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- Attarbaschi, Andishe, et al.
(author)
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Children and adolescents with follicular lymphoma have an excellent prognosis with either limited chemotherapy or with a "watch and wait" strategy after complete resection.
- 2013
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In: Annals of hematology. - : Springer Science and Business Media LLC. - 1432-0584 .- 0939-5555. ; 92:11, s. 1537-1541
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Journal article (peer-reviewed)abstract
- Data on clinical features and outcome in pediatric follicular lymphoma (pFL) are scarce. The aim of this retrospective study including 13 EICNHL and/or i-BFM study group members was to assess clinical characteristics and course in a series of 63 pFL patients. pFL was found to be associated with male gender (3:1), older age (72% ≥10years old), low serum LDH levels (<500U/l in 75%), grade 3 histology (in 88%), and limited disease (87% stage I/II disease), mostly involving the peripheral lymph nodes. Forty-four out of sixty-three patients received any polychemotherapy and 1/63 rituximab only, while 17/63 underwent a "watch and wait" strategy. Of 36 stage I patients, 30 had complete resections. Only one patient relapsed; 2-year event-free survival and overall survival were 94±5 and 100%, respectively, after a median follow-up of 2.2years. Conclusively, treatment outcome in pFL seems to be excellent with risk-adapted chemotherapy or after complete resection and an observational strategy only.
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| 4. |
- Heidel, Florian H., et al.
(author)
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3,4-Diarylmaleimides-a novel class of kinase inhibitors-effectively induce apoptosis in FLT3-ITD-dependent cells
- 2012
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In: Annals of Hematology. - : Springer Science and Business Media LLC. - 1432-0584 .- 0939-5555. ; 91:3, s. 331-344
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Journal article (peer-reviewed)abstract
- FLT3 kinase has become an attractive drug target in AML with up to 30% of cases harboring internal-tandem-duplication (ITD) mutations. For these, conferring a worse prognosis and decreased overall survival, several FLT3 tyrosine kinase inhibitors (TKIs) are currently being tested in clinical trials. However, when using these drugs as monotherapy, the problem of short duration of remissions and high incidence of TKI resistance has emerged. Here, we investigated two members of a novel class of tyrosine kinase inhibitors, 3,4-diarylmaleimides, for their efficacy on mutated FLT3 kinase. These compounds inhibit FLT3 kinase in an ATP-competitive manner and effectively inhibit phosphorylation of downstream targets. 3,4-Diarylmaleimides (DHF125 and 150) induce apoptosis in FLT3-ITD-dependent cells lines and patient blasts at low micromolar concentrations. They are retained in the cytoplasm of exposed cells for more than 24 h and synergize with chemotherapy and midostaurin. Both 3,4-diarylmaleimides show inhbition of FLT3-ITD-related kinase autophosphorylation at distinct tyrosine residues when compared to midostaurin. In conclusion, this novel group of compounds shows differential inhibition patterns with regard to FLT3 kinase and displays a promising profile for further clinical development. Currently, experiments evaluating toxicity in murine models and unraveling the exact binding mechanism are under way to facilitate a potential clinical application.
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| 5. |
- Hellstrand, Kristoffer, 1956, et al.
(author)
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Age-Related Efficacy of Immunotherapy with Histamine Dihydrochloride and Interleukin-2 for Relapse Prevention in Acute Myeloid Leukemia
- 2011
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In: Annals of Hematology. - : Springer Science and Business Media LLC. - 0939-5555 .- 1432-0584. ; 90:Suppl. 1
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Journal article (peer-reviewed)abstract
- Recurrence of leukemia after the completion of induction and consolidation chemotherapy is a significant clinical concern in acute myeloid leukemia (AML). Apart from allogeneic bone marrow transplantation there is no consensus about effective relapse-protective therapy beyond the consolidation phase, and the standard of care for the majority of patients in complete remission (CR) hence is no treatment. Here we present updated results from a phase 3 trial (n=320) evaluating the prevention of relapse in AML patients receiving immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2). This trial was previously reported to meet the primary endpoint of improved leukemia-free survival (LFS) in the primary population of all randomized patients. Our results imply that treatment with HDC/IL-2 prevents relapse in patients 40–70 years old in first CR (p=0.008, leukemia-free survival (LFS), n=190, log rank test) with a more than 80% relative increase in the likelihood of LFS at 3 years. HDC/IL-2 was not significantly efficacious in young patients (<40 years old). Further studies are underway to define the impact of HDC/IL-2 on immune function and the putative efficacy of therapy in genetic subgroups of AML.
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| 7. |
- Liu, C., et al.
(author)
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Inhibitor of differentiation 1 is a candidate prognostic marker in multicentric Castleman's disease
- 2014
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In: Annals of Hematology. - : Springer Science and Business Media LLC. - 0939-5555 .- 1432-0584. ; 93:7, s. 1177-1183
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Journal article (peer-reviewed)abstract
- Castleman's disease (CD) is a benign lymphoproliferative disorder characterized by dysfunctional lymphatic node hyperplasia. Lymphatic node hyperplasia is associated with elevated levels of inhibitor of differentiation 1 (ID1) in many human tumors. To assess the possible role of ID1 expression as a prognostic marker in multicentric CD (MCD), intra-lymph node ID1 expression was analyzed and related to clinical characteristics and outcomes in 48 patients. Furthermore, the correlation between ID1 and possible signaling molecules such as interleukin-6 (IL6), phosphorylated extracellular response kinase (p-ERK), and vascular endothelial growth factor C (VEGFC) was explored on six fresh MCD surgical specimens. Immunohistochemistry revealed that the patients with extensive ID1 expression had significantly poorer prognosis, compared to those with localized ID1. In addition, ID1 was positively associated with levels of IL6, p-ERK, and VEGFC. We conclude that ID1 may ultimately be a prognostic marker in MCD and that the IL6/ERK/VEGFC pathway is involved in the progress of this disease.
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| 9. |
- Nagel, G., et al.
(author)
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Metabolic factors and blood cancers among 578,000 adults in the metabolic syndrome and cancer project (Me-Can)
- 2012
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In: Annals of Hematology. - New York : Springer Science and Business Media LLC. - 0939-5555 .- 1432-0584. ; 91:10, s. 1519-1531
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Journal article (peer-reviewed)abstract
- We investigated associations between metabolic factors and blood cancer subtypes. Data on body mass index (BMI), blood pressure, blood glucose, total cholesterol, and triglycerides from seven prospective cohorts were pooled (n = 578,700; mean age = 44 years). Relative risks of blood cancers were calculated from Cox regression models. During mean follow-up of 12 years, 2,751 incident and 1,070 fatal cases of blood cancers occurred. Overall, higher BMI was associated with an increased blood cancer risk. In gender-specific subgroup analyses, BMI was positively associated with blood cancer risk (p = 0.002), lymphoid neoplasms (p = 0.01), and Hodgkin's lymphoma (p = 0.02) in women. Further associations with BMI were found for high-grade B-cell lymphoma (p = 0.02) and chronic lymphatic leukemia in men (p = 0.05) and women (p = 0.01). Higher cholesterol levels were inversely associated with myeloid neoplasms in women (p = 0.01), particularly acute myeloid leukemia (p = 0.003), and glucose was positively associated with chronic myeloid leukemia in women (p = 0.03). In men, glucose was positively associated with risk of high-grade B-cell lymphoma and multiple myeloma, while cholesterol was inversely associated with low-grade B-cell lymphoma. The metabolic syndrome score was related to 48 % increased risk of Hodgkin's lymphoma among women. BMI showed up as the most consistent risk factor, particularly in women. A clear pattern was not found for other metabolic factors.
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| 10. |
- Olsson, Bob, 1969, et al.
(author)
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Increased number of B-cells in the red pulp of the spleen in ITP
- 2012
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In: Annals of Hematology. - : Springer Science and Business Media LLC. - 1432-0584 .- 0939-5555. ; 91:2, s. 271-277
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Journal article (peer-reviewed)abstract
- Platelets are targeted by autoantibodies and destroyed in the reticuloendothelial system in the spleen, liver and bone marrow in patients with immune thrombocytopenia (ITP). Other mechanisms such as destruction by cytotoxic T-cells and defective production of platelets in the bone marrow also exist. Splenectomy normalizes the platelet count in 70% of ITP patients, however, precious little is known about the spleen in this disease. Our aim was therefore to investigate the splenic morphology and especially the number and localization of splenic leukocytes in patients with ITP and controls and to evaluate factors predicting outcome of splenectomy. Spleen sections from 29 ITP patients and 11 individuals splenectomized due to trauma were analyzed by immunohistochemistry. All except one of the ITP patients had a normalized platelet count 12months after splenectomy and the platelet count was inversely correlated with age. ITP patients had an increased number of B-cells in the red pulp. The number of white pulp B-cells and number of T-cells in both compartments was unchanged. In conclusion, B-cells are increased in the red pulp of the spleen and together with cytotoxic T-cells, helper T-cells and macrophages line the sinusoids enabling the immunological attack on platelets in ITP.
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| 12. |
- Jönsson, Sofia, et al.
(author)
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Good adherence to imatinib therapy among patients with chronic myeloid leukemia--a single-center observational study.
- 2012
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In: Annals of hematology. - 1432-0584. ; 91:5, s. 679-85
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Journal article (peer-reviewed)abstract
- Previous studies have suggested that adherence to imatinib therapy can be an obstacle among patients with chronic myeloid leukemia (CML). We studied adherence to imatinib therapy among CML patients treated at the Sahlgrenska University Hospital. We identified all CML patients that were alive at the 1st of January 2010 (n=70). Nineteen patients were excluded due to a history of allogenic hematopoietic stem cell transplantation, and nine were excluded due to treatment with other tyrosine kinase inhibitors. Thirty-eight out of 42 patients (90%) treated with imatinib accepted inclusion in the study. The patients were interviewed in a structured way, and adherence was evaluated in a standardized way using the nine-item Morisky Medication Adherence Scale that ranges from 1 to 13. A Morisky score ≤10 indicates nonadherence and ≥11 indicates adherence. In addition, predefined follow-up questions were asked to identify factors known to influence adherence to therapy. In contrast to previous studies, our patients showed good adherence to imatinib therapy with a mean Morisky score of 12.3 out of 13 (range, 9-13). The interviews revealed factors known to predict adherence to therapy, namely being well informed and having frequent contact with a single hematologist. Furthermore, the patients had easy access to the treating clinic and felt that they took part in decisions concerning their disease and treatment. We show that adherence to imatinib can be very good in CML patients, and we suggest that simple measures such as increased patient information and continuity of care will increase adherence in patients with CML.
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| 15. |
- Marttinen, Aino, et al.
(author)
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Short-term consumption of probiotic lactobacilli has no effect on acid production of supragingival plaque
- 2012
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In: Clinical Oral Investigations. - Heidelberg : Springer Berlin/Heidelberg. - 1432-6981 .- 1436-3771. ; 16:3, s. 797-803
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Journal article (peer-reviewed)abstract
- Acidogenicity and the levels of mutans streptococci (MS) in dental plaque after the use of Lactobacillus rhamnosus GG (LGG) and Lactobacillus reuteri were determined. The study had a randomised, double-blind, crossover design. Thirteen volunteers used tablets containing LGG or a combination of L. reuteri SD2112 and PTA 5289 for 2 weeks. At baseline and at the end of each tablet period, all available supragingival plaque was collected. Lactic acid production was determined from a fixed volume (8 μl) of fresh plaque and the rest of the plaque was used for culturing MS and lactobacilli. The retention of probiotics to the plaque was assessed using PCR techniques. No probiotic-induced changes were found in the acidogenicity of plaque. Also, MS counts remained at the original level. The number of subjects with lactobacilli in plaque increased in the L. reuteri group (p = 0.011) but not in the LGG group. PCR analysis of plaque revealed the presence of LGG in four and L. reuteri in six subjects after the use of the probiotic. The use of the lactobacilli did not affect the acidogenicity or MS levels of plaque. Short-term consumption of LGG and L. reuteri appeared not to influence the acidogenicity of plaque.
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| 16. |
- Schumann, Barbara, et al.
(author)
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Association of occupation with prevalent hypertension in an elderly East German population : an exploratory cross-sectional analysis
- 2011
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In: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 84, s. 361-369
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Journal article (peer-reviewed)abstract
- Purpose Hypertension is one of the most relevant risk factors for cardiovascular disease; however, little is known about differences in hypertension by occupation. The aim of this study was to explore the association between occupational group and prevalent hypertension. Methods Cross-sectional data of the CARLA study were used, a representative sample of an East German population aged 45–83. Job titles of the current or last held occupation of 967 men and 808 women were coded using the German classification of occupation. Hypertension was defined as blood pressure of ≥140 mmHg (systolic), ≥90 mmHg (diastolic) or use of antihypertensives. Sex-stratified, age-adjusted prevalence risk ratios (PR) with 95% confidence intervals (CI) were calculated for 31 occupational groups. Results Hypertension was prevalent in 79% of the population. In men, highest age-adjusted prevalence ratios were observed in metal-processing workers, carpenters/painters, and electricians with PRs of 1.31 (CI 1.04–1.65), 1.28 (CI 1.00–1.64), and 1.21 (0.95–1.53), respectively, compared to office clerks. In women, highest PRs were found in technicians/forewomen, scrutinisers/storekeepers, and food-processing occupations with PR 1.28 (1.09–1.49), 1.23 (0.99–1.51), and 1.22 (1.01–1.48), respectively. Adjustment for education, smoking, body mass index, and current work hours did not fully explain occupational differences. Excluding currently non-working subjects lead to decreased PRs in men and to increased PR in women. Conclusions Differences in the prevalences of hypertension by occupational group were only partly explained by conventional risk factors and may require workplace interventions targeted at high-risk occupations. Longitudinal data with large cohorts and work-related exposure assessment are needed to confirm a temporal relationship between occupation and incident hypertension.
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