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  • Ferrata Storti Foundation (Haematologica)  (3)
  • Unknown  (3)
  • 1
    Online Resource
    Online Resource
    Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG)
    Ferrata Storti Foundation (Haematologica) ; 2019
    In:  Haematologica Vol. 105, No. 11 ( 2019-12-26), p. 2598-2607
    Details
    In: Haematologica, Ferrata Storti Foundation (Haematologica), Vol. 105, No. 11 ( 2019-12-26), p. 2598-2607
    Abstract: Almost one-third of all patients with chronic lymphocytic leukemia (CLL) express stereotyped B cell receptor immunoglobulins (BcR IG) and can be assigned to distinct subsets, each with a particular BcR IG. The largest stereotyped subsets are #1, #2, #4 and #8, associated with specific clinicobiological characteristics and outcomes in retrospective studies. We assessed the associations and prognostic value of these BcR IG in prospective multicenter clinical trials reflective of two different clinical situations: i) early-stage patients (watch-and-wait arm of the CLL1 trial) (n=592); ii) patients in need of treatment, enrolled in 3 phase III trials (CLL8, CLL10, CLL11), treated with different chemo-immunotherapies (n=1861). Subset #1 was associated with del(11q), higher CLL international prognostic index (CLL-IPI) scores and similar clinical course to CLL with unmutated immunoglobulin heavy variable (IGHV) genes (U-CLL) in both early and advanced stage groups. IGHV-mutated (M-CLL) subset #2 cases had shorter time-to-first-treatment (TTFT) versus other M-CLL cases in the early-stage cohort (HR: 4.2, CI: 2-8.6, p 〈 0.001), and shorter time-to-next-treatment (TTNT) in the advanced-stage cohort (HR: 2, CI: 1.2-3.3, p=0.005). M-CLL subset #4 was associated with lower CLL-IPI scores and younger age at diagnosis; in both cohorts, these patients showed a trend towards better outcomes versus other M-CLL. U-CLL subset #8 was associated with trisomy 12. Overall, this study shows that major stereotyped subsets have distinctive characteristics. For the first time in prospective multicenter clinical trials, subset # 2 appeared as an independent prognostic factor for earlier TTFT and TTNT and should be proposed for risk stratification of patients.
    Type of Medium: Online Resource
    ISSN: 1592-8721 , 0390-6078
    URL: Article
    DOI: 10.3324/haematol.2019.231027
    Language: Unknown
    Publisher: Ferrata Storti Foundation (Haematologica)
    Publication Date: 2019
    detail.hit.zdb_id: 2186022-1
    detail.hit.zdb_id: 2030158-3
    detail.hit.zdb_id: 2805244-4
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Integrative prognostic models predict long-term survival after immunochemotherapy in chronic lymphocytic leukemia patients
    Ferrata Storti Foundation (Haematologica) ; 2021
    In:  Haematologica Vol. 107, No. 3 ( 2021-03-18), p. 615-624
    Details
    In: Haematologica, Ferrata Storti Foundation (Haematologica), Vol. 107, No. 3 ( 2021-03-18), p. 615-624
    Abstract: Chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab (FCR) can induce long-term remissions in patients with chronic lymphocytic leukemia. Treatment efficacy with Bruton's tyrosine kinase inhibitors was found similar to FCR in untreated chronic lymphocytic leukemia patients with a mutated immunoglobulin heavy chain variable (IGHV) gene. In order to identify patients who specifically benefit from FCR, we developed integrative models including established prognostic parameters and gene expression profiling (GEP). GEP was conducted on n=337 CLL8 trial samples, “core” probe sets were summarized on gene levels and RMA normalized. Prognostic models were built using penalized Cox proportional hazards models with the smoothly clipped absolute deviation penalty. We identified a prognostic signature of less than a dozen genes, which substituted for established prognostic factors, including TP53 and IGHV gene mutation status. Independent prognostic impact was confirmed for treatment, β2-microglobulin and del(17p) regarding overall survival and for treatment, del(11q), del(17p) and SF3B1 mutation for progression-free survival. The combination of independent prognostic and GEP variables performed equal to models including only established non-GEP variables. GEP variables showed higher prognostic accuracy for patients with long progression-free survival compared to categorical variables like the IGHV gene mutation status and reliably predicted overall survival in CLL8 and an independent cohort. GEP-based prognostic models can help to identify patients who specifically benefit from FCR treatment. The CLL8 trial is registered under EUDRACT-2004- 004938-14 and clinicaltrials gov. Identifier: NCT00281918.
    Type of Medium: Online Resource
    ISSN: 1592-8721 , 0390-6078
    URL: Article
    DOI: 10.3324/haematol.2020.251561
    Language: Unknown
    Publisher: Ferrata Storti Foundation (Haematologica)
    Publication Date: 2021
    detail.hit.zdb_id: 2186022-1
    detail.hit.zdb_id: 2030158-3
    detail.hit.zdb_id: 2805244-4
    Location Call Number Limitation Availability
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    Online Resource
  • 3
    Online Resource
    Online Resource
    Alternative activation of human macrophages enhances tissue factor expression and production of extracellular vesicles
    Ferrata Storti Foundation (Haematologica) ; 2020
    In:  Haematologica Vol. 106, No. 2 ( 2020-01-23), p. 454-463
    Details
    In: Haematologica, Ferrata Storti Foundation (Haematologica), Vol. 106, No. 2 ( 2020-01-23), p. 454-463
    Abstract: Macrophages are versatile cells that can be polarized by the tissue environment to fulfill required needs. Proinflammatory polarization is associated with increased tissue degradation and propagation of inflammation whereas alternative polarization within a Th2 cytokine environment is associated with wound healing and angiogenesis. To understand if polarization of macrophages can lead to a procoagulant macrophage subset we polarized human monocyte derived macrophages to a proinflammatory and an alternative activation state. Alternative polarization with interleukin-4 and IL-13 led to a macrophage phenotype characterized by increased tissue factor (TF) production and release and by an increase in extracellular vesicle production. In addition, also TF activity was enhanced in extracellular vesicles of alternatively polarized macrophages. This TF induction was dependent on signal transducer and activator of transcription-6 signaling and poly ADP ribose polymerase activity. In contrast to monocytes, human macrophages did not show increased tissue factor expression upon stimulation with lipopolysaccharide and interferon-γ. Previous polarization to either a proinflammatory or an alternative activation subset does not change the subsequent stimulation of TF. The inability of proinflammatory activated macrophages to respond to lipopolysaccharide and interferon-γ with an increase in TF production seems to be due to an increase in TF promoter methylation and was reversible when treating these macrophages with a demethylation agent. In conclusion, we provide evidence that proinflammatory polarization of macrophages does not lead to enhanced procoagulatory function, whereas alternative polarization of macrophages leads to an increased expression of TF and increased production of TF bearing extracellular vesicles by these cells suggesting a procoagulatory phenotype of alternatively polarized macrophages.
    Type of Medium: Online Resource
    ISSN: 1592-8721 , 0390-6078
    URL: Article
    DOI: 10.3324/haematol.2019.220210
    Language: Unknown
    Publisher: Ferrata Storti Foundation (Haematologica)
    Publication Date: 2020
    detail.hit.zdb_id: 2186022-1
    detail.hit.zdb_id: 2030158-3
    detail.hit.zdb_id: 2805244-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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