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3. Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists

Author

Askling, J., Fored, C.M., Baecklund, E., Brandt, L., Backlin, C., Ekbom, A., Sundstrom, C., Bertilsson, L., Coster, L., Geborek, P., Jacobsson, L.T., Lindblad, S., Lysholm, J., Rantapaa-Dahlqvist, S., Saxne, T., Klareskog, L., and Feltelius, N.

Subjects
Malignant lymphomas -- Causes of, Multiple myeloma -- Causes of, Rheumatoid arthritis -- Risk factors, Rheumatoid arthritis -- Drug therapy, Tumor necrosis factor -- Health aspects, Health
Published
2005

5. Antigen Drive in the Natural History of Mantle Cell Lymphoma: Molecular Evidence

Author

Xochelli A, Sutton LA, Agathangelidis A, Stalika E, Karypidou M, Marantidou F, Lopez AN, Papadopoulos G, Supikova J, Groenen P, Boudjogra M, Sundstrom C, Ponzoni M, Francova HS, Anagnostopoulos A, Pospisilova S, Papadaki T, Tzovaras D, GHIA , PAOLO PROSPERO, Pott C, Davi F, Campo E, Rosenquist R, Hadzidimitriou A, Belessi C, Stamatopoulos K., Xochelli, A, Sutton, La, Agathangelidis, A, Stalika, E, Karypidou, M, Marantidou, F, Lopez, An, Papadopoulos, G, Supikova, J, Groenen, P, Boudjogra, M, Sundstrom, C, Ponzoni, M, Francova, H, Anagnostopoulos, A, Pospisilova, S, Papadaki, T, Tzovaras, D, Ghia, PAOLO PROSPERO, Pott, C, Davi, F, Campo, E, Rosenquist, R, Hadzidimitriou, A, Belessi, C, and Stamatopoulos, K.

Abstract

To further our understanding about antigen involvement in mantle cell lymphoma (MCL), we analyzed the expression levels of activation-induced cytidine deaminase (AID), a key player in B-cell responses to antigen triggering, in 133 MCL cases; assessed the functionality of AID by evaluating in vivo class switch recombination in 52 MCL cases; and sought for indications of ongoing antigen interactions by exploring intraclonal diversification within 14 MCL cases. The AID full-length transcript and the most frequent splice variants (AID-ΔE4a, AID-ΔE) were detected in 128 (96.2%), 96 (72.2%), and 130 cases (97.7%), respectively. Higher AID full-length transcript levels were significantly associated (P < 0.001) with lack of somatic hypermutation within the clonotypic immunoglobulin heavy variable (IGHV) genes. Median AID transcript levels were higher in lymph node material compared to cases in which peripheral blood was analyzed, implying that clonal behavior is influenced by the microenvironment. Switched tumor-derived IGHV-IGHD-IGHJ transcripts were identified in 5 of 52 cases (9.6%), all of which displayed somatic hypermutation and AID-mRNA expression. Finally, although most cases exhibited low levels of intraclonal diversification, analysis of the mutational activity revealed a precise targeting of somatic hypermutation indicative of an active, ongoing interaction with antigen(s). Collectively, these findings strongly allude to antigen involvement in the natural history of MCL, further challenging the notion of antigen naivety.

Published
2015

11. Molecular evidence for antigen drive in the natural history of mantle cell lymphoma

Author

Xochelli, A., Sutton, L.A., Agathangelidis, A., Stalika, E., Karypidou, M., Marantidou, F., Lopez, A.N., Papadopoulos, G., Supikova, J., Groenen, P.J., Boudjogra, M., Sundstrom, C., Ponzoni, M., Francova, H.S., Anagnostopoulos, A., Pospisilova, S., Papadaki, T., Tzovaras, D., Ghia, P., Pott, C., Davi, F., Campo, E., Rosenquist, R., Hadzidimitriou, A., Belessi, C., Stamatopoulos, K., Xochelli, A., Sutton, L.A., Agathangelidis, A., Stalika, E., Karypidou, M., Marantidou, F., Lopez, A.N., Papadopoulos, G., Supikova, J., Groenen, P.J., Boudjogra, M., Sundstrom, C., Ponzoni, M., Francova, H.S., Anagnostopoulos, A., Pospisilova, S., Papadaki, T., Tzovaras, D., Ghia, P., Pott, C., Davi, F., Campo, E., Rosenquist, R., Hadzidimitriou, A., Belessi, C., and Stamatopoulos, K.

Abstract

Item does not contain fulltext, To further our understanding about antigen involvement in mantle cell lymphoma (MCL), we analyzed the expression levels of activation-induced cytidine deaminase (AID), a key player in B-cell responses to antigen triggering, in 133 MCL cases; assessed the functionality of AID by evaluating in vivo class switch recombination in 52 MCL cases; and sought for indications of ongoing antigen interactions by exploring intraclonal diversification within 14 MCL cases. The AID full-length transcript and the most frequent splice variants (AID-DeltaE4a, AID-DeltaE) were detected in 128 (96.2%), 96 (72.2%), and 130 cases (97.7%), respectively. Higher AID full-length transcript levels were significantly associated (P < 0.001) with lack of somatic hypermutation within the clonotypic immunoglobulin heavy variable (IGHV) genes. Median AID transcript levels were higher in lymph node material compared to cases in which peripheral blood was analyzed, implying that clonal behavior is influenced by the microenvironment. Switched tumor-derived IGHV-IGHD-IGHJ transcripts were identified in 5 of 52 cases (9.6%), all of which displayed somatic hypermutation and AID-mRNA expression. Finally, although most cases exhibited low levels of intraclonal diversification, analysis of the mutational activity revealed a precise targeting of somatic hypermutation indicative of an active, ongoing interaction with antigen(s). Collectively, these findings strongly allude to antigen involvement in the natural history of MCL, further challenging the notion of antigen naivety.

Published
2015

12. Nordic mcl2-3 trials: mirna-18b overexpression identifies a mantle cell lymphoma subgroup with poor survival and improves mipi-b prediction of prognosis

Author

Husby, Sofie, Ralfkiaer, U., Garde, Christian, Ek, Sara, Kolstad, A., Jerkeman, M., Laurell, A., Raty, R., Ehinger, M., Sundstrom, C., Karjalainen-Lindsberg, M. L., Delabie, J., Clasen-Linde, E., Brown, P. D. N., Workman, Christopher, Geisler, C. H., Gronbaek, K., Husby, Sofie, Ralfkiaer, U., Garde, Christian, Ek, Sara, Kolstad, A., Jerkeman, M., Laurell, A., Raty, R., Ehinger, M., Sundstrom, C., Karjalainen-Lindsberg, M. L., Delabie, J., Clasen-Linde, E., Brown, P. D. N., Workman, Christopher, Geisler, C. H., and Gronbaek, K.

Published
2014

13. Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients : results of a phase II Nordic Lymphoma Group study

Author

Holte, H., Leppa, S., Bjorkholm, M., Fluge, O., Jyrkkio, S., Delabie, J., Sundstrom, C., Karjalainen-Lindsberg, M. -L, Erlanson, Martin, Kolstad, A., Fossa, A., Ostenstad, B., Lofvenberg, E., Nordstrom, M., Janes, R., Pedersen, L. M., Anderson, H., Jerkeman, M., Eriksson, M., Holte, H., Leppa, S., Bjorkholm, M., Fluge, O., Jyrkkio, S., Delabie, J., Sundstrom, C., Karjalainen-Lindsberg, M. -L, Erlanson, Martin, Kolstad, A., Fossa, A., Ostenstad, B., Lofvenberg, E., Nordstrom, M., Janes, R., Pedersen, L. M., Anderson, H., Jerkeman, M., and Eriksson, M.

Abstract

Background: Many patients with aggressive B-cell lymphomas and high clinical risk score still die of lymphoma after conventional R-CHOP chemoimmunotherapy. We hypothesized that intensified chemoimmunotherapy including systemic central nervous system (CNS) prophylaxis improves outcome and reduces the incidence of CNS-related events. Patients and methods: Inclusion criteria were age 18-65 years, primary diffuse large B-cell lymphoma or grade III follicular lymphoma without clinical signs of CNS disease and negative cerebrospinal fluid cytology, age-adjusted International Prognostic Index 2-3 and WHO performance score 0-3. Treatment consisted of six courses of R-CHOEP-14 followed by a course of high-dose cytarabine and a course of high-dose methotrexate. Primary end point was failure-free survival (FFS) at 3 years. Results: A total of 156 eligible patients with a median age of 54 years (range 20-64) were included. Three toxic deaths were observed. Three-year overall survival (OS) and FFS rates (median observation time 52 months for survivors) were 81% and 65%, respectively. Seven patients experienced CNS relapse, all within 6 months. Conclusions: The results are promising with favorable 3-year OS and FFS rates, a low toxic death rate and a lower than expected number of CNS events. CNS progression might be further reduced by earlier CNS prophylaxis. CinicalTrials.gov.identifier: NCT01502982.

Published
2013
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14. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group

Author

Geisler, C.H., Kolstad, A., Laurell, A., Andersen, N.S., Pedersen, L.B., Jerkeman, M., Eriksson, M., Nordstrom, M., Kimby, E., Boesen, A.M., Kuittinen, O., Lauritzsen, G.F., Nilsson-Ehle, H., Ralfkiaer, E., Akerman, M., Ehinger, M., Sundstrom, C., Langholm, R., Delabie, J., Karjalainen-Lindsberg, M.L., Brown, P., Elonen, E., Geisler, C.H., Kolstad, A., Laurell, A., Andersen, N.S., Pedersen, L.B., Jerkeman, M., Eriksson, M., Nordstrom, M., Kimby, E., Boesen, A.M., Kuittinen, O., Lauritzsen, G.F., Nilsson-Ehle, H., Ralfkiaer, E., Akerman, M., Ehinger, M., Sundstrom, C., Langholm, R., Delabie, J., Karjalainen-Lindsberg, M.L., Brown, P., and Elonen, E.

Abstract

Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy with stem cell support has not been tested in large, prospective series. In the 2nd Nordic MCL trial, we treated 160 consecutive, untreated patients younger than 66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy with rituximab (R) + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP), alternating with R + high-dose cytarabine. Responders received high-dose chemotherapy with BEAM or BEAC (carmustine, etoposide, cytarabine, and melphalan/cyclophosphamide) with R-in vivo purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progression-free survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole independent predictor of event-free survival. The nonrelapse mortality was 5%. The majority of stem cell products and patients assessed with polymerase chain reaction (PCR) after transplantation were negative. Compared with our historical control, the Nordic MCL-1 trial, the event-free, overall, and progression-free survival, the duration of molecular remission, and the proportion of PCR-negative stem cell products were significantly increased (P < .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression-free survival of MCL and perhaps cure. Registered at www.isrctn.org as #ISRCTN 87866680 Udgivelsesdato: 2008/10/1

Published
2008

15. Telomere length and correlation with histopathogenesis in B-cell leukemias/lymphomas

Author

Walsh, S.H., Grabowski, P., Berglund, M., Thunberg, U., Thorselius, M., Tobin, G., Aleskog, A., Karlsson, Katarina, Sundstrom, C., Laurell, A., Enblad, G., Rosenquist, R., Roos, G., Walsh, S.H., Grabowski, P., Berglund, M., Thunberg, U., Thorselius, M., Tobin, G., Aleskog, A., Karlsson, Katarina, Sundstrom, C., Laurell, A., Enblad, G., Rosenquist, R., and Roos, G.

Abstract

Telomere length was recently reported to correlate with cellular origin of B-cell malignancies in relation to the germinal center (GC). In this report, we measured telomere length by quantitative-PCR in 223 B-cell lymphomas/leukemias and correlated results with immunoglobulin (Ig) mutation status and immunostainings for GC/non-GC subtypes of diffuse large B-cell lymphoma (DLBCL). Shortest telomeres were found in Ig-unmutated chronic lymphocytic leukemia (CLL) [median telomere to single copy gene value (T/S) 0.33], differing significantly to Ig-mutated CLL (0.63). Contrary to this, mantle cell lymphomas (MCLs) exhibited similar telomere lengths regardless of Ig mutation status (0.47). Telomere length differed significantly between GC-like (0.73) and non-GC-like DLBCLs (0.43), and follicular lymphomas (FLs) had shorter telomeres (0.53) than GC-DLBCL. Hairy cell leukemias, which display Ig gene intraclonal heterogeneity, had longer telomeres (0.62) than FLs and non-GC-DLBCL, but shorter than GC-DLBCL. We conclude that although DLBCL and CLL subsets can be clearly distinguished, telomere length reflects many parameters and may not simply correlate with GC-related origin. © 2007 The Authors.

Published
2007
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16. The G(-248)A polymorphism in the promoter region of the Bax gene does not correlate with prognostic markers or overall survival in chronic lymphocytic leukemia

Author

Skogsberg, A., Tobin, G., Krober, A., Kienle, D., Thunberg, U., Aleskog, A., Karlsson, K., Laurell, A., Merup, M., Vilpo, J., Sundstrom, C., Roos, G., Jernberg-Wiklund, H., Dohner, H., Nilsson, K., Stilgenbauer, S., Rosenquist, R., Skogsberg, A., Tobin, G., Krober, A., Kienle, D., Thunberg, U., Aleskog, A., Karlsson, K., Laurell, A., Merup, M., Vilpo, J., Sundstrom, C., Roos, G., Jernberg-Wiklund, H., Dohner, H., Nilsson, K., Stilgenbauer, S., and Rosenquist, R.

Abstract

The G(-248)A polymorphism in the promoter region of the Bax gene was recently associated with low Bax expression, more advanced stage, treatment resistance and short overall survival in B-cell chronic lymphocytic leukemia (CLL), the latter particularly in treated patients. To investigate this further, we analyzed 463 CLL patients regarding the presence or absence of the G(-248)A polymorphism and correlated with overall survival, treatment status and known prognostic factors, for example, Binet stage, VH mutation status and genomic aberrations. In this material, similar allele and genotype frequencies of the Bax polymorphism were demonstrated in CLL patients and controls (n=207), where 19 and 21% carried this polymorphism, respectively, and no skewed distribution of the polymorphism was evident between different Binet stages and VH mutated and unmutated CLLs. Furthermore, no difference in overall survival was shown between patients displaying the G(-248)A polymorphism or not (median survival 85 and 102 months, respectively, P=0.21), and the polymorphism did not influence outcome specifically in treated CLL. Neither did the polymorphism affect outcome in prognostic subsets defined by VH mutation status or genomic aberrations. In conclusion, the pathogenic role and clinical impact of the Bax polymorphism is limited in CLL. © 2006 Nature Publishing Group All rights reserved.

Published
2006
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17. Lymphomas in RA patients treated with TNF-blockers. Cases found in a post-marketing surveillance in Sweden

Author

Feltelius, N, Geborek, P, Baecklund, E, Sundstrom, C, Bertilsson, L, Jacobsson, L, Lindblad, S, Lysholm, J, Rantapää-Dahlqvist, Solbritt, Saxne, T, Klarskog, L, Feltelius, N, Geborek, P, Baecklund, E, Sundstrom, C, Bertilsson, L, Jacobsson, L, Lindblad, S, Lysholm, J, Rantapää-Dahlqvist, Solbritt, Saxne, T, and Klarskog, L

Abstract

Annual European Congress of Rheumatology (EULAR 2004), Berlin, GERMANY, JUN 09-12, 2004

Published
2004

23. Chronic lymphocytic leukemias utilizing the V(H)3-21 gene display highly restricted V(lambda)2-14 gene use and homologous CDR3s : implicating recognition of a common antigen epitope

Author

Tobin, G, Thunberg, U, Johnson, A, Eriksson, I, Soderberg, O, Karlsson, Karin, Merup, M, Juliusson, Gunnar, Vilpo, J, Enblad, G, Sundstrom, C, Roos, G, Rosenquist, R, Tobin, G, Thunberg, U, Johnson, A, Eriksson, I, Soderberg, O, Karlsson, Karin, Merup, M, Juliusson, Gunnar, Vilpo, J, Enblad, G, Sundstrom, C, Roos, G, and Rosenquist, R

Abstract

The immunoglobulin variable heavy chain (IgV(H)) gene mutation status is an important prognostic factor in chronic lymphocytic leukemia (CLL), since cases with mutated V-H genes show significantly longer survival than unmutated cases. Recently, we reported a preferential use of the V(H)3-21 gene in mutated CLL and showed that mutated V(H)3-21 cases had an inferior overall survival compared with other mutated CLL. In order to further characterize this subset, we performed VH gene analysis in 265 CLL cases and identified 31 V(H)3-21 cases (11.7%), 21 cases had mutated and 10 cases unmutated VH genes. Regardless Of VH gene mutation status, a poor overall survival was found in the VH3-21 cases with a median survival of 83 months. These survival data confirm that V(H)3-21 cases do not fit into the general prognostic grouping of mutated and unmutated CLL. A large fraction Of V(H)3-21 cases also demonstrated unique features with shorter lengths of the third complementarity determining region (CDR3) and CDR3s with highly homologous amino acid sequences. Furthermore, the V(H)3-21 cases showed a striking dominance of X light chain expression, and analysis of the Iglambda gene rearrangements revealed highly restricted use of the Vlambda2-14/J(lambda)3 genes in the majority of cases. Taken together, our new findings strengthen the suggestion that V(H)3-21-using cases comprise a new CLL entity, irrespective Of VH gene mutation status, and implicate that a common antigen epitope, perhaps of pathogenic significance, is recognized by the highly homologous V(H)3-21/V(lambda)2-14 Ig molecules expressed in individual tumors. (Blood. 2003,101:4952-4957).

Published
2003
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24. Somatic hypermutation and V(H) gene usage in mantle cell lymphoma.

Author

Thorselius, M, Walsh, S, Eriksson, I, Thunberg, U, Johnson, A, Backlin, C, Enblad, G, Sundstrom, C, Roos, G, Rosenquist, R, Thorselius, M, Walsh, S, Eriksson, I, Thunberg, U, Johnson, A, Backlin, C, Enblad, G, Sundstrom, C, Roos, G, and Rosenquist, R

Published
2002

33. Paraffin section storage and immunohistochemistry - Effects of time, temperature, fixation, and retrieval protocol with emphasis on p53 protein and MIB1 antigen

Author

Wester, K, Wahlund, E, Sundstrom, C, Ranefall, P, Bengtsson, E, Russell, PJ, Ow, KT, Malmstrom, PU, Busch, C, Wester, K, Wahlund, E, Sundstrom, C, Ranefall, P, Bengtsson, E, Russell, PJ, Ow, KT, Malmstrom, PU, and Busch, C

Abstract

It has been observed that immunoreactivity in paraffin sections decreased during storage. In this study, stored paraffin sections from both biopsy material and cultured cells were assessed for changes in immunoreactivity, using color-based image analysis, Addresses: Wester K, Univ Uppsala, Dept Genet & Pathol, Hammarskjolds 20, S-75185 Uppsala, Sweden. Univ Uppsala, Dept Genet & Pathol, S-75185 Uppsala, Sweden. Univ Uppsala, Dept Urol, S-75185 Uppsala, Sweden. Univ Uppsala, Ctr Image Anal, S-75185 Uppsala

Published
2000

40. Ultraviolet Radiation Exposure and Risk of Malignant Lymphomas

Author

Smedby, K. E., primary, Hjalgrim, H., additional, Melbye, M., additional, Torrang, A., additional, Rostgaard, K., additional, Munksgaard, L., additional, Adami, J., additional, Hansen, M., additional, Porwit-MacDonald, A., additional, Jensen, B. A., additional, Roos, G., additional, Pedersen, B. B., additional, Sundstrom, C., additional, Glimelius, B., additional, and Adami, H.-O., additional

Published
2005
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41. Linear reduction of clonal cells in stem cell enriched grafts intransplanted multiple myeloma.

Author

Thunberg, U, Banghagen, M, Bengtsson, M, Christensen, LD, Geisler, CH, Gimsing, P, Lenhoff, S, Mortensen, BT, Olofsson, T, Simonsson, B, Andersen, NS, Sundstrom, C, Swedin, A, Sallstrom, JF, Thuresson, B, Westin, J, Carlson, K, Thunberg, U, Banghagen, M, Bengtsson, M, Christensen, LD, Geisler, CH, Gimsing, P, Lenhoff, S, Mortensen, BT, Olofsson, T, Simonsson, B, Andersen, NS, Sundstrom, C, Swedin, A, Sallstrom, JF, Thuresson, B, Westin, J, and Carlson, K

Published
1999

47. Exploring the Role of Persuasive Design in Unguided Internet-Delivered Cognitive Behavioral Therapy for Depression and Anxiety Among Adults: Systematic Review, Meta-analysis, and Meta-regression

Author

McCall, Hugh C, Hadjistavropoulos, Heather D, and Sundström, Christopher Richard Francis

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract

BackgroundInternet-delivered cognitive behavioral therapy (ICBT) is an effective treatment that can overcome barriers to mental health care. Various research groups have suggested that unguided ICBT (ie, ICBT without therapist support) and other eHealth interventions can be designed to enhance user engagement and thus outcomes. The persuasive systems design framework captures most design recommendations for eHealth interventions, but there is little empirical evidence that persuasive design is related to clinical outcomes in unguided ICBT. ObjectiveThis study aims to provide an updated meta-analysis of randomized controlled trials of unguided ICBT for depression and anxiety, describe the frequency with which various persuasive design principles are used in such interventions, and use meta-regression to explore whether a greater number of persuasive design elements predicts efficacy in unguided ICBT for depression and anxiety. MethodsWe conducted a systematic review of 5 databases to identify randomized controlled trials of unguided ICBT for depression and anxiety. We conducted separate random effects meta-analyses and separate meta-regressions for depression and anxiety interventions. Each meta-regression included 2 steps. The first step included, as a predictor, whether each intervention was transdiagnostic. For the meta-regression of ICBT for depression, the first step also included the type of control condition. The number of persuasive design principles identified for each intervention was added as a predictor in the second step to reveal the additional variance in effect sizes explained by persuasive design. ResultsOf the 4471 articles we identified in our search, 46 (1.03%) were eligible for inclusion in our analyses. Our meta-analyses showed effect sizes (Hedges g) ranging from 0.22 to 0.31 for depression interventions, depending on the measures taken to account for bias in the results. We found a mean effect size of 0.45 (95% CI 0.33-0.56) for anxiety interventions, with no evidence that the results were inflated by bias. Included interventions were identified as using between 1 and 13 persuasive design principles, with an average of 4.95 (SD 2.85). The meta-regressions showed that a greater number of persuasive design principles predicted greater efficacy in ICBT for depression (R2 change=0.27; B=0.04; P=.02) but not anxiety (R2 change=0.05; B=0.03; P=.17). ConclusionsThese findings show wide variability in the use of persuasive design in unguided ICBT for depression and anxiety and provide preliminary support for the proposition that more persuasively designed interventions are more efficacious, at least in the treatment of depression. Further research is needed to clarify the role of persuasive design in ICBT.

Published
2021
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50. [18F] FDG PET in gastric non-Hodgkin's lymphoma.

Author

Rodriguez, M, Ahlstrom, H, Sundin, A, Rehn, S, Sundstrom, C, Hagberg, H, Glimelius, B, Rodriguez, M, Ahlstrom, H, Sundin, A, Rehn, S, Sundstrom, C, Hagberg, H, and Glimelius, B

Published
1998

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