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Stromberg, Ulla Ohlsson
Alternative names
Publications (10 of 46) Show all publications
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
Kreutzman, A., Yadav, B., Brummendorf, T. H., Gjertsen, B. T., Hee, M. L., Janssen, J., . . . Mustjoki, S. (2019). Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line. Oncoimmunology, 8(9)
Open this publication in new window or tab >>Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line
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2019 (English)In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 8, no 9Article in journal (Refereed) Published
Abstract [en]

Changes in the immune system induced by tyrosine kinase inhibitors (TKI) have been shown to positively correlate with therapy responses in chronic myeloid leukemia (CML). However, only a few longitudinal studies exist and no randomized comparisons between two TKIs have been reported. Therefore, we prospectively analyzed the immune system of newly diagnosed CML patients treated with imatinib (n = 20) or bosutinib (n = 13), that participated in the randomized BFORE trial (NCT02130557). Comprehensive immunophenotyping, plasma protein profiling, and functional assays to determine activation levels of T and NK cells were performed at diagnosis, 3, and 12 months after therapy start. All results were correlated with clinical parameters such as Sokal risk and BCR-ABL load measured according to IS%. At diagnosis, low Sokal risk CML patients had a higher frequency of cytotoxic cells (CD8 + T and NK cells), increased cytotoxic potential of NK cells and lower frequency of naive and central memory CD4 + T cells. Further, soluble plasma protein profile divided patients into two distinct clusters with different disease burden at diagnosis. During treatment, BCR-ABL IS% correlated with immunological parameters such as plasma proteins, together with different memory subsets of CD4+ and CD8 + T cells. Interestingly, the proportion and cytotoxic potential of NK cells together with several soluble proteins increased during imatinib treatment. In contrast, no major immunological changes were observed during bosutinib treatment. In conclusion, imatinib and bosutinib were shown to have differential effects on the immune system in this randomized clinical trial. Increased number and function of NK cells were especially observed during imatinib therapy.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS INC, 2019
Keywords
CML, imatinib, bosutinib, Sokal, BCR-ABL
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-396139 (URN)10.1080/2162402X.2019.1638210 (DOI)000476301700001 ()31428530 (PubMedID)
Available from: 2019-11-08 Created: 2019-11-08 Last updated: 2019-11-08Bibliographically approved
Lauseker, M., Bachl, K., Turkina, A., Faber, E., Prejzner, W., Strömberg, U. O., . . . Pfirrmann, M. (2019). Prognosis of patients with chronic myeloid leukemia presenting in advanced phase is defined mainly by blast count, but also by age, chromosomal aberrations and hemoglobin. American Journal of Hematology, 94(11), 1236-1243
Open this publication in new window or tab >>Prognosis of patients with chronic myeloid leukemia presenting in advanced phase is defined mainly by blast count, but also by age, chromosomal aberrations and hemoglobin
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2019 (English)In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 94, no 11, p. 1236-1243Article in journal (Refereed) Published
Abstract [en]

Chronic myeloid leukemia (CML) is usually diagnosed in chronic phase, yet there is a small percentage of patients that is diagnosed in accelerated phase or blast crisis. Due to this rarity, little is known about the prognosis of these patients. Our aim was to identify prognostic factors for this cohort. We identified 283 patients in the EUTOS population-based and out-study registries that were diagnosed in advanced phase. Nearly all patients were treated with tyrosine kinase inhibitors. Median survival in this heterogeneous cohort was 8.2 years. When comparing patients with more than 30% blasts to those with 20-29% blasts, the hazard ratio (HR) was 1.32 (95%-confidence interval (CI): [0.7-2.6]). Patients with 20-29% blasts had a significantly higher risk than patients with less than 20% blasts (HR: 2.24, 95%-CI: [1.2-4.0], P = .008). We found that the blast count was the most important prognostic factor; however, age, hemoglobin, basophils and other chromosomal aberrations should be considered as well. The ELTS score was able to define two groups (high risk vs non-high risk) with an HR of 3.01 (95%-CI: [1.81-5.00], P < .001). Regarding the contrasting definitions of blast crisis, our data clearly supported the 20% cut-off over the 30% cut-off in this cohort. Based on our results, we conclude that a one-phase rather than a two-phase categorization of de novo advanced phase CML patients is appropriate.

Place, publisher, year, edition, pages
WILEY, 2019
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-396431 (URN)10.1002/ajh.25628 (DOI)000490182700018 ()31456269 (PubMedID)
Available from: 2019-11-06 Created: 2019-11-06 Last updated: 2019-11-06Bibliographically approved
Saussele, S., Richter, J., Guilhot, J., Gruber, F. X., Hjorth-Hansen, H., Almeida, A., . . . Mahon, F.-X. (2018). Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. The Lancet Oncology, 19(6), 747-757
Open this publication in new window or tab >>Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial
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2018 (English)In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 19, no 6, p. 747-757Article in journal (Refereed) Published
Abstract [en]

Background Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with chronic myeloid leukaemia. Many patients have deep molecular responses, a prerequisite for TKI therapy discontinuation. We aimed to define precise conditions for stopping treatment. Methods In this prospective, non-randomised trial, we enrolled patients with chronic myeloid leukaemia at 61 European centres in 11 countries. Eligible patients had chronic-phase chronic myeloid leukaemia, had received any TKI for at least 3 years (without treatment failure according to European LeukemiaNet [ELN] recommendations), and had a confirmed deep molecular response for at least 1 year. The primary endpoint was molecular relapse-free survival, defined by loss of major molecular response (MMR; >0.1% BCR-ABL1 on the International Scale) and assessed in all patients with at least one molecular result. Secondary endpoints were a prognostic analysis of factors affecting maintenance of MMR at 6 months in learning and validation samples and the cost impact of stopping TKI therapy. We considered loss of haematological response, progress to accelerated-phase chronic myeloid leukaemia, or blast crisis as serious adverse events. This study presents the results of the prespecified interim analysis, which was done after the 6-month molecular relapse-free survival status was known for 200 patients. The study is ongoing and is registered with ClinicalTrials.gov, number NCT01596114. Findings Between May 30, 2012, and Dec 3, 2014, we assessed 868 patients with chronic myeloid leukaemia for eligibility, of whom 758 were enrolled. Median follow-up of the 755 patients evaluable for molecular response was 27 months (IQR 21-34). Molecular relapse-free survival for these patients was 61% (95% CI 57-64) at 6 months and 50% (46-54) at 24 months. Of these 755 patients, 371 (49%) lost MMR after TKI discontinuation, four (1%) died while in MMR for reasons unrelated to chronic myeloid leukaemia (myocardial infarction, lung cancer, renal cancer, and heart failure), and 13 (2%) restarted TKI therapy while in MMR. A further six (1%) patients died in chronic-phase chronic myeloid leukaemia after loss of MMR and re-initiation of TKI therapy for reasons unrelated to chronic myeloid leukaemia, and two (<1%) patients lost MMR despite restarting TKI therapy. In the prognostic analysis in 405 patients who received imatinib as first-line treatment (learning sample), longer treatment duration (odds ratio [OR] per year 1.14 [95% CI 1.05-1.23]; p=0.0010) and longer deep molecular response durations (1.13 [1.04-1.23]; p=0.0032) were associated with increasing probability of MMR maintenance at 6 months. The OR for deep molecular response duration was replicated in the validation sample consisting of 171 patients treated with any TKI as first-line treatment, although the association was not significant (1.13 [0.98-1.29]; p=0.08). TKI discontinuation was associated with substantial cost savings (an estimated (sic)22 million). No serious adverse events were reported. Interpretation Patients with chronic myeloid leukaemia who have achieved deep molecular responses have good molecular relapse-free survival. Such patients should be considered for TKI discontinuation, particularly those who have been in deep molecular response for a long time. Stopping treatment could spare patients from treatment-induced side-effects and reduce health expenditure. Copyright (c) 2018 Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-357715 (URN)10.1016/S1470-2045(18)30192-X (DOI)000434153000041 ()29735299 (PubMedID)
Available from: 2018-09-26 Created: 2018-09-26 Last updated: 2018-09-26Bibliographically 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
Pfirrmann, M., Mahon, F.-X., Guilhot, J., Richter, J., Almeida, A., Janssen, J. J., . . . Hjorth-Hansen, H. (2017). CHRONIC MYELOID LEUKEMIA PATIENTS WERE NOT DIFFERENT IN MOLECULAR RELAPSE AFTER STOPPING IMATINIB IN MR4 WHETHER RESIDUAL DISEASE WAS DETECTED OR NOT - WHEN ADJUSTING FOR NUMBER OF CONTROL TRANSCRIPTS. Paper presented at 22nd Congress of the European-Hematology-Association, JUN 22-25, 2017, Madrid, SPAIN. Haematologica, 102(Suppl. 2), 153-153, Article ID S426.
Open this publication in new window or tab >>CHRONIC MYELOID LEUKEMIA PATIENTS WERE NOT DIFFERENT IN MOLECULAR RELAPSE AFTER STOPPING IMATINIB IN MR4 WHETHER RESIDUAL DISEASE WAS DETECTED OR NOT - WHEN ADJUSTING FOR NUMBER OF CONTROL TRANSCRIPTS
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2017 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, no Suppl. 2, p. 153-153, article id S426Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
FERRATA STORTI FOUNDATION, 2017
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-377413 (URN)000404127001320 ()
Conference
22nd Congress of the European-Hematology-Association, JUN 22-25, 2017, Madrid, SPAIN
Available from: 2019-02-20 Created: 2019-02-20 Last updated: 2019-02-20Bibliographically approved
Geelen, I., Strömberg, U. O., Mustjoki, S., Richter, J., Blijlevens, N., Smit, W., . . . Hjorth-Hansen, H. (2017). CLINICAL AND IMMUNOLOGICAL EFFECTS OF NILOTINIB IN COMBINATION WITH PEGYLATED INTERFERON-A2B IN PATIENTS WITH SUBOPTIMAL MOLECULAR RESPONSE ON IMATINIB (NORDDUTCHCML009). Paper presented at 22nd Congress of the European-Hematology-Association, JUN 22-25, 2017, Madrid, SPAIN. Haematologica, 102(Suppl. 2), 435-435, Article ID E1057.
Open this publication in new window or tab >>CLINICAL AND IMMUNOLOGICAL EFFECTS OF NILOTINIB IN COMBINATION WITH PEGYLATED INTERFERON-A2B IN PATIENTS WITH SUBOPTIMAL MOLECULAR RESPONSE ON IMATINIB (NORDDUTCHCML009)
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2017 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, no Suppl. 2, p. 435-435, article id E1057Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
FERRATA STORTI FOUNDATION, 2017
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-377418 (URN)000404127003194 ()
Conference
22nd Congress of the European-Hematology-Association, JUN 22-25, 2017, Madrid, SPAIN
Available from: 2019-02-20 Created: 2019-02-20 Last updated: 2019-02-20Bibliographically approved
El Missiry, M., Hjorth-Hansen, H., Richter, J., Olsson-Strömberg, U., Stenke, L., Porkka, K., . . . Mustjoki, S. (2017). Early BCR-ABL1 Transcript Decline after 1 Month of Tyrosine Kinase Inhibitor Therapy as an Indicator for Treatment Response in Chronic Myeloid Leukemia. PLoS ONE, 12(1), Article ID e0171041.
Open this publication in new window or tab >>Early BCR-ABL1 Transcript Decline after 1 Month of Tyrosine Kinase Inhibitor Therapy as an Indicator for Treatment Response in Chronic Myeloid Leukemia
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, article id e0171041Article in journal (Refereed) Published
Abstract [en]

In chronic myeloid leukemia (CML), early treatment prediction is important to identify patients with inferior overall outcomes. We examined the feasibility of using reductions in BCR-ABL1 transcript levels after 1 month of tyrosine kinase inhibitor (TKI) treatment to predict therapy response. Fifty-two first-line TKI-treated CML patients were included (imatinib n = 26, dasatinib n = 21, nilotinib n = 5), and BCR-ABL1 transcript levels were measured at diagnosis (dg) and 1, 3, 6, 12, 18, 24, and 36 months. The fold change of the BCR-ABL1 transcripts at 1 month compared to initial BCR-ABL1 transcript levels was used to indicate early therapy response. In our cohort, 21% of patients had no decrease in BCR-ABL1 transcript levels after 1 month and were classified as poor responders. Surprisingly, these patients had lower BCR-ABL1 transcript levels at dg compared to responders (31% vs. 48%, p = 0.0083). Poor responders also significantly more often had enlarged spleen (55% vs. 15%; p< 0.01) and a higher percentage of Ph+ CD34+CD38- cells in the bone marrow (91% vs. 75%, p< 0.05). The major molecular response rates were inferior in the poor responders (at 12m 18% vs. 64%, p< 0.01; 18m 27% vs. 75%, p< 0.01; 24m 55% vs. 87%, p< 0.01). In conclusion, early treatment response analysis defines a biologically distinct patient subgroup with inferior long-term outcomes.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2017
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:uu:diva-319650 (URN)10.1371/journal.pone.0171041 (DOI)000396124700041 ()28135325 (PubMedID)
Available from: 2017-04-07 Created: 2017-04-07 Last updated: 2017-11-29Bibliographically approved
Löf, L., Arngården, L., Olsson-Strömberg, U., Siart, B., Jansson, M., Dahlin, J. S., . . . Kamali-Moghaddam, M. (2017). Flow Cytometric Measurement of Blood Cells with BCR-ABL1 Fusion Protein in Chronic Myeloid Leukemia. Scientific Reports, 7, 1-9, Article ID 623.
Open this publication in new window or tab >>Flow Cytometric Measurement of Blood Cells with BCR-ABL1 Fusion Protein in Chronic Myeloid Leukemia
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, p. 1-9, article id 623Article in journal (Refereed) Published
Abstract [en]

Chronic myeloid leukemia (CML) is characterized in the majority of cases by a t(9;22)(q34;q11) translocation, also called the Philadelphia chromosome, giving rise to the BCR-ABL1 fusion protein. Current treatment with tyrosine kinase inhibitors is directed against the constitutively active ABL1 domain of the fusion protein, and minimal residual disease (MRD) after therapy is monitored by real-time quantitative PCR (RQ-PCR) of the fusion transcript. Here, we describe a novel approach to detect and enumerate cells positive for the BCR-ABL1 fusion protein by combining the in situ proximity ligation assay with flow cytometry as readout (PLA-flow). By targeting of the BCR and ABL1 parts of the fusion protein with one antibody each, and creating strong fluorescent signals through rolling circle amplification, PLA-flow allowed sensitive detection of cells positive for the BCR-ABL1 fusion at frequencies as low as one in 10,000. Importantly, the flow cytometric results correlated strongly to those of RQ-PCR, both in diagnostic testing and for MRD measurements over time. In summary, we believe this flow cytometry-based method can serve as an attractive approach for routine measurement of cells harboring BCR-ABL1 fusions, also allowing simultaneously assessment of other cell surface markers as well as sensitive longitudinal follow-up.

National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-319726 (URN)10.1038/s41598-017-00755-y (DOI)000398162400034 ()28377570 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 294409Swedish Cancer SocietySwedish Research Council
Available from: 2017-04-07 Created: 2017-04-07 Last updated: 2017-05-15Bibliographically approved
Ilander, M., Olsson-Strömberg, U., Schlums, H., Guilhot, J., Brück, O., Lähteenmäki, H., . . . Mustjoki, S. (2017). Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia.. Leukemia, 31(5), 1108-1116
Open this publication in new window or tab >>Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia.
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2017 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 5, p. 1108-1116Article in journal (Refereed) Published
Abstract [en]

Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naïve CD56(bright) NK cells had decreased relapse-free survival. In addition, the TNF-α/IFN-γ cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.Leukemia advance online publication, 16 December 2016; doi:10.1038/leu.2016.360.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-310824 (URN)10.1038/leu.2016.360 (DOI)000400464800009 ()27890936 (PubMedID)
Available from: 2016-12-20 Created: 2016-12-20 Last updated: 2018-02-26Bibliographically approved
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