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

Abstract

Serial morphological and cytogenetic investigations were performed in 46 patients with the myelodysplastic syndrome (MDS). Twenty-one patients (45.5%) progressed to AML (greater than 30% blasts in bone marrow smears). Based on sequential determinations of percentages of bone marrow blasts, three 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 myeloid precursors (ALIP) at time of diagnosis experienced prolonged survival (median: 43 months), while ALIP positive patients had shorter survival times (median: 14 months), with high probability of early death from infections and/or bleeding problems. Patients with evolution pattern B (28%) initially had a morphologically stable disease, comparable to cases with evolution pattern A, but showed an abrupt 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 bone marrow blasts. The majority of these cases (8/11) ultimately developed acute myeloid leukaemia (gradual progression to AML), whereas some patients (3/11) died from infections and/or haemorrhagic 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. From this retrospective study we conclude that evolution in MDS shows two 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 haematopoiesis, 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.(ABSTRACT TRUNCATED AT 400 WORDS)

Incidence and prognostic significance of karyotype abnormalities in de novo primary myelodysplastic syndromes: a study on 331 patients from a single institution

“…Numerous reports have demonstrated that MDS karyotype abnormalities significantly affect OS and the risk of MDS/AML progression, [6][7][8][9][10][11][12][13][14][15][18][19][20][21][22][23][24][25][26] even in patients undergoing intensive chemotherapies. 27,28 Therefore, in 1997 the IPSS 15 grouped MDS patients (either untreated or submitted to low-dose chemotherapy or growth factors only) into three prognostically different cytogenetic categories and included the chromosome pattern in a new scoring system which has been validated by various reports.…”

“…[3][4][5][6][7][8][9][10][11][12][13][14][15][18][19][20][21][22][23][24][25][26] Chromosome defects were more common in RAEB and RAEB-t than in RARS and RA. Deletions or gains of entire chromosomes had an incidence of 60.4% and translocations of only 1.8%.…”

“…[3][4][5] In addition, in the 1980s, various studies have demonstrated the prognostic relevance of chromosome abnormalities. [6][7][8][9] Following the FAB classification, five scoring systems based on clinical and laboratory findings have been developed in order to better define overall survival (OS) and the time to MDS/AML progression (PFI) in MDS patients. [10][11][12][13][14] Among these systems two recognize the prognostic value of chromosome defects.…”

Clonal development of myeloproliferative disorders: clues to hematopoietic differentiation and multistep pathogenesis of cancer

“…Acquired chromosomal abnormalities are found in approximately 33-66% of patients with MDS. 85,86 Analysis of G6PD and cytogenetics strongly suggested that a multipotent progenitor was involved in sideroblastic anemia in two patients. 87,88 In addition to marrow cells, erythrocyte, granulocytes and platelets, 21 of 24 EBV-transformed lymphoid lines from one of these patients displayed the same G6PD type.…”

A case of myelodysplastic syndrome developed blastic crisis of chronic myelogenous leukemia with acquisition of major BCR/ABL

“…Transformation to AML is a frequent event in MDS, in which cytogenetic evolution is assumed to play a role [1,3,12]. We describe a patient who presented with MDS (RAEB) and subsequently developed Ph positive CML in the chronic phase then evolved rapidly to the blastic phase.…”