Intensive therapy for high-risk myelodysplastic syndromes and the biological significance of karyotype abnormalities.
Therapy for myelodysplastic syndromes (MDS) has been less than effective when based on low-dose treatment or supportive measures only, including hematopoietic growth factors. Recently, based on the percentage of bone marrow blasts, the number of cytopenic cell lines and cytogenetics, clinical risk groups have been defined more precisely. Recent studies applying intensive acute myeloid leukemia (AML)-type therapy to high-risk MDS have produced remissions ranging from 45 to 79%. Advances in the understanding of the biology of MDS clearly point to cytogenetics rather than morphologic subtype as being of prognostic relevance. Hence, new treatments need to be developed for patients with unfavorable karyotypes and complex abnormalities in particular. These MDS subtypes are characterized by low spontaneous proliferative activity and low autocrine production of hematopoietic growth factors. The subtypes are, however, highly sensitive to external stimulation by granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF). New therapies could emerge from these findings, for example, priming high-risk MDS patients with hematopoietic growth factors in combination with intensive AML-type treatment. Recent studies suggest that incorporating high-dose AraC into an intensive drug combination could further improve the outcome of high-risk MDS.
Hiddemann
W
W
Department of Hematology and Oncology, Georg-August-University, Göttingen, Germany.
Jahns-Streubel
G
G
Verbeek
W
W
Wörmann
B
B
Haase
D
D
Schoch
C
C
D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D003422:Critical Care; D006801:Humans; D007621:Karyotyping; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000628:therapy*; D011379:Prognosis; D012307:Risk Factors