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The purpose of this study is to evaluate the basiliximab for prevention of graft-versus-host disease in unrelated allo-genetic hematopoietic stem cell transplantation for thalassemia major. The objective was to evaluate the effect and safety of basiliximab for acute graft-versus-host disease.

Haploidentical donors are available for most patients who need allografts but do not have matched donors. However, GVHD, rejection, delayed immune reconstitution, and infections have been significant barriers. We designed a haploidentical BMT protocol focusing on prevention of GVHD and rejection. A total of 53 leukemic patients underwent haploidentical G‐CSF‐primed BMT without ex vivo T‐cell depletion. GVHD prophylaxis consisted of antithymocyte globulin, cyclosporine, methotrexate, and mycophenolate mofetil. In all, 38 patients (the CD25 group) received additional anti‐CD25 monoclonal antibody basiliximab. The results were compared to 15 patients who did not receive basiliximab. All patients achieved trilineage engraftment with full‐donor chimerism. The incidence of acute II‐IV GVHD was 11% in the CD25 group vs 33% in the control group (P=0.046). The overall incidence of extensive chronic GVHD was 15%. T, B, and NK cells recovered within 12 months post transplant. The disease‐free survival at 2 years was 53% with a median follow‐up of 31 months. In conclusion, G‐CSF primed haploidentical BMT along with sequential immunosuppressive agents as described here deserves further study.

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BACKGROUND:

</b>Standard practice for immunosuppressive therapy after renal transplantation is quadruple therapy using antibody induction, low-dose tacrolimus, mycophenolate mofetil, and corticosteroids. Long-term steroid intake significantly increases cardiovascular risk factors with negative effects on the outcome, especially post-transplantation diabetes associated with morbidity and mortality. In this trial, we examined the efficacy and safety parameters of rapid steroid withdrawal after induction therapy with either rabbit antithymocyte globulin (rabbit ATG) or basiliximab in immunologically low-risk patients during the first year after kidney transplantation.<b>

METHODS:

</b>In this open-label, multicentre, randomised controlled trial, we randomly assigned renal transplant recipients in a 1:1:1 ratio to receive either basiliximab induction with low-dose tacrolimus, mycophenolate mofetil, and steroid maintenance therapy (arm A), rapid corticosteroid withdrawal on day 8 (arm B), or rapid corticosteroid withdrawal on day 8 after rabbit ATG (arm C). The study was done in 21 centres across Germany. Only participants aged between 18 and 75 years with a low immunological risk who were scheduled to receive a single-organ renal transplant from either a living donor or a deceased donor were considered for enrolment. Patients receiving a second renal transplant were eligible, provided that the first allograft was not lost due to acute rejection within the first year after transplantation. Donor and recipient had to be ABO compatible. Grafts with pre-transplant existing donor-specific human leukocyte antigen (HLA) antibodies were not eligible and the recipients had to have a panel-reactive antibody concentration of 30% or less. Pregnant women and nursing mothers were excluded from the study. The primary endpoint was the incidence of biopsy-proven acute rejection (BPAR) at 12 months. All analyses were done by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00724022.<b>

FINDINGS:

</b>Between Aug 7, 2008, and Nov 30, 2013, 615 patients were randomly assigned to arm A (206), arm B (189), and arm C (192). BPAR rates were not reduced by rabbit ATG (9·9%) compared with either treatment arm A (11·2%) or B (10·6%; A versus C: p=0·75, B versus C p=0·87). As a secondary endpoint, rapid steroid withdrawal reduced post-transplantation diabetes in arm B to 24% and in arm C to 23% compared with 39% in control arm A (A versus B and C: p=0·0004). Patient survival (94·7% in arm A, 97·4% in arm B, and 96·9% in arm C) and censored graft survival (96·1% in arm A, 96·8% in arm B, and 95·8% in arm C) after 12 months were excellent and equivalent in all arms. Safety parameters such as infections or the incidence of post-transplantation malignancies did not differ between the study arms.<b>

INTERPRETATION:

</b>Rabbit ATG did not show superiority over basiliximab induction for the prevention of BPAR after rapid steroid withdrawal within 1 year after renal transplantation. Nevertheless, rapid steroid withdrawal after induction therapy for patients with a low immunological risk profile can be achieved without loss of efficacy and is advantageous in regard to post-transplantation diabetes incidence.<b>Funding: </b>Investigator Initiated Trial; financial support by Astellas Pharma GmbH, Sanofi, and Roche Pharma AG.

A prospective, randomized trial evaluated the combination of everolimus of 1.5 or 3 mg/d with steroids, basiliximab, and low-dose cyclosporine (CsA) adjusted by C2 monitoring in 256 renal transplant recipients. CsA C2 target levels, initially set at 600 ng/mL, were tapered over time posttransplant. The median serum creatinine concentrations were 130 mumol/L in both sirolimus groups (1.5 and 3 mg/d) at 6 months. Biopsy-proven acute rejection (BPAR) occurred in 13.7% and 15.1% of patients in the 1.5 and 3 mg/d groups, respectively. The incidence of BPAR was significantly higher among patients with everolimus trough levels < 3 ng/mL. Posttransplant diabetes mellitus occurred rarely, and blood pressure control appeared favorable; however, serum cholesterol levels were increased by approximately 50%, and serum triglycerides by approximately 100%. Serum testosterone concentrations increased after renal transplantation in both everolimus groups. Concentration-controlled everolimus therapy combined with low-dose CsA provides effective protection against rejection with good renal function and safety profiles.

Introduction There are wide disparities among transplant programs in terms of drugs used for induction of immunosuppression for liver transplantation (LT). T-cell antibody (TCA) induction regimens are used in several centers, while others use corticosteroids (CS) induction regimens. In this meta-analysis, we aim to compare the safety and efficacy of TCA and CS regimens. Methods We conducted a systematic review of Embase and Medline to identify randomized clinical trials comparing TCA induction regimens to CS induction regimens in patients undergoing LT. A meta-analysis of proportions and comparisons was performed. Results Screening of 2099 studies yielded 7 studies enrolling 1260 patients (Table 1). Four studies were comprised of only HCV infected patients. Overall, 427 patients had HCV infection. Daclizumab (DCZ) was compared to a CS induction regimen in three studies. Acute rejection rate was 22% (18-34%), with no significant difference in rejection rate in the DCZ and CS arms (RR 0.97; 0.78-1.20; I2 0%, p= 0.728; Table 2). There was no difference in risk of infectious adverse events (iAEs) in the DCZ and CS arms. The risk of de novo diabetes mellitus (dnDM) was lower in the DCZ arm compared to the CS arm (RR 0.45; 0.32-0.63; I2 33.2%, p= 0.221). The risk of HCV recurrence (rHCV) was lower in the DCZ arm compared to the CS arm (1 study, RR 0.54; 0.39-0.77; I2 0%, p= n/a). Graft survival within one year of LT was 89% (95%CI 86-91%), with no significant difference in graft survival in the DCZ arm and CS arm (0.98, 0.94-1.02, I2 78.5%, p= 0.010). Basiliximab (BSX) was compared to a BSX-free CS induction regimen in one trial and a BSX+CS based regimen in another trial. Acute graft rejection rate was 35% (25-45%), with no significant difference in rejection in the BSX and CS arms (RR 1.10; 0.78-1.20; I2 0%, p= 0.728). There was no significant different in the risk of iAEs, the risk of dnDM, and the risk of rHCV in the BSX and CS arms. There was no significant difference in graft survival within one year of transplant in the BSX and CS arms (RR 1.14; 0.98-1.32; I2 0%, p= 0.604). Overall survival (OS) within one year of LT slightly favored the BSX arm compared to the CS arm (RR 1.14; 95%CI 1-1.31; I2 31.1%, p=0.228). Rabbit anti-thymocyte globulin (rATG) was compared to CS induction regimens in two studies; the acute graft rejection rate was 20% (8-34%), with no significant difference in acute graft rejection in the rATG and CS arms (RR 0.67; 0.33-1.39; I2 0%, p=0.659). There was no significant difference in the risk of iAEs, dnDM, and rHCV in the rATG and CS arms. Conclusion TCA induction regimens are equally safe and efficacious compared to CS induction regimens in terms of graft rejection, infectious AEs, and graft survival within one-year of LT.

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This phase I trial is to find out the best dose, possible benefits and/or side effects of 90Y-DOTA-anti-CD25 basiliximab given together with fludarabine, melphalan, and total marrow and lymphoid irradiation (TMLI) in treating patients with high-risk acute leukemia or myelodysplastic syndrome. 90Y-DOTA-anti-CD25 basiliximab is a monoclonal antibody, called basiliximab, linked to a radioactive agent called 90Y-DOTA. Basiliximab attaches to CD25 positive cancer cells in a targeted way and delivers 90Y-DOTA to kill them. Fludarabine and melphalan are common chemotherapy drugs used to prepare the bone marrow to receive transplanted cells. TMLI is a different type of targeted radiation therapy used to prepare the bone marrow to receive transplanted cells. Giving 90Y-DOTA-anti-CD25 basiliximab together with fludarabine, melphalan, and TMLI may help prepare the bone marrow to receive the transplanted cells for improved transplant outcomes in patients with acute leukemia or myelodysplastic syndrome.

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