高危急性髓系白血病异基因造血干细胞移植后复发的防治

急性髓系白血病（AML）是一组高度异质性的克隆性疾病,化学药物治疗和造血干细胞移植均为治疗AML的方法。对于高危AML患者而言,异基因造血干细胞移植为治疗该疾病的有效手段,但部分AML患者造血干细胞移植后仍可能面临疾病复发的问题,大多数复发患者再行化学药物治疗、二次移植等的效果不佳,是导致患者异基因造血干细胞移植后死亡的主要原因。因此,加强对异基因造血干细胞移植后AML患者的随访,并采取一些合适的手段预防移植后复发显得尤为重要。本文就高危AML患者异基因造血干细胞移植后复发的监测、药物治疗和细胞治疗进行综述,以期为改善高危AML患者异基因造血干细胞移植预后提供参考。     

世界首例胎盘脐血干细胞联合移植成功北大核心CSCD

日前,从解放军第三O七医院获悉,经过16个月的术后观察,由该院造血干细胞移植科主任陈虎团队领衔开展的世界首例胎盘联合脐带血造血干细胞移植治疗重型再生障碍性贫血获得成功。目前,患儿造血功能恢复正常,情况稳定。     

福达拉滨、环磷酰胺、美罗华方案进行预处理的非清髓性异基因干细胞移植治疗复发的滤泡性淋巴瘤

异基因造血干细胞移植是治疗滤泡性淋巴瘤的有效方法,大量研究显示接受异基因造血干细胞移植患者的复发率显著低于接受自体造血干细胞移植的患者.非清髓性异基因造血干细胞移植利用其移植物抗淋巴瘤的免疫作用以达到治疗滤泡性淋巴瘤的目的,但是此策略长期的疗效和毒性仍不明确.本项前瞻性研究分析并评价了非清髓性异基因干细胞移植治疗复发的滤泡性淋巴瘤的8年经验.     

造血干细胞移植后EB病毒相关性淋巴增殖性疾病一例分析

目的研究异基因造血干细胞移植后EB病毒（EBV）相关性淋巴增殖性疾病（EBV—PTLD）的早期诊断和治疗措施。方法1例16岁极重型再生障碍性贫血患者在用环磷酰胺、兔抗人胸腺细胞球蛋白和甲泼尼龙（CY／ATG／MP）预处理后行HLA 1/6位点不合的同胞异基因造血干细胞移植。结果移植后72d发生EBV-PTLD。经及时停用环孢素A（CSA），同时加用丙种球蛋白、α-干扰素及MP治疗，患者病情好转。结论PTLD为造血干细胞移植和实体器官移植后一种少见但致命的并发症，高危患者应注意监测EBV—DNA变化、早期诊断、及时减少或停用免疫抑制剂尤为重要。     

异基因造血干细胞移植治疗慢性活动性EB病毒感染患者的护理

目的总结异基因造血干细胞移植治疗成人慢性活动性EB病毒感染的护理经验。方法回顾性分析7例成人慢性活动性EB病毒感染患者异基因造血干细胞移植的治疗及护理方法。结果 5例患者获得完全缓解,2例死亡。结论慢性活动性EB病毒感染患者病情严重,治疗难度大且预后不佳,异基因造血干细胞移植可改善患者预后。做好患者治疗期间的情绪管理、症状管理及并发症防护是护理的关键。     

自体骨髓间充质干细胞与造血干细胞共移植治疗恶性血液病患者的护理

目的探讨自体骨髓间充质干细胞（MSCs）与造血干细胞共移植治疗恶性血液病患者的护理。方法从无骨髓浸润的恶性血液病患者本人骨髓中分离、培养间充质干细胞,经放化疗等预处理后。与造血干细胞共移植治疗恶性血液病患者5例。并对其进行全程共移植护理。结果在移植过程中5例患者均未出现感染,无移植并发症。自体骨髓间充质干细胞和造血干细胞输注过程中未见明显不良反应。移植后造血功能恢复,中性粒细胞≥0．5×10^9／L的中位时间为9．4（8～11）d,血小板≥20×10^9／L的中住时间为12．2（10～14）d。结论自体骨髓间充质干细胞与造血干细胞共移植治疗恶性血液病安全性好,不良反应小;做好移植护理是减少感染和并发症的重要措施。     

自体骨髓间充质干细胞与造血干细胞共移植治疗恶性血液病患者的护理

目的 探讨自体骨髓间充质干细胞(MSCs)与造血干细胞共移植治疗恶性血液病患者的护理.方法 从无骨髓浸润的恶性血液病患者本人骨髓中分离、培养间充质干细胞.经放化疗等预处理后,与造血干细胞共移植治疗恶性血液病患者5例,并对其进行全程共移植护理.结果 在移植过程中5例患者均未出现感染,无移植并发症.自体骨髓间充质干细胞和造血干细胞输注过程中未见明显不良反应.移植后造血功能恢复,中性粒细胞≥0.5×109/L的中位时间为9.4(8～11)d,血小板≥20×109/L的中位时间为12.2(10～14)d.结论 自体骨髓闻充质干细胞与适血干细胞共移植治疗恶性血液病安全性好,不良反应小;做好移植护理是减少感染和并发症的重要措施.     

造血干细胞移植治疗多发性骨髓瘤(附视频)

自体造血干细胞移植治疗多发性骨髓瘤(MM)始于20世纪80年代。多个历史对照和随机临床研究显示自体造血干细胞移植较传统化疗可提高治疗的反应率、完全缓解率、无事件存活率和/或总存活率,而治疗反应程度与生存相关。由此自体造血干细胞移植在欧美国家已成为年轻、适合移植(年龄≤65岁、肾功能正常和一般状况良好)MM患者的一线标准治疗方法。双次移植有可能进一步提高治疗反应率、无事件存活率和/或总存活率。免疫调节药物沙利度胺及其衍生物来那度胺和蛋白酶体抑制剂硼替佐米等新型抗骨髓瘤药物的发展提高了治疗的反应率和缓解率。目前新药并不能替代自体造血干细胞移植;这些药物运用于移植前后的整体治疗策略进一步提高了移植疗效。尽管如此,MM仍然是难以治愈的疾病。异基因造血干细胞移植有治愈MM的可能,但因清髓性预处理的高死亡率限制了其应用。近年来,联合移植即自体造血干细胞移植后进行减低剂量预处理的异基因造血干细胞移植的研究结果初步显示了其疗效和可行性。     

自体造血干细胞移植治疗1型糖尿病患者的护理

对8例1型糖尿病患者行自体造血干细胞移植治疗．包括CTX方案外周血造血干细胞的动员、干细胞的采集、CTX加ATG方案预处理及干细胞回输4个过程。结果8例1型糖尿病患者移植术后造血功能重建．步行出仓转内分泌科继续监测血糖。提示自体外周血干细胞移植治疗1型糖尿病是一种治疗与免疫有关的1型糖尿病的新方法，做好心理护理、严格执行无菌操作、加强基础护理、预防感染、密切观察病情变化是治疗成功的根本保证。     

造血干细胞移植术后生物学行为的影响

一、造血干细胞简介造血干细胞移植技术飞速进展,已成为当今治愈多种良、恶性血液病与遗传性疾病的重要手段［1］,受益病种还在不断扩大。但是,这种治疗方式对于患者来说仍然具有高风险及高死亡率［2］。国内外相关研究已经证实,在其他癌症人群中,心理因素、免疫功能和临床结果之间有着显著的相关性,但对于接受造血干细胞移植的血液病患者尚无相关的研究报道,这类特殊人群的生物学行为是否与疾病有一定的相关性,能否在预防感染、减轻移植物抗宿主病反应、消除恶性细胞及免疫恢复调节过程中能否起到关键作用,从而降低患者的病死率尚不清楚。国外研究表明,造血干细胞移植后的生物学干预可能会影响移植后的免疫功能状态,造血干细胞移植后的恢复早期可能是进行生物学行为干预的一个窗口期,可能会影响造血干细胞移植患者的生存状态及生活质量［3］。造血干细胞移植治疗过程中实施的一系列方法都是科学及严谨的,但这种治疗方法依然存在着很高的复发率和死亡率。心理神经免疫学研究已广泛应用于其他癌症人群,但对于接受造血干细胞移植的患者却鲜有报道,及时的免疫调节可能在降低发病率、减少并发症及预防复发方面有重要作用。     

亲缘全相合HSCT与强化免疫抑制治疗再生障碍性贫血的疗效比较

目的 对比分析重型再生障碍性贫血(SAA)患者行亲缘全相合造血干细胞移植( HSCT)和强化免疫抑制治疗(IST)的效果.方法 2008年1月至2010年12月新入院并诊断为SAA者41例,其中14例行亲缘全相合HSCT,27例接受以抗胸腺细胞球蛋白(ATG)+环孢素A(CsA)为基础的IST.结果 行亲缘全相合HSCT的14例全部植活,治疗有效率100％,中位随访14个月,患者均无病存活;接受IST的27例中位随访16个月,其中21例治疗有效(77.8％),6例治疗无效,2例死亡,患者脱离输血的中位时间为132 d.接受IST者的治疗有效率、存活率和死亡率与接受亲缘全相合HSCT者相比较,差异有统计学意义(P＜0.01).结论 亲缘全相合HSCT治疗SAA的效果令人满意,优于IST.     

Bone marrow transplantation--present status.

In the short space of the last 10 years, marrow transplantation has become a reasonable treatment option for persons with severe aplastic anemia. It has not as yet convincingly established itself in the treatment of leukemia and other malignancies but shows promise with new approaches. Many of the immunologic problems generic to bone marrow transplantation have been identified, and solutions are actively being pursued in the clinic and at the laboratory bench. As solutions to some of the present-day obstacles to the full therapeutic potential of bone marrow transplantation are met, we should see, in the next 10 years, a wider application of this therapy to various hematologic and malignant disorders.     

Severe aplastic anemia associated with chronic mucocutaneous candidiasis. Immunologic and hematologic reconstitution after allogeneic bone marrow transplantation

Chronic mucocutaneous candidiasis (CMC) is typically associated with the inability of T lymphocytes to proliferate and produce lymphokines in response to Candida antigen. A 7-year-old girl with CMC developed severe aplastic anemia and, after conditioning with cyclophosphamide, 200 mg/kg, underwent bone marrow transplantation from her HLA-identical sister. Engraftment was prompt and complete. The patient is surviving more than 3 years after transplantation with normal donor-derived hemopoiesis and immune function. Manifestations of CMC have resolved completely and she has not received antifungal therapy for more than 2 years.     

Double bone marrow transplantation for severe aplastic anemia after orthotopic liver transplantation: implications for clinical management and immune tolerance

A 2-year-old boy underwent liver transplantation for fulminant hepatic failure of unknown cause. Four months later the child developed severe aplastic anemia. Allogeneic bone marrow transplantation (BMT) was performed using marrow from his 14-month-old HLA-identical sister. Severe aplastic anemia recurred 2.5 months later. After reconditioning a second BMT was performed using the same donor. Tapering of immunosuppression 2 years after BMT led to biopsy-confirmed rejection of the liver. Therapy with high-dose corticosteroids and an increase in cyclosporine A medication readily reversed rejection and a low-dose immunosuppression reflected by cyclosporine trough levels less than 50 ng/ml has been maintained since. Eight years later the boy is in excellent health with both bone marrow and liver functioning perfectly. In summary, this case demonstrates that even recurrent severe aplastic anemia after OLT can be cured by BMT, and that a transplanted liver can tolerate a double conditioning regimen without problems. Tolerance towards the liver through BMT did not develop.     

Allogeneic stem cell transplantation

Allogeneic stem cell transplantation (HSCT) requires the harvest of an adequate number of stem cells (SC) from a histocompatible donor and their infusion into a patient following a conditioning regimen. During the past 35 years, the role of HSCT has changed from an experimental procedure for terminally ill patients to a curative treatment. In 2003, 1170 procedures were registered in Italy (Italian Group for Blood and Marrow Transplantation). The main reported indications were as follows: leukemia, lymphoproliferative diseases, myelodysplasia, and nonmalignant diseases such as thalassemia and severe aplastic anemia. Important changes have been observed in the last 5 years: the shift from bone marrow to peripheral blood as the SC source, the increasing number of alternative donors such as unrelated, partially matched family donors and cord blood SC, and the new extra-hematological indications including solid tumors. Moreover, the development of nonmyeloablative conditioning regimens have allowed physicians to perform HSCT in patients with advanced age or important comorbidities. In contrast, the availability of the Tyrosine kinase inhibitor (STI-571) for treatment of patients affected by chronic myelogenous leukemia, which was formerly the main indication for HSCT, has produced a dramatic decrease in the number of transplantations in this setting. HSCT performed in the early phases of disease and in young patients offers more than a 50% cure rate. The transplant-related mortality still represents the greatest obstacle, ranging from 20%-30%, despite the less toxic conditioning regimens, high-resolution HLA typing, and better supportive care. GvHD and infections remain the main causes of morbidity. As regards relapses, they correlate with disease status at the time of transplantation. Promising results have been recently obtained with haploidentical and with cord blood SC transplantation also in adult patients.     

Bone marrow transplantation. Overview and personal results]

Main indications for allogeneic bone marrow transplantation are severe aplastic anemia, severe combined immunodeficiency, acute leukemia and chronic myeloid leukemia. In standard risk situations survival rates are 50 to 80%. The probability of disease-free survival after bone marrow transplantation is depending on the stage of disease. If possible bone marrow transplantation should be performed early, not in advanced disease when conventional measures failed. Main problems are therapy-related organ toxicity, rejection, graft-versus-host disease and a long lasting risk of infection. Usually histocompatible relatives of the patients are selected as marrow donors. Bone marrow transplantation using unrelated donors is under investigation. Autologous transplantations with cryopreserved marrow are performed in acute leukemia, malignant lymphomas and some solid tumors, but prospective studies comparing transplantation and conventional therapeutic procedures are still missing.     

Mixed bone marrow or mixed stem cell transplantation for prevention or treatment of lupus-like diseases in mice

Scientific analyses fortified by interpretations of immunodeficiency diseases as 'experiments of nature' have revealed the specific immune systems to be comprised of T cells subserving cell-mediated immunities plus B cells and plasma cells which produce and secrete antibodies. These two separate cellular systems regularly interact with each other to produce a coordinated defense which permits mammals to live within a sea of microorganisms that threaten the integrity and the survival of individuals. We have shown that bone marrow transplantation (BMT) can be used as a form of cellular engineering to construct or reconstruct the immune systems and cure otherwise fatal severe combined immunodeficiency. When severe aplastic anemia complicated the first BMT which was performed to cure a fatal severe combined immunodeficiency, a second BMT cured for the first time a complicating severe aplastic anemia. Subsequently, BMT has been used effectively to treat some 75 otherwise fatal diseases such as resistant leukemias, lymphomas, inborn errors of metabolism, and genetic anomalies of the hematopoietic development such as sickle cell anemia, thalassemia, congenital neutropenias, and many other diseases. More recently, we have employed BMT in mice both to cure and cause autoimmunities, and, together, these experiments showed that autoimmunities actually reside in the hematopoietic stem cells. We have also found that mixed BMT or mixed hematopoietic stem cell transplantation (HSCT) can be used to prevent and cure the most complex autoimmunities such as those occurring in BXSB mice and in (NZW x BXSB)F1 W/BF1 mice. Untreated, the former develop fulminating lethal glomerulonephritis plus numerous humoral autoimmunities. Mice of the (W/B)F1 strain develop autoimmune thrombocytopenic purpura, coronary vascular disease with myocardial infarction, glomerulonephritis, and numerous autoantibodies. All of these abnormalities are prevented or cured by mixed syngeneic (autoimmune) plus allogeneic (normal healthy) BMT or mixed peripheral blood HSCT. Thus, the most complex autoimmune diseases can be prevented or cured in experimental animals by mixed syngeneic plus allogeneic BMT or HSCT which produce stable mixed chimerism as a form of cellular engineering.     

Allogeneic bone marrow transplantation in aplastic anemia--report of 25 cases.

Bone marrow transplantation using an HLA-MLC-identical sibling is the most valuable treatment of severe aplastic anemia.2,6,7 Between November 1973 and March 1977, 25 consecutive patients have been treated by marrow transplantation in our unit. Nine patients are alive with complete hematologic restoration between 3 months and 3 years. The high mortality can be largely accounted for by marrow graft rejection (14 patients). Despite the small number of patients, we have tried to identify prognostic factors associated with marrow graft rejection. They are mainly the existence of anti-HLA antibodies, the sex difference, and the normal PHA and MLC response before grafting. After the graft, the disappearance of anti-HLA antibodies has a good prognostic value. The appearance of autolymphocytotoxins seems to correlate strongly either with rejection or graft-versus-host disease.     

Bone marrow transplantation for severe aplastic anemia. Effect of a preparative regimen of cyclophosphamide-low-dose total-lymphoid irradiation and posttransplant cyclosporine-methotrexate therapy

Twenty-nine patients with severe aplastic anemia were entered into a study of pre- and posttransplant immunosuppressive therapy for bone marrow transplantation. Four of twenty-five previously transfused recipients prepared with cyclophosphamide 200 mg/kg and total-lymphoid irradiation 3 Gy experienced graft failure, indicating that this regimen was inadequate to ensure sustained engraftment. Posttransplant treatment with cyclosporine and methotrexate resulted in an actuarial incidence for grade greater than or equal to 2 graft-versus-host disease of 22 +/- 16%. Actuarial survival was 78 +/- 15%. These data indicate that more effective treatment is necessary to prevent graft failure, but since many patients can be successfully retransplanted, overall survival is comparable to other recent studies.