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Laurell, Anna
Publications (10 of 33) Show all publications
Stenman, M., Staehler, M., Szabados, B., Sandström, P., Laurell, A., Lindskog, M. & Harmenberg, U. (2019). Metastatic papillary renal cell carcinoma in the era of targeted therapy: a retrospective study from three European academic centres. Acta Oncologica, 58(3), 306-312
Open this publication in new window or tab >>Metastatic papillary renal cell carcinoma in the era of targeted therapy: a retrospective study from three European academic centres
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2019 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 3, p. 306-312Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Metastatic papillary renal cell carcinoma (mPRCC) is understudied. The disease is often aggressive and specific treatment options are lacking.

PATIENTS AND METHODS: mPRCC patients (n = 86) referred to three academic centres in Sweden and Germany in the years 2005-2015 were retrospectively identified from medical records. Statistical analyses included Kaplan-Meier curves and calculation of Cox proportional hazards, generating hazard ratios with 95% confidence intervals. The aim of the study was to evaluate overall survival (OS) of mPRCC patients treated outside of clinical trials in the era of targeted agents (TA) and to identify clinically useful prognostic factors.

RESULTS: Median OS of all mPRCC patients was 11.2 months. TA were used in 77% of the patients and associated with younger age and better Eastern Cooperative Oncology Group performance status (PS). Brain metastases were common (28%). Patients with synchronous or metachronous metastases had similar OS. Variables independently associated with risk of death included age ≥60 years, worse PS and ≥3 metastatic sites. The MSKCC criteria did not provide additional prognostic information. A subgroup analysis of TA-treated patients revealed an association of lymph node metastasis with risk of death in addition to the other prognostic factors.

CONCLUSION: OS in mPRCC remained short in the era of targeted agents. Age, PS, and number of metastatic sites provided independent prognostic information.

Keywords
metastatic, mRCC, non-clear cell, papillary, survival
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-381855 (URN)10.1080/0284186X.2018.1537505 (DOI)000462947900007 ()30507262 (PubMedID)
Available from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-08-20Bibliographically approved
Jerkeman, M., Eskelund, C. W., Hutchings, M., Raty, R., Wader, K. F., Laurell, A., . . . Kolstad, A. (2018). Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial. Tha Lancet Haematology, 5(3), E109-E116
Open this publication in new window or tab >>Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial
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2018 (English)In: Tha Lancet Haematology, ISSN 2352-3026, Vol. 5, no 3, p. E109-E116Article in journal (Refereed) Published
Abstract [en]

Background Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data on either regimen alone. Methods In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients aged 18 years or older with relapsed or refractory mantle cell lymphoma who had previously been treated with at least one rituximab-containing regimen, an Eastern Cooperative Oncology Group performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56 days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m(2)) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle, whereas oral lenalidomide (15 mg once a day) was given on days 1-21. The primary endpoint was overall response assessed in the intention-totreat population according to Lugano criteria. Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment. The trial is ongoing, but is no longer accruing patients, and is registered with ClinicalTrials. gov, number NCT02460276. Findings Between April 30, 2015, and June 1, 2016, we enrolled 50 patients with relapsed or refractory mantle cell lymphoma at ten centres in Sweden, Finland, Norway, and Denmark. At a median follow-up of 17.8 months (IQR 14.7-20.9), 38 (76%, 95% CI 63-86) patients had an overall response, including 28 (56%, 42-69) patients who had a complete response and ten (20%, 11-33) who had a partial response. The most common grade 3-4 adverse events were neutropenia (in 19 [38%] of 50 patients), infections (in 11 [22%] patients), and cutaneous toxicity (in seven [14%] patients). There were three treatment-related deaths during the study, two due to sepsis and one due to embolic stroke. Interpretation Our results provide preliminary evidence that the triplet combination of ibrutinib, lenalidomide, and rituximab is an active regimen in patients with relapsed or refractory mantle cell lymphoma, and should be evaluated in a prospective randomised controlled trial.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
National Category
Hematology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-350496 (URN)10.1016/S2352-3026(18)30018-8 (DOI)000426417700006 ()29396091 (PubMedID)
Available from: 2018-05-09 Created: 2018-05-09 Last updated: 2018-05-09Bibliographically approved
Eskelund, C. W., Albertsson-Lindblad, A., Kolstad, A., Laurell, A., Raty, R., Pedersen, L. B., . . . Gronbaek, K. (2018). Lenalidomide plus bendamustine-rituximab does not overcome the adverse impact of TP53 mutations in mantle cell lymphoma [Letter to the editor]. Haematologica, 103(11), E541-E543
Open this publication in new window or tab >>Lenalidomide plus bendamustine-rituximab does not overcome the adverse impact of TP53 mutations in mantle cell lymphoma
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2018 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 103, no 11, p. E541-E543Article in journal, Letter (Other academic) Published
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-372521 (URN)10.3324/haematol.2018.194399 (DOI)000451732200011 ()29794145 (PubMedID)
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-08Bibliographically approved
Hellström, V., Tufveson, G., Wallgren, A., Loskog, A., Larsson, E., Tötterman, T., . . . Lorant, T. (2017). Donor Derived and BK Virus Positive Urologic Cancers After Renal Transplantation. Paper presented at American Transplant Congress, APR 29-MAY 03, 2017, Chicago, IL. American Journal of Transplantation, 17(S3), 472-472, Article ID A188.
Open this publication in new window or tab >>Donor Derived and BK Virus Positive Urologic Cancers After Renal Transplantation
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2017 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 17, no S3, p. 472-472, article id A188Article in journal, Meeting abstract (Other academic) Published
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-335823 (URN)10.1111/ajt.14306 (DOI)000404515703188 ()
Conference
American Transplant Congress, APR 29-MAY 03, 2017, Chicago, IL
Available from: 2018-01-15 Created: 2018-01-15 Last updated: 2018-01-15Bibliographically approved
Laurell, A., Lönnemark, M., Brekkan, E., Magnusson, A., Tolf, A., Wallgren, A. C., . . . Karlsson-Parra, A. (2017). Intratumorally injected pro-inflammatory allogeneic dendritic cells as immune enhancers: a first-in-human study in unfavourable risk patients with metastatic renal cell carcinoma.. Journal for immunotherapy of cancer, 5, Article ID 52.
Open this publication in new window or tab >>Intratumorally injected pro-inflammatory allogeneic dendritic cells as immune enhancers: a first-in-human study in unfavourable risk patients with metastatic renal cell carcinoma.
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2017 (English)In: Journal for immunotherapy of cancer, ISSN 2051-1426, Vol. 5, article id 52Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Accumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors. This concept doesn't require MHC-compatibility between injected cells and the patient and therefore introduces the possibility of using pre-produced and freeze-stored DCs from healthy blood donors as an off- the-shelf immune enhancer. The use of MHC-incompatible allogeneic DCs will further induce a local rejection process at the injection site that is expected to further enhance recruitment and maturation of endogenous bystander DCs.

METHODS: Twelve intermediate and poor risk patients with newly diagnosed metastatic renal cell carcinoma (mRCC) where included in a phase I/II study. Pro-inflammatory allogeneic DCs were produced from a leukapheresis product collected from one healthy blood donor and subsequently deep-frozen. A dose of 5-20 × 10(6) DCs (INTUVAX) was injected into the renal tumor twice with 2 weeks interval before planned nephrectomy and subsequent standard of care.

RESULTS: No INTUVAX-related severe adverse events were observed. A massive infiltration of CD8+ T cells was found in 5 out of 12 removed kidney tumors. No objective tumor response was observed and 6 out of 11 evaluable patients have subsequently received additional treatment with standard tyrosine kinase inhibitors (TKI). Three of these 6 patients experienced an objective tumor response including one sunitinib-treated patient who responded with a complete and durable regression of 4 brain metastases. Median overall survival (mOS) is still not reached (currently 42.5 months) but has already passed historical mOS in patients with unfavourable risk mRCC on standard TKI therapy.

CONCLUSIONS: Our findings indicate that intratumoral administration of proinflammatory allogeneic DCs induces an anti-tumor immune response that may prolong survival in unfavourable risk mRCC-patients given subsequent standard of care. A randomized, multi-center, phase II mRCC trial (MERECA) with INTUVAX in conjuction with sunitinib has been initiated.

TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01525017.

Keywords
Allogeneic dendritic cells, Anti-tumor response, INTUVAX, Intratumoral administration, Metastatic renal cell carcinoma, Phase I/II study, Sunitinib, Vaccine
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-325567 (URN)10.1186/s40425-017-0255-0 (DOI)000405222000004 ()28642820 (PubMedID)
Available from: 2017-06-26 Created: 2017-06-26 Last updated: 2017-10-11Bibliographically approved
Kolstad, A., Pedersen, L. B., Eskelund, C. W., Husby, S., Gronbaek, K., Jerkeman, M., . . . Geisler, C. H. (2017). Molecular Monitoring after Autologous Stem Cell Transplantation and Preemptive Rituximab Treatment of Molecular Relapse; Results from the Nordic Mantle Cell Lymphoma Studies (MCL2 and MCL3) with Median Follow-Up of 8.5 Years. Biology of blood and marrow transplantation, 23(3), 428-435
Open this publication in new window or tab >>Molecular Monitoring after Autologous Stem Cell Transplantation and Preemptive Rituximab Treatment of Molecular Relapse; Results from the Nordic Mantle Cell Lymphoma Studies (MCL2 and MCL3) with Median Follow-Up of 8.5 Years
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2017 (English)In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 23, no 3, p. 428-435Article in journal (Refereed) Published
Abstract [en]

The main objectives of the present study were to monitor minimal residual disease (MRD) in the bone marrow of patients with mantle cell lymphoma (MCL) to predict clinical relapse and guide preemptive treatment with rituximab. Among the patients enrolled in 2 prospective trials by the Nordic Lymphoma Group, 183 who had completed autologous stem cell transplantation (ASCT) and in whom an MRD marker had been obtained were included in our analysis. Fresh samples of bone marrow were analyzed for MRD by a combined standard nested and quantitative real-time PCR assay for Bcl-1/immunoglobulin heavy chain gene (IgH) and clonal IgH rear-rangements. Significantly shorter progression-free survival (PFS) and overall survival (OS) was demonstrated for patients who were MRD positive pre-ASCT (54 patients) or in the first analysis post-ASCT (23 patients). The median PFS was only 20 months in those who were MRD-positive in the first sample post-ASCT, compared with 142 months in the MRD-negative group (P <.0001). OS was 75% at 10 years and median not reached in the MRD-negative group, compared with only 35 months in the MRD-positive group (P <.0001). Of the 86 patients (47%) who remained in continuous molecular remission, 73% were still in clinical remission after 10 years. For all patients, the median time from ASCT to first molecular relapse was 55 months, with a continuous occurrence of late molecular relapses. Fifty-eight patients who experienced MRD relapse received rituximab as preemptive treatment on 1 or more occasions, and in this group, the median time from first molecular relapse to clinical relapse was 55 months. In most cases, rituximab converted patients to MRD negativity (87%), but many patients became MRD-positive again later during follow-up (69%). By multivariate analysis, high-risk Mantle Cell Lymphoma International Prognostic Index score and positive MRD status pre-ASCT predicted early molecular relapse. In conclusion, preemptive rituximab treatment converts patients to MRD negativity and likely postpones clinical relapse. Molecular monitoring offers an opportunity to select some patients for therapeutic intervention and to avoid unnecessary treatment in others. MRD-positive patients in the first analysis post-ASCT have a dismal prognosis and thus are in need of novel strategies.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2017
Keywords
Mantle cell lymphoma, Autologous stem cell, transplantation, Minimal residual disease, Preemptive rituximab
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-320346 (URN)10.1016/j.bbmt.2016.12.634 (DOI)000395367300009 ()28039078 (PubMedID)
Note

Written for the Nordic Lymphoma Group

Available from: 2017-04-19 Created: 2017-04-19 Last updated: 2019-04-02Bibliographically approved
Eskelund, C. W., Kolstad, A., Jerkeman, M., Raty, R., Laurell, A., Eloranta, S., . . . Geisler, C. H. (2016). 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau. British Journal of Haematology, 175(3), 410-418
Open this publication in new window or tab >>15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau
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2016 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 175, no 3, p. 410-418Article in journal (Refereed) Published
Abstract [en]

In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 114years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 127 and 85years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.

Keywords
Mantle Cell Lymphoma, Non-Hodgkin Lymphoma, clinical trials, high dose therapy
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-308900 (URN)10.1111/bjh.14241 (DOI)000386908300008 ()27378674 (PubMedID)
Funder
Novo Nordisk
Available from: 2016-12-01 Created: 2016-12-01 Last updated: 2019-04-02Bibliographically approved
Hellström, V., Enström, Y., von Zur-Mühlen, B., Hagberg, H., Laurell, A., Nyberg, F., . . . Lorant, T. (2016). Malignancies in transplanted patients: Multidisciplinary evaluation and switch to mTOR inhibitors after kidney transplantation - experiences from a prospective, clinical, observational study. Acta Oncologica, 55(6), 774-781
Open this publication in new window or tab >>Malignancies in transplanted patients: Multidisciplinary evaluation and switch to mTOR inhibitors after kidney transplantation - experiences from a prospective, clinical, observational study
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2016 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 6, p. 774-781Article in journal (Refereed) Published
Abstract [en]

Background Solid organ transplant recipients are at increased risk of developing malignancies. The objective of this prospective, observational, one-armed study was to study the feasibility to add a mammalian target of rapamycin (mTOR) inhibitor to the immunosuppressive regimen in transplanted patients with post-transplant malignancies. During the trial the need to improve identification of post-transplant malignancies and to reassure adequate oncological treatment of these patients became evident. Multidisciplinary team (MDT) evaluation of oncological and immunosuppressive treatments was implemented for all patients with malignancies after renal or combined renal and pancreas transplantation because of the trial.Material and methods At Uppsala University Hospital, Sweden, a MDT consisting of transplant surgeons, nephrologists, oncologists and dermatologists evaluated 120 renal or combined renal and pancreas-transplanted recipients diagnosed with malignancies from September 2006 to July 2012. To identify all malignancies, the population was linked to the Regional Tumor Registry (RTR). We recorded to which extent a switch to mTOR inhibitors was possible and how often the originally planned oncological managements were adjusted. All patients were followed for three years. (ClinicalTrials.gov: NCT02241564).Results In 76 of 120 patients (63%) a switch to mTOR inhibitors was possible. Immunosuppression was interrupted in seven patients (6%), reduced in three patients (2%) and remained unchanged in 34 of 120 patients (28%). Identification of post-transplant malignancies increased significantly after linkage to RTR (p=0.015). The initially recommended oncological treatment was adjusted in 23 of 44 patients (52%) with solid or hematological malignancies; 36 of these patients (82%) were treated according to national guidelines.Conclusion In two thirds of the patients the immunosuppressive treatment could be changed to an mTOR inhibitor with anti-tumor effects in transplanted patients with post-transplant malignancies. The use of regional tumor registers considerably improved the identification of patients with post-transplant malignancies indicating that post-transplant malignancies might be timely underreported in transplant registers.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016
Keywords
Malignant tumours, Renal transplantation
National Category
Cancer and Oncology
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-282106 (URN)10.3109/0284186X.2015.1130855 (DOI)000377122300017 ()26824275 (PubMedID)
Available from: 2016-04-02 Created: 2016-04-01 Last updated: 2018-11-16Bibliographically approved
Hoster, E., Geisler, C. H., Doorduijn, J., van der Holt, B., Walewski, J., Bloehdorn, J., . . . Hermine, O. (2016). Total body irradiation after high-dose cytarabine in mantle cell lymphoma: a comparison of Nordic MCL2, HOVON-45, and European MCL Younger trials [Letter to the editor]. Leukemia, 30(6), 1428-1430
Open this publication in new window or tab >>Total body irradiation after high-dose cytarabine in mantle cell lymphoma: a comparison of Nordic MCL2, HOVON-45, and European MCL Younger trials
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2016 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 30, no 6, p. 1428-1430Article in journal, Letter (Refereed) Published
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:uu:diva-299975 (URN)10.1038/leu.2015.322 (DOI)000377492800029 ()26598017 (PubMedID)
Available from: 2016-08-01 Created: 2016-08-01 Last updated: 2017-11-28Bibliographically approved
Magnusson, A., Wallgren, A., Brekkan, E., Lönnemark, M., Karlsson-Parra, A. & Laurell, A. (2015). Long-term survival in unfavorable-risk mRCC patients after intratumoral administration of a cell-based allogeneic vaccine adjuvant.. Paper presented at Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), MAY 29-JUN 02, 2015, Chicago, IL. Journal of Clinical Oncology, 33(15)
Open this publication in new window or tab >>Long-term survival in unfavorable-risk mRCC patients after intratumoral administration of a cell-based allogeneic vaccine adjuvant.
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2015 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 15Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-261482 (URN)000358036902598 ()
Conference
Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), MAY 29-JUN 02, 2015, Chicago, IL
Note

Meeting Abstract: e14006

Available from: 2015-09-03 Created: 2015-09-01 Last updated: 2017-12-04Bibliographically approved
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