The myelodysplastic syndromes: different evolution patterns based on sequential morphological and cytogenetic investigations

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Abstract
Serial morphological and cytogenetic investigations were performed in 46 patients with the myelodysplastic syndrome (MDS). Twenty-one patients (45.5%) progressed to AML [acute myeloid leukemia] (> 30% blasts in bone marrow smears). Based on sequential determinations of percentages of bone marrow blasts, 3 patterns of evolution were observed in MDS. Patients with evolution pattern A (48%) had an apparently stable disease with minimal or no increase in bone marrow blasts. Exceptionally they developed new or additional chromosomal anomalies during the course of their disease. Cases in this group, who showed no abnormal localization of immature myleloid precursors (ALIP) at time of diagnosis experienced prolonged survival (median: 43 mo.), while ALIP positive patients had shorter survival times (median: 14 mo.), with high probability of early death from infections and/or bleeding problems. Patients with evolution pattern B (28%) initially had a morphologically stable disase, comparable to cases with evolution pattern A, but showed an aburpt shift from MDS to AML. Most of these patients (82%) were ALIP positive and a substantial proportion (46%) showed karyotype anomalies at diagnosis. The abrupt shift to AML in these patients was frequently (61.5%) associated with additional cytogenetic anomalies. Patients with evolution pattern C (24%) showed a gradual increase in bovine marrow blasts. The majority of these cases (8/11) ultimately developed AML (gradual progression to AML), whereas some patients (3/11) died from infections and/or hemorrhagic complications before they had reached the level of clinical AML. All of these patients were ALIP positive at diagnosis and no additional cytogenetic alterations occurred during evolution. Acquisition of new karyotypic anomalies during the course of MDS was almost invariably associated with abrupt shift to AML. Evolution in MDS shows 2 important aspects, which seem to be preponderant in determining the course and outcome of the disease: one is the proliferative capacity and resulting growth advantage of the neoplastic clone over normal hematopoiesis, as measured by increasing percentages of bone marrow blasts in sequential aspirates; the other one is instability of the clone. Unstable clones have a high propensity to further intraclonal changes; they are expressed morphologically by the abrupt increase in bone marrow blasts and cytogenetically by the acquisition of new or additional karyotype anomalies. In this concept, patients with evolutionary pattern A have stable clones with low proliferative capacities, patients with unstable clones, but having low proliferative capacities, show evolutionary pattern B: evolutionary pattern C is characterized by stable clones with pronounced proliferative capacities. Evolutionary pattern D should be characterized by unstable clones, showing pronounced proliferative capacities. Although the latter evolutionary pattern was not enocountered, patients with therapy-related MDS may frequently show such type of evolution.