The clinical significance of cytogenetic studies in 100 patients with multiple myeloma, plasma cell leukemia, or amyloidosis

Abstract

Chromosome studies were done on 82 patients with multiple myeloma, 11 with amyloidosis, 2 with multiple myeloma and amyloidosis, and 5 with plasma cell leukemia to investigate their chromosomal abnormalities and to determine the usefulness of cytogenetic studies. A chromosomally abnormal clone was found in 29 patients but was observed most often in those with active disease: in 18% of patients with newly diagnosed multiple myeloma, in 63% with aggressive disease, and in 40% with plasma cell leukemia. Survival among the newly diagnosed patients was significantly shorter (P = .0089) for those in whom an abnormal clone was identified (median survival, six months) than for those in whom only normal metaphases were observed (median survival, greater than 12 months). Among all of the patients, survival from the time of chromosome analysis was shorter for those in whom a chromosomally abnormal clone was found: the median survival was three months for patients with all abnormal metaphases and eight months for patients with normal and abnormal metaphases and has not yet been reached for patients with only normal metaphases. The most common anomalous chromosomes in patients with a plasma cell proliferative disorder were 1, 11, and 14: 11 patients had an abnormality involving chromosome 14q32 and nine patients had an anomalous chromosome 11. The single most common abnormality, a t(11;14)(q13;q32), occurred in three patients. Among the patients who developed preleukemia or acute nonlymphocytic leukemia, the most common anomaly involved chromosome 7. The results suggest that cytogenetic studies are useful for identifying patients who have a poor prognosis and can help distinguish patients with a cytopenia because of preleukemia from those with an aggressive plasma cell proliferative process.

Cytogenetic study of 30 patients with multiple myeloma: comparison of 3 and 6 day bone marrow cultures stimulated or not with cytokines by using a miniaturized karyotypic method

“…MM is cytogenetically characterized by complex numerical and structural aberrations, none of them being totally specific. Our cytogenetic results in 30 MM patients are also in full agreement with the most consistent cytogenetic findings showing breakpoint clusters on chromosomes 1, 14q32 breakpoint (Ferti et al, 1984;Dewald et al, 1985;Weh et al, 1993) and other abnormalities of B-cell disorders, such as the reciprocal t(11;14)(q13;q32) (Meeus et al, 1995).…”

“…The detection of aneuploid malignant PC by flow cytometry and fluorescence in situ hybridization in about 80% of patients (Zandecki et al, 1994;Drach et al, 1995), demonstrated that the 20-60% incidence of karyotypic abnormalities (Dewald et al, 1985;Gould et al, 1988;Gutensohn et al, 1992;Cigudosa et al, 1994;Lai et al, 1995;Sawyer et al, 1995) largely underestimated the frequency of genetic damage in MM (Zandecki et al, 1996).…”

“…In most cases this is probably due to the low proliferative index of malignant PC, as evidenced by studies of the percentage of PC in S phase (Greipp et al, 1993). The percentage of patients with detectable karyotypic abnormalities in most series varied from 20% to 60% with a median of 30-40% (Dewald et al, 1985;Gould et al, 1988;Gutensohn et al, 1992;Cigudosa et al, 1994;Lai et al, 1995;Sawyer et al, 1995). As IL-6 and GM-CSF stimulate the proliferation of malignant PC in vitro (Zhang et al, 1990;Klein et al, 1995), some groups tested and showed that addition of IL-6 (Weh et al, 1993) or IL-6 + GM-CSF (Facon et al, 1993) to 3 or 6 d BM liquid cultures improved the detection of clonal karyotypic abnormalities in MM.…”

Syndecan‐1 and angiogenic cytokines in multiple myeloma: correlation with bone marrow angiogenesis and survival

“…This fact has spurred the search for valid prognostic factors. Several prognostic markers have been identified (Dewald et al, 1985;Bataille et al, 1992;Greipp et al, 1993), leading to the proposal of different prognostic systems. Recent studies have introduced serum HGF and serum syndecan-1 as prognostic markers for survival in myeloma patients (Seidel et al, 1998(Seidel et al, , 2000b.…”

The t(4;14) is associated with poor prognosis in myeloma patients undergoing autologous stem cell transplant

“…The most frequent IgH translocations in MM are t(11;14), involving cyclin D1 and t(4;14), involving FGFR3. The t(11;14) is detectable in 5% of MM patients by conventional cytogenetics (Dewald et al, 1985;Sawyer et al, 1995;Fonseca et al, 1998) and is detected in 15-20% of MM patients by FISH (Konigsberg et al, 2000;Avet-Loiseau et al, 2002;Fonseca et al, 2002). It is thought to be associated with good prognosis (Fonseca et al, 2002(Fonseca et al, , 2003Moreau et al, 2002).…”