Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Feb 2006
Comparative StudyImpaired allogeneic activation and T-helper 1 differentiation of human cord blood naive CD4 T cells.
CD4 T cells, particularly those of the T-helper 1 (Th1) subset, are important effectors in alloimmune diseases, such as graft-versus-host disease, and in controlling infections with intracellular pathogens. Thus, it is plausible that impaired neonatal CD4 T-cell immunity might contribute to the low incidence of acute graft-versus-host disease after allogeneic transplantation of hematopoietic stem cells using cord blood (CB) compared with adult sources of hematopoietic stem cells. In support of this hypothesis, we found that CB naive CD4 T cells had reduced activation and impaired early Th1 differentiation compared with adult peripheral blood naive CD4 T cells after stimulation by allogeneic dendritic cells derived from adult monocytes. ⋯ CB naive CD4 T cells had low basal levels of signal transduction and activation of transcription 4 messenger RNA and protein, and, after alloantigen stimulation, reduced interleukin-12-induced signal transduction and activation of transcription 4 tyrosine phosphorylation, compared with adult peripheral blood naive T cells. Lastly, FoxP3 protein expression, a marker for regulatory CD25(high) CD4 T cells, was lower for naive CD4 T cells of CB compared with those of adult peripheral blood, which argued against increased T-regulatory activity as a mechanism for the decreased Th1 differentiation of CB CD4 T cells. Together, these intrinsic limitations in T-cell activation and Th1 differentiation may impair the ability of T cells in CB and the neonate to respond to allogeneic or infectious challenges.
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Biol. Blood Marrow Transplant. · Jan 2006
Clinical TrialUnique abnormalities of CD4(+) and CD8(+) central memory cells associated with chronic graft-versus-host disease improve after extracorporeal photopheresis.
Chronic graft-versus-host disease (cGVHD) remains a problematic complication of allogeneic hematopoietic stem cell transplantation. Laboratory parameters correlated with cGVHD have not been fully defined, although changes in CD4/CD8 ratios occur and a decrease in CD4(+) central memory T cells has been noted. Extracorporeal photopheresis (ECP) is an effective therapy for steroid-refractory cGVHD. ⋯ The normalization of central and effector memory populations in response to ECP coincident with clinical improvement of cGVHD support a correlation between these laboratory parameters and cGVHD. Further studies are needed to demonstrate whether laboratory measurements of the magnitude of changes in central and effector memory populations are useful prognostically or can be used to guide response to therapy. The contrasting change in central memory cells (CD8(+) increased versus CD4(+) decreased) in cGVHD provide support for recent reports suggesting unique differences in the differentiation pathways for CD8(+) versus CD4(+) T cells.
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Biol. Blood Marrow Transplant. · Jan 2006
The importance of age, fludarabine, and total body irradiation in the incidence and severity of chronic renal failure after allogeneic hematopoietic cell transplantation.
Nonmalignant late effects, including chronic renal failure (CRF), impair the quality of life of long-term survivors after allogeneic hematopoietic cell transplantation. One of the major risk factors is the use of total body irradiation (TBI) in the preparative regimen; TBI is currently fractionated in an attempt to reduce toxicity. We analyzed 241 patients who had TBI-based preparative regimens for allogeneic hematopoietic cell transplantation. ⋯ Statistical analysis revealed that older age (P < .001) and fludarabine administration (P = .016) had a significant effect on the incidence of CRF. Furthermore, single-fraction TBI was also significantly associated with CRF severity, because 7 (6.3%) of 111 patients in the 7.5S group developed severe CRF, as opposed to 1 (0.8%) of 130 patients in the 12F and 14.4F groups combined (P = .044). However, these conclusions should be regarded as preliminary in view of the retrospective and nonrandomized nature of this study.
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Biol. Blood Marrow Transplant. · Nov 2005
Comparative StudyEffect of conditioning regimen on the outcome of bone marrow transplantation from an unrelated donor.
Little information is available regarding the effect of the conditioning regimen on the outcome of bone marrow transplantation (BMT) from an unrelated donor. Therefore, we retrospectively compared the outcome after a cyclophosphamide/total body irradiation (Cy-TBI) regimen, an intensified Cy-TBI regimen (Cy-TBI+), a busulfan and cyclophosphamide (Bu-Cy) regimen, and a Bu-Cy regimen with total lymphoid irradiation (Bu-Cy-TLI). Clinical data of 1875 adult patients who underwent unmanipulated unrelated BMT for leukemia or myelodysplastic syndrome by using 1 of the 4 regimens between 1993 and 2002 were extracted from the database of the Japan Marrow Donor Program. ⋯ The Bu-Cy-TLI regimen decreased relapse (RR, 0.13; P = .039) but increased nonrelapse mortality (RR, 1.89; P = .0061). The Cy-TBI+ regimen resulted in increased nonrelapse mortality (RR, 1.48; P = .0003) and inferior survival (RR, 1.45; P < .0001). The results of this retrospective study suggested that the Cy-TBI regimen was superior to other regimens in unrelated BMT.
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Biol. Blood Marrow Transplant. · Oct 2005
Incidence, clinical outcome, and management of virus-induced hemorrhagic cystitis in children and adolescents after allogeneic hematopoietic cell transplantation.
We analyzed the incidence, etiology, risk factors, and clinical management of hemorrhagic cystitis (HC) in 102 children who underwent allogeneic stem cell transplantation: 28 from matched siblings, 57 from unrelated donors, and 17 from mismatched relatives. Conditioning regimens consisted of high-dose chemotherapy (n=83) or total body irradiation (n=19). In all children, urine and plasma were prospectively screened for human polyomavirus (HPV; BK virus [BKV] and JC virus [JCV]) or adenovirus (AdV) DNA with a polymerase chain reaction-based assay. ⋯ In all treated patients but 1, the clinical symptoms were moderate, and no HC-related death was observed. We conclude that virus-induced HC is a frequent complication after allogeneic hematopoietic cell transplantation. Treatment with cidofovir is feasible, and further studies are warranted to evaluate its activity in HC mediated by BKV or JCV.