Signe Spetalen

• Hamnvik, Lars Henrik Dahl; Tjønnfjord, Geir Erland; Spetalen, Signe & Dalgaard, Jakob (2024). Long-lasting severe anemia following treatment with natalizumab for relapsing–remitting multiple sclerosis: a case report. Journal of Medical Case Reports. ISSN 1752-1947. 18(1). doi: 10.1186/s13256-024-04562-8.
• Brunetti, Marta; Andersen, Kristin; Spetalen, Signe; Lenartova, Andrea; Osnes, Liv T. N. & Vålerhaugen, Helen [Show all 8 contributors for this article] (2024). NUP214 fusion genes in acute leukemias: genetic characterization of rare cases. Frontiers in Oncology. ISSN 2234-943X. 14. doi: 10.3389/fonc.2024.1371980.
• Nyquist, Emil; Dalgaard, Jakob; Spetalen, Signe; Torkildsen, Synne; Frøen, Hege & Galteland, Eivind [Show all 17 contributors for this article] (2023). Pathogenic DDX41 variants, possible response predictors to low-dose melphalan in hypo- and normocellular MDS and AML. British Journal of Haematology. ISSN 0007-1048. 204(2), p. 724–729. doi: 10.1111/bjh.19226. Full text in Research Archive
• Spasevska, Ivana; Sharma, Ankush; Steen, Chloe Beate; Josefsson, Sarah Elisabet; Blaker, Yngvild Nuvin & Kolstad, Arne [Show all 26 contributors for this article] (2023). Diversity of intratumoral regulatory T cells in B-cell non-Hodgkin lymphoma. Blood Advances. ISSN 2473-9529. 7(23), p. 7216–7230. doi: 10.1182/bloodadvances.2023010158. Full text in Research Archive
• Skånland, Sigrid S; Inngjerdingen, Marit; Bendiksen, Henrik; York, Jamie Piers; Spetalen, Signe & Munthe, Ludvig Andre [Show all 7 contributors for this article] (2022). Functional testing of relapsed chronic lymphocytic leukemia guides precision medicine and maps response and resistance mechanisms. An index case. Haematologica. ISSN 0390-6078. 107(8), p. 1994–1998. doi: 10.3324/haematol.2021.280393. Full text in Research Archive
• Jørgensen, Silje Fjellgård; Buechner, Jochen; Myhre, Anders Eivind; Galteland, Eivind; Spetalen, Signe & Kulseth, Mari Ann [Show all 19 contributors for this article] (2021). A Nationwide Study of GATA2 Deficiency in Norway-the Majority of Patients Have Undergone Allo-HSCT. Journal of Clinical Immunology. ISSN 0271-9142. doi: 10.1007/s10875-021-01189-y. Full text in Research Archive Show summary

  Purpose: GATA2 deficiency is a rare primary immunodeficiency that has become increasingly recognized due to improved molecular diagnostics and clinical awareness. The only cure for GATA2 deficiency is allogeneic hematopoietic stem cell transplantation (allo-HSCT). The inconsistency of genotype-phenotype correlations makes the decision regarding "who and when" to transplant challenging. Despite considerable morbidity and mortality, the reported proportion of patients with GATA2 deficiency that has undergone allo-HSCT is low (~ 35%). The purpose of this study was to explore if detailed clinical, genetic, and bone marrow characteristics could predict end-point outcome, i.e., death and allo-HSCT. Methods: All medical genetics departments in Norway were contacted to identify GATA2 deficient individuals. Clinical information, genetic variants, treatment, and outcome were subsequently retrieved from the patients' medical records. Results: Between 2013 and 2020, we identified 10 index cases or probands, four additional symptomatic patients, and no asymptomatic patients with germline GATA2 variants. These patients had a diverse clinical phenotype dominated by cytopenia (13/14), myeloid neoplasia (10/14), warts (8/14), and hearing loss (7/14). No valid genotype-phenotype correlations were found in our data set, and the phenotypes varied also within families. We found that 11/14 patients (79%), with known GATA2 deficiency, had already undergone allo-HSCT. In addition, one patient is awaiting allo-HSCT. The indications to perform allo-HSCT were myeloid neoplasia, disseminated viral infection, severe obliterating bronchiolitis, and/or HPV-associated in situ carcinoma. Two patients died, 8 months and 7 years after allo-HSCT, respectively. Conclusion: Our main conclusion is that the majority of patients with symptomatic GATA2 deficiency will need allo-HSCT, and a close surveillance of these patients is important to find the "optimal window" for allo-HSCT. We advocate a more offensive approach to allo-HSCT than previously described.

• Leppä, Sirpa; Jørgensen, Judit; Tierens, Anne; Meriranta, Leo; Østlie, Ingunn & Brown, Peter de Nully [Show all 23 contributors for this article] (2020). Patients with high-risk DLBCL benefit from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis. Blood Advances. ISSN 2473-9529. 4(9), p. 1906–1915. doi: 10.1182/bloodadvances.2020001518. Full text in Research Archive Show summary

  Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of central nervous system (CNS) progression is relatively high. We conducted a phase 2 trial in 139 patients aged 18 to 64 years who had primary DLBCL with an age-adjusted International Prognostic Index (aaIPI) score of 2 to 3 or site-specific risk factors for CNS recurrence. The goal was to assess whether a dose-dense immunochemotherapy with early systemic CNS prophylaxis improves the outcome and reduces the incidence of CNS events. Treatment consisted of 2 courses of high-dose methotrexate in combination with biweekly rituximab (R), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-14), followed by 4 courses of R-CHOP-14 with etoposide (R-CHOEP) and 1 course of high-dose cytarabine with R. In addition, liposomal cytarabine was administered intrathecally at courses 1, 3, and 5. Coprimary endpoints were failure-free survival and CNS progression rates. Thirty-six (26%) patients experienced treatment failure. Progression occurred in 23 (16%) patients, including three (2.2%) CNS events. At 5 years of median follow-up, failure-free survival, overall survival, and CNS progression rates were 74%, 83%, and 2.3%, respectively. Treatment reduced the risk of progression compared with our previous trial, in which systemic CNS prophylaxis was given after 6 courses of biweekly R-CHOEP (hazard ratio, 0.49; 95% CI, 0.31-0.77; P = .002) and overcame the adverse impact of an aaIPI score of 3 on survival. In addition, outcome of the patients with BCL2/MYC double-hit lymphomas was comparable to the patients without the rearrangements. The results are encouraging, with a low toxic death rate, low number of CNS events, and favorable survival rates. This trial was registered at www.clinicaltrials.gov as #NCT01325194.

• Kolstad, Arne; Illidge, Tim; Bolstad, Nils; Spetalen, Signe; Madsbu, Ulf Erik & Stokke, Caroline [Show all 19 contributors for this article] (2020). Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma. Blood Advances. ISSN 2473-9529. 4(17), p. 4091–4101. doi: 10.1182/bloodadvances.2020002583. Show summary

  For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20-based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the "cold" anti-CD37 antibody lilotomab. The most common adverse events (AEs) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%) with neutrophil and platelet count nadirs 5 to 7 weeks after RIT. The most frequent nonhematologic AE was grade 1/2 nausea (15.8%). With a single administration, the overall response rate was 61% (65% in patients with FL), including 30% complete responses. For FL with ≥2 prior therapies (n = 37), the overall response rate was 70%, including 32% complete responses. For patients with rituximab-refractory FL ≥2 prior therapies (n = 21), the overall response rate was 67%, and the complete response rate was 24%. The overall median duration of response was 13.6 months (32.0 months for patients with a complete response). 177Lu-lilotomab satetraxetan may provide a valuable alternative treatment approach in relapsed/refractory non-Hodgkin lymphoma, particularly in patients with comorbidities unsuitable for more intensive approaches. This trial was registered at www.clinicaltrials.gov as #NCT01796171.

• Munthe-Kaas, Monica Cheng; Forthun, Rakel Brendsdal; Brendehaug, Atle; Kildal Eek, Anette; Høysæter, Trude & Osnes, Liv T. N. [Show all 9 contributors for this article] (2020). Partial response to sorafenib in a child with a myeloid/lymphoid neoplasm, eosinophilia, and a ZMYM2-FLT3 fusion. Journal of Pediatric Hematology/Oncology. ISSN 1077-4114. 00:1890, p. 1–4. doi: 10.1097/MPH.0000000000001890. Show summary

  Dysregulated tyrosine kinases in myeloid/lymphoid neoplasms with eosinophilia are rare, but do occur in children. To increase awareness of this diagnosis, we present a child who was diagnosed after a 3-year disease history. The patient was initially treated according to a T-cell lymphoblastic lymphoma protocol, but genetic analyses at recurrence revealed microdeletions resulting in an in-frame fusion of ZMYM2 and FLT3. Treatment with sorafenib, an FLT3 tyrosine kinase inhibitor, rapidly resulted in significant reduction of lymphadenopathy and normalization of white blood cell and eosinophil counts. At 17 months of treatment, he remains in complete hematological, but not molecular remission.

• Nabel, Christopher S.; Sameroff, Stephen; Shilling, Dustin; Alapat, Daisy; Ruth, Jason R. & Kawano, Mitsuhiro [Show all 16 contributors for this article] (2019). Virome capture sequencing does not identify active viral infection in unicentric and idiopathic multicentric Castleman disease. PLOS ONE. ISSN 1932-6203. 14:e0218660(6), p. 1–13. doi: 10.1371/journal.pone.0218660.
• Torkildsen, Synne; Gorunova, Ludmila; Heim, Sverre; Tjønnfjord, Geir Erland; Spetalen, Signe & Risberg, Bente [Show all 8 contributors for this article] (2019). Molecular Genetic Characterization of Acute Myeloid Leukemia With Trisomy 4 as the Sole Chromosome Abnormality. Cancer Genomics & Proteomics. ISSN 1109-6535. 16(3), p. 175–178. doi: 10.21873/cgp.20123. Full text in Research Archive
• Habberstad, Andreas Hanssønn; Tran, Hoa Thi Tuyet; Randen, Ulla; Spetalen, Signe; Dybedal, Ingunn & Tjønnfjord, Geir Erland [Show all 7 contributors for this article] (2018). Neutropenia caused by hairy cell leukemia in a patient with myelofibrosis secondary to polycythemia vera: A case report. Journal of Medical Case Reports. ISSN 1752-1947. 12(1). doi: 10.1186/s13256-018-1663-6. Full text in Research Archive
• Panagopoulos, Ioannis; Gorunova, Ludmila; Spetalen, Signe; Bassarova, Assia Vassileva; Beiske, Klaus & Micci, Francesca [Show all 7 contributors for this article] (2017). Fusion of the genes ataxin 2 like, ATXN2L, and Janus kinase 2, JAK2, in cutaneous CD4 positive T-cell lymphoma. OncoTarget. ISSN 1949-2553. 8(61), p. 103775–103784. doi: 10.18632/oncotarget.21790.
• Torkildsen, Synne; Brunetti, Marta; Gorunova, Ludmila; Spetalen, Signe; Beiske, Klaus & Heim, Sverre [Show all 7 contributors for this article] (2017). Rearrangement of the chromatin organizer special AT-rich binding protein 1 gene, SATB1, resulting from a t(3;5)(p24;q14) chromosomal translocation in acute myeloid leukemia. Anticancer Research. ISSN 0250-7005. 37(2), p. 693–698. doi: 10.21873/anticanres.11365.
• Panagopoulos, Ioannis; Gorunova, Ludmila; Kerndrup, Gitte; Spetalen, Signe; Tierens, Anne & Osnes, Liv T. N. [Show all 11 contributors for this article] (2016). Rare MLL-ELL fusion transcripts in childhood acute myeloid leukemia-association with young age and myeloid sarcomas? Experimental hematology and oncology. ISSN 2162-3619. 5:8. doi: 10.1186/s40164-016-0037-2. Show summary

  Background The chromosomal translocation t(11;19)(q23;p13) with a breakpoint within subband 19p13.1 is found mainly in acute myeloid leukemia (AML) and results in the MLL-ELL fusion gene. Variations in the structure of MLL-ELL seem to influence the leukemogenic potency of the fusion in vivo and may lie behind differences in clinical features. The number of cases reported so far is very limited and the addition of more information about MLL-ELL variants is essential if the possible clinical significance of rare fusions is to be determined. Case presentation Cytogenetic and molecular genetic analyses were done on the bone marrow cells of a 20-month-old boy with an unusual form of myelomonocytic AML with multiple myeloid sarcomas infiltrating bone and soft tissues. The G-banding analysis together with FISH yielded the karyotype 47,XY, +6,t(8;19;11)(q24;p13;q23). FISH analysis also demonstrated that MLL was split. RNA-sequencing showed that the translocation had generated an MLL-ELL chimera in which exon 9 of MLL (nt 4241 in sequence with accession number NM_005933.3) was fused to exon 6 of ELL (nt 817 in sequence with accession number NM_006532.3). RT-PCR together with Sanger sequencing verified the presence of the above-mentioned fusion transcript. Conclusions Based on our findings and information on a few previously reported patients, we speculate that young age, myelomonoblastic AML, and the presence of extramedullary disease may be typical of children with rare MLL-ELL fusion transcripts.

• Blaker, Yngvild Nuvin; Spetalen, Signe; Eide, Marianne Brodtkorb; Lingjærde, Ole Christian; Beiske, Klaus & Østenstad, Bjørn [Show all 13 contributors for this article] (2016). The tumour microenvironment influences survival and time to transformation in follicular lymphoma in the rituximab era. British Journal of Haematology. ISSN 0007-1048. 175(1), p. 102–114. doi: 10.1111/bjh.14201.
• Bassarova, Assia Vassileva; Trøen, Gunhild; Spetalen, Signe; Micci, Francesca; Tierens, Anne & Delabie, Jan (2015). Lymphoplasmacytic lymphoma and marginal zone lymphoma in the bone marrow: Paratrabecular involvement as an important distinguishing feature. American Journal of Clinical Pathology. ISSN 0002-9173. 143(6), p. 797–806. doi: 10.1309/AJCP6ZODWV1CIDME. Show summary

  Objectives: The differential diagnosis between bone marrow involvement by lymphoplasmacytic lymphoma (LPL) and marginal zone lymphoma (MZL) is challenging because histology and immunophenotype of both diseases overlap. We revisited the diagnostic pathology features of both diseases in the bone marrow. Methods: We studied a series of bone marrow trephine biopsy specimens from 59 patients with Waldenström macroglobulinemia without extramedullary involvement and bone marrow biopsy specimens from 23 patients with well- characterized MZL who also had bone marrow involvement. H&E- and immunoperoxidase-stained sections of bone marrow trephine biopsy specimens as well as flow cytometry and classic cytogenetics performed on aspirations were reviewed. The study was complemented with MYD88 L265P mutation analysis of all samples. Results: The most distinguishing features of LPL with respect to MZL were focal paratrabecular involvement ( P < .001), the presence of lymphoplasmacytoid cells ( P < .001) and Dutcher bodies ( P < .001), increased numbers of mast cells ( P < .001), and the MYD88 L265P mutation ( P < .001). Conclusions: LPL can be reliably distinguished from MZL in the bone marrow by using a combination of pathology characteristics. Our findings stress the diagnostic importance of using the combination of the following parameters for a correct LPL diagnosis: paratrabecular infiltration, the presence of lymphoplasmacytoid cells and cells with Dutcher bodies, and an increased number of mast cells in addition to the presence of mutation.

• Fiskvik, Idun Hege; Beiske, Klaus; Delabie, Jan; Yri, Olav Erich; Spetalen, Signe & Karjalainen-Lindsberg, Marja-Liisa [Show all 10 contributors for this article] (2015). Combining MYC, BCL2 and TP53 gene and protein expression alterations improves risk stratification in diffuse large B-cell lymphoma. Leukemia and Lymphoma. ISSN 1042-8194. 56(6), p. 1742–1749. doi: 10.3109/10428194.2014.970550.
• Kleiveland, Charlotte Ramstad; Hult, Lene Therese Olsen; Spetalen, Signe; Kaldhusdal, Magne; Christoffersen, Trine Eker & Bengtsson, Oskar [Show all 9 contributors for this article] (2013). The Noncommensal Bacterium Methylococcus capsulatus (Bath) Ameliorates Dextran Sulfate (Sodium Salt)-Induced Ulcerative Colitis by Influencing Mechanisms Essential for Maintenance of the Colonic Barrier Function. Applied and Environmental Microbiology. ISSN 0099-2240. 79(1), p. 48–56. doi: 10.1128/AEM.02464-12.
• Halvorsen, Charlotte Marie; Kolstad, Frode; Hald, John K; Johannesen, Tom Børge; Krossnes, Bård Kronen & Langmoen, Iver Arne [Show all 11 contributors for this article] (2010). Long-term Outcome After Resection of Intraspinal Ependymomas: Report of 86 Consecutive Cases. Neurosurgery. ISSN 0148-396X. 67(6), p. 1622–1631. doi: 10.1227/NEU.0b013e3181f96d41.
• Spetalen, Signe; Sandvik, Leiv; Blomhoff, Svein & Jacobsen, Morten (2009). Rectal Visceral Sensitivity in Women with Irritable Bowel Syndrome without Psychiatric Comorbidity Compared with Healthy Volunteers. Gastroenterology Research and Practice. ISSN 1687-6121. 2009. doi: 10.1155/2009/130684.

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• Lindahl, Jørn Petter Hanto; Barlinn, Regine; Abrahamsen, Ingerid Weum; Spetalen, Signe; Midtvedt, Karsten & Jenssen, Trond Geir (2022). Case Report: Pure Red Cell Aplasia Caused by Refractory Parvovirus B19 Infection After Pancreas Transplantation Alone. Frontiers in medicine. ISSN 2296-858X. 9. doi: 10.3389/fmed.2022.849783. Full text in Research Archive
• Malecka, Agnieszka Maria; Tierens, Anne; Østlie, Ingunn; Schmitz, Roland; Trøen, Gunhild & Spetalen, Signe [Show all 10 contributors for this article] (2015). Primary diffuse large B-cell lymphoma associated with clonally-related monoclonal B lymphocytosis indicates a common precursor cell. Haematologica. ISSN 0390-6078. 100(10), p. e415–e418. doi: 10.3324/haematol.2015.126656.
• Midtvedt, Øyvind; Gran, Jan Tore; Solheim, Hanne; Kirkhus, Eva & Spetalen, Signe (2014). En mann i 40-årene med hevelse i begge øyehuler. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 134(15), p. 1472–1476. doi: 10.4045/tidsskr.13.0115.
• Midtvedt, Øyvind; Gran, Jan Tore; Solheim, Hanne; Kirkhus, Eva & Spetalen, Signe (2014). Ø. Midtvedt og medarbeidere svarer:. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 134(19). doi: 10.4045/tidsskr.14.1151.
• Kleiveland, Charlotte Ramstad; Hult, Lene Therese Olsen; Spetalen, Signe; Kaldhusdal, Magne; Christoffersen, Trine Eker & Bengtsson, Oskar [Show all 9 contributors for this article] (2012). protective role of a non-commensal methanotroph bacterium in a mouse model of colitis.
• Hult, Lene Therese Olsen; Kleiveland, Charlotte Ramstad; Spetalen, Signe; Jacobsen, Morten & Lea, Tor Erling (2012). På sporet av et nytt behandlingsprinsipp for IBD.

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