Cytogenetic features of multiple myeloma: impact of gender, age, disease phase, culture time, and cytokine stimulation.
ABSTRACT Relatively little is known about the cytogenetic features of multiple myeloma (MM) when compared to other hematologic malignancies. The reasons for this are most likely manifold, and include a low mitotic index of the malignant cells and the presence of cytogenetically cryptic abnormalities as well as of complex karyotypes with poor chromosome morphology. In the present study, we have investigated whether various culture conditions may influence the yield of abnormal metaphases in MM and, in the related plasma cell dyscrasias, monoclonal gammopathy of undetermined significance (MGUS) and plasmacytomas (PC). In addition, the possible impact of age, gender, and disease phase on the cytogenetic features has been analyzed. A total of 95 samples from 74 cases (68 MM, three PC, and three MGUS patients) were obtained for cytogenetic analysis. The samples were cultured either in conventional medium or in medium containing IL-6 and GM-CSF, and the culture times varied from 24 to 120 h. In total, 186 cultures were analyzed. Metaphase fluorescence in situ hybridization analysis using probes specific for 14q32, i.e. IGH rearrangements, could be performed in 57 of the 74 cases, and revealed 14q32 aberrations in 10 cases not seen by conventional G-banding. Abnormal karyotypes were detected in 77 (41%) of the 186 cultures, 46 (48%) of the 95 samples, and in 41 (55%) of the 74 patients, revealing a total of 20 chromosomal aberrations previously not reported in plasma cell dyscrasias. We found no evidence that gender, age, disease phase, culture time, or cytokine stimulation significantly influences the karyotypic features of MM.
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ABSTRACT: Several trials have shown the superior impact of high-dose melphalan (usually 200 mg/m(2), MEL200) vs standard therapy in myeloma patients. Intermediate-dose melphalan (100 mg/m(2), MEL100) is also superior to the standard dose, but has not been clinically compared with MEL200. A total of 90 patients at diagnosis were treated with two MEL100 courses. Their clinical outcome was compared with that of a control group of 90 pair mates matched for serum beta2-microglobulin levels and Durie and Salmon clinical stage. These patients were treated at diagnosis with two MEL200 courses. Patient characteristics were similar in both groups except that the median age of the MEL100 group was significantly higher (P<0.0001). Complete remission was 35% after MEL100 and 48% after MEL200 (P=0.08). Median event-free survival (EFS) was 32 months in the MEL100 group and 42 months in the MEL200 group (P<0.005), but overall survival (OS) was not different. Transplant-related mortality was not significantly different. Haematological and extra-haematological toxicity was significantly reduced after MEL100. Despite the significant age difference, tandem MEL100 was less toxic than tandem MEL200, and MEL100 was inferior to MEL200 in terms of EFS but not in terms of OS. The intensified nonmyeloablative MEL100 regimen is an effective first-line treatment.Leukemia 01/2004; 18(1):133-8. DOI:10.1038/sj.leu.2403196 · 9.38 Impact Factor
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ABSTRACT: BACKGROUND:: Cytogenetic alterations in patients with multiple myeloma (MM) represent important risk factors in terms of prognosis. In this study, the impact of the cytogenetic aberrations of MM on patient clinical features and outcome was investigated. METHODS:: Conventional cytogenetic analysis with R-banding technique and molecular cytogenetic characterization by interphase fluorescence in situ hybridization (FISH) were used to detect aberrant chromosomal arrangements, including 17p13 and 13q14 deletions, 14q32 rearrangement and 1q21 amplification, in bone marrow nucleated cells from 65 patients. RESULTS:: About 16.9% of patients showed aberrations by conventional cytogenetic analysis, whereas 49.2% of patients showed aberrations by interphase FISH analysis. Abnormalities of 13q14, 1q21, 14q32 and 17p13 were detected in 27.7%, 13.8%, 16.9% and 29.2%, respectively. Patients with a 13q14 deletion or combined with 17p13 deletion frequently had a late stage of the disease, and tended to have elevated serum levels of β2 microglobulin and lower levels of albumin. The progression-free survival and overall survival of FISH-positive patients were lower than for those without detectable abnormalities, especially in the conventional chemotherapy arm. CONCLUSIONS:: These findings demonstrate that myeloma cells are prone to exhibiting a complex aberration and that FISH is superior to conventional cytogenetic analysis with a higher detection rate of chromosomal abnormalities. Patients with a 17p13 or 13q14 deletion, 14q32 rearrangement and 1q21 amplification were more likely to have a poor prognosis for MM.The American Journal of the Medical Sciences 09/2012; 345(2). DOI:10.1097/MAJ.0b013e31825b32bc · 1.52 Impact Factor