TRANSPLANTATION FOR MYELODYSPLASIA AND MYELOFIBROSIS

异基因干细胞移植是唯一已知的治愈方法。 用于骨髓发育不良(MDS)。这种疾病是异质性的，我们以前的 经验表明，调整移植方法是可能的 具体的临床情况。在患有较不严重的MDS的患者中(即， 无过量爆炸的MDS)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<5%，主要 失败的原因是与治疗相关的死亡。在这样的病人中 接受人类白细胞抗原(HL A)相合的亲缘供者 移植后，肝肺屏蔽的CY-TBI方案将被 评估此方法是否可以减少与治疗相关的 致命性而不增加复发率。在不太晚期的患者中 接受无血缘关系供者移植的MDS，以保留足够的 免疫抑制，同时降低细胞毒成分的毒性， 以BU水平为靶点的BU-CY方案将是 已评估。在患有晚期MDS(即，MDS伴有过度爆炸)的患者中 或慢性粒单核细胞白血病)常规制备方案 导致高复发率和强化的准备方案，如 BU-CY-TBI可减少复发，但增加毒性。在这类未成年患者中 56，我们将测试一种BU-TBI方案是否保留了优越的抗- BU-CY-TBI的肿瘤效应，但毒性降低。在老年患者中， 晚期MDS，移植手术的致命性毒性高 BU-CY血药动学靶向方案的研究 将会受到考验。骨髓纤维化是一种与克隆性髓系疾病相关的 进行性纤维化会导致危及生命的细胞减少症和 器官性的。干细胞移植为此类疾病提供了根治疗法 患者，但很少有人尝试。同种异体移植的可行性 骨髓增生性疾病患者的移植治疗 将对与骨髓纤维化相关的疾病进行检测。

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.