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Juliusson, Gunnar
Publications (10 of 41) Show all publications
Mulligan, S. P., -Karlsson, K., Stromberg, M., Jonsson, V., Gill, D., Hammerstrom, J., . . . Juliusson, G. (2014). Cladribine prolongs progression-free survival and time to second treatment compared to fludarabine and high-dose chlorambucil in chronic lymphocytic. Leukemia and Lymphoma, 55(12), 2769-2777
Open this publication in new window or tab >>Cladribine prolongs progression-free survival and time to second treatment compared to fludarabine and high-dose chlorambucil in chronic lymphocytic
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2014 (English)In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 55, no 12, p. 2769-2777Article in journal (Refereed) Published
Abstract [en]

We conducted a randomized phase III trial to compare the efficacy and safety of two purine analogs, cladribine and fludarabine, with high-dose chlorambucil, in patients with previously untreated chronic lymphocytic leukemia (CLL). Between 1997 and 2004, 223 patients with CLL were randomly assigned to cladribine, fludarabine or chlorambucil, for six cycles of therapy with frequent health-related quality of life assessments. There was no statistical difference for the primary endpoint of overall response with cladribine (70%), fludarabine (67%) and chlorambucil (59%), or complete remission (12%, 7% and 8%), respectively. However, the median progression-free survival (25, 10, 9 months) and median time to second treatment (40, 22, 21 months) were superior with cladribine. There was no significant difference in overall survival (96, 82 and 91 months), nor in toxicity or HRQoL assessments. Monotherapy with cladribine gives superior PFS and longer response duration than fludarabine and chlorambucil as first-line treatment of CLL.

Place, publisher, year, edition, pages
Informa Healthcare, 2014
Keywords
Lymphoid leukemia; chemotherapeutic approaches; pharmacotherapeutics; CLL
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:liu:diva-113371 (URN)10.3109/10428194.2014.893306 (DOI)000346571100016 ()24524339 (PubMedID)
Available from: 2015-01-16 Created: 2015-01-16 Last updated: 2017-12-05
E Johnsen, H., Geisler, C., Juvonen, E., Remes, K., Juliusson, G., Hornsten, P., . . . Boegsted, M. (2011). 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. BONE MARROW TRANSPLANTATION, 46(1), 44-51
Open this publication in new window or tab >>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
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2011 (English)In: BONE MARROW TRANSPLANTATION, ISSN 0268-3369, Vol. 46, no 1, p. 44-51Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2011
Keywords
SCF, priming, mobilization, lymphoma, clinical trial
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-65568 (URN)10.1038/bmt.2010.84 (DOI)000286136000010 ()
Available from: 2011-02-11 Created: 2011-02-11 Last updated: 2011-02-11
Gimsing, P., Carlson, K., Turesson, I., Fayers, P., Waage, A., Vangsted, A., . . . Wisloeff, F. (2010). Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial. LANCET ONCOLOGY, 11(10), 973-982
Open this publication in new window or tab >>Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial
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2010 (English)In: LANCET ONCOLOGY, ISSN 1470-2045, Vol. 11, no 10, p. 973-982Article in journal (Refereed) Published
Abstract [en]

Background Compared with placebo, prophylactic treatment with bisphosphonates reduces risk of skeletal events in patients with multiple myeloma. However, because of toxicity associated with long-term bisphosphonate treatment, establishing the lowest effective dose is important. This study compared the effect of two doses of pamidronate on health-related quality of life and skeletal morbidity in patients with newly diagnosed multiple myeloma. Methods This double-blind, randomised, phase 3 trial was undertaken at 37 clinics in Denmark, Norway, and Sweden. Patients with multiple myeloma who were starting antimyeloma treatment were randomly assigned in a 1:1 ratio to receive one of two doses of pamidronate (30 mg or 90 mg) given by intravenous infusion once a month for at least 3 years. Randomisation was done by use of a central, computerised minimisation system. Primary outcome was physical function after 12 months estimated by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire (scale 0-100). All patients who returned questionnaires at 12 months and were still on study treatment were included in the analysis of the primary endpoint. This study is registered with ClinicalTrials. gov, number NCT00376883. Findings From January, 2001, until August, 2005, 504 patients were randomly assigned to pamidronate 30 mg or 90 mg (252 in each group). 157 patients in the 90 mg group and 156 in the 30 mg group were included in the primary analysis. Mean physical function at 12 months was 66 points (95% CI 62.9-70.0) in the 90 mg group and 68 points (64.6-71.4) in the 30 mg group (95% CI of difference -6.6 to 3.3; p=0.52). Median time to first skeletal-related event in patients who had such an event was 9.2 months (8.1-10.7) in the 90 mg group and 10-2 months (7.3-14.0) in the 30 mg group (p=0.63). In a retrospective analysis, eight patients in the pamidronate 90 mg group developed osteonecrosis of the jaw compared with two patients in the 30 mg group. Interpretation Monthly infusion of pamidronate 30 mg should be the recommended dose for prevention of bone disease in patients with multiple myeloma.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam., 2010
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-61183 (URN)10.1016/S1470-2045(10)70198-4 (DOI)000283210600023 ()
Available from: 2010-11-05 Created: 2010-11-05 Last updated: 2010-11-05
Carstensen, J., Billström, R., Gruber, A., Hellström-Lindberg, E., Höglund, M., Karlsson, K., . . . Nordenskjöld, K. (2006). Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival. Leukemia, 20(1), 42-47
Open this publication in new window or tab >>Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival
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2006 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 20, no 1, p. 42-47Article in journal (Refereed) Published
Abstract [en]

Combination chemotherapy may induce remission from acute myeloid leukemia (AML), but validated criteria for treatment of elderly are lacking. The remission intention (RI) rate for elderly patients, as reported to the Swedish Leukemia Registry, was known to be different when comparing the six health care regions, but the consequences of different management are unknown. The Leukemia Registry, containing 1672 AML patients diagnosed between 1997 and 2001, with 98% coverage and a median follow-up of 4 years, was completed with data from the compulsory cancer and population registries. Among 506 treated and untreated patients aged 70 -79 years with AML (non-APL), there was a direct correlation between the RI rate in each health region (range 36 -76%) and the two-year overall survival, with no censored observations (6 -21%) (χ2 for trend=11.3, P<0.001, r2=0.86, P<0.02, nonparametric). A 1-month landmark analysis showed significantly better survival in regions with higher RI rates (P=0.003). Differences could not be explained by demographics, and was found in both de novo and secondary leukemias. The 5-year survival of the overall population aged 70 -79 years was similar between the regions. Survival of 70 -79-year-old AML patients is better in regions where more elderly patients are judged eligible for remission induction. © 2006 Nature Publishing Group All rights reserved.

National Category
Social Sciences
Identifiers
urn:nbn:se:liu:diva-36336 (URN)10.1038/sj.leu.2404004 (DOI)31025 (Local ID)31025 (Archive number)31025 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Lenhoff, S., Hjorth, M., Westin, J., Brinch, L., Backstrom, B., Carlson, K., . . . Turesson, I. (2006). Impact of age on survival after intensive therapy for multiple myeloma: A population-based study by the Nordic Myeloma Study Group. British Journal of Haematology, 133(4), 389-396
Open this publication in new window or tab >>Impact of age on survival after intensive therapy for multiple myeloma: A population-based study by the Nordic Myeloma Study Group
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2006 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 133, no 4, p. 389-396Article in journal (Refereed) Published
Abstract [en]

The value of intensive therapy, including autologous stem cell transplantation, in newly diagnosed myeloma patients >60 years is not clear. We evaluated the impact of age (<60 years vs. 60-64 years) on survival in a prospective, population-based setting and compared survival with conventionally treated historic controls. The prospective population comprised 452 patients registered between 1998 and 2000. Of these, 414 received intensive therapy. The historic population, derived from our most recent population-based study on conventional therapy, comprised 281 patients. Of these, 243 fulfilled our eligibility criteria for intensive therapy. For patients undergoing intensive therapy it was found that two factors, beta-2-microglobulin and age <60 years vs. 60-64 years, had independent prognostic impact on survival. However, compared with the historic controls a survival advantage was found both for patients <60 (median 66 months vs. 43 months, P < 0.001) and 60-64 years (median 50 months vs. 27 months, P = 0.001). We conclude that in a population-based setting higher age adversely influences outcome after intensive therapy. Our results indicate that intensive therapy prolongs survival also at age 60-64 years but with less superiority than in younger patients. © 2006 Blackwell Publishing Ltd.

Keywords
Age, Myeloma, Population based, Survival, Transplantation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-50229 (URN)10.1111/j.1365-2141.2006.06042.x (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12
Juliusson, G., Theorin, N., Karlsson, K., Frödin, U. & Malm, C. (2006). Subcutaneous alemtuzumab vs ATG in adjusted conditioning for allogeneic transplantation: Influence of Campath dose on lymphoid recovery, mixed chimerism and survival. Bone Marrow Transplantation, 37(5), 503-510
Open this publication in new window or tab >>Subcutaneous alemtuzumab vs ATG in adjusted conditioning for allogeneic transplantation: Influence of Campath dose on lymphoid recovery, mixed chimerism and survival
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2006 (English)In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 37, no 5, p. 503-510Article in journal (Refereed) Published
Abstract [en]

Sixty-nine consecutive patients (median age 54 years) were prospectively enrolled in a single-institution protocol for allogeneic transplantation with adjusted non-myeloablative fludarabine-melfalan-based conditioning including cyclosporin A and MMF, and one of three modes of serotherapy. Thirty-one donors (45%) were unrelated. The first cohort of 29 had ATG (Thymoglobulin 2 mg/kg × 3 days), the subsequent 26 had Campath 30 mg × 3 days subcutaneously, and the final cohort of 14 had 30 mg Campath once. The groups were similar as regards age, diagnosis and risk factors. Campath-patients had no acute toxicity, fewer days with fever and antibiotics, and required fewer transfusions than ATG-treated patients. 3-d-Campath patients showed lower lymphocyte counts from day + 4, and CD4 +, CD8 +, CD19 + and NK cells recovered slower than in ATG-treated patients. More Campath patients developed mixed chimerism that required DLI. 3-d-Campath induced more serious and opportunistic infections than ATG, which resulted in a greater non-relapse mortality and an impaired overall survival despite a low tumor-related mortality. The change of the Campath dosing schedule to one dose abrogated the deleterious effect of 3-d-Campath on immune recovery, severe infections and survival. Subcutaneous Campath is simple and provides strong immune suppression with no early toxicity, but dose limitation to 30 mg once is recommended. © 2006 Nature Publishing Group. All rights reserved.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-37781 (URN)10.1038/sj.bmt.1705263 (DOI)38533 (Local ID)38533 (Archive number)38533 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Lotfi, K., Karlsson, K., Fyrberg, A., Juliusson, G., Jonsson, V., Peterson, C., . . . Albertioni, F. (2006). The pattern of deoxycytidine- and deoxyguanosine kinase activity in relation to messenger RNA expression in blood cells from untreated patients with B-cell chronic lymphocytic leukemia. Biochemical Pharmacology, 71(6), 882-890
Open this publication in new window or tab >>The pattern of deoxycytidine- and deoxyguanosine kinase activity in relation to messenger RNA expression in blood cells from untreated patients with B-cell chronic lymphocytic leukemia
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2006 (English)In: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 71, no 6, p. 882-890Article in journal (Refereed) Published
Abstract [en]

Deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) catalyze the first step in the intracellular cascade of fludarabine (2-fluoroadenine-β- d-arabinofuranoside) and cladribine (2-chlorodeoxyadenosine) phosphorylation, which leads to activation of these prodrugs, commonly used for treatment of chronic lymphocytic leukemia (CLL). Thus, resistance to nucleoside analogues may primarily be due to low levels of deoxynucleoside kinase activity. The purpose of this study was to investigate the activity profiles of dCK and dGK and characterize the possible relationship between the levels of dCK enzymatic activities and mRNA levels in B-CLL cells from untreated patient samples in an attempt to determine the best approach for predicting sensitivity to nucleoside analogues and thereby optimizing treatment of CLL. For this purpose, dCK and dGK analyses were done in blood cells from 59 untreated symptomatic patients with CLL. The dGK activity towards 2-chlorodeoxyadenosine was significantly lower than of dCK (median 73 pmol/mg protein/min (85-121, 95% CI) versus 353 pmol/mg protein/min (331-421)). The median dCK mRNA level was 0.107 (0.096-0.120, 95% CI). There was a lack of correlation between the activities of dCK and dGK, which indicates that these proteins are regulated independently. We also found that the dCK and dGK activity measurement towards their endogenous substrates were comparable to the nucleoside analogues tested. Such variations in enzyme activities and mRNA levels may well explain differences in clinical responses to treatment. There was no correlation between the levels of dCK mRNAs and enzymatic activities using a quantitative real-time PCR procedure. Sequencing of dCK mRNA did not reveal alternate splicing or mutations in the coding region. The relation between activity and mRNA levels was studied by short interfering RNA (siRNA) method, which showed that in the siRNA treated cells the down-regulation of dCK expression, and activity followed each other. However, in control cells the mRNA levels remained stable but the protein activity markedly decreased. These data demonstrate that the dCK activity is not reflected by dCK mRNA expression that indicates a post-translational mechanism(s). © 2005 Elsevier Inc. All rights reserved.

Keywords
Purine analogues; Deoxycytidine kinase; Deoxyguanosine kinase; Chronic lymphocytic leukemia
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-36125 (URN)10.1016/j.bcp.2005.12.007 (DOI)30004 (Local ID)30004 (Archive number)30004 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2018-03-21
Castor, A., Nilsson, L., Åstrand-Grundström, I., Buitenhuis, M., Ramirez, C., Anderson, K., . . . Jacobsen, S. E. (2005). Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia. Nature Medicine, 11(6), 630-637
Open this publication in new window or tab >>Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia
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2005 (English)In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 11, no 6, p. 630-637Article in journal (Refereed) Published
Abstract [en]

The cellular targets of primary mutations and malignant transformation remain elusive in most cancers. Here, we show that clinically and genetically different subtypes of acute lymphoblastic leukemia (ALL) originate and transform at distinct stages of hematopoietic development. Primary ETV6-RUNX1 (also known as TEL-AML1) fusions and subsequent leukemic transformations were targeted to committed B-cell progenitors. Major breakpoint BCR-ABL1 fusions (encoding P210 BCR-ABL1) originated in hematopoietic stem cells (HSCs), whereas minor BCR-ABL1 fusions (encoding P190 BCR-ABL1) had a B-cell progenitor origin, suggesting that P190 and P210 BCR-ABL1 ALLs represent largely distinct tumor biological and clinical entities. The transformed leukemia-initiating stem cells in both P190 and P210 BCR-ABL1 ALLs had, as in ETV6-RUNX1 ALLs, a committed B progenitor phenotype. In all patients, normal and leukemic repopulating stem cells could successfully be separated prospectively, and notably, the size of the normal HSC compartment in ETV6-RUNX1 and P190 BCR-ABL1 ALLs was found to be unaffected by the expansive leukemic stem cell population.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-31659 (URN)10.1038/nm1253 (DOI)17472 (Local ID)17472 (Archive number)17472 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13
Lotfi, K., Peterson, C. & Juliusson, G. (2005). Letter: Monitoring oral cyclosporine therapy [Letter to the editor]. Bone Marrow Transplantation, 36, 367-367
Open this publication in new window or tab >>Letter: Monitoring oral cyclosporine therapy
2005 (English)In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 36, p. 367-367Article in journal, Letter (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-30893 (URN)16556 (Local ID)16556 (Archive number)16556 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
Crawley, C., Lalancette, M., Szydlo, R., Gilleece, M., Peggs, K., Mackinnon, S., . . . Bjorkstrand, B. (2005). Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT. Blood, 105(11), 4532-4539
Open this publication in new window or tab >>Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT
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2005 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 105, no 11, p. 4532-4539Article in journal (Refereed) Published
Abstract [en]

We report the outcome of 229 patients who received an allograft for myeloma with reduced-intensity conditioning (RIC) regimens from 33 centers within the European Group for Blood and Marrow Transplantation (EBMT). The median age was 52 years and 64% were male. Conditioning regimens were heterogeneous, but most were fludarabine based and T cell depleted with antithymocyte globulin or alemtuzumab. Transplantation-related mortality (TRIM) at 1 year was 22%. The 3-year overall survival (OS) and progression-free survival (PFS) were 41% and 21 %, respectively. Adverse OS was associated with chemoresistant disease (relative risk [RR], 2.9), more than 1 prior transplantation (RR, 2.0), and male patients with female donors (FIR, 1.45). Adverse PFS was associated with chemoresistance (RR, 2.4) and alemtuzumab (RR, 1.8). TRM was increased with female-to-male donation (RR, 2.5) and transplantation more than 1 year from diagnosis (RR, 2.3). Grades II to IV acute graft-versus-host disease (aGvHD) occurred in 31%. Chronic GvHD was associated with better OS and PFS and were 84% and 46% for limited, 58% and 30% for extensive, and 29% and 12% in its absence suggesting that a graft-versus-myeloma effect is important. While RIC is feasible, heavily pretreated patients and patients with progressive disease do not benefit.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-46112 (URN)10.1182/blood-2004-06-2387 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
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