (rituximab) significantly improved the results of conventional chemotherapy. Because data on patients with less frequent entities like mantle cell lymphoma, T-cell lymphoma, Burkitt's lymphoma, or lymphoblastic lymphoma are insufficient, the role of HDT/ASCT needs further study.     

Autologous stem cell transplantation: a possible treatment for refractory juvenile chronic arthritis?

OBJECTIVE: In adults, autologous stem cell transplantation (ASCT) has been described recently as a possible treatment for severe autoimmune disease refractory to conventional treatment. We report here the four first children with severe forms of juvenile chronic arthritis (JCA) treated with ASCT. METHODS: We studied three children with systemic JCA and one child with polyarticular JCA. Unprimed bone marrow was harvested 1 month prior to ASCT. T-cell depletion of the graft was performed with CD2 and CD3 antibodies. We used a preparative regimen of antithymocyte globulin (ATG; 20 mg/kg), cyclophosphamide (Cy; 200 mg/kg) and low-dose total body irradiation (TBI; 4 Gy). Methotrexate (MTX) and cyclosporin A (CsA) were stopped before ASCT; prednisone was tapered after 2 months. RESULTS: After ASCT, our patients showed an anti-inflammatory-drug-free follow-up of 6-18 months with a marked decrease in joint swelling, pain and morning stiffness. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and haemoglobin (Hb) returned to near-normal values within 6 weeks. Despite T-cell depletion, there was a very rapid immune reconstitution. Two patients developed a limited varicella zoster virus (VZV) eruption which was treated by acyclovir.     

Autologous stem cell transplantation in first-line treatment of high-risk aggressive non-Hodgkin's lymphoma

A single center, retrospective analysis evaluating the outcome of patients with poor-risk aggressive non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy and autologous stem cell transplantation (ASCT) as a part of firstline therapy. Forty-seven patients younger than 65 years with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL) or alk-negative anaplastic large cell lymphoma (ALCL) underwent ASCT between July 1997 and November 2005. Patients with DLBCL and alk-negative ALCL had 2 or 3 age-adjusted International Prognostic Index risk factors. All patients were transplanted after MACOP-B induction therapy followed by 2 courses of DHAP and myeloablative chemotherapy BEM or CBV. The complete response rate to the high-dose therapy was 79% with an estimated 5-year progression-free survival of 66%. At a median follow-up of 35 months (range, 16 to 112 months) the estimated overall survival at five years was 59%. There were 4 treatment-related deaths. Twenty-nine of 47 patients remain in complete remission. Our results confirm the efficacy of high-dose therapy with ASCT during first-line treatment of patients with poor-prognosis aggressive lymphoma, with substantial number of patients cured by using this treatment approach.     

自体骨髓干细胞移植治疗系统性红斑狼疮的临床研究

目的 探讨自体骨髓干细胞移植（ＡＢＭＳＣＴ）对系统性红斑狼疮（ＳＬＥ）的疗效。方法 采集自体骨髓移植ＣＤ３４＾＋造血干细胞,预处理用环磷酰胺（ＣＴＸ）６０ｍｇ／ｋｇ连续２天静滴,马法兰１４０ｍｇ／ｍ＾２分次口服,用格拉诺赛特（Ｇ－ＣＳＦ）刺激粒细胞的恢复,用间接免疫荧光法检测抗核抗体、放免法测抗ＤＮＡ抗体、流式细胞仪测淋巴细胞亚群,观察ＡＢＭＳＣＴ前后临床表现和免疫学指标的变化．结果 ＡＢＭＳＣＴ