Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Mar 2008
Comparative Study Clinical TrialReduced-intensity allogeneic transplant in patients older than 55 years: unrelated umbilical cord blood is safe and effective for patients without a matched related donor.
The lower morbidity and mortality of reduced-intensity conditioning (RIC) regimens have allowed allogeneic hematopoietic cell transplantation (HCT) in older patients. Unrelated umbilical cord blood (UCB) has been investigated as an alternative stem cell source to suitably HLA matched related (MRD) and adult volunteer unrelated donors. We hypothesized that RIC HCT using UCB would be safe and efficacious in older patients, and compared the treatment-related mortality (TRM) and overall survival (OS) of RIC HCT in patients older than 55 years using either MRD (n = 47) or, in patients with no 5 of 6 or 6 of 6 HLA compatible related donors, UCB (n = 43). ⋯ Our study supports the use of HLA mismatched UCB as an alternative graft source for older patients who need a transplant but do not have an MRD. The use of RIC and UCB extends the availability of transplant therapy to older patients previously excluded on the basis of age and lack of a suitable MRD. A careful review of existing comorbidities is necessary when considering older patients for HCT.
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Biol. Blood Marrow Transplant. · Mar 2008
Impact of acute kidney injury on long-term mortality after nonmyeloablative hematopoietic cell transplantation.
Acute kidney injury (AKI) occurs frequently after nonmyeloablative hematopoietic cell transplantation (HCT). The severity of AKI after nonmyeloablative HCT has association with short-term mortality. However, the long-term effect of AKI on survival after nonmyeloablative HCT is not known. ⋯ The adjusted hazards ratio of nonrelapse mortality (NRM) associated with AKI was 1.72 (95% CI 0.9-3.1; P = .07). AKI is an independent predictor of overall mortality after nonmyeloablative HCT. This finding reiterates the importance of identifying preventative strategies in nonmyeloablative HCT for attenuating incidence and severity of AKI.
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Biol. Blood Marrow Transplant. · Mar 2008
Growth and differentiation advantages of CD4+ OX40+ T cells from allogeneic hematopoietic stem cell transplantation recipients.
OX40 (CD134), an activation-induced costimulatory molecule, is mainly expressed on CD4(+) T cells. Several reports, including previous reports from our laboratory, suggest that OX40-mediated signaling plays an important role in the development of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (Allo HSCT). Here, we show that peripheral blood CD4(+)OX40(+) T cells are a unique cell subset as they possess the homing receptors of lymph nodes, and some of them have an exceptional capacity to produce high levels of interleukin-2 (IL-2) upon the stimulation through T cell receptors. ⋯ Simultaneous, but not sequential, ligation of the T cell receptor and OX40 induces CD4(+)OX40(+) T cells to produce far more IL-2, which causes them to proliferate abundantly and differentiate readily into Th1- or Th2-biased effector memory T cells, especially in Allo HSCT recipients. Although not all the CD4(+)OX40(+) T cells had IL-2-producing capacity, Allo HSCT recipients with chronic GVHD (cGVHD) had a significantly higher frequency of IL-2-producing OX40(+) cells in their peripheral blood CD4(+) T cell subset than Allo HSCT recipients without cGVHD. Collectively, CD4(+)OX40(+) T cells with IL-2-producing potential are expected to be privileged for growth and differentiation in lymph nodes upon antigen presentation, suggesting that they might be involved in the process of inducing or maintaining cGVHD.
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Biol. Blood Marrow Transplant. · Mar 2008
Comparative StudyEffects of the NK cell recovery on outcomes of unmanipulated haploidentical blood and marrow transplantation for patients with hematologic malignancies.
The goal of this study was to investigate the association of natural killer (NK) cell recovery with clinical outcomes after unmanipulated haploidentical blood and marrow transplantation. We sequentially monitored the reconstitution kinetics of circulating NK cells, CD56(bright) and CD56(dim), in 43 patients by flow cytometry, and the functionality recovery of cytokine or cytotoxicity of NK cells by flow cytometry or lactate dehydrogenase release assay after transplantation. Reconstitution of NK cells was rapid but accompanied by skewing of cell subsets mainly in CD56(bright), which recovered earlier. ⋯ Compared with nonacute graft-versus-host disease (GVHD) patients, patients with acute GVHD (aGVHD) had a higher level of NK subsets during week 2 posttransplantation. Cox regression analysis revealed that the patients with more CD56(bright) NK cells in the recovery stage had a higher survival rate (hazard risk [HR], 0.406; P = .017) and the patients with a higher ratio of T/NK (>1.0) had a higher chance of getting aGVHD (HR, 3.436; P = .059) and chronic GVHD (HR, 3.925; P = .028). Our results suggest that the recovery of NK cells is and can be used as an indicator to predicate the clinical outcomes after unmanipulated haploidentical transplantation.
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Biol. Blood Marrow Transplant. · Mar 2008
Comparative StudyPeripheral blood versus bone marrow as a source of hematopoietic stem cells for allogeneic transplantation in children with class I and II beta thalassemia major.
Peripheral blood stem cell transplantation (PBSCT) has been extended to treating hematologic disorders, but the benefits over bone marrow transplantation (BMT) still remain unclear, especially in nonmalignant hematologic disorders. In this study, we compared class I-II thalassemic children who underwent HLA-matched PBSCT and BMT for treatment. Conditioning regimens consisted of busulfan and cyclophosphamide, followed by cyclosporine +/- methotrexate for graft-versus-host disease (GVHD) prophylaxis. ⋯ There was no difference in the 2-year overall survival after PBSCT and BMT (83% and 89%, respectively). The 2-year disease-free survival was 76% in both groups. These results show some advantages of PBSCT, but to improve the risk of GVHD in PBSCT, a better conditioning and prophylaxis regimen is needed.