Haematologica 2003 - Supplements
Share Embed Flag
Download ePaper

Haematologica 2003 - Supplements

Haematologica 2003 - Supplements Haematologica 2003 - Supplements

supplements.haematologica.org
from supplements.haematologica.org More from this publisher
13.11.2014 Views

OPG had no effect on constitutive levels of apoptosis in human myeloma cell lines or primary myeloma cells. Media conditioned by MG63 osteoblast-like cells was also found to significantly protect human myeloma cells from TRAIL-induced apoptosis in a concentration-dependent manner (p

7. New prognostic criteria for classification and monitoring MM 7.1 Prognostic markers 163 Prevalence and prognostic significance of sMUC-1 levels in plasma cell dyscrasias Maria Goldaniga, Stefano Luminari, Fulvia Ceccherelli, Rossella Calori, Andrea Guffanti, Emilio Bombardieri, Raffaella Marcheselli, Lilla Cro, Mariangela Colombi, Massimo Federico, Antonino Neri and Luca Baldini. 1)Unità di Ematologia 1, Dipartimento di Ematologia ed Oncologia, Ospedale Maggiore IRCCS, Milan, Italy 2)Dipartimento di Oncologia ed Ematologia, Università di Modena e Rggio Emilia, Italy 3)Laboratorio di analisi chimico-cliniche e Microbiologia, Ospedale Maggiore IRCCS, Milan, Italy 4)Divisione di Medicina I, Ospedale Fatebenefratelli ed Oftalmico, Milan, Italy 5) Unità di Medicina Nucleare, Istituto Nazionale dei Tumori, Milan, Italy High serum sMUC-1 levels have been detected in adenocarcinoma patients and seem to correlate with tumour burden. It has been shown that patients with multiple myeloma (MM) have high peripheral blood and bone marrow levels, and that the latter directly correlate with tumour mass. To define the prevalence of high sMUC-1 levels in patients with plasma cell dyscrasias, we tested 89 monoclonal gammopathy of undetermined significance (MGUS), 76 MM and six plasma cell leukemia (PCL), admitted consecutively to our Institution during the last ten years. Peripheral blood samples were collected at the time of diagnosis or at any time during follow-up from MGUS patients; for MM and PCL patients were analized stored serum aliquots, collected at the time of diagnosis,. Samples obtained from 65, age and sex matched, healthy subjects, attending our Transfusion Department, were also evaluated. All of the samples were tested using Immunolite B27.29 antibody against MUC-1 protein. The sera from the MM/PCL patients were also tested using Abbot IMX CA15.3, Boehringer Mannheim Enzymmun CA15-3 and Centrocor CA15-3 in accordance with the manufacturers’ protocols. High sMUC-1 levels were found in 11/89 subjects with MGUS (12.4%), 13/76 with MM (17.1%) and 3/6 with PCL, while in the healthy control group only one subject had high levels (1.5%) (p=0.001). The mean sMUC-1 levels were significantly higher in the Monoclonal Component carrying patients than in the healthy subjects (43.2 vs 26 U/ml; p=0.001). The median follow-up of the 82 MM/PCL cases was 30 months (range 6 -114), during which 51 patients died: 39/66 (59%) with normal and 12/16 (75%) with high sMUC-1 levels. The median overall survival (OS) was 44 months. There was a difference in OS between the MM/PCL patients with normal or increased sMUC-1 levels: median OS 49 vs 25 months, 3-year OS 63% and 25% (p=0.036). Furthermore, increased sMUC-1 levels in MM patients correlated with some features associated with high tumour burden, such as anemia and high serum LDH levels. Finally we tested the hypothesis that the various antibodies used in sMUC-1 assays recognise distinct antigen epitopes and their different degrees of reactivity may depend on the extent of the glycosilation of the CA15.3 antigen, as reported by many autors. In our MM patients evaluated using different methods, we found differences in absolute values but multiple comparisons (Bonferroni’s test) showed a high degree of correlation. In conclusion, this study shows that a subset of MM and MGUS patients, and most PCL cases, had increased sMUC-1 levels. The frequent presence of high MUC-1 levels in PCL patients suggest a possible relationship between them and tumor malignancy (cell proliferation, genetic instability). In patients with MM, high sMUC-1 levels identify a group with a poor prognosis, showing a possible role of MUC-1 in tumor progession. Given the short follow-up of the MGUS patients (median 12 months; range 6 -30) and the absence of any MM transformation during this time, no conclusions can be drawn concerning a possible correlation between high sMUC levels and the relative risk of MM evolution. 164 Serum MUC1 as a Marker of disease status in Multiple Myeloma (MM) Patients Receiving Thalidomide ± Interferon-α-2b Linda R. Mileshkin1,HM Prince1, James J Biagi1, Paul Mitchell2, David Westerman1, Craig Underhill3, Andrew Grigg4, Richard Bell5, Joe McKendrick6, Peter Briggs7, John F. Seymour1 1Peter MacCallum Cancer Institute, Melbourne; 2Austin Repatriation Medical Centre, Melbourne; 3Border Medical Oncology, Albury; 4Royal Melbourne Hospital, Melbourne; 5The Geelong Hospital, Geelong; 6Box Hill Hospital, Box Hill; 7Monash Medical Centre, Clayton; Victoria, Australia Objective: MUC-1 is a glycosylated transmembrane protein normally found on the luminal surface of secretory glands. Serum MUC-1 (measured by serum CA15-3 assay) has also been detected on the surface of plasma cells in MM. The aim of this study was to prospectively assess the role of CA15-3 as a marker of response. Methods: We took serial measurements of MUC-1 from pts as part of a phase-II trial of thalidomide (T) ± interferon-α-2b (INF) in advanced MM pts. Pts commenced T at 200 mg/d po, increasing by 200 mg q14d, to 800 mg/d. After 12 weeks pts were planned to continue T and start concurrent INF (1.5–3.0 MU, SC, TIW), continuing T ± INF until progressive disease (PD) or intolerance. CA 15-3 levels were measured at baseline and then monthly by automated mouse monoclonal B27.29 antibody immunoassay (ULN of 31U/mL). Bone marrow trephines 36 of pts were stained for MUC1 by immunohistochemistry (IHC) and correlated with the serum CA15-3 level. Results: Analysis of 75 enrolled pts was performed. Overall response rate (CR+PR) was 28%. 62 of 75 pts had baseline CA15-3 levels recorded. 22/62 (35%) had CA15-3 levels >ULN. Median level was 46 U/mL (range 32-158). Of those with elevated levels, in 19% the level was 32-50U/mL, in 11% >50- 100U/mL and in 5% >100U/mL. There was no correlation between the baseline CA15-3 and baseline levels of the majority of other conventional markers (CRP, LDH, Creatinine, Hemoglobin, Platelet count, %Bone marrow infiltrate, Serum paraprotein, Bence Jones protein). There was a weak correlation with baseline levels of Beta-2-microglobulin: correlation coefficient 0.25 (P =0.0471). The serum level of CA 15-3 was correlated with the IHC score (% positive plasma cells x intensity): correlation coefficient 0.43 (P =0.047). Of responding pts, baseline levels were >ULN in 14/18 pts (78%) and ≤ULN in 4/18 (22%). There was no significant difference in percentage of pts with baseline CA15-3 >ULN who achieved SD or PD. In univariate analysis there was a trend to CA15-3 ≤ ULN being predictive of response to S160

OPG had no effect on constitutive levels of apoptosis in human<br />

myeloma cell lines or primary myeloma cells. Media conditioned by<br />

MG63 osteoblast-like cells was also found to significantly protect<br />

human myeloma cells from TRAIL-induced apoptosis in a<br />

concentration-dependent manner (p

logo

products

Resources

Company

Terms of service
Privacy policy
Cookie policy
Cookie settings
Imprint
Change language
Made with love in Switzerland
© 2024 Yumpu.com all rights reserved

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!