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  • 1
    Online Resource
    Online Resource
    Conditioning with Treosulfan and Fludarabine for Patients with Refractory or Relapsed Non-Hodgkin Lymphoma (NHL),
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 4106-4106
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4106-4106
    Abstract: Abstract 4106 Background: Treatment of refractory or relapsed non-Hodgkin lymphoma (NHL) remains challenging. Here, 88 patients with refractory or relapsed NHL received treosulfan and fludarabine as a reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Material and Methods: 73/88 intensely pre-treated patients experienced a relapse (R) with 18/88 early relapses (ER 〈 6 months from the last chemotherapy). At the time of allo-HSCT, 26 patients were in complete (CR) and 43 in partial remission (PR), twelve patients had progressive disease (PD) and seven stable disease (SD). 47 patients received an autologous graft followed by allo-HSCT. Results: After allo-HSCT, 69 of 88 patients were in CR, seven patients in PR, resulting in an overall response rate of 86.4% (76/88). Thirty-three patients achieved a CR from PR as well as six patients from PD and five from SD. 43/88 (49 %) patients were alive at the end of follow-up. Patients undergoing directly allo-HSCT without preceding auto-HSCT showed a better disease-free survival (DFS, p =.038) with a trend (p =.077) for better overall survival (OS). Patients with ER showed an OS of.35 ±.12 after three and seven years. Chronic graft-versus-host disease (cGvHD) had a positive impact on both OS and DFS (for limited cGVHD versus no cGvHD p =.002 and.004, respectively). Conclusion: Allogeneic stem cell transplantation following conditioning with treosulfan and fludarabine constitutes a good therapeutical option for patients with refractory or relapsed NHL and should be considered early in the course of salvage treatment. Disclosures: Schmitt: Medac: Participation in Conferences. Sayer:Medac: Travel grant to ASH 2009. Koenigsmann:Medac: Research Funding. Casper:Medac: Participation in Conferences. Beelen:Medac: Participation in Conferences. Freund:Medac: Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.4106.4106
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    Online Resource
    Online Resource
    The age of the bone marrow microenvironment influences B-cell acute lymphoblastic leukemia progression via CXCR5-CXCL13
    American Society of Hematology ; 2021
    In:  Blood Vol. 138, No. 19 ( 2021-11-11), p. 1870-1884
    Details
    In: Blood, American Society of Hematology, Vol. 138, No. 19 ( 2021-11-11), p. 1870-1884
    Abstract: B-cell acute lymphoblastic leukemia (B-ALL) occurs most commonly in children, whereas chronic myeloid leukemia is more frequent in adults. The myeloid bias of hematopoiesis in elderly individuals has been considered causative, but the age of the bone marrow microenvironment (BMM) may be contributory. Using various murine models of B-ALL in young vs old mice, we recapitulated B-ALL preponderance in children vs adults. We showed differential effects of young vs old BM macrophages on B-ALL cell function. Molecular profiling using RNA- and ATAC-sequencing revealed pronounced differences in young vs old BMM-derived macrophages and enrichment for gene sets associated with inflammation. In concordance with the role of C-X-C motif chemokine (CXCL) 13 for disease-associated B-cell chemoattraction, we found CXCL13 to be highly expressed in young macrophages on a translational compared with a transcriptional level. Inhibition of CXCL13 in BM macrophages impaired leukemia cell migration and decreased the proliferation of cocultured B-ALL cells, whereas recombinant CXCL13 increased pAKT and B-ALL cell expansion. Pretreatment of B-ALL–initiating cells with CXCL13 accelerated B-ALL progression. Deficiency of Cxcr5, the receptor for CXCL13, on B-ALL–initiating cells prolonged murine survival, whereas high expression of CXCR5 in pediatric B-ALL may predict central nervous system relapse. CXCL13 staining was increased in bone sections from pediatric compared with adult patients with B-ALL. Taken together, our study shows that the age of the BMM and, in particular, BM macrophages influence the leukemia phenotype. The CXCR5-CXCL13 axis may act as prognostic marker and an attractive novel target for the treatment of B-ALL.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.2021011557
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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