Background: Myelodysplastic syndromes (MDS) are acquired hematopoietic stem cell disorders characterized by ineffective hematopoiesis, cellular dysfunction and an increased risk of transformation into acute myeloid leukemia (AML). One of the hallmarks of MDS is their prognostic heterogeneity which complicates therapeutic decisions. Therapeutic decisions are further hampered by the advanced age of most patients and the problem of attendant comorbidities. With the exception of allogeneic stem cell transplantation, no treatment modality has been proven to be of benefit over supportive care. The purpose of this review is to summarize the diagnostic work-up as well as current approaches to the treatment of MDS.
Diagnosis and risk stratification: The diagnosis of MDS is based on routine laboratory and peripheral blood evaluation. Bone marrow examination along with cytogenetic analyses are required for confirming und classifying MDS according to FAB or WHO proposals as well as performing a risk analysis according to the International Prognostic Scoring System (IPSS) which distinguishes four risk groups with different life expectancies and AML incidences.
Therapeutic strategies: Supportive treatment remains the mainstay of therapy, but does not alter the natural course of MDS. The only curative treatment of MDS is allogeneic stem cell transplantation which can be performed in high-risk patients up to an age of 60 years. The disease-free survival varies between 29% and 40% at 6-7 years after transplant. Unfavorable prognostic factors of survival in allogeneic stem cell transplantation are older age, advanced MDS stage, high-risk cytogenetics, high IPSS score and marrow fibrosis. For patients with high-risk MDS younger than 40 years, a matched unrelated donor transplant should be considered. AML-type chemotherapy is increasingly used in younger patients with high-risk MDS and yields complete remission rates between 45% and 79%. Despite high relapse rates, combination chemotherapy offers a chance of long-term remission for selected patients. For patients without HLA-matched allogeneic sibling donor, autologous stem cell transplantation may be used as consolidation therapy after successful conventional induction chemotherapy. For older patients with high-risk MDS in whom aggressive chemotherapy is contraindicated, intravenous treatment with 5-azacytidine and 5-aza-2'-deoxycytidine (decitabine) or oral treatment with low-dose melphalan are promising new treatment options which yielded overall response rates of 40-63%. Based on new insights into the pathobiology of MDS, additional treatment approaches have been developed in recent years including differentiation therapy with hematopoietic growth factors and retinoids, immunosuppressive therapy with antithymocyte globulin or cyclosporine, cytokine inhibition by amifostine, pentoxifylline or soluble TNF-alpha receptor as well as angiogenesis inhibition by thalidomide.
Conclusion: Increased understanding of the natural course and pathophysiology of MDS has resulted in several new treatment approaches which must be further evaluated in appropriate clinical trials. In Germany, such trials are performed and coordinated by the German MDS Study Group which is part of the program "Kompetenznetzwerk Akute und Chronische Läukemien".