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Derolf, Å., Juliusson, G., Benson, L., Flöisand, Y., Lazarevic, V., Antunovic, P., . . . Deneberg, S. (2020). Decreasing early mortality in acute myeloid leukaemia in Sweden 1997-2014: improving performance status is a major contributing factor [Letter to the editor]. British Journal of Haematology, 188(1), 187-191
Open this publication in new window or tab >>Decreasing early mortality in acute myeloid leukaemia in Sweden 1997-2014: improving performance status is a major contributing factor
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2020 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 188, no 1, p. 187-191Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
WILEY, 2020
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-403037 (URN)10.1111/bjh.16265 (DOI)000505278200021 ()31863470 (PubMedID)
Available from: 2020-01-22 Created: 2020-01-22 Last updated: 2020-01-22Bibliographically approved
Juliusson, G., Höglund, M. & Lehmann, S. (2020). Hypo, Hyper, or Combo: new paradigm for treatment of acute myeloid leukemia in older people. Haematologica, 105(2), 249-251
Open this publication in new window or tab >>Hypo, Hyper, or Combo: new paradigm for treatment of acute myeloid leukemia in older people
2020 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 105, no 2, p. 249-251Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
FERRATA STORTI FOUNDATION, 2020
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-407111 (URN)10.3324/haematol.2019.238857 (DOI)000510846700014 ()32005651 (PubMedID)
Available from: 2020-03-19 Created: 2020-03-19 Last updated: 2020-03-19Bibliographically approved
Larfors, G., Richter, J., Själander, A., Stenke, L. & Höglund, M. (2020). Increased Risk of Chronic Myeloid Leukemia Following Gastric Conditions Indicating Helicobacter pylori Infection: A Case-Control Study. Cancer Epidemiology, Biomarkers and Prevention, 29(1), 151-156
Open this publication in new window or tab >>Increased Risk of Chronic Myeloid Leukemia Following Gastric Conditions Indicating Helicobacter pylori Infection: A Case-Control Study
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2020 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 29, no 1, p. 151-156Article in journal (Refereed) Published
Abstract [en]

Background: On the basis of a previous report of increased chronic myeloid leukemia (CML) risk following peptic ulcer, we hypothesized that chronic Helicobacter pylori infection could serve as a risk factor for CML.

Methods: In a population-based, retrospective case-control study, we used Swedish registry data on 980 patients with CML and 4,960 age- and sex-matched controls to investigate associations between markers of previous infection with Helicobacter pylori and CML incidence.

Results: Previous diagnoses of dyspepsia, gastritis or peptic ulcers, as well as previous proton pump inhibitor (PPI) medication, were all associated with a significantly increased risk of CML (RRs, 1.5-2.0; P = 0.0005-0.05). Meanwhile, neither inflammatory bowel disease nor intake of NSAIDs were associated with CML, indicating that it is not gastrointestinal ulcer or inflammation per se that influences risk.

Conclusions: The consistent associations suggest a shared background between gastric conditions and CML, and strengthen the case that Helicobacter pylori could constitute this common risk factor.

Impact: As the etiology of CML is practically unknown, and Helicobacter pylori could potentially be a therapeutic target, even this indirect evidence encourages further studies on the potential involvement of Helicobacter pylori in CML etiology.

Place, publisher, year, edition, pages
AMER ASSOC CANCER RESEARCH, 2020
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-408919 (URN)10.1158/1055-9965.EPI-19-0758 (DOI)000521285100019 ()31619405 (PubMedID)
Available from: 2020-04-17 Created: 2020-04-17 Last updated: 2020-04-17Bibliographically approved
Mattsson, M., Sandin, F., Kimby, E., Höglund, M. & Glimelius, I. (2020). Increasing prevalence of chronic lymphocytic leukemia with an estimated future rise: a nationwide population-based study [Letter to the editor]. American Journal of Hematology, 95(2), E36-E38
Open this publication in new window or tab >>Increasing prevalence of chronic lymphocytic leukemia with an estimated future rise: a nationwide population-based study
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2020 (English)In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 95, no 2, p. E36-E38Article in journal, Letter (Other academic) Published
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-397704 (URN)10.1002/ajh.25681 (DOI)000498907500001 ()31725930 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2019-11-23 Created: 2019-11-23 Last updated: 2020-04-16Bibliographically approved
Juliusson, G., Jädersten, M., Deneberg, S., Lehmann, S., Möllgard, L., Wennström, L., . . . Höglund, M. (2020). The prognostic impact of FLT3-ITD and NPM1 mutation in adult AML is age-dependent in the population-based setting. BLOOD ADVANCES, 4(6), 1094-1101
Open this publication in new window or tab >>The prognostic impact of FLT3-ITD and NPM1 mutation in adult AML is age-dependent in the population-based setting
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2020 (English)In: BLOOD ADVANCES, ISSN 2473-9529, Vol. 4, no 6, p. 1094-1101Article in journal (Refereed) Published
Abstract [en]

In acute myeloid leukemia (AML) FLT3 internal tandem duplication (ITD) and nucleophosmin 1 (NPM1) mutations provide prognostic information with clinical relevance through choice of treatment, but the effect of age and sex on these molecular markers has not been evaluated. The Swedish AML Registry contains data on FLT3-ITD and NPM1 mutations dating to 2007, and 1570 adult patients younger than 75 years, excluding acute promyelocytic leukemia, had molecular results reported. Females more often had FLT3(ITD) and/or NPM1(mut) (FLT3(ITD) : female, 29%; male, 22% [P - .00151; NPM1(mut) : female, 36%; male, 27% [P < .0001]), and more males were double negative (female, 53%; male, 64%; P < .0001). Patients with FLT3(ITD) were younger than those without (59 vs 62 years; P = .023), in contrast to patients with NPM1(mut) (62 vs 60 years; P = .059). Interestingly, their prognostic effect had a strong dependence on age: FLT3(ITD) indicated poor survival in younger patients (<60 years; P = .00003), but had no effect in older patients (60-74 years; P = .5), whereas NPM1(mut) indicated better survival in older patients (P = .00002), but not in younger patients (P = .95). In FLT3(ITD)/NPM1(mut) patients, the survival was less dependent on age than in the other molecular subsets. These findings are likely to have clinical relevance for risk grouping, study design, and choice of therapy.

Place, publisher, year, edition, pages
American Society of Hematology, 2020
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-409846 (URN)10.1182/bloodadvances.2019001335 (DOI)000521788300016 ()32203582 (PubMedID)
Funder
Swedish Cancer SocietySwedish Association of Local Authorities and RegionsRegion Skåne
Available from: 2020-05-28 Created: 2020-05-28 Last updated: 2020-05-28Bibliographically approved
Lubking, A., Dreimane, A., Sandin, F., Isaksson, C., Markevarn, B., Brune, M., . . . Olsson-Strömberg, U. (2019). Allogeneic stem cell transplantation for chronic myeloid leukemia in the TKI era: population-based data from the Swedish CML registry. Bone Marrow Transplantation, 54(11), 1764-1774
Open this publication in new window or tab >>Allogeneic stem cell transplantation for chronic myeloid leukemia in the TKI era: population-based data from the Swedish CML registry
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2019 (English)In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 54, no 11, p. 1764-1774Article in journal (Refereed) Published
Abstract [en]

Two decades after the introduction of tyrosine kinase inhibitors (TKI), a sizeable portion of patients with chronic myeloid leukemia (CML) in chronic phase (CP) still undergo allogeneic stem cell transplantation (allo-HSCT). We investigated the indications for allo-HSCT, clinical outcome, management of relapse, and post-transplant TKI treatment in a population-based setting using the Swedish CML registry. Of 118 CML patients transplanted between 2002 and 2017, 56 (47.4%) received allo-HSCT in first CP, among whom TM resistance was the most common transplant indication (62.5%). For patients diagnosed with CML in CP at <65 years of age, the cumulative probability of undergoing allo-HSCT within 5 years was 9.7%. Overall 5-year survival was 96.2%, 70.1% and 36.9% when transplanted in first CP, second or later CP, and in accelerated phase or blast crisis, respectively. Risk factors for relapse were EBMT score >2 and reduced intensity conditioning, and for death, CP > 2 at time point of allo-HSCT only. Non-relapse mortality for patients transplanted in CP was 11.6%. Our data indicate that allo-HSCT still constitutes a reasonable therapeutic option for patients with CML in first CP, especially those resistant to TKI treatment, providing high long-term survival and low non-relapse mortality.

National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-397685 (URN)10.1038/s41409-019-0513-5 (DOI)000495103300009 ()30962502 (PubMedID)
Available from: 2019-11-28 Created: 2019-11-28 Last updated: 2019-11-28Bibliographically approved
Angenendt, L., Röllig, C., Montesinos, P., Martinez-Cuadron, D., Barragan, E., Garcia, R., . . . Schliemann, C. (2019). Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia: A Pooled Analysis of Individual Patient Data From Nine International Cohorts. Journal of Clinical Oncology, 37(29), 2632-2642
Open this publication in new window or tab >>Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia: A Pooled Analysis of Individual Patient Data From Nine International Cohorts
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2019 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 37, no 29, p. 2632-2642Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Nucleophosmin 1 (NPM1) mutations are associated with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms-related tyrosine kinase 3 gene (FLT3) is absent (FLT3-ITDneg) or present with a low allelic ratio (FLT3-ITDlow). The 2017 European LeukemiaNet guidelines assume this is true regardless of accompanying cytogenetic abnormalities. We investigated the validity of this assumption.

METHODS: We analyzed associations between karyotype and outcome in intensively treated patients with NPM1(mut)/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers.

RESULTS: Among 2,426 patients with NPM1(mut)/FLT3-ITDneg/low AML, 2,000 (82.4%) had a normal and 426 (17.6%) had an abnormal karyotype, including 329 patients (13.6%) with intermediate and 83 patients (3.4%) with adverse-risk chromosomal abnormalities. In patients with NPM1(mut)/FLT3-ITDneg/low AML, adverse cytogenetics were associated with lower complete remission rates (87.7%, 86.0%, and 66.3% for normal, aberrant intermediate, and adverse karyotype, respectively; P < .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P < .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P < .001), and a higher 5-year cumulative incidence of relapse (43.6%, 44.2%, 51.9%, respectively; P = .0012). These associations remained in multivariable mixed-effects regression analyses adjusted for known clinicopathologic risk factors (P < .001 for all end points). In patients with adverse-risk chromosomal aberrations, we found no significant influence of the NPM1 mutational status on outcome.

CONCLUSION: Karyotype abnormalities are significantly associated with outcome in NPM1(mut)/FLT3-ITDneg/low AML. When adverse-risk cytogenetics are present, patients with NPM1(mut) share the same unfavorable prognosis as patients with NPM1 wild type and should be classified and treated accordingly. Thus, cytogenetic risk predominates over molecular risk in NPM1(mut)/FLT3-ITDneg/low AML.

Place, publisher, year, edition, pages
AMER SOC CLINICAL ONCOLOGY, 2019
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:uu:diva-396959 (URN)10.1200/JCO.19.00416 (DOI)000491485600006 ()31430225 (PubMedID)
Funder
German Research Foundation (DFG), DFG EXC 1003
Available from: 2019-11-13 Created: 2019-11-13 Last updated: 2019-11-13Bibliographically approved
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
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2468-0226

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