Publications by authors named "Geir Erland Tjønnfjord"

21 Publications

  • Page 1 of 1

Tissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia.

Sci Rep 2021 Mar 4;11(1):5127. Epub 2021 Mar 4.

Department of Haematology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450000, China.

The infiltration of chronic lymphocytic leukemia (CLL) cells into lymphoid organs correlates with disease severity. CXCL12 is a key chemotactic factor for the trafficking of CLL. Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor and plays a role in CXCL12-mediated hematopoietic stem cell homing. We aim to explore the role of TFPI in CXCL12-mediated migration of CLL cells. In this study, plasma TFPI concentrations were measured by ELISA. CLL cells were isolated from patients and used for trans-endothelial migration (TEM) assays. Quantitative RT-PCR and Western blotting were used to detect the expression of CXCR7, CXCR4 and β-catenin. Immunofluorescence and co-immunoprecipitation was used to detect the binding of TFPI and glypican-3 (GPC3). We found that plasma TFPI levels in CLL patients were higher than in healthy controls, particularly in the patients with advanced disease. TFPI enhanced CXCL12-mediated TEM of CLL cells by increasing the expression of the CXCL12 receptor CXCR7, but not of the CXCL12 receptor CXCR4. The effect of TFPI on TEM was abolished by the CXCR7 inhibitor, CCX771, while the CXCR4 inhibitor AMD3100 strongly increased TEM. TFPI co-localized with GPC3 on the cell surface. An antibody to GPC3, HS20, decreased CXCR7 expression and abolished the effect of TFPI on TEM. TFPI activated β-catenin and the Wnt/β-catenin inhibitor IWP4 repressed the effect of TFPI on CXCR7 expression and TEM. We conclude that TFPI may contribute to organ infiltration in CLL patients.
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http://dx.doi.org/10.1038/s41598-021-84695-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933411PMC
March 2021

HLA class I depletion by citric acid, and irradiation of apheresis platelets for transfusion of refractory patients.

Transfusion 2021 Apr 13;61(4):1222-1234. Epub 2021 Feb 13.

Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway.

Background: Patients can form antibodies to foreign human leukocyte antigen (HLA) Class I antigens after exposure to allogeneic cells. These anti-HLA class I antibodies can bind transfused platelets (PLTs) and mediate their destruction, thus leading to PLT refractoriness. Patients with PLT refractoriness need HLA-matched PLTs, which require expensive HLA typing of donors, antibody analyses of patient sera and/or crossmatching. An alternative approach is to reduce PLT HLA Class I expression using a brief incubation in citric acid on ice at low pH.

Methods And Materials: Apheresis PLT concentrates were depleted of HLA Class I complexes by 5 minutes incubation in ice-cold citric acid, at pH 3.0. Surface expression of HLA Class I complexes, CD62P, CD63, phosphatidylserine, and complement factor C3c was analyzed by flow cytometry. PLT functionality was tested by thromboelastography (TEG).

Results: Acid treatment reduced the expression of HLA Class I complexes by 71% and potential for C3c binding by 11.5-fold compared to untreated PLTs. Acid-treated PLTs were significantly more activated than untreated PLTs, but irrespective of this increase in steady-state activation, CD62P and CD63 were strongly upregulated on both acid-treated and untreated PLTs after stimulation with thrombin receptor agonist peptide. Acid treatment did not induce apoptosis over time. X-ray irradiation did not significantly influence the expression of HLA Class I complexes, CD62P, CD63, and TEG variables on acid treated PLTs.

Conclusion: The relatively simple acid stripping method can be used with irradiated apheresis PLTs and may prevent transfusion-associated HLA sensitization and overcome PLT refractoriness.
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http://dx.doi.org/10.1111/trf.16282DOI Listing
April 2021

Transformation to plasmablastic lymphoma in CLL upon ibrutinib treatment.

BMJ Case Rep 2020 Sep 29;13(9). Epub 2020 Sep 29.

Department of Haematology, Oslo Universitetssykehus, Oslo, Norway.

Chronic lymphatic leukaemia (CLL) is the most common leukaemia in the Western world. Ibrutinib, a tyrosine kinase inhibitor, is the treatment of choice on relapse or p53-dysfunction. Richter's transformation to diffuse large B cell lymphoma is most often seen. However, transformation to other aggressive lymphomas as plasmablastic lymphoma (PBL) does occur. PBL is an extremely aggressive lymphoma and is usually treated using a CHOP-like regimen (cyclophosphamide, doxorubicin, vincristine and prednisone/dexamethasone), but with poor outcome. The only curative treatment is allogeneic stem cell transplant (ASCT).We report on a case of CLL treated with ibrutinib that underwent transformation to PBL. Due to high expression of CD138, we added daratumumab to the chemotherapy with a good, but transitory response. The case did not make it to an ASCT. Targeting CD138 by daratumumab may be added to chemoimmune therapy for PBL.
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http://dx.doi.org/10.1136/bcr-2020-235816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526319PMC
September 2020

Antitumor, Anti-Inflammatory and Antiallergic Effects of Mushroom Extract and the Related Medicinal Basidiomycetes Mushrooms, and : A Review of Preclinical and Clinical Studies.

Nutrients 2020 May 8;12(5). Epub 2020 May 8.

Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway.

Since the 1980s, medicinal effects have been documented in scientific studies with the related mushrooms Murill (AbM), (HE) and (GF) from Brazilian and Eastern traditional medicine. Special focus has been on their antitumor effects, but the mushrooms' anti-inflammatory and antiallergic properties have also been investigated. The antitumor mechanisms were either direct tumor attack, e.g., apoptosis and metastatic suppression, or indirect defense, e.g., inhibited tumor neovascularization and T helper cell (Th) 1 immune response. The anti-inflammatory mechanisms were a reduction in proinflammatory cytokines, oxidative stress and changed gut microbiota, and the antiallergic mechanism was amelioration of a skewed Th1/Th2 balance. Since a predominant Th2 milieu is also found in cancer, which quite often is caused by a local chronic inflammation, the three conditions-tumor, inflammation and allergy-seem to be linked. Further mechanisms for HE were increased nerve and beneficial gut microbiota growth, and oxidative stress regulation. The medicinal mushrooms AbM, HE and GF appear to be safe, and can, in fact, increase longevity in animal models, possibly due to reduced tumorigenesis and oxidation. This article reviews preclinical and clinical findings with these mushrooms and the mechanisms behind them.
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http://dx.doi.org/10.3390/nu12051339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285126PMC
May 2020

Two Consecutive Episodes of Severe Delayed Hemolytic Transfusion Reaction in a Sickle Cell Disease Patient.

Case Rep Hematol 2020 14;2020:2765012. Epub 2020 Apr 14.

Department of Haematology, Oslo University Hospital, Oslo, Norway.

Patients with sickle cell disease (SCD) suffer from anemia and painful vaso-occlusive crisis (VOC) and sometimes need blood transfusions. Delayed hemolytic transfusion reaction (DHTR) is a rare life-threatening complication observed in SCD and mimics VOC. We describe a female SCD patient undergoing three surgical procedures during which DHTR developed following the first two. Prior to a planned tonsillectomy, she received transfusion and three days after surgery developed severe hemolysis as well as pain and respiratory symptoms. On suspicion of VOC, she received additional transfusions and became hemodynamically unstable, and her hemolytic anemia worsened. Gradually, she recovered and could be discharged after two weeks; DHTR was not suspected. Sixteen months later, an arthroplasty was performed due to avascular necrosis, and again she was transfused preoperatively. Similar to the initial surgery, she developed symptoms and signs of VOC after three days, but this time, DHTR was suspected and further transfusions were withheld. Although immunosuppressive medication did not alleviate the condition, she improved on combined treatment with darbepoietin, rituximab, and eculizumab. Six months later, a second arthroplasty was performed uneventfully after prophylaxis with rituximab and without transfusion. DHTR should be considered in the presence of severe, unexplained hemolysis following a recent transfusion, and additional transfusions in this setting should be given only on vital indication.
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http://dx.doi.org/10.1155/2020/2765012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180413PMC
April 2020

Chronic lymphocytic leukemia and secondary hematological malignancies: A nation-wide cancer registry study.

Eur J Haematol 2020 Jun 4;104(6):546-553. Epub 2020 Mar 4.

Department of Hematology, Oslo University Hospital, Oslo, Norway.

Objective: Chronic lymphocytic leukemia (CLL) treatment has changed dramatically, and landscape of second hematologic malignancies (SHM) evolves in the new era of targeted therapy. No data were available about the real-world burden of SHM.

Methods: All 2631 patients with CLL in the Cancer registry of Norway registered 2003-2012 were included.

Results: After median follow-up of 6.6 years, 103 patients (4%) developed SHM. Diffuse large B-cell lymphoma (DLBCL) was most common (n = 65; 63%). Median survival was 9.3 years (95% CI; 8.9-9.8) in non-SHM patients and 1.7 years in DLBCL, 0.8 years in Hodgkin lymphoma (n = 12), and 2.8 years in myeloid neoplasia (n = 15; 95% CI: 0.3-2.6, 0.6-2.9, and 0.4-5.3, respectively; P < .001). Outcomes were poorest for SHM patients treated for CLL (HR 2.76, 95% CI 1.4-5.5, P = 0.003). A higher proportion of men and younger age were found in SHM patients (median age 66 vs 72 years in non-SHM; P < .001; men 68% vs 57%, P = .03). Myeloid neoplasia was rare (incidence rate 1/1000 person-years; 95% CI: 0.6-1.5) and tended to occur later than DLBCL in patients treated for CLL (median time from CLL to SHM 62 vs 45 months; P = .09).

Conclusions: SHM and especially myeloid malignancies were rare in chemoimmunotherapy era.
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http://dx.doi.org/10.1111/ejh.13396DOI Listing
June 2020

The Systemic Metabolic Profile Early after Allogeneic Stem Cell Transplantation: Effects of Adequate Energy Support Administered through Enteral Feeding Tube.

Biol Blood Marrow Transplant 2020 02 14;26(2):380-391. Epub 2019 Oct 14.

Section for Hematology, Department of Medicine, Haukeland University Hospital, Bergen, Norway; Section for Hematology, Institute of Clinical Science, University of Bergen, Bergen, Norway.

Patients undergoing allogeneic stem cell transplantation usually require nutritional support. There is no consensus on whether enteral support through tube feeding should be preferred. A recent randomized study could not detect any difference between enteral and parenteral feeding with regard to post-transplant outcomes, whereas 2 retrospective studies described an association between enteral feeding and a favorable post-transplant outcome. We compared pre- and post-transplant plasma metabolomic profiles for 10 patients receiving mainly enteral nutritional support and 10 patients receiving mainly parenteral support. Samples were collected before conditioning and 3 weeks post-transplant; 824 metabolites were analyzed using mass spectrometry. The pretransplant metabolite profiles showed a significant overlap between the 2 groups. Post-transplant samples for both patient groups showed an increase of secondary bile acids and endocannabinoids, whereas reduced levels were seen for food preservatives, plasmalogens, and retinol metabolites. The main post-transplant differences between the groups were decreased levels of fatty acids and markers of mitochondrial activation in the control group, indicating that these patients had insufficient energy intake. A significant effect was also seen for heme/bilirubin metabolism for the parenteral support. To conclude, allotransplant recipients showed altered metabolic profiles early after transplantation; this was mainly due to the conditioning/transplantation/reconstitution, whereas the type of nutritional support had minor effects.
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http://dx.doi.org/10.1016/j.bbmt.2019.10.005DOI Listing
February 2020

Richter syndrome epidemiology in a large population based chronic lymphocytic leukemia cohort from Norway.

Cancer Epidemiol 2019 06 12;60:128-133. Epub 2019 Apr 12.

Department of Haematology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Centre for B-Cell malignancies, University of Oslo, Oslo, Norway.

Background: Transformation to aggressive lymphoma (Richter syndrome, RS) occurs in a substantial subset of patients who must discontinue targeted therapy for chronic lymphocytic leukemia (CLL). RS has an extremely poor prognosis.

Methods: Using the nation-wide database of The Cancer Registry of Norway of 7664 CLL patients registered between 1953-2012, we identified 107 patients experiencing RS.

Results: Seventy seven (72%) of RS patients were identified among 2631 CLL patients diagnosed between 2003-2012; diffuse large B-cell lymphoma (DLBCL) was identified in 65 (84%), Hodgkin lymphoma (HL) in 12 (16%) patients and the diagnosis was confirmed in 50 (65%) available biopsy specimens. The incidence rate in this period was 4.7/1000 person-years (95% CI: 3.8-5.9). The median survival from CLL diagnosis was 1.7 years (95% CI: 0.34-2.3) for RS patients while it was 10.3 years (95% CI: 9.5-10.9) for the remaining CLL patients. Male gender predominated among RS patients (69%) compared to CLL population (58%) and RS patients were diagnosed with CLL at a significantly younger age than the remaining patients (65 vs. 72 years). Median time from diagnosis of CLL to RS was 2 years (Range, 0-13 years). No CLL treatment was administered in 25 (33%) patients prior RS diagnosis; a median of 1 treatment line was administered to pretreated patients. The median duration of survival after RS diagnosis was 27 months (95% CI; 9-88).

Conclusions: Collectively, RS was a rare complication of CLL in the chemoimmunotherapy era, occurred early in the CLL course in younger, and both treatment naïve and pretreated patients, and shortened survival substantially.
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http://dx.doi.org/10.1016/j.canep.2019.04.002DOI Listing
June 2019

A Case of Posttransfusion Purpura with Severe Refractory Thrombocytopenia but No Cutaneous Manifestations.

Case Rep Hematol 2018 29;2018:8187659. Epub 2018 Oct 29.

Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway.

Posttransfusion purpura is a serious adverse effect of transfusion due to HPA-antibodies. A young female was diagnosed with acute leukaemia, and treatment commenced. Severe thrombocytopenia ensued. No platelet increment was achieved despite transfusions with buffy coat, HLA-compatible, and HPA-1a negative platelets. The workup indicated the presence of anti-HPA-1a. When the diagnosis of posttransfusion purpura was sufficiently substantiated, she had experienced a fatal intracerebral haemorrhage.
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http://dx.doi.org/10.1155/2018/8187659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231382PMC
October 2018

STIM1 R304W causes muscle degeneration and impaired platelet activation in mice.

Cell Calcium 2018 12 5;76:87-100. Epub 2018 Oct 5.

Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway. Electronic address:

STIM1 and ORAI1 regulate store-operated Ca entry (SOCE) in most cell types, and mutations in these proteins have deleterious and diverse effects. We established a mouse line expressing the STIM1 R304 W gain-of-function mutation causing Stormorken syndrome to explore effects on organ and cell physiology. While STIM1 R304 W was lethal in the homozygous state, surviving mice presented with reduced growth, skeletal muscle degeneration, and reduced exercise endurance. Variable STIM1 expression levels between tissues directly impacted cellular SOCE capacity. In contrast to patients with Stormorken syndrome, STIM1 was downregulated in fibroblasts from Stim1 mice, which maintained SOCE despite constitutive protein activity. In studies using foetal liver chimeras, STIM1 protein was undetectable in homozygous megakaryocytes and platelets, resulting in impaired platelet activation and absent SOCE. These data indicate that downregulation of STIM1 R304 W effectively opposes the gain-of-function phenotype associated with this mutation, and highlight the importance of STIM1 in skeletal muscle development and integrity.
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http://dx.doi.org/10.1016/j.ceca.2018.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481308PMC
December 2018

Improved outcome in patients following autologous stem cell transplantation for multiple myeloma in south eastern Norway 2001-2010: a retrospective, population based analysis.

BMC Cancer 2018 Aug 8;18(1):801. Epub 2018 Aug 8.

Department of Haematology, Oslo University Hospital, P.O.Box 4950 Nydalen, 0424, Oslo, Norway.

Background: With the advent of novel drugs improved overall survival in patients with multiple myeloma, including patients who received up-front autologous stem cell transplantation (ASCT), has been reported from several centers. Here we report on overall survival in a population-based cohort of patients receiving ASCT as first line treatment and in whom novel agents were an option for second and later lines of treatment.

Methods: Patients with multiple myeloma ≤ 65 years of age who were considered for ASCT from 01.01.2001-31.06.2005 (period 1) and from 01.07.2005 until 31.12.2009 (period 2) at Oslo University Hospital (OUH) were identified. Relevant data were collected from the patients' medical records.

Results: Altogether, 293/355 patients received ASCT. In all, median OS was 82.9 months in patients ≤ 60 years of age and 59.0 months in patients 61-65 years. For patients ≤ 60 years of age median OS increased from 70.6 months to 87.7 months (p = 0. 22) and median survival after start of second line therapy increased from 34.5 months to 46.5 months (p = 0.015) between the two periods. For patients 61-65 years of age median OS increased from 57.3 months to 61.2 months (p = 0. 87) and median survival after start of second line therapy was practically unchanged (32.6 months vs. 33.1 months (p = 0.97) between the periods. In patients ≤ 60 years of age salvage ASCT was used in 34% of the patients while in patients 61-65 years of age salvage ASCT was used in 7.3% of the patients. The use of salvage ASCT and novel drugs, as well as the number of treatment lines, were higher in patients ≤ 60 years of age and increased during the study period.

Conclusion: In patients ≤ 60 years of age an increased median OS of 17 months between the two periods were noted, but the difference failed to reach statistical significance. However, a statistically significant difference in median survival of 12 months after start of second line therapy was found in this age group, which may be explained by a more active second line treatment. In patients 61-65 years only a slight increase of survival, not statistically significant, was noted between the periods.
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http://dx.doi.org/10.1186/s12885-018-4722-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083560PMC
August 2018

Cost-utility of allogeneic hematopoietic stem cell transplantation in Norway.

Bone Marrow Transplant 2018 05 22;53(5):657-660. Epub 2018 Jan 22.

Department of Haematology and Oncology, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.

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http://dx.doi.org/10.1038/s41409-018-0091-yDOI Listing
May 2018

Prophylactic use of eculizumab during surgery in chronic cold agglutinin disease.

BMJ Case Rep 2017 May 9;2017. Epub 2017 May 9.

Department of Hematology, Institute of Clinical Medicine, Oslo Universitetssykehus, Oslo, Norway.

Primary chronic cold agglutinin disease (CAD) is an autoimmune haemolytic anaemia in which a specific bone marrow lymphoproliferative disorder causes production of cold agglutinins (CA). Binding of CA to erythrocyte surface antigens results in a predominantly extravascular haemolysis that is entirely complement dependent. Because of complement activation, exacerbations are common during febrile infections, trauma or major surgery. Involvement of the terminal complement pathway with C5-mediated intravascular haemolysis is probably not prominent in stable disease but is supposed to be of importance in exacerbations following acute phase reaction.We report on a patient with CAD prone to exacerbation of haemolysis during acute phase reactions who was scheduled for cardiac surgery. To prevent her having an exacerbation of haemolysis, we chose to treat her prophylactically with eculizumab along with the usual perioperative precautions. Aortic valve replacement was undertaken with full cardiopulmonary bypass at normothermia. The procedure was successful; no exacerbation of haemolysis was observed, and transfusion requirements did not exceed what could be expected.
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http://dx.doi.org/10.1136/bcr-2016-219066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612509PMC
May 2017

National trends in incidence and survival of chronic lymphocytic leukemia in Norway for 1953-2012: a systematic analysis of population-based data.

Cancer Med 2016 12 4;5(12):3588-3595. Epub 2016 Nov 4.

Department of Haematology, Oslo University Hospital, P.O.Box 4950 Nydalen, Oslo, 0424, Norway.

Chronic lymphocytic leukemia is a disease of the elderly, and despite major advances in treatment, remains incurable. The Cancer Registry of Norway has registered data on patients with chronic lymphocytic leukemia since 1953. We aimed to analyze trends in incidence and survival of chronic lymphocytic leukemia in Norway. We identified 7664 patients reported with chronic lymphocytic leukemia to the registry between 1953 and 2012. We gathered information on sex, age at diagnosis, date of death and basis for diagnosis. The age-standardized incidence increased from 0.6/100.000 person-years in 1953 to 3.1/100,000 person-years in 2012. We found a significant decrease in median age between 1993-2002 and 2003-2012 (75 vs. 72 years, 95%CI: 2.52-3.98, P < 0.001). Men were diagnosed at a significantly younger age than women. Immunophenotyping has become the most important diagnostic method after 2002. Median observed survival increased from 3 years in 1952-1963 to 8.5 years in 2003-2012. Five- and 10-year age-standardized net survival increased throughout the whole period across age groups and reached 79% and 57%, respectively. Median observed survival was significantly shorter in men than in women in 1993-2002 (4.9 vs. 6.1 years, P < 0.001). The gap between survival rates for men and women was diminishing in 2003-2012 in patients younger than 60 years while it remained considerable in older patients. Despite an aging Norwegian population, chronic lymphocytic leukemia (CLL) patients become younger at diagnosis. A fourfold increase in incidence, a prolonged survival, and major changes in diagnostic methods in Norway were observed.
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http://dx.doi.org/10.1002/cam4.849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5224846PMC
December 2016

Persistent bone marrow depression following short-term treatment with temozolomide.

BMJ Case Rep 2016 Apr 29;2016. Epub 2016 Apr 29.

Oslo University Hospital, Oslo, Norway.

Temozolomide (TMZ) is, in combination with radiotherapy (RT), the treatment of choice for glioblastoma multiforme. Although generally well tolerated, haematological side effects are observed in approximately 1-10% of patients receiving TMZ. We report a case of a patient who developed severe bone marrow failure (BMF) after only 3 weeks of concomitant TMZ. The BMF was grave with no signs of improvement for 12 months, resulting in more than 100 transfusions of blood cells.
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http://dx.doi.org/10.1136/bcr-2016-215797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854153PMC
April 2016

Therapeutic complement inhibition – from experimental to clinical medicine.

Tidsskr Nor Laegeforen 2015 Oct 20;135(19):1745-9. Epub 2015 Oct 20.

Forskningslaboratoriet Nordlandssykehuset Bodø og Senter for molekylær inflammasjonsforskning (SFF-CEMIR) Norges teknisk-naturvitenskapelige universitet.

Internationally, the use of the C5-inhibiting monoclonal antibody eculizumab has in the course of just a few years become the first choice of treatment of atypical haemolytic uraemic syndrome and the most severe phenotypes of paroxysmal nocturnal haemoglobinuria. At present eculizumab is the only complement inhibitor in ordinary clinical use. This despite the fact that there only exists one randomised, placebo-controlled trial of eculizumab for paroxysmal nocturnal haemoglobinuria and none for atypical haemolytic uraemic syndrome, and that the therapy is very costly. There is reason to believe that complement inhibition as therapy will increase in the future, and that other drugs will also prove to be effective.
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http://dx.doi.org/10.4045/tidsskr.15.0049DOI Listing
October 2015

Immunomodulatory effects of the Agaricus blazei Murrill-based mushroom extract AndoSan in patients with multiple myeloma undergoing high dose chemotherapy and autologous stem cell transplantation: a randomized, double blinded clinical study.

Biomed Res Int 2015 18;2015:718539. Epub 2015 Jan 18.

Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway ; Department of Immunology and Transfusion Medicine, Oslo University Hospital, 0424 Oslo, Norway.

Forty patients with multiple myeloma scheduled to undergo high dose chemotherapy with autologous stem cell support were randomized in a double blinded fashion to receive adjuvant treatment with the mushroom extract AndoSan, containing 82% of Agaricus blazei Murrill (19 patients) or placebo (21 patients). Intake of the study product started on the day of stem cell mobilizing chemotherapy and continued until the end of aplasia after high dose chemotherapy, a period of about seven weeks. Thirty-three patients were evaluable for all study endpoints, while all 40 included patients were evaluable for survival endpoints. In the leukapheresis product harvested after stem cell mobilisation, increased percentages of Treg cells and plasmacytoid dendritic cells were found in patients receiving AndoSan. Also, in this group, a significant increase of serum levels of IL-1ra, IL-5, and IL-7 at the end of treatment was found. Whole genome microarray showed increased expression of immunoglobulin genes, Killer Immunoglobulin Receptor (KIR) genes, and HLA genes in the Agaricus group. Furthermore, AndoSan displayed a concentration dependent antiproliferative effect on mouse myeloma cells in vitro. There were no statistically significant differences in treatment response, overall survival, and time to new treatment. The study was registered with Clinicaltrials.gov NCT00970021.
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http://dx.doi.org/10.1155/2015/718539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312620PMC
October 2015

Malignant phyllodes tumor and acute megakaryoblastic leukemia sharing a common clonal origin.

Case Rep Hematol 2013 17;2013:934781. Epub 2013 Dec 17.

Department of Pathology, University of Oslo, P.O. Box 4950, Nydalen, 0424 Oslo, Norway ; Department of Pathology, Oslo University Hospital, Radiumhospitalet, P.O. Box 4950, Nydalen, 0424 Oslo, Norway.

There is a well-known association in male patients between mediastinal germ cell tumors (GCT) and hematologic malignancies, with a propensity towards acute megakaryoblastic leukemia. These rare malignancies have been shown to share a common clonal origin, often deduced from the finding of isochromosome 12p, i(12p), in cells from both the solid tumor and the leukemia, and thus are now known to represent different manifestations of the same clonal process. We treated a young female patient with a malignant phyllodes tumor followed by an acute megakaryoblastic leukemia and found several of the same marker chromosomes by karyotype analysis of cells from both the tumor and the leukemia implying a common clonal origin of the two. To the best of our knowledge, this has not been demonstrated in phyllodes tumors before, but indicates that the same type of leukemization may occur of this tumor as has been described in mediastinal GCT.
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http://dx.doi.org/10.1155/2013/934781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877602PMC
January 2014

Patient knowledge of late effects of acute lymphoblastic leukaemia.

Tidsskr Nor Laegeforen 2012 Oct;132(18):2052-5

Department of Paediatric Medicine, Women and Children's Division, Oslo University Hospital, Rikshospitalet, Norway.

Background: Over 80% of children with acute lymphatic leukaemia (ALL) survive, but many develop long-term effects after the therapy. The aim of the study was to reveal how much Norwegian adults treated for acute lymphatic leukaemia before the age of 16 know about the risk of long-term effects.

Material And Method: The participants (n = 139) were recruited from a cross-sectional study (ALLBARN) of adults treated for acute lymphatic leukaemia before the age of 16 in the period 1970-2002. Their knowledge of diagnosis, treatment and long-term effects was investigated in a semi-structured interview.

Results: A median number of 23 years after treatment for acute lymphatic leukaemia, 85 (61%) of the participants were unable to give examples of possible long-term effects of cancer treatment. Reduced fertility was known to 35 participants (25%), while few were aware of the risk of heart failure (n = 3) or secondary malignancy (n = 5). Those who were aware of long-term effects usually had personal experience of the problem. However, the participants had a sound knowledge of their own diagnosis and the therapy they had been submitted to.

Interpretation: Long-term survivors of acute lymphatic leukaemia in childhood and adolescence know little of the risk of long-term effects. The dissemination of information about the potential consequences of the therapy should be improved.
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http://dx.doi.org/10.4045/tidsskr.12.0153DOI Listing
October 2012

Plasma alemtuzumab levels in patients with chronic lymphocytic leukemia treated with alemtuzumab combined with chemotherapy reflect the efficacy of the treatment: a hypothesis.

Leuk Lymphoma 2013 Apr 4;54(4):790-3. Epub 2013 Jan 4.

Department of Hematology, Rigshospitalet, Copenhagen, Denmark.

In the HOVON68 trial comparing subcutaneous low-dose alemtuzumab (LD-A) used together with fludarabine (F) and cyclophosphamide (C) with FC alone in high-risk chronic lymphocytic leukemia (CLL), LD-AFC resulted in significantly more clinical and molecular responses than FC, but also in more opportunistic infections. In a subgroup analysis of alemtuzumab trough levels during treatment by a sensitive enzyme-linked immunosorbent assay (ELISA) method, detectable levels were found in 4/6 complete and 0/3 partial responders. A relationship between alemtuzumab plasma levels, response and duration of lymphocytopenia was evident. We hypothesize that following combination therapy, the response may not be a function of the alemtuzumab levels, but the opposite, that plasma alemtuzumab levels are a function of the efficacy of the entire treatment, and the fewer leukemic target cells that are remaining, the higher are the levels of plasma alemtuzumab. This concept may well provide a guide for alemtuzumab dosage in future trials.
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http://dx.doi.org/10.3109/10428194.2012.720373DOI Listing
April 2013

Immune reconstitution after allogeneic stem cell transplantation: the impact of stem cell source and graft-versus-host disease.

Haematologica 2005 Jan;90(1):86-93

Medical Department, Rikshosptialet University Hospital N-0027 Oslo, Norway.

Background And Objectives: Bone marrow (BM) and blood stem cell (BSC) allografts differ considerably with respect to their content of progenitor cells and progenitor cell subsets as well as mature lymphocytes. The aim of this prospective, randomized study was to determine whether these differences have an impact on early post-transplant immune recovery.

Design And Methods: In a prospective randomised study, we found enhanced immune recovery in recipients of BSC allografts compared to in recipients of BM allografts despite transplantation of a lower number of lymphoid progenitors, particularly B-cell progenitors. The large number of mature lymphocytes in BSC allografts is a plausible explanation for this observation. At the progenitor cell level, we found a comparable and very high proportion of progenitor cells involved in lymphopoiesis in both study groups.

Results: Patients with extensive chronic GVHD, irrespective of the allograft received, had low immunoglobulin (Ig) levels in serum, low B-cell counts in blood and low numbers of B-cell progenitors in the bone marrow. They also showed high T-cell counts, particularly CD3+CD8+ T-cell counts, which was paralleled by a high number of T-cell progenitors in the bone marrow. In patients with extensive chronic GVHD we found low natural killer (NK)-cell counts which has not been reported previously.

Interpretation And Conclusions: Early immune recovery is enhanced following BSC allografting compared with BM allografting. This is plausibly explained by the large inoculum of mature lymphocytes in BSC allografts. Following allografting, a higher proportion of the BM progenitor cell compartment is involved in lymphopoiesis than it is in healthy adults. However, B-lymphopoiesis is inhibited in patients with extensive chronic GVHD resulting in impaired B-cell recovery. These patients also seem to show impaired NK-cell recovery.
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January 2005