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Höglund, Martin
Publications (10 of 79) Show all publications
Nilsson, C., Hulegardh, E., Garelius, H., Mollgard, L., Brune, M., Wahlin, A., . . . Lehmann, S. (2019). Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting. Biology of blood and marrow transplantation, 25(9), 1770-1778
Open this publication in new window or tab >>Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting
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2019 (English)In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 25, no 9, p. 1770-1778Article in journal (Refereed) Published
Abstract [en]

Secondary AML (s-AML), including AML with an antecedent hematologic disorder (AHD-AML) and therapy-related AML (t-AML), constitutes a large proportion of patients with AML and is considered to confer a dismal prognosis. The role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML and the extent to which HCT is performed in these patients has been little studied to date. We used the population-based Swedish AML Registry comprising 3337 intensively treated adult patients over a 17-year period to study the role of HCT within the group of patients with s-AML as well as compared with patients with de novo AML. HCT was performed in 576 patients (22%) with de novo AML, in 74 patients (17%) with AHD-AML, and in 57 patients (20%) with t-AML. At 5 years after diagnosis, there were no survivors among patients with previous myeloproliferative neoplasms who did not undergo HCT, and corresponding survival for patients with antecedent myelodysplastic syndromes and t-AML was and 2% and 4%, respectively. HCT was compared with chemotherapy consolidation in s-AML using 3 models: (1) a 200-day landmark analysis, in which HCT was favorable compared with conventional consolidation (P = .04, log-rank test); (2) a multivariable Cox regression with HCT as a time-dependent variable, in which the hazard ratio for mortality was 0.73 (95% confidence interval, 0.64 to 0.83) for HCT and favored HCT in all subgroups; and (3) a propensity score matching analysis, in which the 5-year overall survival (OS) and relapse-free survival in patients with s-AML in first complete remission (CR1) was 48% and 43%, respectively, for patients undergoing HCT versus 20% and 21%, respectively, for those receiving chemotherapy consolidation (P = .01 and .02, respectively, log-rank test). Our observational data suggest that HCT improves survival and offers the only realistic curative treatment option in patients with s-AML. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2019
Keywords
Secondary AML, Therapy-related AML, Allogeneic hematopoietic cell transplantation, Population-based
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-396629 (URN)10.1016/j.bbmt.2019.05.038 (DOI)000488887800008 ()31176789 (PubMedID)
Funder
Swedish Cancer SocietySwedish Research Council
Available from: 2019-11-08 Created: 2019-11-08 Last updated: 2019-11-08Bibliographically 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
Lazarevic, V. L., Bredberg, A., Lorenz, F., Ohlander, E., Antunovic, P., Cammenga, J., . . . Juliusson, G. (2018). Acute myeloid leukemia in very old patients [Letter to the editor]. Haematologica, 103(12), E578-E580
Open this publication in new window or tab >>Acute myeloid leukemia in very old patients
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2018 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 103, no 12, p. E578-E580Article in journal, Letter (Other academic) Published
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-372514 (URN)10.3324/haematol.2018.196691 (DOI)000451736600006 ()29954935 (PubMedID)
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-08Bibliographically approved
Mattsson, M., Sandin, F., Kimby, E., Höglund, M. & Glimelius, I. (2018). Continuous Increasing Prevalence of Chronic Lymphocytic Leukemia (CLL) with an Estimated Future Rise-a Nationwide Population-Based Study from Sweden. Paper presented at 60th Annual Meeting of the American-Society-of-Hematology (ASH), DEC 01-04, 2018, San Diego, CA. Blood, 132
Open this publication in new window or tab >>Continuous Increasing Prevalence of Chronic Lymphocytic Leukemia (CLL) with an Estimated Future Rise-a Nationwide Population-Based Study from Sweden
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2018 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 132Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
AMER SOC HEMATOLOGY, 2018
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-378244 (URN)10.1182/blood-2018-99-114058 (DOI)000454842800273 ()
Conference
60th Annual Meeting of the American-Society-of-Hematology (ASH), DEC 01-04, 2018, San Diego, CA
Available from: 2019-03-08 Created: 2019-03-08 Last updated: 2019-03-08Bibliographically approved
Glimelius, B., Melin, B., Enblad, G., Alafuzoff, I., Beskow, A. H., Ahlström, H., . . . Sjöblom, T. (2018). U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.. Acta Oncologica, 57(2), 187-194
Open this publication in new window or tab >>U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
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2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 187-194Article in journal (Refereed) Published
Abstract [en]

Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

National Category
Cancer and Oncology Urology and Nephrology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-325565 (URN)10.1080/0284186X.2017.1337926 (DOI)000423473200003 ()28631533 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2017-06-26 Created: 2017-06-26 Last updated: 2019-03-29Bibliographically approved
Geelen, I. G. P., Sandin, F., Thielen, N., Janssen, J. J. W., Hoogendoorn, M., Visser, O., . . . Westerweel, P. E. (2018). Validation of the EUTOS long-term survival score in a recent independent cohort of "real world" CML patients. Leukemia, 32(10), 2299-2303
Open this publication in new window or tab >>Validation of the EUTOS long-term survival score in a recent independent cohort of "real world" CML patients
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2018 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 32, no 10, p. 2299-2303Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-367403 (URN)10.1038/s41375-018-0136-7 (DOI)000446171800028 ()29743721 (PubMedID)
Available from: 2018-12-03 Created: 2018-12-03 Last updated: 2018-12-03Bibliographically approved
Olsson, R., Höglund, M. & Juliusson, G. (2017). A Population-Based Study on First AML Relapse in Sweden. Annals of Hematology, 96(Suppl. 1), S65-S65
Open this publication in new window or tab >>A Population-Based Study on First AML Relapse in Sweden
2017 (English)In: Annals of Hematology, ISSN 0939-5555, E-ISSN 1432-0584, Vol. 96, no Suppl. 1, p. S65-S65Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
SPRINGER, 2017
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-320994 (URN)000394105400086 ()
Available from: 2017-04-27 Created: 2017-04-27 Last updated: 2017-04-27Bibliographically approved
Söderlund, S., Dahlén, T., Sandin, F., Olsson-Strömberg, U., Creignou, M., Dreimane, A., . . . Höglund, M. (2017). Advanced phase chronic myeloid leukaemia (CML) in the tyrosine kinase inhibitor era: a report from the Swedish CML register. European Journal of Haematology, 98(1), 57-66
Open this publication in new window or tab >>Advanced phase chronic myeloid leukaemia (CML) in the tyrosine kinase inhibitor era: a report from the Swedish CML register
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2017 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 98, no 1, p. 57-66Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: The primary goal in management of chronic phase (CP) chronic myeloid leukaemia (CML) is to prevent disease progression to accelerated phase (AP) or blast crisis (BC). We have evaluated progression rates in a decentralised healthcare setting and characterised patients progressing to AP/BC on TKI treatment.

METHODS: Using data from the Swedish CML register, we identified CP-CML patients diagnosed 2007-2011 who progressed to AP/BC within 2 yrs from diagnosis (n = 18) as well as patients diagnosed in advanced phase during 2007-2012 (n = 36) from a total of 544 newly diagnosed CML cases. We evaluated baseline characteristics, progression rates, outcome and adherence to guidelines for monitoring and treatment.

RESULTS: The cumulative progression rate at 2 yrs was 4.3%. All 18 progression cases had been treated with imatinib, and six progressed within 6 months. High-risk EUTOS score was associated to a higher risk of progression. Insufficient cytogenetic and/or molecular monitoring was found in 33%. Median survival after transformation during TKI treatment was 1.4 yrs. In those presenting with BC and AP, median survival was 1.6 yrs and not reached, respectively.

CONCLUSION: In this population-based setting, progression rates appear comparable to that reported from clinical trials, with similar dismal patient outcome. Improved adherence to CML guidelines may minimise the risk of disease progression.

National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-310827 (URN)10.1111/ejh.12785 (DOI)000393166600009 ()27428357 (PubMedID)
Available from: 2016-12-20 Created: 2016-12-20 Last updated: 2018-02-26Bibliographically approved
Lehmann, S., Deneberg, S., Antunovic, P., Rangert-Derolf, A., Garelius, H., Lazarevic, V., . . . Juliusson, G. (2017). Early death rates remain high in high-risk APL: update from the Swedish Acute Leukemia Registry 1997-2013 [Letter to the editor]. Leukemia, 31(6), 1457-1459
Open this publication in new window or tab >>Early death rates remain high in high-risk APL: update from the Swedish Acute Leukemia Registry 1997-2013
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2017 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 6, p. 1457-1459Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:uu:diva-332749 (URN)10.1038/leu.2017.71 (DOI)000402832700028 ()28232742 (PubMedID)
Available from: 2017-11-15 Created: 2017-11-15 Last updated: 2018-02-26Bibliographically approved
Kontro, M., Kumar, A., Majumder, M. M., Eldfors, S., Parsons, A., Pemovska, T., . . . Porkka, K. (2017). HOX gene expression predicts response to BCL-2 inhibition in acute myeloid leukemia. Leukemia, 31(2), 301-309
Open this publication in new window or tab >>HOX gene expression predicts response to BCL-2 inhibition in acute myeloid leukemia
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2017 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 2, p. 301-309Article in journal (Refereed) Published
Abstract [en]

Inhibitors of B-cell lymphoma-2 (BCL-2) such as venetoclax (ABT-199) and navitoclax (ABT-263) are clinically explored in several cancer types, including acute myeloid leukemia (AML), to selectively induce apoptosis in cancer cells. To identify robust biomarkers for BCL-2 inhibitor sensitivity, we evaluated the ex vivo sensitivity of fresh leukemic cells from 73 diagnosed and relapsed/refractory AML patients, and then comprehensively assessed whether the responses correlated to specific mutations or gene expression signatures. Compared with samples from healthy donor controls (nonsensitive) and chronic lymphocytic leukemia (CLL) patients (highly sensitive), AML samples exhibited variable responses to BCL-2 inhibition. Strongest CLL-like responses were observed in 15% of the AML patient samples, whereas 32% were resistant, and the remaining exhibited intermediate responses to venetoclax. BCL-2 inhibitor sensitivity was associated with genetic aberrations in chromatin modifiers, WT1 and IDH1/IDH2. A striking selective overexpression of specific HOXA and HOXB gene transcripts were detected in highly BCL-2 inhibitor sensitive samples. Ex vivo responses to venetoclax showed significant inverse correlation to β2-microglobulin expression and to a lesser degree to BCL-XL and BAX expression. As new therapy options for AML are urgently needed, the specific HOX gene expression pattern can potentially be used as a biomarker to identify venetoclax-sensitive AML patients for clinical trials.Leukemia advance online publication, 2 September 2016; doi:10.1038/leu.2016.222.

National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-310826 (URN)10.1038/leu.2016.222 (DOI)000394058800005 ()27499136 (PubMedID)
Available from: 2016-12-20 Created: 2016-12-20 Last updated: 2018-02-26Bibliographically approved
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