74 research outputs found
Age-adjusted recipient pretransplantation telomere length and treatment-related mortality after hematopoietic stem cell transplantation
Telomere attrition induces cell senescence and apoptosis. We hypothesized that age-adjusted pretransplantation telomere length might predict treatment-related mortality (TRM) after hematopoietic stem cell transplantation (HSCT). Between 2000 and 2005, 178 consecutive patients underwent HSCT from HLA-identical sibling donors after myeloablative conditioning regimens, mainly for hematologic malignancies (n = 153). Blood lymphocytes' telomere length was measured by real-time quantitative PCR before HSCT. Age-adjusted pretransplantation telomere lengths were analyzed for correlation with clinical outcomes. After age adjustment, patients' telomere-length distribution was similar among all 4 quartiles except for disease stage. There was no correlation between telomere length and engraftment, GVHD, or relapse. The overall survival was 62% at 5 years (95% confidence interval [CI], 54-70). After a median follow-up of 51 months (range, 1-121 months), 43 patients died because of TRM. The TRM rate inversely correlated with telomere length. TRM in patients in the first (lowest telomere length) quartile was significantly higher than in patients with longer telomeres (P = .017). In multivariate analysis, recipients' age (hazard ratio, 1.1; 95% CI, .0-1.1; P = .0001) and age-adjusted telomere length (hazard ratio, 0.4; 95% CI; 0.2-0.8; P = .01) were independently associated with TRM. In conclusion, age-adjusted recipients' telomere length is an independent biologic marker of TRM after HSCT. (Blood. 2012;120(16):3353-3359)National Institutes of Health Intramural Research Program, National Heart, Lung, and Blood InstituteAA and Myelodysplastic Syndrome International FoundationFrance HPNFAPES
Prognostic impact of Epstein-Barr virus serostatus in patients with nonmalignant hematological disorders undergoing allogeneic hematopoietic cell transplantation: the study of Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation
BackgroundIn patients with acute leukemia, lymphoma and chronic malignancies, donor and/or recipient Epstein-Barr virus (EBV) seropositive status increases the risk of development of chronic graft-versus-host disease (cGVHD) after allo-hematopoietic cell transplantation (allo-HCT), while it has no influence on other transplant outcomes. No data are available on the impact of EBV serostatus on transplant outcomes in patients with nonmalignant hematological disorders. ObjectiveWe analyzed the influence of the recipient's (R) and donor's (D) EBV serostatus on transplant outcomes (overall survival (OS); relapse-free survival (RFS); relapse incidence (RI); nonrelapse mortality (NRM); acute graft-versus-host disease (aGVHD); cGVHD) in patients with nonmalignant hematological disorders undergoing allo-HCT. Patients and MethodsA total of 2,355 allo-HCTs performed between 1997 and 2016 for acquired bone marrow failure or hemoglobinopathies were included in this retrospective Registry megafile Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation (IDWP-EBMT) study. ResultsArray ConclusionsAllo-HCT from EBV-seropositive versus EBV-seronegative donors are at 31% higher risk of cGVHD in patients with nonmalignant hematological disorders undergoing allo-HCT; however this difference is nonsignificant in multivariate analysis
Stem cell transplantation for congenital dyserythropoietic anemia : an analysis from the European Society for Blood and Marrow Transplantation
Non peer reviewe
Discovering C3 targeting therapies for paroxysmal nocturnal hemoglobinuria: Achievements and pitfalls
: The treatment of paroxysmal nocturnal hemoglobinuria (PNH) was revolutionized by the introduction of the anti-C5 agent eculizumab, which resulted in sustained control of intravascular hemolysis, leading to transfusion avoidance and hemoglobin stabilization in at least half of all patients. Nevertheless, extravascular hemolysis mediated by C3 has emerged as inescapable phenomenon in PNH patients on anti-C5 treatment, frequently limiting its hematological benefit. More than 10 years ago we postulated that therapeutic interception of the complement cascade at the level of C3 should improve the clinical response in PNH. Compstatin is a 13-residue disulfide-bridged peptide binding to both human C3 and C3b, eventually disabling the formation of C3 convertases and thereby preventing complement activation via all three of its activating pathways. Several generations of compstatin analogs have been tested in vitro, and their clinical evaluation has begun in PNH and other complement-mediated diseases. Pegcetacoplan, a pegylated form of the compstatin analog POT-4, has been investigated in two phase I/II and one phase III study in PNH patients. In the phase III study, PNH patients with residual anemia already on eculizumab were randomized to receive either pegcetacoplan or eculizumab in a head-to-head comparison. At week 16, pegcetacoplan was superior to eculizumab in terms of hemoglobin change from baseline (the primary endpoint), as well as in other secondary endpoints tracking intravascular and extravascular hemolysis. Pegcetacoplan showed a good safety profile, even though breakthrough hemolysis emerged as a possible risk requiring additional attention. Here we review all the available data regarding this innovative treatment that has recently been approved for the treatment of PNH
MICA-129 Genotype, Soluble MICA and Anti-MICA Antibodies as Biomarkers of Chronic Graft Versus Host Disease.
Sequential Treatment with Chemotherapy and Reduced-Intensity Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in Fanconi Anemia Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome.
Evaluation of NIH Consensus Criteria for Classification of Late Acute and Chronic Gvhd in Reduce Intensity Conditioning (RIC) Stem Cell Transplantation (SCT).
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