Evaluation of the risk of therapy-related MDS/AML after autologous stem cell transplantation

A major complication of autologous stem cell transplantation (ASCT) is the development of therapy-related myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). This complication likely results from previous exposure of the autologous stem cells to chemotherapy as well as to the high doses of chemotherapy and radiation therapy that are used as part of the conditioning regimen. A number of centers are reporting that, second to disease relapse, therapy-related MDS and AML are, among the major causes of morbidity and mortality after ASCT. There is abundant evidence that therapy-related MDS and AML are clonal hemopathies that are the consequence of an acquired somatic mutation that confers a proliferative and/or survival advantage to hematopoietic progenitors. However, no single mutation or gene rearrangement is sufficient for the development of therapy-related AML, and the identification of a single gene rearrangement or point mutation may not necessarily be predictive of the development of therapy-related AML in the post-ASCT setting, a caveat that must be kept in mind when risk is assessed. There are at least 5 methods for assessing risk based on the presence of clonal abnormalities in hematopoietic cells, including standard cytogenetics, interphase fluorescence in situ hybridization, analysis for loss of hererozygosity, polymerase chain reaction for point mutations, and X-inactivation-based clonality assays. Each of these approaches has strengths and weaknesses that are discussed here in detail.