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Hagberg, H
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Publications (10 of 42) Show all publications
Lockmer, S., Östenstad, B., Hagberg, H., Holte, H., Wahlin, B. E., Wader, K. F., . . . Kimby, E. (2019). Is Longer Progression-Free Survival a Goal Worth Pursuing in Follicular Lymphoma?: Reply [Letter to the editor]. Journal of Clinical Oncology, 37(9), 759-760
Open this publication in new window or tab >>Is Longer Progression-Free Survival a Goal Worth Pursuing in Follicular Lymphoma?: Reply
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2019 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 37, no 9, p. 759-760Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
AMER SOC CLINICAL ONCOLOGY, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-382024 (URN)10.1200/JCO.18.02362 (DOI)000462408300012 ()30735430 (PubMedID)
Funder
Stockholm County Council
Available from: 2019-04-23 Created: 2019-04-23 Last updated: 2019-04-23Bibliographically approved
Zucca, E., Rondeau, S., Vanazzi, A., Ostenstad, B., Mey, U. J. M., Rauch, D., . . . Strandberg, M. (2019). Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy. Blood, 134(4), 353-362
Open this publication in new window or tab >>Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy
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2019 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 134, no 4, p. 353-362Article in journal (Refereed) Published
Abstract [en]

The SAKK 35/10 phase 2 trial, developed by the Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group, compared the activity of rituximab vs rituximab plus lenalidomide in untreated follicular lymphoma patients in need of systemic therapy. Patients were randomized to rituximab (375 mg/m(2) IV on day 1 of weeks 1-4 and repeated during weeks 12-15 in responding patients) or rituximab (same schedule) in combination with lenalidomide (15 mg orally daily for 18 weeks). Primary end point was complete response (CR)/unconfirmed CR (CRu) rate at 6 months. In total, 77 patients were allocated to rituximab monotherapy and 77 to the combination (47% poor-risk Follicular Lymphoma International Prognostic Index score in each arm). A significantly higher CR/CRu rate at 6 months was documented in the combination arm by the investigators (36%; 95% confidence interval [CI], 26%-48% vs 25%; 95% CI, 16%-36%) and confirmed by an independent response review of computed tomography scans only (61%; 95% CI, 49%-72% vs 36%; 95% CI, 26%-48%). After a median follow-up of 4 years, significantly higher 30-month CR/CRu rates and longer progression-free survival (PFS) and time to next treatment (TTNT) were observed for the combination. Overall survival (OS) rates were similar in both arms (>= 90%). Toxicity grade >= 3 was more common in the combination arm (56% vs 22% of patients), mainly represented by neutropenia (23% vs 7%). Addition of lenalidomide to rituximab significantly improved CR/CRu rates, PFS, and TTNT, with expected higher, but manageable toxicity. The excellent OS in both arms suggests that chemotherapy-free strategies should be further explored.

Place, publisher, year, edition, pages
AMER SOC HEMATOLOGY, 2019
National Category
Hematology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-391364 (URN)10.1182/blood-2018-10-879643 (DOI)000477070300006 ()31101627 (PubMedID)
Available from: 2019-09-24 Created: 2019-09-24 Last updated: 2019-09-24Bibliographically approved
Enblad, G., Karlsson, H., Gammelgård, G., Wenthe, J., Lövgren, T., Amini, R.-M., . . . Loskog, A. (2018). A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia. Clinical Cancer Research, 24(24), 6185-6194
Open this publication in new window or tab >>A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia
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2018 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 24, no 24, p. 6185-6194Article in journal (Refereed) Published
Abstract [en]

Purpose: The chimeric antigen receptor (CAR) T-cell therapy has been effective for patients with CD19(+) B-cell malignancies. Most studies have investigated the second-generation CARs with either CD28 or 4-1BB costimulatory domains in the CAR receptor. Here, we describe the first clinical phase I/IIa trial using third-generation CAR T cells targeting CD19 to evaluate safety and efficacy.

Patients and Methods: Fifteen patients with B-cell lymphoma or leukemia were treated with CAR T cells. The patients with lymphoma received chemotherapy during CAR manufacture and 11 of 15 were given low-dose cyclophosphamide and fludarabine conditioning prior to CAR infusion. Peripheral blood was sampled before and at multiple time points after CAR infusion to evaluate the persistence of CAR T cells and for immune profiling, using quantitative PCR, flow cytometry, and a proteomic array.

Results: Treatment with third-generation CAR T cells was generally safe with 4 patients requiring hospitalization due to adverse reactions. Six of the 15 patients had initial complete responses [4/11 lymphoma and 2/4 acute lymphoblastic leukemia (ALL)], and 3 of the patients with lymphoma were in remission at 3 months. Two patients are still alive. Best predictor of response was a good immune status prior to CAR infusion with high IL12, DC-Lamp, Fas ligand, and TRAIL. Responding patients had low monocytic myeloid-derived suppressor cells (MDSCs; CD14(+)CD33(+)HLA(-)DR(-)) and low levels of IL6, IL8, NAP3, sPDL1, and sPDL2.

Conclusions: Third-generation CARs may be efficient in patients with advanced B-cell lymphoproliferative malignancy with only modest toxicity. Immune profiling pre- and posttreatment can be used to find response biomarkers.

National Category
Cancer and Oncology Hematology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-372924 (URN)10.1158/1078-0432.CCR-18-0426 (DOI)000453267600012 ()30097433 (PubMedID)
Funder
Swedish Research CouncilAFA InsuranceSwedish Cancer Society
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-03-29Bibliographically approved
Hall, K. S., Bruland, O. S., Bjerkehagen, B., Zaikova, O., Engellau, J., Hagberg, O., . . . Eriksson, M. (2018). Adjuvant chemotherapy and postoperative radiotherapy in high-risk soft tissue sarcoma patients defined by biological risk factors-A Scandinavian Sarcoma Group study (SSG XX). European Journal of Cancer, 99, 78-85
Open this publication in new window or tab >>Adjuvant chemotherapy and postoperative radiotherapy in high-risk soft tissue sarcoma patients defined by biological risk factors-A Scandinavian Sarcoma Group study (SSG XX)
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2018 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 99, p. 78-85Article in journal (Refereed) Published
Abstract [en]

Purpose: To investigate the outcome following adjuvant doxorubicin and ifosfamide in a prospective non-randomised study based on a soft tissue sarcoma (STS) patient subgroup defined by specific morphological characteristics previously shown to be at a high-risk of metastatic relapse. The expected 5-year cumulative incidence of metastases in patients with this risk profile has previously been reported to be about 50% without adjuvant chemotherapy.

Methods: High-risk STS was defined as high-grade morphology (according to the Federation Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade II-III) and either vascular invasion or at least two of the following criteria: tumour size >= 8.0 cm, infiltrative growth and necrosis. Six cycles of doxorubicin (60 mg/m(2)) and ifosfamide (6 g/m(2)) were given. Postoperative accelerated radiotherapy was applied and scheduled between cycles 3 and 4.

Results: For the 150 eligible patients, median follow-up time for metastases-free survival was 3.9 years (range 0.2-8.7). Five-year metastases-free survival (MFS) was 70.4% (95% confidence interval [CI]: 63.1-78.4) with a local recurrence rate of 14.0% (95% CI: 7.8-20.2). For overall survival (OS), the median follow-up time was 4.4 years (range: 0.2-8.7). The five-year OS was 76.1% (95% CI: 68.8-84.2). Tumour size, deep location and reduced dose intensity (<80%) had a negative impact on survival. Toxicity was moderate with no treatment-related death.

Conclusions: A benefit of adjuvant chemotherapy, compared to similar historical control groups, was demonstrated in STS patients with defined poor prognostic factors. Vascular invasion, tumour size, growth pattern and necrosis may identify patients in need of adjuvant chemotherapy.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
Keywords
Soft tissue sarcoma, Adjuvant treatment, Prognostic factors, Vascular invasion, Growth pattern, Tumour size, Necrosis, Survival
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-360179 (URN)10.1016/j.ejca.2018.05.011 (DOI)000437355200009 ()29929092 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-09-13 Created: 2018-09-13 Last updated: 2018-09-13Bibliographically approved
Lockmer, S., Ostenstad, B., Hagberg, H., Holte, H., Johansson, A.-S., Wahlin, B. E., . . . Kimby, E. (2018). Chemotherapy-Free Initial Treatment of Advanced Indolent Lymphoma Has Durable Effect With Low Toxicity: Results From Two Nordic Lymphoma Group Trials With More Than 10 Years of Follow-Up. Journal of Clinical Oncology, 36(33), 3315-3323
Open this publication in new window or tab >>Chemotherapy-Free Initial Treatment of Advanced Indolent Lymphoma Has Durable Effect With Low Toxicity: Results From Two Nordic Lymphoma Group Trials With More Than 10 Years of Follow-Up
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2018 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 36, no 33, p. 3315-3323Article in journal (Refereed) Published
Abstract [en]

Purpose: For indolent lymphoma, the optimal timing, sequence, and choice of therapeutic regimens remain a matter of debate. In two Nordic Lymphoma Group randomized trials, symptomatic or clearly progressing patients were treated first line with a rituximab-containing regimen without chemotherapy. The purpose of this study was to assess long-term survival, risk of transformation, and need of new therapies.

Methods: Data were collected at cross-sectional follow-up for 321 patients with indolent lymphoma (84% with follicular lymphomas [FL]) included in one of two Nordic Lymphoma Group trials (accrual 1998 to 1999 and 2002 to 2008). All patients received first-line therapy with one or two cycles of four weekly infusions of rituximab 375 mg/m(2), and 148 were randomly allocated to the addition of interferon alfa-2a. Follow-up data were retrieved from initial trial databases and medical records on repeated clinical evaluations.

Results: At the end of follow-up, 73% of patients were alive, with a median follow-up after random assignment of 10.6 years. Among all, 36% (38% with FL) had never needed chemotherapy. For patients with FL who required new therapy within 24 months because of early disease progression, the 10-year survival rate was 59% versus 81% for those with longer remission. Interferon was not shown to improve long-term outcome. Transformation was diagnosed in 20% of all patients (2.4% per person-year) and in 18% with FL. An additional malignancy was found in 12%.

Conclusion: Approximately one third of patients with symptomatic indolent lymphoma (30% with FL, 23% without FL) did not need new therapy in the long term after first-line rituximab without chemotherapy. In the entire cohort, 10-year survival was excellent with no major safety issues, which suggests that chemotherapy can be delayed safely in the majority of patients.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-372711 (URN)10.1200/JCO.18.00262 (DOI)000451965300006 ()30285560 (PubMedID)
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-08Bibliographically approved
Drott, K., Hagberg, H., Papworth, K., Relander, T. & Jerkeman, M. (2018). Valproate in combination with rituximab and CHOP as first-line therapy in diffuse large B-cell lymphoma (VALFRID). BLOOD ADVANCES, 2(12), 1386-1392
Open this publication in new window or tab >>Valproate in combination with rituximab and CHOP as first-line therapy in diffuse large B-cell lymphoma (VALFRID)
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2018 (English)In: BLOOD ADVANCES, ISSN 2473-9529, Vol. 2, no 12, p. 1386-1392Article in journal (Refereed) Published
Abstract [en]

The aims of the present study were to establish the maximally tolerated dose (MTD) of the histone deacetylase inhibitor valproate together with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with diffuse large B-cell lymphoma (DLBCL). A phase 1 dose escalation study of valproate together with R-CHOP followed by a dose expansion study using the established MTD of valproate was performed. MTD of valproate together with R-CHOP was established at 60 mg/kg per day, as higher doses resulted in auditory adverse events (AEs). In the study population, 2-year progression-free survival was 84.7% (95% confidence interval [CI], 73.2%-98%). The 2-year overall survival (OS) was 96.8% (n = 31; 95% CI, 90.8%-100%). These data were compared with 2 risk-factor matched populations of R-CHOP-treated patients from the Swedish Lymphoma Registry (cohort A, n = 330 and B, n = 165). As compared with the matched cohorts, we observed a statistically significant (P = .034 and 0.028, respectively) beneficial effect of the addition of valproate to R-CHOP on the OS in the studied population. In conclusion, addition of valproate to R-CHOP is a feasible strategy in first-line treatment of DLBCL. The proposed phase 2 dose is 60 mg/kg per day together with prednisone. Auditory AEs were unexpected and warrant close monitoring. Our findings suggest that drugs that target histone deacetylation may add benefit and are tolerable when combined with standard R-CHOP in DLBCL.

Place, publisher, year, edition, pages
AMER SOC HEMATOLOGY, 2018
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-360005 (URN)10.1182/bloodadvances.2018019240 (DOI)000436548300004 ()29903707 (PubMedID)
Available from: 2018-09-07 Created: 2018-09-07 Last updated: 2018-09-07Bibliographically approved
Lövgren, T., Wenthe, J., Karlsson, S. C., Gammelgård, G., Essand, M., Savoldo, B., . . . Loskog, A. (2017). Immunological biomarkers correlate to survival in CAR19-treated patients. Paper presented at 44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN. Scandinavian Journal of Immunology, 86(4), 337-337
Open this publication in new window or tab >>Immunological biomarkers correlate to survival in CAR19-treated patients
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2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 337-337Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-346970 (URN)000411865200208 ()
Conference
44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN
Available from: 2018-03-27 Created: 2018-03-27 Last updated: 2018-03-27Bibliographically approved
Dahlin, J. S., Ekoff, M., Grootens, J., Löf, L., Amini, R.-M., Hagberg, H., . . . Nilsson, G. (2017). KIT signaling is dispensable for human mast cell progenitor development. Blood, 130(16), 1785-1794
Open this publication in new window or tab >>KIT signaling is dispensable for human mast cell progenitor development
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2017 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 130, no 16, p. 1785-1794Article in journal (Refereed) Published
Abstract [en]

Human hematopoietic progenitors are generally assumed to require stem cell factor (SCF) and KIT signaling during differentiation for the formation of mast cells. Imatinib treatment, which inhibits KIT signaling, depletes mast cells in vivo. Furthermore, the absence of SCF or imatinib treatment prevents progenitors from developing into mast cells in vitro. However, these observations do not mean that mast cell progenitors require SCF and KIT signaling throughout differentiation. Here, we demonstrate that circulating mast cell progenitors are present in patients undergoing imatinib treatment. In addition, we show that mast cell progenitors from peripheral blood survive, mature, and proliferate without SCF and KIT signaling in vitro. Contrary to the prevailing consensus, our results show that SCF and KIT signaling are dispensable for early mast cell development.

National Category
Hematology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-339750 (URN)10.1182/blood-2017-03-773374 (DOI)000413246200005 ()28790106 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer SocietyCancer and Allergy FoundationThe Cancer Society in StockholmThe Cancer Research Funds of RadiumhemmetThe Karolinska Institutet's Research Foundation
Available from: 2018-01-25 Created: 2018-01-25 Last updated: 2019-03-29Bibliographically approved
Enblad, G., Martinsson, G., Baecklund, E., Hesselager, G., Sundström, C., Amini, R.-M. & Hagberg, H. (2017). Population-based experience on primary central nervous system lymphoma 2000-2012: the incidence is increasing. Acta Oncologica, 56(4), 599-607
Open this publication in new window or tab >>Population-based experience on primary central nervous system lymphoma 2000-2012: the incidence is increasing
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2017 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 4, p. 599-607Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Primary central nervous system lymphomas (PCNSL) are rare lymphomas with a poor prognosis. Recently, an increased incidence has been reported. The present study is a population-based study of all patients with PCNSL in the Uppsala/Örebro region of middle Sweden.

PATIENTS AND METHODS: All patients diagnosed with a PCNSL at Uppsala University Hospital 2000-2012 were identified. Altogether, 96 patients (50 women and 46 men) were included. The median age at diagnosis was 66 years (17-95).

RESULTS: There was a statistically significant increase in age-standardized incidence during the study period, 30 patients were diagnosed in the first half and 66 in the second half of the period. No patient had an HIV-infection. Two patients had undergone kidney transplantation and were treated with immunosuppressive drugs. A high proportion of the patients, 29%, had a history of an autoimmune or inflammatory disease. The prognosis was poor with a median survival of only four months. In the 70 (73%) patients treated with curative intention the median survival was 12 months. Patients treated with high-dose methotrexate, radiotherapy and/or temozolomide appeared to have a better survival. There was no improvement in survival during the study period or after the introduction of rituximab. There also was no difference in any of the analyzed variables that could explain the increased incidence.

CONCLUSION: In this population-based study we could confirm the previously described increased incidence of PCNSL. The prognosis remains poor despite the inclusion of treatment with rituximab during the study period. A high proportion of the patients had a history of an autoimmune or inflammatory disease not previously described but there was no increase during the study period.

National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-318300 (URN)10.1080/0284186X.2016.1270465 (DOI)000399499600014 ()28084866 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2017-03-24 Created: 2017-03-24 Last updated: 2020-01-08Bibliographically approved
Enblad, G., Karlsson, H., Wenthe, J., Wikström, K. I., Essand, M., Savoldo, B., . . . Loskog, A. (2016). A Clinical Trial Using Third Generation CD19 Targeting CAR T Cells for Relapsed Lymphoma and Leukemia. Paper presented at 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), MAY 04-07, 2016, Washington, DC. Molecular Therapy, 24, S295-S296
Open this publication in new window or tab >>A Clinical Trial Using Third Generation CD19 Targeting CAR T Cells for Relapsed Lymphoma and Leukemia
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2016 (English)In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 24, p. S295-S296Article in journal, Meeting abstract (Other academic) Published
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-299273 (URN)000375264200736 ()
Conference
19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), MAY 04-07, 2016, Washington, DC
Available from: 2016-07-18 Created: 2016-07-18 Last updated: 2017-11-28Bibliographically approved
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