Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Jan 2011
ReviewStem cell transplantation for indolent lymphoma and chronic lymphocytic leukemia.
The indolent lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) remain incurable with standard therapy. Autologous hematopoietic stem cell transplantation (HSCT) is feasible and has low treatment-related mortality in follicular lymphoma, but there are questions relating to optimal timing of the procedure, conditioning regimen, and late effects. Myeloablative allogeneic HSCT is associated with high treatment-related morbidity and mortality, few late relapses, but is applicable to only a small number of patients. ⋯ Steps to further decrease the morbidity and mortality of the RIC HSCT and in particular to reduce the incidence of chronic extensive graft-versus-host disease (GVHD) while maintaining tumor control remain the major focus. Many potential treatments are available for indolent lymphomas and CLL, and appropriate patient selection and the timing of HSCT remain controversial. The use of HSCT must always be weighed against the risk of the underlying disease, particularly in a setting where improvements in treatment are leading to improved outcome.
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Biol. Blood Marrow Transplant. · Jan 2011
Clinical TrialLinearity and stability of intravenous busulfan pharmacokinetics and the role of glutathione in busulfan elimination.
High-dose busulfan (Bu) is frequently used in preparative myeloablative conditioning (MAC) regimens for patients undergoing hematopoietic stem cell transplantation (HSCT). MAC and reduced-intensity conditioning (RIC) protocols for i.v. Bu infusion have been developed to achieve reliable systemic exposure while minimizing toxicity and treatment failure (relapse). ⋯ Blood GSH concentrations before Bu dosing were positively correlated with Bu clearance (adjusted R(2) = 0.45; P = .009). Our data indicate that Bu PK parameters are linear, stable, and predictable in different i.v. protocols and are unaffected by coadministration of fludarabine. Differences in whole blood GSH might contribute to variability in Bu clearance.
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Biol. Blood Marrow Transplant. · Jan 2011
Methotrexate Reduces the Incidence of Severe Acute Graft-versus-Host Disease without Increasing the Risk of Relapse after Reduced-Intensity Allogeneic Stem Cell Transplantation from Unrelated Donors.
Optimized prophylaxis against graft-versus-host disease (GVHD) after unrelated reduced-intensity allogeneic transplantation when preceded by a conditioning regimen utilizing antithymocyte globulin (ATG) is poorly defined. To investigate the effects of methotrexate (MTX) in this treatment setting, we conducted a retrospective analysis. Sixty-three patients were selected based on the administration of a total dose of 5 mg/kg of ATG in the conditioning regimen and then separated into either group M+ (n = 39), which received MTX or group M- (n = 24), which did not. ⋯ Multivariate analysis indicated that grade III-IV aGVHD was favored by both the absence of MTX and the provision of a female donor for a male recipient. At 2 years, the M+ and M- groups exhibited, respectively: overall survival of 69% and 40% (P = .06), disease-free survival of 57% and 43% (P = .2), nonrelapse mortality of 20% and 44% (P = .1), and incidence of relapse of 27% and 35% (P = .6). These data suggest that MTX reduces the incidence of severe aGVHD without increasing the risk of relapse but with an accompanying trend toward improved survival after unrelated reduced-intensity transplantation with ATG in the conditioning regimen.
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Biol. Blood Marrow Transplant. · Jan 2011
The Outcome of Unrelated Hematopoietic Stem Cell Transplants with Total Body Irradiation (800 cGy) and Cyclophosphamide (120 mg/kg) in Adult Patients with Acquired Severe Aplastic Anemia.
To verify the feasibility of 800 cGy of total body irradiation (TBI) with 120 mg/kg of cyclophosphamide (TBI-800/Cy-120) as a conditioning regimen for unrelated stem cell transplantation (u-SCT) in adult patients with severe aplastic anemia, we analyzed 50 consecutive patients who underwent u-SCT, including 26 patients from our previous pilot study. Seventeen patients received transplants from mismatched donors via high-resolution DNA typing (8 of 8). Thirty-eight patients received bone marrow and 12 peripheral blood stem cells (PBSCs). ⋯ The cumulative incidences of acute grade II-IV GVHD (aGVHD) and chronic GVHD (cGVHD) were 46.0% and 50.3%, respectively. Only an HLA-mismatched donor was associated with the occurrence of aGVHD on multivariate analyses, whereas prior aGVHD and the use of PBSCs were associated with the occurrence of cGVHD on univariate analyses. In conclusion, the excellent outcomes of u-SCT with TBI-800/Cy-120 suggest that u-SCT may be applicable to patients with severe aplastic anemia even without prior treatment with immunosuppressive therapy, which will require testing in prospective trials in the future.