| 1. |
- Birgegård, Gunnar, 1944-
(författare)
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New perspectives in managing myeloproliferative disorders : focus on the patient
- 2009
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Ingår i: Hematological Oncology. - : Wiley. - 0278-0232 .- 1099-1069. ; 27:Suppl.1, s. 5-7
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Tidskriftsartikel (refereegranskat)abstract
- Risk stratification is the basis for treatment decisions in the chronic myeloproliferative disorders, and in addition to the three established risk factors of previous thrombosis, age and platelets >1500 x 10(9), cardiovascular risk factors should be addressed. In addition, premorbidity with regard to possible side effects of platelet-reducing drugs as well as the impact on quality of life of such side effects should be considered. The near-to-normal life expectancy and long term nature of treatment also makes it necessary to consider the potential leukaemogenic effects of some cytostatic drugs.
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| 2. |
- Campo, Chiara, et al.
(författare)
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Bortezomib-induced peripheral neuropathy : A genome-wide association study on multiple myeloma patients
- 2018
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Ingår i: Hematological Oncology. - : Wiley. - 0278-0232. ; 36:1, s. 232-237
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Tidskriftsartikel (refereegranskat)abstract
- The proteasome-inhibitor bortezomib was introduced into the treatment of multiple myeloma more than a decade ago. It is clinically beneficial, but peripheral neuropathy (PNP) is a side effect that may limit its use in some patients. To examine the possible genetic predisposing factors to PNP, we performed a genome-wide association study on 646 bortezomib-treated German multiple myeloma patients. Our aim was to identify genetic risk variants associated with the development of PNP as a serious side effect of the treatment. We identified 4 new promising loci for bortezomib-induced PNP at 4q34.3 (rs6552496), 5q14.1 (rs12521798), 16q23.3 (rs8060632), and 18q21.2 (rs17748074). Even though the results did not reach genome-wide significance level, they support the idea of previous studies, suggesting a genetic basis for neurotoxicity. The identified single nucleotide polymorphisms map to genes or next to genes involved in the development and function of the nervous system (CDH13, DCC, and TENM3). As possible functional clues, 2 of the variants, rs12521798 and rs17748074, affect enhancer histone marks in the brain. The rs12521798 may also impact expression of THBS4, which affects specific signal trasduction pathways in the nervous system. Further research is needed to clarify the mechanism of action of the identified single nucleotide polymorphisms in the development of drug-induced PNP and to functionally validate our in silico predictions.
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| 3. |
- Ellin, Fredrik, et al.
(författare)
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Impact of comorbidity on survival in peripheral T-cell lymphomas : A Swedish Lymphoma Registry study
- 2018
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Ingår i: Hematological Oncology. - : Wiley. - 0278-0232. ; 36:1, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Comorbidity impacts survival in B-cell lymphoma patients, but the influence in peripheral T-cell lymphomas (PTCLs) has been little studied. To investigate the impact of comorbidity on outcome in PTCL, we identified adult patients with newly diagnosed PTCL from 2000 to 2009 in the Swedish Lymphoma Registry. Data on comorbidity at diagnosis were retrospectively collected according to the Charlson Comorbidity Index (CCI). Comorbid conditions were present in 263 out of 694 (38%) patients. A CCI score of ≥2 was associated with inferior overall survival (OS) (hazard ratio [HR] 1.63, P < .001) and progression-free survival (HR 1.54, P < .001) in multivariate analysis. In patients undergoing front-line autologous stem cell transplantation (auto SCT), CCI >0 was associated with inferior OS (HR 2.40, P = .013). Chemotherapy regimens were classified as curative or low-intensity treatments. Among patients aged ≥75 years (n = 214), low-intensity and curative treatment groups had similar OS (HR 0.8, P = .6), also when adjusted for CCI. In summary, our results demonstrate CCI to be independently associated with survival in PTCLs. Even limited comorbidity impacted survival after front-line auto SCT, which needs to be considered in treatment decisions. Intensive anthracycline-based chemotherapy in elderly PTCL patients might be of limited benefit.
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| 4. |
- Friman, Vanda, 1952, et al.
(författare)
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Secondary immunodeficiency in lymphoproliferative malignancies
- 2016
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Ingår i: Hematological Oncology. - : Wiley. - 0278-0232 .- 1099-1069. ; 34:3, s. 121-132
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Tidskriftsartikel (refereegranskat)abstract
- Secondary immunodeficiencies occur as a consequence of various diseases, including hematological malignancies, and the use of pharmacological therapies, such as immunosuppressive, anti-inflammatory, and biological drugs. Infections are the main cause of morbidity and mortality in multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients. Recent advances in treatment have prolonged the duration of remission and the time between relapse phases in MM and CLL patients. However, managing multiple relapses and the use of salvage therapies can lead to cumulative immunosuppression and a higher risk of infections. The pathogenesis of immune deficiency secondary to lymphoproliferative malignancy is multifactorial including disease- and treatment-related factors. Supportive treatment, including early vaccination, anti-infective prophylaxis, and replacement immunoglobulin, plays a key role in preventing infections in MM and CLL. This article provides an overview of the basic immunology necessary to understand the pathogenesis of secondary immunodeficiency and the infectious complications in MM and CLL. We also discuss the evidence supporting the role of prophylactic replacement immunoglobulin treatment in patients with antibody failure secondary to MM and CLL and the indications for its use. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
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| 5. |
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| 6. |
- Lagunas-Rangel, Francisco Alejandro
(författare)
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DNA damage accumulation and repair defects in FLT3‐ITD acute myeloid leukemia : Implications for clonal evolution and disease progression
- 2023
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Ingår i: Hematological Oncology. - : John Wiley & Sons. - 0278-0232 .- 1099-1069. ; 41:1, s. 26-38
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Forskningsöversikt (refereegranskat)abstract
- Acute myeloid leukemia is a group of hematological diseases that have a high mortality rate. During the development of this pathology, hematopoietic cells acquire chromosomal rearrangements and multiple genetic mutations, including FLT3-ITD. FLT3-ITD is a marker associated with a poor clinical prognosis and involves the activation of pathways such as PI3K/AKT, MAPK/ERK, and JAK/STAT that favor the survival and proliferation of leukemic cells. In addition, FLT3-ITD leads to overproduction of reactive oxygen species and defective DNA damage repair, both implicated in the appearance of new mutations and leukemic clones. Thus, the purpose of this review is to illustrate the molecular mechanisms through which FLT3-ITD generates genetic instability and how it facilitates clonal evolution with the generation of more resistant and aggressive cells. Likewise, this article discusses the feasibility of combined therapies with FLT3 inhibitors and inhibitors of DNA repair pathways.
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| 7. |
- Lindberg, Åsa, et al.
(författare)
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Pre-treatment health-related quality of life parameters have prognostic impact in patients >65 years with newly diagnosed mantle cell lymphoma : The Nordic Lymphoma Group MCL4 (LENA-BERIT) experience
- 2022
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Ingår i: Hematological Oncology. - : Wiley. - 0278-0232 .- 1099-1069. ; 40:1, s. 23-31
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Tidskriftsartikel (refereegranskat)abstract
- Mantle cell lymphoma (MCL) is a rare, often aggressive type of B-cell lymphoma with poor survival and no cure. Cancer and cancer treatment has a negative impact on health-related quality of life (HRQOL) both during active disease and in the long term, and improvement of HRQOL is a crucial objective of cancer therapy in older patients and no curative intent. Baseline HRQOL has in other lymphoma populations been shown to be predictive of outcome. Here, we explored HRQOL, and its association with survival, by the EORTC QLQ-C30 questionnaire, before, during and after chemotherapy in a patient cohort with MCL, treated within the NLG-MCL4 trial, designed to evaluate the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment. Fifty-one patients were enrolled, median age was 71 years (range 62–84), 37 were men (73%). Pre-treatment HRQOL was similar to scores from the reference population with healthy individuals. During treatment, HRQOL deteriorated, but reverted to the same level as the reference population after treatment. There was a correlation between physical function (p = 0.001) and role function (p = 0.006) at baseline and WHO performance status, but not with other clinical or genetic prognostic factors. None of the baseline factors were predictive for treatment related to HRQOL in this cohort. Pre-treatment physical (p = 0.011) and role function (p = 0.032) were independent factors associated with overall survival, and physical function (p = 0.002) was also associated with progression free survival. These findings may possibly be used to design support during treatment and improve rehabilitation. Further investigations are needed for assessment of long-term HRQOL.
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| 8. |
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| 9. |
- Tobin, Gerard, et al.
(författare)
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What is the current evidence for antigen involvement in the development of chronic lymphocytic leukemia?
- 2006
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Ingår i: Hematological Oncology. - : Wiley. - 0278-0232 .- 1099-1069. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- For many years it has been evident that B-cell chronic lymphocytic leukemia (CLL) displays preferential usage of individual immunoglobulin (Ig) variable heavy chain (VJapanese sourceH) genes. The VH1-69 gene was the first to be reported overrepresented in a large number of CLL patients, where the VH1-69+ CLL rearrangements showed characteristic molecular features, such as unmutated VH genes, usage of specific diversity/joining gene segments, and a longer than average complementarity determining region (CDR) 3 with certain common amino acid motifs. Also, biased usage of the VH3-07 and VH4-34 genes with specific rearrangement characteristics was reported in CLL. These findings led to the speculation that antigens could be involved during CLL development by triggering proliferation of B-cells with specific B-cell receptors (BCRs) leading to an increased risk of transforming events. Recently, we characterized a subset of CLL utilizing the VH3-21 gene that also displayed peculiar Ig features, e.g. very short and homologous CDR3s, predominant λ expression and preferential Vλ2-14 gene usage. This VH3- 21+ subgroup also had poor prognosis despite the fact that two-thirds of cases carried mutated VH genes. Moreover, we and others have thereafter described further CLL subsets with very similar heavy and light chain gene rearrangement features. These latter findings of subsets expressing restricted BCRs have emphasized the hypothesis that antigens could play a role during the pathogenesis of CLL. Interestingly, recombinant antibodies produced from these restricted subsets showed similar cytoplasmatic reactivity within each group, thus suggesting recognition of a limited number of autoantigens. Further characterization of antigens is now necessary in order to understand their nature and exact role in CLL development.
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