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.
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