Cytogenetic evolution following the transformation of myelodysplastic syndrome to acute myelogenous leukemia: implications on the overlap between the two diseases.

Cytogenetic evolution in the myelodysplastic syndrome (MDS) has been associated with an abrupt shift to acute myelogenous leukemia (AML). To investigate the 'evolution' of MDS to AML we compared the karyotypes of MDS patients at presentation and at development of AML. Of 170 patients with MDS who developed AML, 63 had banded karyotypes done at both time points. Fifteen patients had refractory anemia (RA) or RA with ringed sideroblasts (RARS), 27 had RA with excess blasts (RAEB), and 21 had RAEB in transformation (RAEBT). Patients had MDS for at least 12 weeks prior to developing AML. Thirty-one patients received cytotoxic therapy for MDS. Seventeen of 63 patients (27%) acquired a cytogenetic change when they developed AML. This percentage was significantly higher in RA/RARS patients compared to RAEB/RAEBT (53.3 vs. 18.8%, p < 0.01). Age, prior malignancy, cytotoxic therapy for MDS, and time to development of AML did not influence the probability of acquiring a cytogenetic change. The small number of patients did not allow testing for the effect of specific karyotypes on the incidence of cytogenetic change or the effect of this change on AML prognosis. The only recurring cytogenetic change was addition of chromosome 13 which occurred in four of 17 patients who changed. These data suggest that a cytogenetic change may be partly responsible for the transformation of RA/RARS, but not RAEB or RAEBT, to AML. This supports the concept that RAEB, RAEBT, and AML are different manifestations of the same disease, whereas RA/RARS are conditions that predispose to acute leukemia.