| 1. |
- Andreasson, Björn, et al.
(författare)
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Plasma erythropoietin concentrations in polycythaemia vera with special reference to myelosuppressive therapy.
- 2000
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Ingår i: Leukemia & lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 37:1-2, s. 189-95
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Tidskriftsartikel (refereegranskat)abstract
- In 80 patients with polycythaemia vera (PV) a total of 108 venous blood samples were obtained and analysed for EDTA-plasma erythropoietin (EPO) concentration. At the time of study 21 of the PV patients were newly diagnosed and had prior to blood sampling neither received phlebotomy treatment nor therapy with myelosuppressive agents; these subjects had a mean plasma EPO concentration of 0.5+/-0.9 IU/L. Thirty-seven patients treated with phlebotomy only had a mean plasma EPO concentration of 2.5+/-2.9 IU/L. The mean plasma EPO concentrations for 26 patients treated with hydroxyurea, 13 patients treated with radiophosphorous and 11 patients given a combination of myelosuppressive agents were 8.9+/-8.0, 10.9+/-12.6 and 7.2+/-7.4 IU/L, respectively. Untreated patients and patients on phlebotomy only had significantly lower values for plasma EPO than patients on therapy with myelosuppressive drugs. This finding persisted also after a correction for differences in haemoglobin levels had been introduced. Thereby, the present results would suggest a difference in the EPO feedback system in untreated and phlebotomised PV patients compared to PV patients treated with myelosuppressive agents.
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| 2. |
- Andreasson, Björn, et al.
(författare)
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The relation between plasma thrombopoietin and erythropoietin concentrations in polycythaemia vera and essential thrombocythaemia.
- 2001
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Ingår i: Leukemia & lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 41:5-6, s. 579-84
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Tidskriftsartikel (refereegranskat)abstract
- Plasma thrombopoietin (TPO) was measured, by immunoenzymometric assay, in 39 patients with polycythaemia vera (PV), 33 patients with essential thrombocythaemia (ET) and 10 healthy volunteers. The mean TPO concentration was significantly higher in ET patients than in PV patients (p=0.04) and normals (p<0.001). The 6 untreated ET patients had a significantly lower mean TPO concentration compared to the 27 ET patients who were on myelosuppressive regimens (p=0.01). The mean plasma TPO for the 5 PV patients treated with phlebotomy only did not differ significantly from the corresponding mean for the 34 PV patients treated with myelosuppressive agents. Concomitantly, plasma EPO was measured in 25 of the PV patients and in 30 of the ET patients by an immunoradiometric assay with normal reference interval in adults 3.7-16 IU/L. In the 14 PV patients with EPO <3.7 IU/L mean plasma TPO did not differ significantly from the mean for the 11 PV patients with EPO >or=3.7 IU/L; neither of these two groups had plasma TPO concentrations significantly different from the mean for the control subjects. The 7 ET patients with subnormal plasma EPO had significantly lower mean plasma TPO compared to the ET patients with normal and high plasma EPO concentrations (p=0.03 and p=0.02, respectively). Also, the 16 ET patients with normal plasma EPO had significantly lower plasma TPO compared to the 8 patients with high plasma EPO (p=0.04). The mean plasma TPO for each of these three groups of ET patients was significantly higher than the corresponding mean for the controls (p<0.001 for each group). The results of the present study indicate that a relationship between plasma EPO and TPO concentrations may exist and that myelosuppressive treatment affects the TPO concentration in ET but not in PV patients.
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| 3. |
- Aurelius, Johan, 1980, et al.
(författare)
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Anthracycline-based consolidation may determine outcome of post-consolidation immunotherapy in AML
- 2019
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Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 60:11, s. 2771-2778
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Tidskriftsartikel (refereegranskat)abstract
- Consolidation chemotherapy in acute myeloid leukemia (AML) aims at eradicating residual leukemic cells and mostly comprises high-dose cytarabine with or without the addition of anthracyclines, including daunorubicin. Immunogenic cell death (ICD) may contribute to the efficacy of anthracyclines in solid cancer, but the impact of ICD in AML is only partly explored. We assessed aspects of ICD, as reflected by calreticulin expression, in primary human AML blasts and observed induction of surface calreticulin upon exposure to daunorubicin but not to cytarabine. We next assessed immune phenotypes in AML patients in complete remission (CR), following consolidation chemotherapy with or without anthracyclines. These patients subsequently received immunotherapy with histamine dihydrochloride (HDC) and IL-2. Patients who had received anthracyclines for consolidation showed enhanced frequencies of CD8(+) T-EM cells in blood along with improved survival. We propose that the choice of consolidation therapy prior to AML immunotherapy may determine clinical outcome.
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| 4. |
- Bram Ednersson, Susanne, et al.
(författare)
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Proteomic analysis in diffuse large B-cell lymphoma identifies dysregulated tumor microenvironment proteins in non-GCB/ABC subtype patients
- 2021
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Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 62:10, s. 2360-2373
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Tidskriftsartikel (refereegranskat)abstract
- The complexity of the activated B-cell like (ABC) diffuse large B-cell lymphoma (DLBCL) subtype is probably not only explained by genetic alterations and methods to measure global protein expression could bring new knowledge regarding the pathophysiology. We used quantitative proteomics to analyze the global protein expression of formalin-fixed paraffin-embedded (FFPE) tumor tissues from 202 DLBCL patients. We identified 6430 proteins and 498 were significantly regulated between the germinal center B-cell like (GCB) and non-GCB groups. A number of proteins previously not described to be upregulated in non-GCB or ABC DLBCL was found, e.g. CD64, CD85A, guanylate-binding protein 1 (GBP1), interferon-induced proteins with tetratricopeptide repeat (IFIT)2, and mixed lineage kinase domain-like protein (MLKL) and immunohistochemical staining showed higher expression of GBP1 and MLKL. A cluster analysis revealed that the most prominent cluster contained proteins involved in the tumor microenvironment and regulation of the immune system. Our data suggest that the therapeutic focus should be expanded toward the tumor microenvironment in non-GCB/ABC subtype patients.
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| 5. |
- Bram Ednersson, Susanne, et al.
(författare)
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TBLR1 and CREBBP as potential novel prognostic immunohistochemical biomarkers in diffuse large B-cell lymphoma
- 2020
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Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 61:11, s. 2595-2604
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have identified prognostic mutational clusters for diffuse large B-cell lymphoma (DLBCL) patients, both within and outside the original cell-of-origin (COO) classification. For many of these mutations, there is limited information regarding the corresponding protein expression. With the aim to determine the relationship of protein expression and intensity to COO and prognosis, we used digital image analysis to quantitate immunohistochemical staining of CREBBP, IRF8, EZH2, and TBLR1 in 209 DLBCL patients. We found that patients with strong nuclear expression of TBLR1 had inferior progression-free survival (PFS) and overall survival (OS) in univariable analysis and inferior PFS in multivariable analysis. Patients with higher proportion of intermediate to strong nuclear CREBBP expression had a worse PFS and OS in univariable analysis. CREBBP was expressed with stronger intensity in non-GCB patients and the prognostic impact was restricted to this subgroup. These findings suggest that high nuclear protein expression of TBLR1 and CREBBP is negatively associated with prognosis in DLBCL.
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| 6. |
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| 7. |
- Johansson, P., et al.
(författare)
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Highly increased risk of fracture in patients with myeloproliferative neoplasm
- 2021
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Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 62:1, s. 211-217
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Tidskriftsartikel (refereegranskat)abstract
- The risk for hip and vertebral fracture was determined in 10,752 patients diagnosed with myeloproliferative neoplasms (MPN) in Sweden 1995-2015. The mean follow-up time were 6.34 years. Five percent developed hip fracture and 1.3% a vertebral fracture. There was a significant increased risk for fracture among the MPN patients compared with the Swedish population. The ratio of observed (obs) and expected (exp) number of hip fracture in all MPN patients, polycythemia vera (PV), essential thrombocythemia and MPN undetermined (MPNu) was 1.20 (95% confidence interval (CI): 1.10-1.31), 1.37 (95% CI: 1.19-1.58), 1.02 (95% CI: 0.87-1.19), and 1.28 (95% CI: 1.07-1.52), respectively. Corresponding figures for vertebral fractures were 1.94 (95% CI: 1.64-2.29), 2.09 (95% CI: 1.56-2.75), 1.50 (95% CI: 1.06-2.07) and 2.47 (95% CI: 1.77-3.35), respectively. Patients with MPN had an increased risk of hip and vertebral fracture, especially patients with PV and MPNu in comparison with the entire Swedish population.
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| 8. |
- Kutti, Jack, et al.
(författare)
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Diagnostic and differential criteria of essential thrombocythemia and reactive thrombocytosis.
- 1996
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Ingår i: Leukemia & lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 22 Suppl 1, s. 41-5
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Tidskriftsartikel (refereegranskat)abstract
- Among the chronic myeloproliferative disorders essential thrombocythemia (ET) is known to be a distinct clinical entity in which an excessive number of morphologically and functionally abnormal platelets are produced. The clonal nature of the disease is well established. Based on a review of the literature the present authors propose the following novel criteria for the diagnosis of ET: A1. Platelet count in excess of 600 x 10(9)/L. A2. No increase in red-cell mass (RCM) in the presence of stainable iron in the bone marrow or failure of iron trial (RCM < 36 mL/kg in males and < 32 mL/kg in females; or RCM < 25% above mean normal predicted value*). A3. No Philadelphia chromosome. A4. Megakaryocytic hyperplasia (= increased megakaryocyte number and size) in histological sections of bone marrow and/or increased megakaryocytic ploidy (two-color flow cytometry); no collagen fibrosis. B1. Splenomegaly on isotopic scan or echogram. B2. Unstimulated growth of BFU-E and/or CFU-Meg present. B3. Normal ESR/fibrinogen. The diagnosis of ET is considered to be established if A1 + A2 + A3 + A4 or A1 + A2 + A3 + two B-criteria are fulfilled. (* Br J Haematol 1995; 89:748-756.)
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| 9. |
- Malmberg, Erik, et al.
(författare)
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Minimal residual disease assessed with deep sequencing of NPM1 mutations predicts relapse after allogeneic stem cell transplant in AML
- 2019
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 60:2, s. 409-417
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in NPM1 can be used for minimal residual disease (MRD) analysis in acute myeloid leukemia (AML). We here applied a newly introduced method, deep sequencing, allowing for simultaneous analysis of all recurrent NPM1 insertions and thus constituting an attractive alternative to multiple PCRs for the clinical laboratory. We retrospectively used deep sequencing for measurement of MRD pre- and post-allogeneic hematopoietic stem cell transplantation (alloHCT). For 29 patients in morphological remission at the time of alloHCT, the effect of deep sequencing MRD on outcome was assessed. MRD positivity was defined as variant allele frequency ≥0.02%. Post-transplant MRD status was significantly and independently associated with clinical outcome; 3-year relapse-free survival 20% vs 85% (p <.001), HR 45 (95% CI 2–1260), and overall survival 20% vs 89% (p <.001), HR 49 (95% CI 2–1253). Thus, the new methodology deep sequencing is an applicable and predictive tool for MRD assessment in AML.
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| 10. |
- Rosso, Aldana, et al.
(författare)
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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
- 2021
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 62:8
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Tidskriftsartikel (refereegranskat)abstract
- 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. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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