Publications by authors named "Lovisa Wennström"

18 Publications

  • Page 1 of 1

Successful tyrosine kinase inhibitor discontinuation outside clinical trials - data from the population-based Swedish chronic myeloid leukaemia registry.

Br J Haematol 2021 Mar 30. Epub 2021 Mar 30.

Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.

Clinical trials show that tyrosine kinase inhibitor (TKI) treatment can be discontinued in selected patients with chronic myeloid leukaemia (CML). Although updated CML guidelines support such procedure in clinical routine, data on TKI stopping outside clinical trials are limited. In this retrospective study utilising the Swedish CML registry, we examined TKI discontinuation in a population-based setting. Out of 584 patients diagnosed with chronic-phase CML (CML-CP) in 2007-2012, 548 had evaluable information on TKI discontinuation. With a median follow-up of nine years from diagnosis, 128 (23%) discontinued TKI therapy (≥1 month) due to achieving a DMR (deep molecular response) and 107 (20%) due to other causes (adverse events, allogeneic stem cell transplant, pregnancy, etc). Among those stopping in DMR, 49% re-initiated TKI treatment (median time to restart 4·8 months). In all, 38 patients stopped TKI within a clinical study and 90 outside a study. After 24 months 41·1% of patients discontinuing outside a study had re-initiated TKI treatment. TKI treatment duration pre-stop was longer and proportion treated with second-generation TKI slightly higher outside studies, conceivably affecting the clinical outcome. In summary we show that TKI discontinuation in CML in clinical practice is common and feasible and may be just as successful as when performed within a clinical trial.
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http://dx.doi.org/10.1111/bjh.17392DOI Listing
March 2021

Is there an impact of measurable residual disease as assessed by multiparameter flow cytometry on survival of AML patients treated in clinical practice? A population-based study.

Leuk Lymphoma 2021 Mar 10:1-9. Epub 2021 Mar 10.

Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.

The Swedish national guidelines for treatment of acute myeloid leukemia (AML) recommend analysis of measurable residual disease (MRD) by multiparameter flow cytometry (MFC) in bone marrow in the routine clinical setting. The Swedish AML registry contains such MRD data in AML patients diagnosed 2011-2019. Of 327 patients with AML (non-APL) with MRD-results reported in complete remission after two courses of intensive chemotherapy 229 were MRD-negative (70%), as defined by <0.1% cells with leukemia-associated immunophenotype in the bone marrow. MRD-results were reported to clinicians in real time. Multivariate statistical analysis adjusted for known established risk factors did not indicate an association between MFC-MRD and overall survival (HR: 1.00 [95% CI 0.61, 1.63]) with a median follow-up of 2.7 years. Knowledge of the importance of MRD status by clinicians and individualized decisions could have ameliorated the effects of MRD as an independent prognostic factor of overall survival.
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http://dx.doi.org/10.1080/10428194.2021.1889539DOI Listing
March 2021

Clinical and genomic characterization of patients diagnosed with the provisional entity acute myeloid leukemia with BCR-ABL1, a Swedish population-based study.

Genes Chromosomes Cancer 2021 Jun 22;60(6):426-433. Epub 2021 Jan 22.

Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.

Acute myeloid leukemia (AML) with t(9;22)(q34;q11), also known as AML with BCR-ABL1, is a rare, provisional entity in the WHO 2016 classification and is considered a high-risk disease according to the European LeukemiaNet 2017 risk stratification. We here present a retrospective, population-based study of this disease entity from the Swedish Acute Leukemia Registry. By strict clinical inclusion criteria we aimed to identify genetic markers further distinguishing AML with t(9;22) as a separate entity. Twenty-five patients were identified and next-generation sequencing using a 54-gene panel was performed in 21 cases. Interestingly, no mutations were found in NPM1, FLT3, or DNMT3A, three frequently mutated genes in AML. Instead, RUNX1 was the most commonly mutated gene, with aberrations present in 38% of the cases compared to around 10% in de novo AML. Additional mutations were identified in genes involved in RNA splicing (SRSF2, SF3B1) and chromatin regulation (ASXL1, STAG2, BCOR, BCORL1). Less frequently, mutations were found in IDH2, NRAS, TET2, and TP53. The mutational landscape exhibited a similar pattern as recently described in patients with chronic myeloid leukemia (CML) in myeloid blast crisis (BC). Despite the concomitant presence of BCR-ABL1 and RUNX1 mutations in our cohort, both features of high-risk AML, the RUNX1-mutated cases showed a superior overall survival compared to RUNX1 wildtype cases. Our results suggest that the molecular characteristics of AML with t(9;22)/BCR-ABL1 and CML in myeloid BC are similar and do not support a distinction of the two disease entities based on their underlying molecular alterations.
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http://dx.doi.org/10.1002/gcc.22936DOI Listing
June 2021

The prognostic impact of FLT3-ITD and NPM1 mutation in adult AML is age-dependent in the population-based setting.

Blood Adv 2020 03;4(6):1094-1101

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

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 FLT3ITD and/or NPM1mut (FLT3ITD: female, 29%; male, 22% [P = .0015]; NPM1mut: female, 36%; male, 27% [P = .0001]), and more males were double negative (female, 53%; male, 64%; P < .0001). Patients with FLT3ITD were younger than those without (59 vs 62 years; P = .023), in contrast to patients with NPM1mut (62 vs 60 years; P = .059). Interestingly, their prognostic effect had a strong dependence on age: FLT3ITD indicated poor survival in younger patients (<60 years; P = .00003), but had no effect in older patients (60-74 years; P = .5), whereas NPM1mut indicated better survival in older patients (P = .00002), but not in younger patients (P = .95). In FLT3ITD/NPM1mut 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.
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http://dx.doi.org/10.1182/bloodadvances.2019001335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094014PMC
March 2020

Incidence and prognostic significance of isolated trisomies in adult acute myeloid leukemia: A population-based study from the Swedish AML registry.

Eur J Haematol 2017 May 9;98(5):493-500. Epub 2017 Mar 9.

Department of Clinical Genetics, University and Regional Laboratories Region Skåne, Lund, Sweden.

Objectives And Methods: To ascertain the incidence/clinical implications of isolated autosomal trisomies in adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry.

Results: Of the 3179 cytogenetically informative AMLs diagnosed January 1997-May 2015, 246 (7.7%) had isolated trisomies. The frequency increased by age (2.4% at age 18-60 years vs. 23% at >60 years; P<.0001); the median age was 69 years. The five most common were +8 (4.0%), +13 (0.9%), +11 (0.8%), +21 (0.7%), and +4 (0.5%). Age and gender, types of AML and treatment, and complete remission and early death rates did not differ between the single trisomy and the intermediate risk (IR) groups or among cases with isolated gains of chromosomes 4, 8, 11, 13, or 21. The overall survival (OS) was similar in the single trisomy (median 1.6 years) and IR groups (1.7 years; P=.251). The OS differed among the most frequent isolated trisomies; the median OS was 2.5 years for +4, 1.9 years for +21, 1.5 years for +8, 1.1 years for +11, and 0.8 years for +13 (P=.013).

Conclusion: AML with single trisomies, with the exception of +13, should be grouped as IR.
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http://dx.doi.org/10.1111/ejh.12861DOI Listing
May 2017

Acute de novo Leukemia in Estonia and Western Sweden 1982-2006: Positive Trend in the Survival of Acute Leukemia over 25 Years.

Acta Haematol 2016 19;136(3):167-73. Epub 2016 Aug 19.

Department of Internal Medicine/Hematology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

This study focuses on the incidence, treatment, and survival of de novo acute leukemia in a 25-year perspective in western Sweden and Estonia. At the beginning of our study, Estonia was a part of the Eastern bloc with planned economy, but since 1991 it is a member of the European Union and transforming into a market economy. Survival rates have steadily increased in both countries. However, a gap between their survival curves remains. Based on our data, it is difficult to explain the big difference in the 5-year relative survival in favor of western Sweden (55 vs. 22%). In Germany, there was a big difference in overall cancer survival between East and West Germany after the fall of the iron curtain, but today no difference is seen. Differences in survival are probably due to a higher proportion of intense chemotherapy regimens and a higher rate of hematopoietic stem cell transplantations in Sweden. Other important factors might be better supportive care and diagnostics as well as better adjuvant therapy. Better staff training and conditions in wards are also factors that might play an essential role.
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http://dx.doi.org/10.1159/000446525DOI Listing
December 2016

Acute Myeloid Leukemia in Adolescents and Young Adults Treated in Pediatric and Adult Departments in the Nordic Countries.

Pediatr Blood Cancer 2016 Jan 18;63(1):83-92. Epub 2015 Aug 18.

Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.

Background: Studies on adolescents and young adults with acute lymphoblastic leukemia suggest better results when using pediatric protocols for adult patients, while corresponding data for acute myeloid leukemia (AML) are limited.

Procedure: We investigated disease characteristics and outcome for de novo AML patients 10-30 years old treated in pediatric or adult departments. We included 166 patients 10-18 years of age with AML treated according to the pediatric NOPHO-protocols (1993-2009) compared with 253 patients aged 15-30 years treated in hematology departments (1996-2009) in the Nordic countries.

Results: The incidence of AML was 4.9/million/year for the age group 10-14 years, 6.5 for 15-18 years, and 6.9 for 19-30 years. Acute promyelocytic leukemia (APL) was more frequent in adults and in females of all ages. Pediatric patients with APL had similar overall survival as pediatric patients without APL. Overall survival at 5 years was 60% (52-68%) for pediatric patients compared to 65% (58-70%) for adult patients. Cytogenetics and presenting white blood cell count were the only independent prognostic factors for overall survival. Age was not an independent prognostic factor.

Conclusions: No difference was found in outcome for AML patients age 10-30 years treated according to pediatric as compared to adult protocols.
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http://dx.doi.org/10.1002/pbc.25713DOI Listing
January 2016

Prognostic significance of high hyperdiploid and triploid/tetraploid adult acute myeloid leukemia.

Am J Hematol 2015 Sep 22;90(9):800-5. Epub 2015 Jul 22.

Department of Clinical Genetics, University and Regional Laboratories Region Skåne, Lund, Sweden.

To ascertain the clinical implications of high hyperdiploid (HH; 49-65 chromosomes) and triploid/tetraploid (TT; >65 chromosomes) adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry. Of the 3,654 cytogenetically informative cases diagnosed between January 1997 and May 2014, 68 (1.9%) were HH (n = 50)/TT (n = 18). Patients with HH/TT were older than those with intermediate risk (IR) AML (median 71 years vs. 67 years; P = 0.042) and less often had de novo AML (63% vs. 79%; P = 0.004); no such differences were observed between HH/TT and complex karyotype (CK) AML. The overall survival (OS) was similar between patients with HH/TT and CK AML (median 0.9 years vs. 0.6 years; P = 0.082), whereas OS was significantly longer (median 1.6 years; P = 0.028) for IR AML. The OS was shorter for cases with HH than with TT (median 0.6 years vs. 1.4 years; P = 0.032) and for HH/TT AMLs with adverse abnormalities (median 0.8 years vs. 1.1 years; P = 0.044). In conclusion, HH/TT AML is associated with a poor outcome, but chromosome numbers >65 and absence of adverse aberrations seem to translate into a more favorable prognosis. Thus, HH/TT AMLs are clinically heterogeneous and should not automatically be grouped as high risk.
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http://dx.doi.org/10.1002/ajh.24091DOI Listing
September 2015

Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: a report from the Swedish Acute Leukemia Registry.

Am J Hematol 2015 Mar 16;90(3):208-14. Epub 2015 Jan 16.

Department of Medicine and Regional Tumor Registry, Sahlgrenska University Hospital, Göteborg, Sweden.

Patients with secondary acute myeloid leukemia (AML) often escape inclusion in clinical trials and thus, population-based studies are crucial for its accurate characterization. In this first large population-based study on secondary AML, we studied AML with an antecedent hematological disease (AHD-AML) or therapy-related AML (t-AML) in the population-based Swedish Acute Leukemia Registry. The study included 3,363 adult patients of which 2,474 (73.6%) had de novo AML, 630 (18.7%) AHD-AML, and 259 (7.7%) t-AML. Secondary AML differed significantly compared to de novo AML with respect to age, gender, and cytogenetic risk. Complete remission (CR) rates were significantly lower but early death rates similar in secondary AML. In a multivariable analysis, AHD-AML (HR 1.51; 95% CI 1.26-1.79) and t-AML (1.72; 1.38-2.15) were independent risk factors for poor survival. The negative impact of AHD-AML and t-AML on survival was highly age dependent with a considerable impact in younger patients, but without independent prognostic value in the elderly. Although patients with secondary leukemia did poorly with intensive treatment, early death rates and survival were significantly worse with palliative treatment. We conclude that secondary AML in a population-based setting has a striking impact on survival in younger AML patients, whereas it lacks prognostic value among the elderly patients.
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http://dx.doi.org/10.1002/ajh.23908DOI Listing
March 2015

Sequential population-based studies over 25 years on the incidence and survival of acute de novo leukemias in Estonia and in a well-defined region of western Sweden during 1982-2006: a survey of patients aged ≥65 years.

Med Oncol 2013 Mar 9;30(1):487. Epub 2013 Feb 9.

Clinic of Hematology and Oncology, Tartu University Clinic, Tartu, Estonia.

Estonia regained independence in 1991 after five decades of occupation by the Soviet Union. The present population-based survey was carried out over five consecutive 5-year study periods (1982-2006) on the incidence and survival of de novo acute leukemia patients aged ≥65 years at diagnosis in Estonia and in a well-defined area in western Sweden. During the study period of retrospective work (1982-1996), the first 10 years were carried out while Estonia was still under the mentorship of the Soviet Union. Over these years, Estonian hematologists did not have access to therapeutic measures readily available to Swedish hematologists, and the results for survival for western Swedish patients with acute myeloid leukemia (AML) far exceeded those of their Estonian counterparts. However, the results for acute lymphoblastic leukemia were equally dismal in the two countries. Subsequent prospective population-based studies were carried out during the years 1997-2006. A gradual improvement as to long-term relative survival of the Estonian AML patients was observed. When studying 2002-2006, no difference as regards relative survival at 5 years was anymore present between the two countries. Over the first 20 years of our population-based studies, it was repeatedly observed that the age-standardized incidence rate particularly for de novo AML was considerably higher for the western Swedish as compared to the Estonian cohorts. During the last 5-year study period (2002-2006), no such difference between the two countries was present, indicating that some true changes in the reporting procedure in Estonia had occurred.
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http://dx.doi.org/10.1007/s12032-013-0487-xDOI Listing
March 2013

The incidence and survival of acute de novo leukemias in Estonia and in a well-defined region of western Sweden during 1997-2001: a survey of patients aged 16-64 years.

Acta Haematol 2011 13;126(3):176-85. Epub 2011 Aug 13.

Department of Internal Medicine/Hematology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Background: In a recent retrospective study, we investigated the incidence and survival of de novo acute leukemia (AL) patients aged 16-64 years over three 5-year periods (1982-1996) in Estonia and in the Western Swedish Health Care Region. The incidence rates were similar in the two countries, but the survival data were highly different. Thus, relative survival at 5 years for de novo AL patients in Estonia was virtually negligible, whereas the corresponding figures for the Swedish patients increased from 20.3 to 38.9% during the study period.

Aim: To prospectively compare the results for incidence and outcome of de novo AL between the two countries during 1997-2001.

Results: Incidence rates for de novo AL were lower in Estonia than in western Sweden but not significantly so. However, the survival for de novo AL patients in Estonia had improved considerably, with the relative survival at 5 years being 16.4%; such improvement was particularly seen in acute myeloid leukemia patients. For the Swedish patients, no change in survival was recorded.

Conclusion: In Estonia, a remarkable improvement in outcome for young de novo AL patients was seen after 1996. Nevertheless, relative survival for the Estonian patients had still not reached the levels found in the Swedish cohort.
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http://dx.doi.org/10.1159/000329526DOI Listing
November 2011

The incidence and survival of acute de novo leukemias in Estonia and in a well-defined region of western Sweden during 1997-2001: a survey of patients aged >or=65 years.

Cancer Epidemiol 2010 Feb 13;34(1):24-8. Epub 2010 Jan 13.

Department of Hematology, North Estonian Regional Hospital, Tallinn, Estonia.

Background: In a recently published retrospective population-based study over three 5-year periods (1982-1996) we investigated the outcome for de novo acute leukemia (AL) patients aged >or=65 years at diagnosis in Estonia (a country that had been occupied by the Soviet Union over 5 decades) and in the so-called Western Swedish Health Care Region. The age-standardized yearly incidence rates regarding the total number of de novo AL was 5.3/100000 inhabitant for Estonia and 8.0 for Sweden, this difference being statistically significant merely as regards acute myeloid leukemia (AML). The relative survival for the total cohort of de novo AL as well as for de novo AML was significantly longer (p<0.001) for Swedish as compared to Estonian patients.

Methods: In view of the miserable outcome for the Estonian patients we decided to prospectively compare the results for incidence and outcome of de novo AL between the two countries.

Results: The present report covers the first 5-year period comprising 1997-2001 and deals only with patients aged >or=65 years at diagnosis. The age-adjusted annual incidence rates for de novo AML were lower in Estonia (6.4/100000) than in Sweden (9.2/100000) but not significantly so. The present results also show that the outcome for the Estonian AML patients had improved considerably over the study period; thus, at no time point, i.e., at 1, 3 and 5 years did relative survival between the two countries differ significantly.

Conclusion: Yet, as compared to the Swedish cohort relative survival for the Estonian patients did still not reach an acceptable level.
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http://dx.doi.org/10.1016/j.canep.2009.12.004DOI Listing
February 2010

The incidence and survival of acute de novo leukaemias in Estonia and in a well defined region of Western Sweden during 1982-1996: a survey of patients aged 16-64 years.

Leuk Lymphoma 2004 May;45(5):915-21

Haematology and Coagulation Section, Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.

In the present work the incidence and survival of acute de novo leukaemias in two neighbouring countries, were studied retrospectively over three 5-year periods, 1982-1996. The aim was to compare the above variables, particularly with respect to political/socio-economic and environmental factors, in a well defined area of Sweden, the so-called Western Swedish Health Care Region, with Estonia. Population-wise the Western Swedish Region and Estonia are very similar; area-wise they are also well comparable. The present report covers only patients diagnosed between the ages of 16-64 years. The number of acute de novo leukaemias in the two regions was quite similar (Western Sweden n = 282 and Estonia n = 237). The age standardized incidence rate regarding total acute de novo leukaemias was slightly lower in Estonia than in Western Sweden (1.49/100,000 inhabitants/year for Estonia and 1.76 for Sweden, respectively), the difference being not statistically significant. However, the survival data for the two countries were highly different (P < 0.001). Thus, the relative survival for the total group of patients aged 16-64 years in Estonia at 1 year was 20.7% and at 5 years 3.6%, respectively. The corresponding figures for the Swedish patients were considerably higher, 65.2 and 29.4%, respectively. Further, the 5 year survival significantly (P < 0.05) increased for the Swedish patients over the 3 consecutive 5-year periods. No such improvement was recorded for the Estonian patients.
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http://dx.doi.org/10.1080/10428190310001623865DOI Listing
May 2004

Increased risk for vascular complications in PRV-1 positive patients with essential thrombocythaemia.

Br J Haematol 2003 Nov;123(3):513-6

Haematology and Coagulation Section, Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.

Essential thrombocythaemia (ET) is a heterogeneous disorder with respect to plasma erythropoietin concentration at diagnosis and clonality of haematopoiesis. Polycythaemia rubra vera-1 (PRV-1) positivity, i.e. PRV-1 mRNA overexpression, is known to be present in the vast majority of patients with polycythaemia vera and also in some patients with ET. In the present study, PRV-1 expression was quantified by real-time polymerase chain reaction in 70 ET patients; 17 of them (24%) were found to be PRV-1 positive. Ten of the 17 PRV-1 positive ET patients had experienced thromboembolic complications compared with 14 of 53 PRV-1 negative patients, the difference between the two groups being statistically significant (P=0.02). In addition, the frequency of total vascular complications, thromboembolic events and major bleedings, was significantly higher in the group of PRV-1 positive as compared with PRV-1 negative ET patients (P=0.03). The time from diagnosis of ET to the requirement of platelet-lowering therapy was significantly shorter in PRV-1 positive compared with PRV-1 negative ET patients (P=0.014). It can be concluded that PRV-1 positive patients appear to suffer from a more aggressive disorder with increased risk for vascular complications and a greater need for platelet-lowering therapy, compared with PRV-1 negative ET patients.
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http://dx.doi.org/10.1046/j.1365-2141.2003.04634.xDOI Listing
November 2003

The presence of a significant association between elevated PRV-1 mRNA expression and low plasma erythropoietin concentration in essential thrombocythaemia.

Eur J Haematol 2003 Jun;70(6):358-62

Haematology and Coagulation Section, Department of Medicine, Sahlgrenska University Hospital, University of Göteborg, Göteborg, Sweden.

Approximately 45% of newly diagnosed patients with essential thrombocythaemia (ET) demonstrate subnormal plasma erythropoietin (EPO) concentrations, which constitutes a risk factor for occlusive vascular events. In 58 ET patients, a possible association between polycythaemia rubra vera-1 (PRV-1) overexpression and subnormal plasma EPO was investigated, which was always measured prior to the institution of platelet lowering agents. At the time when PRV-1 expression was measured, 28 of 58 (48%) ET patients had received platelet lowering treatment. PRV-1 expression was measured by quantitative real-time reverse transcription-polymerase chain reaction assay of mRNA extracted from purified peripheral blood buffy coat. The cycle threshold (CT) value of PRV-1 was determined and was divided with the CT value for the housekeeping GAPDH gene transcript. A quotient <0.93 was defined as PRV-1 positive. Of the ET patients 12 of 58 (21%) were PRV-1 positive and 19 of 58 (33%) demonstrated subnormal plasma EPO. In the 58 ET patients there was a significant association between low plasma EPO and PRV-1 positive results (P = 0.001). The 30 ET patients who had not received any platelet lowering treatment showed a significant (P = 0.005) relation between PRV-1 positivity and subnormal plasma EPO. No such relationship was present in the 28 ET patients who had received prior treatment with the above drugs (P = 0.147).
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http://dx.doi.org/10.1034/j.1600-0609.2003.00079.xDOI Listing
June 2003