| 1. |
- Christiansen, Ilse, et al.
(författare)
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Elevated serum levels of soluble ICAM-1 are elevated in non-Hodgkin´s lymphomas and correlate with tumor burden, disease activity and other diagnostic markers
- 1996
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Ingår i: British Journal of Haematology. - 0007-1048 .- 1365-2141. ; 92:3, s. 639-46
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Tidskriftsartikel (refereegranskat)abstract
- The serum levels of soluble ICAM-1 (CD54) were significantly elevated in patients with non-Hodgkin's lymphomas (NHL, n=127) and hairy cell leukaemia (HCL, n=15) compared with healthy controls (n=31). In high-grade malignant NHL (n=79) the sICAM-1 levels correlated with the tumour mass as reflected in the Ann Arbor staging system but not with bulky disease. Further, the sICAM-1 levels correlated with disease activity as reflected by the presence of B symptoms and with other known prognostic markers. In particular serum thymidine kinase (sTK). In patients with low-grade malignant NHL (n=48) a trend towards higher serum levels of sICAM-1 was found in patients with advanced stage and B symptoms. In both low and high-grade malignant NHL, elevated levels of sICAM-1 were associated with poorer overall and disease-free survival. The present results indicated that sICAM-1 levels have a prognostic power equal to that of other serum markers claimed to be of prognostic value in NHL, namely serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), beta-2-microglobulin (beta2m), serum thymidine kinase (sTK), albumin and orosomucoid. The cellular origin and the possible interactions between soluble and surface ICAM-1 and its ligands needs further exploration.
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| 2. |
- Christiansen, Ilse, et al.
(författare)
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Elevated serum levels of soluble vascular cell adhesion molecule-1(sVCAM-1) closely reflect tumour burden in chronic B-lymphocytic leukaemia
- 1998
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 103:4, s. 1129-1137
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Tidskriftsartikel (refereegranskat)abstract
- The present study is the first to report elevated serum levels of soluble (s)VCAM-1 in B-cell chronic lymphocytic leukaemia (B-CLL). A large cohort of 106 untreated patients was studied. sVCAM-1 was compared to known prognostic serum markers (soluble (s)ICAM-1; lactate dehydrogenase, LDH; sCD23; thymidine kinase, TK; beta2microglobulin, beta2m). The serum levels of sVCAM-1 reflected tumour burden as expressed by Binet/Rai stages more closely than any other marker. sVCAM-1 also reflected the kinetics of the disease as revealed by lymphocyte doubling time. sVCAM-1 was the only one of the studied markers which showed elevated levels in smouldering disease compared to controls. sVCAM-1, sICAM-1 and sCD23 (but not LDH, TK, beta2m) separated smouldering from non-smouldering B-CLL. Only sICAM-1, sCD23 and TK added independent prognostic information for survival to that of stage and lymphocyte doubling time. The expression of both adhesion molecules was examined in lymph node and splenic specimens. VCAM-1 and ICAM-1 were overexpressed by vascular endothelium and stroma, but the intensity of expression correlated poorly with serum levels of the soluble molecules. In conclusion, serum levels of sVCAM-1 correlated with tumour burden and other prognostic markers in B-CLL. VCAM-1 was overexpressed in tumour tissue as was ICAM-1. sVCAM-1 could prove a valuable marker in younger early-stage patients eligible for therapeutic trials.
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| 3. |
- Christiansen, Ilse, et al.
(författare)
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Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) are elevated in advanced stage of non-Hodgkin's lymphomas
- 1998
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Ingår i: European Journal of Haematology. - 0902-4441 .- 1600-0609. ; 61:5, s. 311-318
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Tidskriftsartikel (refereegranskat)abstract
- The serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in 116 patients with non-Hodgkin's lymphomas (NHL) tested previously for soluble intercellular adhesion molecule-1 (sICAM-1). In contrast to Hodgkin's disease and chronic lymphocytic leukaemia, the sVCAM-1 levels in NHL patients were not significantly different from the levels of healthy controls (n=31). However, sVCAM-1 was elevated in advanced stage disease, i.e. stages III+IV. Elevated serum levels of sVCAM-1 were associated with significantly poorer disease-free (p = 0.024) and overall (p = 0.02) survival. sVCAM-1 correlated poorly with other known prognostic variables (LDH, sTK and beta2m) and with sICAM-1. None of the tested markers added prognostic information for disease-free survival independently of Ann Arbor stage and B-symptoms. The expression of VCAM-1 and ICAM-1 in tumour biopsies from 15 patients representing 7 different histologies were examined and compared with the serum levels of the soluble adhesion molecules. No correlation was found between the adhesion molecule expression by vascular endothelium and the corresponding serum levels.
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| 4. |
- Christiansen, Ilse, et al.
(författare)
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Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) are elevated in advanced stages of non-Hodgkin's lymphomas
- 1999
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Ingår i: European Journal of Haematology. - 0902-4441 .- 1600-0609. ; 62:3, s. 202-209
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Tidskriftsartikel (refereegranskat)abstract
- The serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in 116 patients with non-Hodgkin's lymphomas (NHL) tested previously for soluble intercellular adhesion molecule-1 (sICAM-1). In contrast to Hodgkin's disease and chronic lymphocytic leukaemia, the sVCAM-1 levels in NHL patients were not significantly different from the levels of healthy controls (n = 31). However, sVCAM-1 was elevated in advanced stage disease, i.e. stages III + IV. Elevated serum levels of sVCAM-1 were associated with significantly poorer disease-free (p = 0.024) and overall (p = 0.02) survival. sVCAM-1 correlated poorly with other known prognostic variables (LDH, sTK and beta 2m) and with sICAM-1. None of the tested markers added prognostic information for disease-free survival independently of Ann Arbor stage and B-symptoms. The expression of VCAM-1 and ICAM-1 in tumour biopsies from 15 patients representing 7 different histologies were examined and compared with the serum levels of the soluble adhesion molecules. No correlation was found between the adhesion molecule expression by vascular endothelium and the corresponding serum levels.
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| 5. |
- Christiansen, Ilse, et al.
(författare)
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Soluble ICAM-1 in Hodgkin´s disease : a promising independent predictive marker for survival
- 1995
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 19:3-4, s. 243-51
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Tidskriftsartikel (refereegranskat)abstract
- The serum levels of soluble ICAM-1 (sICAM-1, sCD54) were significantly elevated (p = .0006) in patients with Hodgkin's disease (HD) (n = 101) compared to healthy controls (n = 31). Serum levels of sICAM-1 in HD correlated significantly with the presence of B-symptoms, histology and tumour burden as reflected in the Ann Arbor staging system, but not to bulky disease. sICAM-1 was compared to other serum factors claimed to be of prognostic significance in HD, including erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), deoxythymidine kinase (TK), soluble interleukin-2 receptor (sIL-2R, sCD25) and soluble CD30 (sCD30, sKi-1-antigen). Serum levels of sICAM-1 correlated positively with all of these markers. In univariate regression analyses, all but ESR correlated with disease-free survival but only sICAM-1, sIL-2R and sCD30 correlated with overall survival. In multivariate analyses only sIL-2R (as a continuous variable) added independent prognostic information in addition to age, stage and B-symptoms. sICAM-1 and sCD30 approached significance (p = 0.07 and p = 0.08, respectively) for disease-free survival. sCD30 correlated with overall survival (p = 0.03) while sICAM-1 did not. When dichotomised at optimal cut-off levels, sICAM-1 as well as sIL-2R and sCD30 added independent prognostic information for both disease-free and overall survival. Based on the present observations, it appears that sICAM-1 may be a predictor for relapse and survival in HD. Determination of serum levels of sICAM-1 (in addition to sIL-2R and sCD30) may thus be of potential value when selecting HD patients eligible for intensive therapy in clinical trials.
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| 6. |
- Christiansen, Ilse
(författare)
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Soluble intercellular and vascular cell adhesion molecules-1 in lymphoid neoplasms : A clinical and prognostic study of Hodgkin's disease, non-Hodgkin's lymphomas and chronic B-lymphocytic leukaemia
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The interaction of soluble adhesion molecules with adhesion ligands expressed by immunological cells interfere with the cell-cell adhesion essential for the signal transductions that initiate immunological responses. Preliminary data suggest that soluble adhesion molecules also promote angiogenesis. Thus dysregulated production of soluble adhesion molecules may emerge as participants of disturbed immuno- surveillance, lymphocyte trafficking and dissemination of cancer cells. Vascular cell adhesion molecule-l (VCAM-1) and intercellular adhesion molecule-l (ICAM-1) are inducible and/or upregulated by cytokines in different cells types such as endothelial cells, follicular dendritic cells, and stromal cells. Lymphoid neoplasms, representing malignant counterparts of immunological cells, are characterised by heterogeneous histopathologies and clinical manifestations.Serum levels of soluble ICAM-1 (sICAM-1) and soluble VCAM-1 (sVCAM-1) were elevated in Hodgkin's disease (HD) and chronic B-lymphocytic leukaemia (B-CLL), while only sICAM-1 was elevated in non-Hodgkin's lymphomas (NHL). Serum levels of sICAM-1 and sVCAM-1 correlated with tumour burden and other known prognostic markers. sICAM-1 was an independent prognostic variable in HD and B-CLL. sVCAM-1 was an independent prognostic variable in HD. The discriminative power of serum levels of sVCAM-1 in smouldering and non-smouldering B-CLL could prove clinically valuable.Both ICAM-1 and VCAM-1 were overexpressed by vascular endothelium and stroma in biopsies of HD, B-CLL and NHL. No correlation between tissue expression of the adhesion molecules and the serum levels of sICAM-1 and sVCAM-1 appeared. VCAM-1 was expressed by two of seven HD cell lines, and sVCAM-1 was detectable in supernatants from these two cell lines. ICAM-1 was expressed by all I-ID cell lines and detectable in supernatants. In the majority of B-CLL and NHL cultures, ICAM-1 expression was upregulated by tumour cells, resulting in detectable sICAM-1 in supernatants.In conclusion, serum levels of both sICAM-1 and sVCAM-1 had prognostic powers equalling or surpassing known prognostic markers in lymphoid neoplasms. The functional consequences of dysregulated serum levels of sICAM-1 and sVCAM-1 in lymphoid neoplasms is at present largely unknown.
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| 7. |
- Christiansen, Ilse, et al.
(författare)
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Soluble vascular cell adhesion molecule-1 (sVCAM-1) is an independent prognostic marker in Hodgkin's disease
- 1998
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 102:3, s. 701-9
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Tidskriftsartikel (refereegranskat)abstract
- Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1. sCD106) were significantly elevated in patients with Hodgkin's disease (HD) (n = 101) compared to controls (n= 31) (P<0.0001). sVCAM-1 correlated with histology, stage, B-symptoms, and prognostic markers (sICAM-1, sCD30, sIL-2R, LDH). sVCAM-1, sICAM-1 and sCD30 added independent prognostic information for both disease-free and overall survival. 14 biopsies from 13 patients with HD were immunostained for VCAM-1 and ICAM-1. The vascular endothelium stained positive for VCAM-1 in 10/12 evaluable biopsies and for ICAM-1 in all evaluable biopsies. A stromal expression of both adhesion molecules precluded a precise evaluation of HRS-cells. This led us to investigate VCAM-1 (and ICAM-1) expression in six Hodgkin cell lines (HDLM-2, L428, L540, L591, DEV, KM-H2). Two cell lines stained positive for VCAM-1 (HDLM-2, L591). All cell lines stained positive for ICAM-1. sVCAM-1 is a new prognostic marker in HD; its predictive power equals or surpasses that of sCD30 and sICAM-1. Furthermore, two Hodgkin cell lines stained positive for VCAM-1. This indicates that VCAM-1 may be expressed by some HD tumour cells in vivo.
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| 8. |
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| 9. |
- Eichhorst, B., et al.
(författare)
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First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia.
- 2023
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 388:19, s. 1739-1754
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Tidskriftsartikel (refereegranskat)abstract
- Background Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking. Methods In a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) or 12 cycles of venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. Ibrutinib was discontinued after two consecutive measurements of undetectable minimal residual disease or could be extended. The primary end points were undetectable minimal residual disease (sensitivity,
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| 10. |
- Johnsen, Hans E., et al.
(författare)
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Improved Survival for Multiple Myeloma in Denmark Based on Autologous Stem Cell Transplantation and Novel Drug Therapy in Collaborative Trials: Analysis of Accrual, Prognostic Variables, Selection Bias, and Clinical Behavior on Survival in More Than 1200 Patients in Trials of the Nordic Myeloma Study Group
- 2010
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Ingår i: Clinical Lymphoma, Myeloma & Leukemia. - 2152-2650. ; 10:4, s. 290-296
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Tidskriftsartikel (refereegranskat)abstract
- Background: An unexplained survival difference was observed in the Nordic Myeloma Study Group (NMSG) high-dose therapy trial 5/94 in Denmark compared with Sweden and Norway; however, this difference was eliminated in the subsequent NMSG trial 7/98. It was hypothesized that a detailed analysis of potential explanations would reveal important information for future designs of clinical trials for multiple myeloma (MM) patients in Denmark. Patients and Methods: The analysis is based on 3 consecutive clinical trials coordinated by NMSG from 1990 to 2000: NMSG 4/90 including 583 patients, NMSG 5/94 including 274 patients and NMSG 7/98 including 414 patients with newly diagnosed MM. Event-free and total survival rates were calculated according to the Kaplan-Meier method, and survival comparisons were made by the log-rank test. The Cox proportional hazards regression model was used to estimate the prognostic importance of selected variables. Results: The analysis revealed no differences in disease stages, prognostic variables, or inclusion bias at diagnosis between the 3 consecutive NMSG trials. However, the number of initial treatment failures was low, and post-relapse survival was superior in Swedish patients as compared to Danish patients. These differences were explained by a defensive clinical practice in Denmark during 1994-1997 for patients with poor risk refractory or relapsed disease. Conclusion: These initially observed differences were subsequently eliminated most likely as a consequence of international collaboration improving diagnosis, research infrastructure, clinical training, and education as planned within the European Myeloma Network (EMN).
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