Showing papers by "Stein Kvaløy published in 2003"

Molecular Diagnosis of Primary Mediastinal B Cell Lymphoma Identifies a Clinically Favorable Subgroup of Diffuse Large B Cell Lymphoma Related to Hodgkin Lymphoma

Abstract: Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64% compared with 46% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL.

Immunohistochemical expression of CD23 and CD40 may identify prognostically favorable subgroups of diffuse large B-cell lymphoma: a Nordic Lymphoma Group Study.

Abstract: Purpose: In search for subgroups of diffuse large B-cell lymphoma (DLBCL) with different histogenetic origin and prognosis, as has been described by gene expression profiling, we examined tumor specimens from 125 patients with DLBCL, uniformly treated by either cyclophosphamideAdriamycin-vincristine-prednisone or methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin in a multicenter trial set by the Nordic Lymphoma Group 1989–1994. Experimental Design: Bcl -6, CD10, and CD40 were chosen as markers for a germinal center phenotype, CD23 as a marker of pre/early germinal center origin, and CD138 as a marker for postgerminal center origin. In addition, expression of the apoptotic regulators bcl -2 and bax was analyzed. Immunohistochemical analysis was performed using the EnVision method. Results: CD10 was positive in 51%, bcl -6 in 97%, and CD138 only in 2% of the cases. No prognostic conclusions could be drawn from analysis of these factors. CD40 was positive in 76% of the cases. This group was associated with superior time to treatment failure ( P = 0.027) and overall survival (OS; P = 0.0068). By Cox regression analysis, positivity for CD40 was shown to be a prognostic factor for OS, independent of International Prognostic Index. CD23 was positive in 16% of the cases (all CD5 negative and all CD40 positive). This group showed a strong tendency for better OS ( P = 0.033). CD40 expression correlated with bax but not with bcl -2 expression. Conclusions: CD23 and CD40 expression seems to be prognostically favorable in DLBCL. This may be secondary to a germinal center origin or attributable to increased apoptosis via induction of bax and/or enhanced T-cell interaction, resulting in improved autologous tumor response. Confirmatory studies are necessary.

The CARES-SF used for prospective assessment of health-related quality of life after stem cell transplantation.

Abstract: Objective: By employing the Cancer Rehabilitation and Evaluation System short form (CARES-SF) prospectively we wanted to focus on the rehabilitation needs after high-dose chemotherapy (HDC) and stem cell transplantation, in order to identify problems that should be addressed by health-care professionals during the course of disease and treatment Methods: The CARES-SF was administered before and at 2, 6 and 12 months post-transplant to 130 cancer patients treated with HDC and allogeneic (SCT) or autologous stem cell transplantation (ASCT) Physical function scale scores were compared with the corresponding scale of the EORTC QLQ-C30 Results: The SCT group reported significantly better physical function than the ASCT group before transplant on both the CARES-SF (p<00001) and the EORTC QLQ-C30 (p<001) Almost identical mean CARES-SF scores across groups (SCT: 07–14, ASCT: 08–13) were found at the subsequent assessments, consistent with the QLQ-C30 data Correlations between CARES-SF and QLQ-C30 Physical Function Scales ranged from 045 to 065 The SCT group had better psychosocial subscale scores (mean 04 and 05 versus ASCT: 07 and 08, p < 001) at the 6 and 12-month assessments, as well as better satisfaction on the marital subscale ( p=001) 6 months post-transplant Few patients requested specific help: 19% at baseline with ‘fear of the cancer progressing’ and 9% with ‘reduction in physical energy’ after 6 and 12 months Conclusion: The CARES-SF detected differences across groups of patients as well as within-patient changes over time The possibility for patients to express their need for professional assistance renders the CARES-SF appropriate after SCT/ASCT The sexual, marital and medical interaction subscales in particular address specific issues of relevance for follow-up care, compared with more traditional questionnaires assessing health related quality of life (HRQOL) Copyright © 2003 John Wiley & Sons, Ltd

Immunohistochemical Expression of CD23 and CD40 May Identify Prognostically Favorable Subgroups of Diffuse Large B-cell Lymphoma

Abstract: Purpose: In search for subgroups of diffuse large B-cell lymphoma (DLBCL) with different histogenetic origin and prognosis, as has been described by gene expression profiling, we examined tumor specimens from 125 patients with DLBCL, uniformly treated by either cyclophosphamideAdriamycin-vincristine-prednisone or methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin in a multicenter trial set by the Nordic Lymphoma Group 1989–1994. Experimental Design: Bcl -6, CD10, and CD40 were chosen as markers for a germinal center phenotype, CD23 as a marker of pre/early germinal center origin, and CD138 as a marker for postgerminal center origin. In addition, expression of the apoptotic regulators bcl -2 and bax was analyzed. Immunohistochemical analysis was performed using the EnVision method. Results: CD10 was positive in 51%, bcl -6 in 97%, and CD138 only in 2% of the cases. No prognostic conclusions could be drawn from analysis of these factors. CD40 was positive in 76% of the cases. This group was associated with superior time to treatment failure ( P = 0.027) and overall survival (OS; P = 0.0068). By Cox regression analysis, positivity for CD40 was shown to be a prognostic factor for OS, independent of International Prognostic Index. CD23 was positive in 16% of the cases (all CD5 negative and all CD40 positive). This group showed a strong tendency for better OS ( P = 0.033). CD40 expression correlated with bax but not with bcl -2 expression. Conclusions: CD23 and CD40 expression seems to be prognostically favorable in DLBCL. This may be secondary to a germinal center origin or attributable to increased apoptosis via induction of bax and/or enhanced T-cell interaction, resulting in improved autologous tumor response. Confirmatory studies are necessary.