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103. 450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments

Author

Cahill, N, primary, Bergh, A-C, additional, Kanduri, M, additional, Göransson-Kultima, H, additional, Mansouri, L, additional, Isaksson, A, additional, Ryan, F, additional, Smedby, K E, additional, Juliusson, G, additional, Sundström, C, additional, Rosén, A, additional, and Rosenquist, R, additional

Published
2012
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104. Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials

Author

Palumbo, A., primary, Waage, A., additional, Hulin, C., additional, Beksac, M., additional, Zweegman, S., additional, Gay, F., additional, Gimsing, P., additional, Leleu, X., additional, Wijermans, P., additional, Sucak, G., additional, Pezzatti, S., additional, Juliusson, G., additional, Pegourie, B., additional, Schaafsma, M., additional, Galli, M., additional, Turesson, I., additional, Kolb, B., additional, van der Holt, B., additional, Baldi, I., additional, Rolke, J., additional, Ciccone, G., additional, Wetterwald, M., additional, Lokhorst, H., additional, Boccadoro, M., additional, Rodon, P., additional, and Sonneveld, P., additional

Published
2012
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105. 13Q DELETIONS IN LYMPHOID MALIGNANCIES

Author

HERMANSON, M, GRANDER, D, MERUP, M, WU, XS, HEYMAN, M, RASOOL, O, JULIUSSON, G, GAHRTON, G, DETLOFSSON, R, NIKIFOROVA, N, BUYS, C, SODERHALL, S, YANKOVSKY, N, ZABAROVSKY, E, and EINHORN, S

Subjects
immune system diseases, CHRONIC LYMPHOCYTIC-LEUKEMIA, RETINOBLASTOMA GENE, ABNORMALITIES, hemic and lymphatic diseases, CELLS, LOCUS
Abstract

Previous studies have indicated that a candidate tumor suppressor gene resides telomeric of the RB1 gene at 13q14, a region that is commonly deleted in B-cell chronic lymphocytic leukemia (B-CLL). In this study, we have evaluated the frequency and minimal region of overlap for 13q deletions in malignant cells from various lymphoid neoplasms. We observed losses at 13q14 in 33/75 (44%) B-CLL cases, four of 16 (25%) non-Hodgkin's lymphoma (NHL) cases, eight of 29 (28%) patients with acute lymphocytic leukemia (ALL), and one of 15 T-cell lines. In some ALL cases, inactivation of the RB1 gene is suggested as the important event in the 13q deletions. The most commonly deleted marker in CLL and NHL was D13S319, between RBkpt and the D13S25 loci. Homozygous deletions of this marker were observed in 10 of 75 B-CLL cases, in six of which the homozygous deletions included only the D13S319 locus. Our data suggest that 13q deletions are common in lymphoid neoplasms, and that deletion of a candidate tumor suppressor gene(s) in the vicinity of the D13S319 marker is a tumorigenic event in these diseases. (C) 1995 by The American Society of Hematology.

Published
1995

106. EGR2mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia

Author

Young, E, Noerenberg, D, Mansouri, L, Ljungström, V, Frick, M, Sutton, L-A, Blakemore, S J, Galan-Sousa, J, Plevova, K, Baliakas, P, Rossi, D, Clifford, R, Roos-Weil, D, Navrkalova, V, Dörken, B, Schmitt, C A, Smedby, K E, Juliusson, G, Giacopelli, B, Blachly, J S, Belessi, C, Panagiotidis, P, Chiorazzi, N, Davi, F, Langerak, A W, Oscier, D, Schuh, A, Gaidano, G, Ghia, P, Xu, W, Fan, L, Bernard, O A, Nguyen-Khac, F, Rassenti, L, Li, J, Kipps, T J, Stamatopoulos, K, Pospisilova, S, Zenz, T, Oakes, C C, Strefford, J C, Rosenquist, R, and Damm, F

Abstract

Recurrent mutations within EGR2were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2hotspot region including a screening (n=1283) and two validation cohorts (UK CLL4 trial patients, n=366; CLL Research Consortium (CRC) patients, n=490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations. EGR2mutations were detected in 91/2403 (3.8%) investigated cases, and associated with younger age at diagnosis, advanced clinical stage, high CD38 expression and unmutated IGHV genes. EGR2-mutated patients frequently carried ATMlesions (42%), TP53aberrations (18%) and NOTCH1/FBXW7mutations (16%). EGR2mutations independently predicted shorter time-to-first-treatment (TTFT) and overall survival (OS) in the screening cohort; they were confirmed associated with reduced TTFT and OS in the CRC cohort and independently predicted short OS from randomization in the UK CLL4 cohort. A particularly dismal outcome was observed among EGR2-mutated patients who also carried TP53aberrations. In summary, EGR2mutations were independently associated with an unfavorable prognosis, comparable to CLL patients carrying TP53aberrations, suggesting that EGR2-mutated patients represent a new patient subgroup with very poor outcome.

Published
2017
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107. Coexistence of trisomies of chromosomes 12 and 19 in chronic lymphocytic leukemia occurs exclusively in the rare IgG-positive variant

Author

Ibbotson, R, primary, Athanasiadou, A, additional, Sutton, L-A, additional, Davis, Z, additional, Gardiner, A, additional, Baliakas, P, additional, Gunnarsson, R, additional, Anagnostopoulos, A, additional, Juliusson, G, additional, Rosenquist, R, additional, Oscier, D, additional, and Stamatopoulos, K, additional

Published
2011
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108. Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia

Author

Gunnarsson, R., primary, Mansouri, L., additional, Isaksson, A., additional, Goransson, H., additional, Cahill, N., additional, Jansson, M., additional, Rasmussen, M., additional, Lundin, J., additional, Norin, S., additional, Buhl, A. M., additional, Smedby, K. E., additional, Hjalgrim, H., additional, Karlsson, K., additional, Jurlander, J., additional, Geisler, C., additional, Juliusson, G., additional, and Rosenquist, R., additional

Published
2011
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109. LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia

Author

Kaderi, M. A., primary, Kanduri, M., additional, Buhl, A. M., additional, Sevov, M., additional, Cahill, N., additional, Gunnarsson, R., additional, Jansson, M., additional, Smedby, K. E., additional, Hjalgrim, H., additional, Jurlander, J., additional, Juliusson, G., additional, Mansouri, L., additional, and Rosenquist, R., additional

Published
2011
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111. A phase I/II study of the MDR modulator Valspodar (PSC 833) combined withdaunorubicin and cytarabine in patients with relapsed and primaryrefractory acute myeloid leukemia.

Author

Gruber, A, Bjorkholm, M, Brinch, L, Evensen, S, Gustavsson, B, Hedenus, M, Juliusson, G, Lofvenberg, E, Nesthus, I, Simonsson, B, Sjo, M, Stenke, L, Tangen, JM, Tidefelt, U, Uden, AM, Paul, C, Liliemark, J, Gruber, A, Bjorkholm, M, Brinch, L, Evensen, S, Gustavsson, B, Hedenus, M, Juliusson, G, Lofvenberg, E, Nesthus, I, Simonsson, B, Sjo, M, Stenke, L, Tangen, JM, Tidefelt, U, Uden, AM, Paul, C, and Liliemark, J

Published
2003

115. Priming with r-metHuSCF and filgrastim or chemotherapy and filgrastim in patients with malignant lymphomas: a randomized phase II pilot study of mobilization and engraftment

Author

Johnsen, H E, primary, Geisler, C, additional, Juvonen, E, additional, Remes, K, additional, Juliusson, G, additional, Hörnsten, P, additional, Kvaloy, S, additional, Kvalheim, G, additional, Jürgensen, G W, additional, Pedersen, L M, additional, Bergmann, O J, additional, Schmitz, A, additional, and Boegsted, M, additional

Published
2010
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116. High-density screening reveals a different spectrum of genomic aberrations in chronic lymphocytic leukemia patients with 'stereotyped' IGHV3-21 and IGHV4-34 B-cell receptors

Author

Marincevic, M., primary, Cahill, N., additional, Gunnarsson, R., additional, Isaksson, A., additional, Mansouri, M., additional, Goransson, H., additional, Rasmussen, M., additional, Jansson, M., additional, Ryan, F., additional, Karlsson, K., additional, Adami, H.-O., additional, Davi, F., additional, Jurlander, J., additional, Juliusson, G., additional, Stamatopoulos, K., additional, and Rosenquist, R., additional

Published
2010
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117. Large but not small copy-number alterations correlate to high-risk genomic aberrations and survival in chronic lymphocytic leukemia: a high-resolution genomic screening of newly diagnosed patients

Author

Gunnarsson, R, primary, Isaksson, A, additional, Mansouri, M, additional, Göransson, H, additional, Jansson, M, additional, Cahill, N, additional, Rasmussen, M, additional, Staaf, J, additional, Lundin, J, additional, Norin, S, additional, Buhl, A M, additional, Smedby, K E, additional, Hjalgrim, H, additional, Karlsson, K, additional, Jurlander, J, additional, Juliusson, G, additional, and Rosenquist, R, additional

Published
2009
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118. Etoposide, doxorubicin, cyclophosphamide and high-dose betamethasone (EACB) as outpatient salvage therapy for refractory multiple myeloma

Author

Ohrling, M., primary, Björkholm, M., additional, Österborg, A., additional, Juliusson, G., additional, Björeman, M., additional, Brenning, G., additional, Carlson, K., additional, Celsing, F., additional, Gahrton, G., additional, Grimfors, G., additional, Gruber, A., additional, Gyllenhammar, H., additional, Hast, R., additional, Johansson, B., additional, Järnmark, M., additional, Kimby, E., additional, Lerner, R., additional, Linder, O., additional, Merk, K., additional, Paul, C., additional, Simonsson, B., additional, Smedmyr, B., additional, Svedmyr, E., additional, Stalfelt, A.-M., additional, Udén, A.-M., additional, Ösby, E., additional, and Mellstedt, H., additional

Published
2009
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119. Alternating combination chemotherapy (VMCP/VBAP) is not superior to melphalan/prednisone in the treatment of multiple myeloma patients stage III -A randomized study from MGCS

Author

Österborg, A., primary, Ahre, A., additional, Björkholm, M., additional, Björeman, M., additional, Brenning, G., additional, Gahrton, G., additional, Gyllenhammar, H., additional, Johansson, B., additional, Juliusson, G., additional, Järnmark, M., additional, Killander, A., additional, Kimby, E., additional, Lerner, R., additional, Nilsson, B., additional, Paul, C., additional, Simonsson, B., additional, Stalfelt, A.-M., additional, Strander, H., additional, Smedmyr, B., additional, Svedmyr, E., additional, Udén, A.-M., additional, Wadman, B., additional, Wedelin, C., additional, and Mellstedt, H., additional

Published
2009
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123. Mitoxantrone, etopside and ara-C vs doxorubicin-DNA, ara-C, thioguanine, voncristine and prednisolone in the treatment of patients with acute myelocytic leukemia. A randomized comparison.

Author

Bjorkholm, M, Liliemark, J, Gahrton, G, Grimfors, G, Gruber, A, Hast, R, Juliusson, G, Jarnmark, M, Killander, A, Kimby, E, Lerner, R, Ljungman, P, Lonnqvist, B, Palmblad, J, Paul, C, Pettersson, C, Simonsson, B, Stalfelt, A-M, Stenke, L, Sundstrom, C, Tidefelt, U, Uden, A-M, Oberg, G, Ost, Å, Bjorkholm, M, Liliemark, J, Gahrton, G, Grimfors, G, Gruber, A, Hast, R, Juliusson, G, Jarnmark, M, Killander, A, Kimby, E, Lerner, R, Ljungman, P, Lonnqvist, B, Palmblad, J, Paul, C, Pettersson, C, Simonsson, B, Stalfelt, A-M, Stenke, L, Sundstrom, C, Tidefelt, U, Uden, A-M, Oberg, G, and Ost, Å

Published
1995

130. Recombinant human erythropoietin in transfusion-dependent anemic patients with multiple myeloma and non-Hodgkin's lymphoma--a randomized multicenter study. The European Study Group of Erythropoietin (Epoetin Beta) Treatment in Multiple Myeloma and Non-Hodgkin's Lymphoma

Author

Osterborg, A, primary, Boogaerts, MA, additional, Cimino, R, additional, Essers, U, additional, Holowiecki, J, additional, Juliusson, G, additional, Jager, G, additional, Najman, A, additional, and Peest, D, additional

Published
1996
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132. 13q deletions in lymphoid malignancies

Author

Liu, Y, primary, Hermanson, M, additional, Grander, D, additional, Merup, M, additional, Wu, X, additional, Heyman, M, additional, Rasool, O, additional, Juliusson, G, additional, Gahrton, G, additional, and Detlofsson, R, additional

Published
1995
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140. Chlorambucil/prednisone vs. CHOP in symptomatic low-grade non-Hodgkin's lymphomas: A randomized trial from the Lymphoma Group of Central Sweden

Author

Kimby, E., primary, Björkholm, M., additional, Gahrton, G., additional, Glimelius, B., additional, Hagberg, H., additional, Johansson, B., additional, Johansson, H., additional, Juliusson, G., additional, Järnmark, M., additional, Löfvenberg, E., additional, Killander, A., additional, Lerner, R., additional, Lindemalm, C., additional, Pettersson, U., additional, Robért, K.-H., additional, Simonsson, B., additional, Stalfelt, A.-M., additional, Sundström, C., additional, Svedmyr, E., additional, Udén, A.-M., additional, Wadman, B., additional, Wahlin, A., additional, Öst, Å., additional, and Mellstedt, H., additional

Published
1994
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141. 450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments.

Author

Cahill, N, Bergh, A-C, Kanduri, M, Göransson-Kultima, H, Mansouri, L, Isaksson, A, Ryan, F, Smedby, K E, Juliusson, G, Sundström, C, Rosén, A, and Rosenquist, R

Subjects
CHRONIC lymphocytic leukemia, DNA methylation, GENE expression, LYMPH nodes, GENETIC mutation
Abstract

In chronic lymphocytic leukemia (CLL), the microenvironment influences gene expression patterns; however, knowledge is limited regarding the extent to which methylation changes with time and exposure to specific microenvironments. Using high-resolution 450K arrays, we provide the most comprehensive DNA methylation study of CLL to date, analyzing paired diagnostic/follow-up samples from IGHV-mutated/untreated and IGHV-unmutated/treated patients (n=36) and patient-matched peripheral blood and lymph node samples (n=20). On an unprecedented scale, we revealed 2239 differentially methylated CpG sites between IGHV-mutated and unmutated patients, with the majority of sites positioned outside annotated CpG islands. Intriguingly, CLL prognostic genes (for example, CLLU1, LPL, ZAP70 and NOTCH1), epigenetic regulator (for example, HDAC9, HDAC4 and DNMT3B), B-cell signaling (for example, IBTK) and numerous TGF-β and NF-κB/TNF pathway genes were alternatively methylated between subgroups. Contrary, DNA methylation over time was deemed rather stable with few recurrent changes noted within subgroups. Although a larger number of non-recurrent changes were identified among IGHV-unmutated relative to mutated cases over time, these equated to a low global change. Similarly, few changes were identified between compartment cases. Altogether, we reveal CLL subgroups to display unique methylation profiles and unveil methylation as relatively stable over time and similar within different CLL compartments, implying aberrant methylation as an early leukemogenic event. [ABSTRACT FROM AUTHOR]

Published
2013
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148. Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry.

Author

Lehmann, S., Ravn, A., Carlsson, L., Antunovic, P., Deneberg, S., Möllgård, L., Rangert Derolf, Å, Stockelberg, D., Tidefelt, U., Wahlin, A., Wennström, L., Höglund, M., and Juliusson, G.

Subjects
ACUTE leukemia, CLINICAL trials, POPULATION statistics, SWEDES, AGE factors in disease, SEX factors in disease, EARLY death, HEMORRHAGE risk factors, DISEASES, PATIENTS
Abstract

Our knowledge about acute promyelocytic leukemia (APL) patients is mainly based on data from clinical trials, whereas population-based information is scarce. We studied APL patients diagnosed between 1997 and 2006 in the population-based Swedish Adult Acute Leukemia Registry. Of a total of 3897 acute leukemia cases, 3205 (82%) had non-APL acute myeloid leukemia (AML) and 105 (2.7%) had APL. The incidence of APL was 0.145 per 100 000 inhabitants per year. The median age at the time of diagnosis was 54 years; 62% were female and 38% male. Among younger APL patients, female sex predominated (89% of patients <40 years). Of the 105 APL patients, 30 (29%) died within 30 days (that is, early death (ED)) (median 4 days) and 28 (26%) within 14 days from diagnosis. In all, 41% of the EDs were due to hemorrhage; 35% of ED patients never received all-trans-retinoic acid treatment. ED rates increased with age but more clearly with poor performance status. ED was also associated with high white blood cells, lactate dehydrogenase, creatinine, C-reactive protein and low platelet count. Of non-ED patients, 97% achieved complete remission of which 16% subsequently relapsed. In total, 62% are still alive at 6.4 years median follow-up. We conclude that ED rates remain very high in an unselected APL population. [ABSTRACT FROM AUTHOR]

Published
2011
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149. Allogeneic haematopoietic stem-cell transplantation with reduced intensity conditioning for advanced stage Hodgkin's lymphoma in Sweden: high incidence of post transplant lymphoproliferative disorder.

Author

Johansson, J.-E., Remberger, M., Lazarevic, V.Lj., Hallböök, H., Wahlin, A., Kimby, E., Juliusson, G., Omar, H., and Hägglund, H.

Subjects
HEMATOPOIETIC stem cell transplantation, HODGKIN'S disease, LYMPHOPROLIFERATIVE disorders, AUTOTRANSPLANTATION
Abstract

Allogeneic transplantation after reduced intensity conditioning (allo-RIC) is a treatment option for patients with Hodgkin's lymphoma (HL) relapsing after autologous transplantation. In all, 23 adult patients with HL underwent allo-RIC in Sweden between 2000 and 2007. The median number of previous treatment lines was five and 20 patients (87%) were previously autografted. TRM at 100 days and at 1 year was 13 and 22% respectively. Acute GVHD grades II-IV developed in 7 out of 23 patients (30%) and chronic GVHD in 10 out of 20 patients at risk (50%). The OS and EFS at three years was 59 and 27%, respectively. Four patients (17%) developed post transplant lymphoproliferative disease (PTLD) after a median time of 55 days (range 38-95); two of these patients later died. The study confirmed that allo-RIC is feasible, but associated with a substantial relapse rate: only 20% of the patients were still alive 7 years after the transplant. A finding of high incidence of PTLD needs to be confirmed in a larger trial that includes patients with non-HL and CLL. [ABSTRACT FROM AUTHOR]

Published
2011
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150. Priming with r-metHuSCF and filgrastim or chemotherapy and filgrastim in patients with malignant lymphomas: a randomized phase II pilot study of mobilization and engraftment.

Author

Johnsen, H. E., Geisler, C., Juvonen, E., Remes, K., Juliusson, G., H&x#x00F6;rnsten, P., Kvaloy, S., Kvalheim, G., Jürgensen, G. W., Pedersen, L. M., Bergmann, O. J., Schmitz, A., and Boegsted, M.

Subjects
DRUG therapy, LYMPHOMA treatment, GROWTH factors, NEUTROPENIA, CYTOKINES
Abstract

SCF has been shown to synergize with G-CSF to mobilize CD34+ PBPCs. In this study we report results from this combination after a phase II trial of 32 patients with malignant lymphoma randomized to receive recombinant methionyl human SCF (ancestim, r-metHuSCF) in combination with recombinant methionyl human G-CSF (filgrastim, r-metHuG-CSF) (experimental arm A) or routine chemotherapy plus filgrastim (conventional arm B). The primary objective was to evaluate the side effects and toxicity during priming and mobilization. The secondary objectives were efficacy by the level of blood-circulating PBPCs, the number of harvest days and the time to three-lineage engraftment after autografting. First, during priming 5 patients had 8 serious events, 4 in each arm. A summary of all adverse events revealed 30 (94%) patients suffering from 132 events of all grading. Second, neutropenia and thrombocytopenia was documented in arm B. Third, 9/14 (64%) patients in arm A reached the target of 5 million CD34+ cells/kg body weight (bw) compared with 13/15 (87%) in arm B. The results represent the first randomized trial of growth factor plus chemotherapy priming and indicate that a formal phase III trial very unlikely may challenge chemotherapy plus r-metHuG-CSF priming in candidates for high-dose therapy. [ABSTRACT FROM AUTHOR]

Published
2011
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