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Myelodysplastic syndromes (MDS) constitute a heterogenous group of acquired bone marrow disorders characterized by ineffective hematopoiesis, cellular dysfunction and an increased risk of transformation into acute myeloid leukemia (AML). The percentage of medullary blast cells and the karyotype at diagnosis are the most important predictors of survival. Patients with more than 10% blast cells or an unfavourable karyotype (chromosome 7 abnormalities or complex aberrations) usually survive less than 12 months. This review article focuses on the roles of intensive AML-type chemotherapy, autologous stem cell transplantation and allogeneic bone marrow transplantation in the management of patients with advanced MDS. Recent studies suggest that, with appropriate selection of patients, intensive chemotherapy produces high rates of complete remission. Chances of entering remission are particularly high in patients with a good Karnofsky score, bone marrow blast count < 30% and normal karyotype. When compared with acute myeloid leukemia, results of autologous bone marrow transplantation in MDS are disappointing. A major disadvantage of this approach is the delayed recovery of hematopoiesis. Autologous peripheral blood progenitor cell transplantation overcomes this difficulty and is currently explored as consolidation therapy after successful remission induction with polychemotherapy in an intergroup study of the EORTC and EBMT. Allogeneic bone marrow transplantation remains the treatment of choice for younger MDS patients, offering a good chance of cure if the transplantation is performed at an early stage of disease or if the patient receives the transplant in complete remission after conventional chemotherapy.

For patients younger than 60 years with multiple myeloma in a stage requiring chemotherapy high dose chemotherapy followed by autologous blood stem cell transplantation appears to be the best therapeutic option. Conditioning regimens resulting in a high proportion of patients with 90% tumor reduction (very good partial or complete remissions) should be preferred. A good quality of remission is a prerequisite for prolonging the disease free survival. World-wide the tandem high dose melphalan protocol developed by Barlogie and coworkers is deemed the most effective conditioning regimen. A pilot study in our clinic with an intensified high dose regimen combining idarubicin, melphalan and cyclophosphamide showed similar remission rates. The application of peripheral blood stem cells reduces the treatment related mortality to less than 10%. It is expected that more than 50% of patients treated with high dose chemotherapy and autologous peripheral blood stem cell transplantation will survive at least 5 years. Therefore, the prognosis of such patients is significantly improved compared with patients treated with conventional chemotherapy. Treatment related mortality after allogeneic blood stem cell transplantation is about 40%. Therefore, during the first 2 to 3 years after transplantation the prognosis of patients after allogeneic transplantation is inferior to that of patients receiving autologous transplants. Subsequently, patients with allogeneic transplants do better, because the relapse rate after allogeneic transplantation is decreased and some patients may achieve long term remissions or even cures. Therefore, we recommend allogneic blood stem cell transplantation for patients younger than 50 years if an HLA-identical sibling donor is available and there are no contraindications. For patients older than 60 years the Alexanian protocol is still the therapeutic standard. On the other hand, successful application of high dose chemotherapy and autologous blood stem cell transplantation in patients of this age group has been reported. Therefore, clinical trials are required to clarify whether the prognosis of patients older than 60 years can be improved with treatment strategies including high dose chemotherapy.

There is experimental evidence for recombinant human granulocyte colony-stimulating factor (rhG-CSF)-induced stimulation of hemostaseologic parameters including platelets. Using the closure time of the in vitro bleeding test (IVBT, Thrombostat 4000, VDG, Seeon) and different hemostaseologic parameters, our results are suggestive of a directly or indirectly induced in vivo stimulation of platelets following rhG-CSF stimulation in healthy stem cell donors. According to the negative transcranial Doppler microembolic monitoring of the middle cerebral artery, there is no evidence for clinically silent cerebral microembolism supporting a prothrombotic state facilitating the formation of arterial thrombi with subsequent cerebral embolization.