Prognostic significance of the S-phase fraction of light-chain-restricted cytoplasmic immunoglobulin (cIg) positive plasma cells in patients with newly diagnosed multiple myeloma enrolled on eastern cooperative oncology group treatment trial E9486

Abstract

The bone marrow plasma cell labeling index (PCLI) as measured by bromodeoxyuridine uptake is a well-established independent prognostic factor for patients with newly diagnosed multiple myeloma, but the test is not easily done in most laboratories. The purpose of this study was to determine if the proliferative activity (% S-phase) as determined by two-color flow cytometry for cytoplasmic immunoglobulin (cIg) light chain and DNA content also had prognostic significance. As part of Eastern Cooperative Oncology Group clinical trial E9486, 500 patients had successful performance of the bone marrow PCLI. Of 349 patients who had flow cIg and DNA content cytometry, 210 had adequate data to reliably calculate S-phase %. Patients with low % S-phase fraction (<2%) had a significant overall survival advantage over patients high % S-phase fraction (≥2%), median survivals 4.1 vs. 2.9 years (P = 0.032). Measurement of the S-phase % by flow cytometry gives significant prognostic information in patients with newly diagnosed myeloma. However, in multivariate analysis, S-phase % did not add prognostic information when PCLI was in the model. S-phase % added prognostic information only when all cases with flow measurement of S-phase % were included, and when PCLI was excluded from the model. Discriminating a population of only cIg positive cells proved difficult in patients with a low percentage of bone marrow plasma cells. Methodology to measure S-phase % in patients with a low percent plasma cells is needed before this technique can be used for diagnosis and prognosis in myeloma. Am. J. Hematol. 61:232-237, 1999.

Prognostic value of serum markers of bone metabolism in untreated multiple myeloma patients

“…We believe that the prognostic information provided by these serum markers will help in determining which patients are better candidates for interventions that specifically target bone disease in MM (Berenson et al , 1996). Data derived from this correlative laboratory study have already provided valuable information regarding the role of different biological factors for prognostication in MM (Greipp et al , 1994, 1998; Trendle et al , 1999). To substantiate the value of measuring serum bone markers in MM prospectively, it will be necessary to incorporate such studies into future trials that test the efficacy of drugs that impact on MM bone disease, as has been done by Elomaa et al (1996).…”

“…The bone alkaline phosphatase assay (normal range 24–146 U/l) and TRAP (normal range 2·62–4·8 U/l) were done in the general chemistry laboratory using standard assays. S‐phase analysis was performed using a flow cytometric method (Trendle et al , 1999). Similarly, measurement of other important biological factors was performed as described previously (Greipp et al , 1998).…”

The prognostic significance of CD45 expression by clonal bone marrow plasma cells in patients with newly diagnosed multiple myeloma

“…(14, 15) PCLI levels of greater than 3% were considered high as they have been conventionally associated with an aggressive disease course. (16) LDH levels greater than 222 U/L were considered abnormally elevated by our clinical laboratory assay used in this study. Receiver operating characteristics (ROC) analysis was performed to determine the optimal cut off for percent of CD45 expressing clonal PCs that predicted for worse two-year OS outcomes.…”

Mieloma Múltiplo: 50 casos diagnosticados por citometria de fluxo

“…Hiperdiploidias estão associadas com melhor prognóstico, enquanto hipodiploidias indicam pior evolução. 3,18 Quantidades elevadas de células em fase de síntese também condizem com pior evolução 19,20 por traduzirem o índice de proliferação das células neoplásicas. Os valores de referência para esse parâmetro variam de doença para doença de acordo com a capacidade de proliferação da célula envolvida.…”