Therapy Related MDS

Therapy-related MDS (t-MDS) and AML (t-AML), have become among the most feared long-term complications of cancer therapy. The incidence of t-MDS and t-AML is increasing because of the widespread and successful use of chemora-diotherapy135 and high-dose therapy with autologous stem cell transplantation (ASCT).189

In contrast to primary MDS, most cases of t-MDS are difficult to classify according to FAB criteria. The bone marrow is often hypocellular and fibrotic and severe dysplastic changes are observed. In such cases bone marrow biopsy is important in establishing the diagnosis.190 Chromosomal abnormalities are found in 76 to 97 percent of cases.161 Deletions or loss of chromosomes 7 and 5 are commonly associated with exposure to alkylating agents and also seen in t-MDS/AML following ASCT,135,161,189 and balanced translocations involving chromosome bands 11q23 can occur after treatment with DNA topoi-somerase II inhibitors.123,191 It was thought that t-MDS was clinically separate from primary MDS; however, cytogenetic stratification suggests that the clinical course is more dependent on specific cytogenetic abnormalities than on the presence or absence of a history of toxic exposure.25,82,83 It is well known that patients with t-MDS are more likely to have karyotypic abnormalities that are associated with poor prognosis.136,163

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