TRANSPLANTATION FOR MYELODYSPLASIA AND MYELOFIBROSIS

骨髓增生异常和骨髓纤维化的移植

• 批准号: 6202257
• 负责人: FREDERICK APPLEBAUM
• 金额: $ 17.57万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6202257
• 关键词: age difference; antileukocyte isoantibody; artificial immunosuppression; blood disorder chemotherapy; bone marrow purging; bone marrow transplantation; busulfan; clinical research; combination chemotherapy; cyclophosphamide; dyserythropoietic anemia; graft versus host disease; histocompatibility typing; homologous transplantation; human subject; human therapy evaluation; myelofibrosis; radiation immunosuppression; relapse /recurrence; tissue /cell culture; transplant rejection

Allogeneic stem cell transplantation is the only known curative treatment for myelodysplasia (MDS). The disease is heterogeneous and our previous experience suggests that it is possible to adjust transplant approaches to specific clinical situations. In patients with less advanced MDS (that is, MDS without excess blasts) the risk of relapse after conventional transplant preparative regimens of cyclophosphamide (CY) and total body irradiation (TBI) or busulfan (BU) and CT is less than 5% and the major cause of failure is treatment-related fatality. In such patients undergoing human leukocyte antigen (HLA)-identical related donor transplantation, a regimen of CY-TBI with liver and lung shielding will be evaluated to estimate whether this approach can reduce treatment-related fatality without an increase in relapse. In patients with less advanced MDS undergoing unrelated donor transplantation, to retain sufficient immunosuppression while reducing toxicity of the cytotoxic component, a regimen of BU-CY with pharmacokinetic targeting of BU levels will be evaluated. In patients with advanced MDS (that is, MDS with excess blasts or chronic myelomonocytic leukemia) conventional preparative regimens result in high relapse rates and intensified preparative regimens such as BU-CY-TBI reduce relapse but increase toxicity. In such patients under age 56, we will test whether a regimen of BU-TBI retains the superior anti- tumor effect of BU-CY-TBI, but reduces toxicity. In older patients with advanced MDS, fatal toxicity of the transplant procedure is high and therefor the regimen of BU-CY with pharmacokinetic targeting of BU levels will be tested. Myelofibrosis is a related clonal myeloid disorder in which progressive fibrosis results in life-threatening cytopenias and organomegaly. Stem cell transplantation offers curative treatment to such patients but has rarely been attempted. The feasibility of allogeneic transplantation in patients with underlying myeloproliferative disorders associated with marrow fibrosis will be tested.

异基因干细胞移植是唯一已知的治愈性治疗方法 骨髓增生异常综合征（MDS）。 这种疾病是异质性的， 经验表明，有可能调整移植方法， 具体临床情况。 在不太晚期的MDS患者中（即， MDS无过量原始细胞）常规治疗后复发的风险 环磷酰胺（CY）和全身移植准备方案 照射（TBI）或白消安（BU）和CT小于5%， 失败的原因是治疗相关的死亡。 在此类患者中 接受人类白细胞抗原（HLA）相合的亲属供者 移植，CY-TBI与肝和肺屏蔽方案将 评估这种方法是否可以减少治疗相关的 而不会增加复发率。 在不太晚期的患者中 接受无关供体移植的MDS，以保留足够的 免疫抑制，同时降低细胞毒性组分的毒性， 以BU水平为药代动力学目标的BU-CY方案将 评估。 在晚期MDS（即原始细胞过多的MDS）患者中 或慢性粒单核细胞白血病）的常规制备方案 导致高复发率和强化的准备方案， BU-CY-TBI减少复发但增加毒性。 在这些未成年患者中， 56，我们将测试BU-TBI的方案是否保留了上级抗-TBI。 BU-CY-TBI的肿瘤作用，但降低了毒性。 老年患者 晚期MDS，移植程序的致命毒性高， 因此，具有BU水平的药代动力学靶向的BU-CY方案 会得到考验 骨髓纤维化是一种相关的克隆性骨髓疾病， 进行性纤维化导致危及生命的血细胞减少， 器官肥大 干细胞移植为这些疾病提供了治愈性治疗。 患者，但很少尝试。 同种异体移植的可行性 骨髓增生性疾病患者的移植 与骨髓纤维化相关的疾病。