Serum MUC‐1 as a marker of disease status in multiple myeloma patients receiving thalidomideписьмо
Аннотация: We read with interest the recent publication (Luminari et al, 2003) regarding the assessment of serum mucin-1 (sMUC-1) levels in plasma cell dyscrasias. Their study involved an analysis of consecutive patients referred to their Institute. Although not stated, we assume that the subgroup of multiple myeloma (MM) patients would have been heterogeneous in terms of amount of prior therapy and subsequent treatment. One of their conclusions was that elevated sMUC-1 levels correlated with a shorter survival in MM patients. We too have been interested in the value of sMUC-1 as a potential prognostic indicator but have not been able to demonstrate the same finding. We prospectively measured sMUC-1 in patients with relapsed/refractory MM as part of a recently published phase-II clinical trial of thalidomide therapy (Mileshkin et al, 2003). sMUC-1 levels were measured at baseline in 62 of the 75 patients using the same method as Luminari et al (2003) (Chiron diagnostics: upper limit of normal = 31 U/ml). Of note, sMUC-1 levels were elevated in 35% of our patients, a substantially higher proportion than that observed by Luminari et al (2003) (17%). Nonetheless, the median sMUC-1 level of 46 U/ml (range 32–158 U/ml) that we observed was very similar to their analysis (43·2 U/ml). The reason for our observation of a higher frequency of elevated sMUC-1 is unclear but may relate to differences in the populations studied. Like their study, we were unable to demonstrate a correlation between sMUC-1 levels and various parameters of MM, namely bone marrow plasma cell infiltrate, serum/urine paraprotein level, immunoglobulin or light chain subtype, β2-microglobulin level, C-reactive protein, platelet count or serum creatinine. Furthermore, we were unable to confirm their observation of a correlation between elevated sMUC-1 and elevated lactate dehydrogenase or anaemia. Similar to Treon et al (2000), we demonstrated that patients with more advanced disease were most likely to have an elevated baseline sMUC-1 [stage 1, zero of three patients (0%); stage 2, 14 of 39 (36%) and stage 3, nine of 20 (45%); P = 0·19]. A subset (n = 36) of our patients had bone marrow biopsy sections stained for MUC-1 expression by immunohistochemistry (IHC) using a mouse monoclonal antibody (BC2). Serum MUC-1 levels correlated with the bone marrow IHC score (% positive plasma cells × intensity): R = 0·43 (P = 0·047). However, six patients (27%) with elevated sMUC-1 had negligible marrow plasma cell staining for MUC-1. In univariate analysis, we found a trend for a higher response rate (RR) among patients with normal levels of sMUC-1 (RR 35% versus 14% for those with elevated levels: P = 0·084). However, in multivariate analysis, sMUC-1 was not predictive of response. At 18 months median follow-up we could find no difference between patients with normal versus elevated sMUC-1 levels in terms of progression-free survival (median 6·1 months versus 5 months, P = 0·31) or overall survival (15 months versus 16 months, P = 0·25). In summary, our results in a group of heavily pretreated patients managed in a homogeneous fashion contradicts that of Luminari et al (2003), as we have been unable to demonstrate a relationship between sMUC-1 and survival. Nonetheless, we believe that the value of sMUC-1 levels does require further study. Newer techniques such as array analysis may give additional insights into its role in disease pathogenesis. To fully evaluate the role of sMUC-1 as a prognostic marker, studies with larger patient numbers are required, particularly examining patients with previously untreated disease. We also continue to explore the relationship between sMUC-1 levels and marrow plasma cell MUC-1 expression, and the role of sMUC-1 as a measure of response to therapy.
Год издания: 2003
Авторы: Linda Mileshkin, H. Miles Prince, John F. Seymour, James Biagi
Издательство: Wiley
Источник: British Journal of Haematology
Ключевые слова: Multiple Myeloma Research and Treatments, Glycosylation and Glycoproteins Research, Monoclonal and Polyclonal Antibodies Research
Другие ссылки: British Journal of Haematology (PDF)
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PubMed (HTML)
British Journal of Haematology (HTML)
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Открытый доступ: bronze
Том: 123
Выпуск: 4
Страницы: 747–748