Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
-
Biol. Blood Marrow Transplant. · Jun 2011
Prophylaxis with sirolimus and tacrolimus ± antithymocyte globulin reduces the risk of acute graft-versus-host disease without an overall survival benefit following allogeneic stem cell transplantation.
Methotrexate (MTX) is a standard agent used in combination with calcineurin inhibitors for graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic hematopoietic cell (HCT) transplantation. We retrospectively compared the incidence of acute GVHD (aGVHD), transplant-related morbidity, and mortality in patients given sirolimus/tacrolimus ± antithymocyte globulin (ATG) versus MTX/tacrolimus or cyclosporine and allogeneic transplantation for hematologic malignancies. Between January 1, 2005, and April 30, 2009, 106 consecutive patients received peripheral blood HCT or bone marrow grafts after 1 of 6 myeloablative conditioning regimens. ⋯ The incidence of thrombotic microangiopathy or interstitial pneumonitis was not significantly different between groups. The reduction in the risk of severe aGVHD was offset by an increased (20% versus 4%, P = .015) incidence of and mortality from sinusoidal obstructive syndrome (SOS). Sirolimus/tacrolimus appears to reduce the incidence of aGVHD after conventional allotransplantion compared to MTX-calcineurin inhibitor prophylaxis; however, this did not improve survival.
-
Biol. Blood Marrow Transplant. · Nov 2009
Clinical TrialImproved nonrelapse mortality and infection rate with lower dose of antithymocyte globulin in patients undergoing reduced-intensity conditioning allogeneic transplantation for hematologic malignancies.
We sought to reduce the risk of infectious complications and nonrelapse mortality (NRM) associated with the use of antithymocyte globulin (ATG) without compromising control of acute graft-versus-host disease (aGVHD) in patients undergoing reduced-intensity conditioning (RIC) transplantation. As part of an ongoing quality improvement effort, we lowered the dose of rabbit ATG from 7.5 mg/kg of ATG (R-ATG) (n = 39) to 6.0 mg/kg of ATG (r-ATG) (n = 33) in association with fludarabine (Flu) and busulfan (BU) RIC transplantation and then monitored patients for adverse events, relapse, and survival. Of the 72 mostly high risk (82%) patients studied, 89% received unrelated donor allografts, 25% of which were HLA-mismatched. ⋯ When R-ATG versus r-ATG patients were compared, we observed no significant difference in the cumulative incidence of grade II-IV aGVHD (32% versus 27%; P = .73) or grade III-IV aGVHD (23% versus 11%; P = .28). However, the r-ATG group had significantly less cytomegalovirus (CMV) reactivation (64% versus 30%; P = .005) and bacterial infections (56% versus 18%; P = .001), a better 1-year cumulative incidence of NRM (18% versus 3%; P = .03), and a trend for better 1-year overall survival (OS) (64% versus 84%; P = .07) compared to R-ATG patients. A seemingly modest reduction in the dose of rabbit ATG did not compromise control of aGVHD or achievement of donor chimerism, but led to a significant decrease in the risk of serious infections and NRM in high-risk RIC allograft recipients.
-
Biol. Blood Marrow Transplant. · Jan 2001
Community respiratory virus infections in bone marrow transplant recipients: the M.D. Anderson Cancer Center experience.
Community respiratory virus (CRV) infections are common among bone marrow transplant (BMT) recipients during community outbreaks. At M. D. ⋯ For BMT recipients with respiratory syncytial virus URTIs, treatment with ribavirin and intravenous immunoglobulin may be helpful in preventing progression to pneumonia and thus in reducing mortality, but this approach requires confirmation in controlled clinical trials. Prevention of CRV infection in this vulnerable patient population is crucial to reducing morbidity and mortality. Aggressive infection control precautions, which have been in effect at MDACC since 1994, have reduced nosocomial transmission of these potentially lethal infections.
-
Biol. Blood Marrow Transplant. · Sep 2015
Inhibition of the Immunoproteasome Subunit LMP7 with ONX 0914 Ameliorates Graft-versus-Host Disease in an MHC-Matched Minor Histocompatibility Antigen-Disparate Murine Model.
In the current study we evaluated the effects of immunoproteasome inhibition using ONX 0914 (formerly PR-957) to ameliorate graft-versus-host disease (GVHD). ONX 0914, an LMP7-selective epoxyketone inhibitor of the immunoproteasome, has been shown to reduce cytokine production in activated monocytes and T cells and attenuate disease progression in mouse models of rheumatoid arthritis, colitis, systemic lupus erythematosus, and, more recently, encephalomyelitis. Inhibition of LMP7 with ONX 0914 in the B10. ⋯ BR anti-CBA) settings. In addition, a reduction in the expression of the MHC class I-restricted SIINFEKL peptide was observed in splenocytes from transgenic C57BL/6-Tg(CAG-OVA)916Jen/J mice exposed to ONX 0914. Taken together, these data support that LMP7 inhibition in the context of BMT modulates allogeneic responses by decreasing endogenous miHA presentation and that the consequential reduction in allogeneic stimulation and cytokine production reduces GVHD development.
-
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.