Hypodiploidy and 22q11 rearrangements at diagnosis are associated with poor prognosis in patients with multiple myeloma

Abstract

Summary.Our aim was to evaluate the clinical use of cytogenetic analysis as a prognostic factor in the outcome of newly diagnosed multiple myeloma (MM) patients. The present series includes 111 newly diagnosed MM patients treated with one of three standard-dose regimens or autologous transplantation over an 8-year time interval. As expected, the presence of an abnormal karyotype (39% of patients) correlated with poor prognosis (progression rate 63% v 47%, P ¼ 0 . 042), shorter event-free (EFS, P ¼ 0 . 014) and overall (OS, P ¼ 0 . 005) survival. Two distinct cytogenetic abnormalities were the most significant variables that influenced EFS and OS in the univariate analysis. The presence of hypodiploid karyotypes or rearrangements of band 22q11 were associated with higher progression rate (P ¼ 0 . 001) and shorter EFS (P < 0 . 024) and OS (P < 0 . 004). The median EFS and OS for patients with hypodiploidy was 4 and 7 months respectively. Multivariate analysis showed that absence of hypodiploidy was the most favourable prognostic variable for OS (P ¼ 0 . 022) followed by stage рIIA, serum calcium р2875 mmol/l, and absence of abnormalities 22q. The data suggest that the presence of hypodiploid karyotypes and rearrangements on 22q11 band show a higher progression rate and shorter survival in MM patients.

Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different diseases

“…However, 14 out of 18 patients with such involvement belonged to the hypodiploid group. The adverse significance of 11q implication was previously reported by Tricot et al 33,34 Conversely, in agreement with the results reported by Calasanz et al, 31 the present study did not confirm the poor outcome associated with partial or total deletion of chromosome 13. [33][34][35] The conflicting results could be explained by the fact that our correlations were established on a series including only abnormal karyo types, and that our patients received different treatment regimens while all the patients reported by Tricot et al 33 entered an identical intensive treatment program.…”

“…In such series, the number of normal karyotypes makes it difficult to demonstrate the prognostic value of any chromosomal pattern or individual defect. Poor response to therapy of hypodiploid patients vs other patients was first reported by Gould et al 18 and recently by Calasanz et al 31 Likewise, flow cytometry studies demonstrated a different outcome according to the DNA content: for Smith et al, 23 hypodiploid and biclonal myeloma did not respnd to chemotherapy. The biclonal pattern of these patients could correspond to the hypo and/or near-tetraploid karyotypes.…”

Early lymphocyte recovery predicts longer survival after autologous peripheral blood stem cell transplantation in multiple myeloma

“…22,23 The presence of chromosome 13 deletions and other chromosomal abnormalities is also associated with poorer survival. [24][25][26][27][28] Early ALC recovery after ASCT has been shown to be a prognostic factor for survival in patients with AML, breast cancer, Hodgkin's lymphoma, T/NK-cell lymphoma and primary systemic amyloidosis. 10,[12][13][14]16 Similar findings have been reported in MM, 11 but, to date, no studies have confirmed the survival benefits of early ALC recovery after ASCT in MM.…”

Ploidy, as detected by fluorescence in situ hybridization, defines different subgroups in multiple myeloma

“…[1][2][3][4][5][6][7] This cytogenetic classification is clinically valuable since patients with hyperdiploidy seem to present a better outcome than nonhyperdiploid patients. [7][8][9][10] However, this prognostic value has been demonstrated only in a few retrospective studies based on the analysis of karyotypes. Since cytogenetics is informative in only one-third of the patients, the prognostic significance of hyperdiploid vs nonhyperdiploid status in patients with uninformative karyotypes is not known.…”