Background Calcineurin inhibitors reduce short-term kidney transplant failure, but may contribute to late transplant loss. The role of alemtuzumab (a potent lymphocyte-depleting antibody) as induction therapy followed by an early reduction in CNI exposure after kidney transplantation is uncertain. The 3C Study aims to assess the efficacy and safety of alemtuzumab (followed by low-dose CNI) compared to basiliximab (with standard dose CNI) among patients receiving kidney transplants. Methods This randomized trial included 852 patients scheduled to receive a kidney transplant who were randomly assigned alemtuzumab-based induction therapy (followed by low-dose tacrolimus and mycophenolate) or basiliximab-based induction therapy (followed by standard-dose tacrolimus, mycophenolate and steroids). The primary outcome is biopsy-proven acute rejection at 6 months. Key secondary outcomes include delayed graft function, steroid resistant rejection, transplant survival, serious infections (defined as opportunistic infections or infection requiring hospitalisation) and cause-specific mortality. Tertiary outcomes include the incidence of the primary outcome in different types of transplant recipient. Results 426 participants were assigned alemtuzumab and 426 to basiliximab. Average age was 51 years and 65% were male. Approximately one-third of transplants followed each of donation after brain death, donation after cardiac death and living donation. During the first 6 months of follow-up, about 100 participants had biopsy-proven acute rejection, about 30 transplants failed and over 250 participants had a serious infection. Conclusion The 3C Study is the largest randomized trial to assess the clinical efficacy and safety of alemtuzumab-based induction in kidney transplantation and the unblinded clinical efficacy results would be presented for the first time during the WTC meeting. With about 100 rejection episodes and 250 serious infections, the study has excellent statistical power to detect clinically important treatment effects. These results should have an important impact on the choice of induction therapy at the time of kidney transplantation.

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BACKGROUND:

Cytomegalovirus (CMV) is a common opportunistic infections in renal transplant recipients. Indian studies about CMV viremia in renal transplant patients especially in those receiving ATG or basiliximab induction are very few. Present study was conducted to prospectively assess CMV viremia in patients with quantitative CMV DNA PCR monitoring at regular intervals.

AIM OF THE STUDY:

To prospectively assess CMV viremia in patients with quantitative CMV DNA PCR monitoring at regular intervals.

METHODS:

This was a single center prospective study. Nineteen patients in basiliximab and forty patients in ATG group were recruited. Follow up duration was 6 months post transplant. Quantitative CMV DNA PCR monitoring was done at the baseline; week 1; 2; 3; 4; 6; 8 and then months 3; 4; 5; 6. Primary outcome was the incidence of CMV infection and tissue invasive disease. Other outcomes studied were graft and patient survival; graft function and biopsy proven acute rejection (BPAR).

RESULTS:

Final analysis included 18 patients in basiliximab and 31 in ATG arm were. At baseline there was significantly higher HLA mismatch in basiliximab arm. CMV IgG was D+R+ for all. Incidence of CMV infection was comparable in ATG and basiliximab arm (26% vs 27%; p=1). Other outcome parameters including patient survival; graft survival; BPAR and serum creatinine at one and six months were comparable between the two arms. CMV infection occurred significantly earlier in ATG group. Outcome parameters were comparable between CMV and non-CMV infected groups.

CONCLUSIONS:

Incidence of CMV viremia in the present study was 27%. CMV disease was rare. Not all with significant CMV viremia required antiviral treatment. There was no significant difference in CMV incidence in patients receiving ATG versus basiliximab induction.

The number of acute rejections and infections after pediatric kidney transplantation (KTX) could not be reduced in the last years. To reduce these events, we investigated a new immunosuppressive protocol in a prospective trial. After KTX, 20 children (median age 12 years, range 1-17) were initially treated with Basiliximab, ciclosporine A (CsA) (trough-level = C0 200-250 ng/mL) and prednisolone. After 2 weeks, CsA dose was reduced to 50% (C0 75-100 ng/mL, after 6 months: 50-75 ng/mL) and everolimus (1.6 mg/m2/day) was started (C0 3-6 ng/mL). Six months after KTX prednisolone was set to alternate dose and stopped 3 months later. All 20 protocol biopsies 6 months after KTX showed no acute rejection or borderline findings. Indication biopsies resulted in no acute rejections and two borderline findings. Mean glomerular filtration rate (GFR) 1 year after KTX was 71 ± 25 mL/min/1.73 m2. Without cytomegalovirus (CMV)-prophylaxis, only two primary CMV infections were seen despite a donor/recipient-CMV-constellation pos./neg. in 10/20 children. In pediatric KTX, de novo immunosuppression with low-dose CsA, everolimus and steroid withdrawal after 9 months led to promising results according to numbers of acute rejections and infections. Further follow up is needed. Future larger trials will have to confirm our findings. © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

This study aims to study the effects that two standard of care immunosuppression induction regimens have on regulatory T cells (Treg) in live donor renal transplant recipients. Both regimens are currently used in this hospital for early immunosuppression induction but the effects on Treg numbers and function is not well understood and likely will impact long term immune function.

This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. There was no significant difference in resource use and costs for patients treated with basiliximab therapy or placebo in addition to triple therapy, although the clinical outcomes were superior with basiliximab.

BACKGROUND:

Steroid resistance represents a major clinical problem in the treatment of ulcerative colitis. In vitro, interleukin-2 renders lymphocytes steroid resistant.

AIM:

To explore the therapeutic potential of interleukin-2 receptor blockade in steroid-resistant ulcerative colitis with both in vitro measures and a pilot in vivo study.

METHODS:

Ten patients with steroid-resistant ulcerative colitis received a single bolus of 40 mg of intravenous basiliximab plus steroid treatment in an open-label, uncontrolled, 24-week study. The outcome was assessed using the Ulcerative Colitis Symptom Score, rectal biopsy and Inflammatory Bowel Disease Questionnaire. Lymphocyte steroid sensitivity was measured in vitro in 39 subjects in the presence or absence of basiliximab.

RESULTS:

Nine of the 10 patients achieved clinical remission within 8 weeks. At 24 weeks, seven patients were in clinical remission. Marked improvement in the Ulcerative Colitis Symptom Score was seen by 1 week (P = 0.004) and on rectal biopsy and Inflammatory Bowel Disease Questionnaire by 2 weeks (both P < 0.05). Improvements persisted to 24 weeks (Ulcerative Colitis Symptom Score, Inflammatory Bowel Disease Questionnaire, both P < 0.005). Eight of the nine responders relapsed (median, 9 weeks), but remission was re-achieved with further corticosteroids and the addition of azathioprine. At 24 weeks, seven patients were in full clinical remission, five off all steroid therapy. In vitro measurement of lymphocyte steroid sensitivity demonstrated steroid resistance in 22% of subjects. All were rendered steroid sensitive in the presence of basiliximab.

CONCLUSIONS:

Basiliximab appears to be effective at inducing remission in steroid-resistant ulcerative colitis. In vitro, basiliximab also produced a dramatic increase in lymphocyte steroid sensitivity in healthy subjects. Confirmation in randomized controlled studies is required.

Background: Antibodies may be used for induction of immunosuppression in heart transplantation (HT). rATG is commonly used but thrombocytopenia may prevent repeated doses and Basiliximab can be used as an alternate agent. The relative efficacy of these rATG and Basiliximab on allograft rejection and clinical outcomes is uncertain. Aim. To compare survival, incidence of rejection and episodes of infection in the first year after HT in patients who received induction with rATG alone versus patients who were unable to complete induction with rATG. Methods: We studied 72 consecutive patients who underwent HT between January 2013 and December 2014 at Papworth Hospital. Patients were grouped according to the induction therapy received; (A) 3 doses rATG (cumulative dose 1.75 mg/kg) and (B) 1 dose rATG (1 mg/kg) followed by Basiliximab (40 mg) when thrombocytopenia prevented further use of rATG. The primary endpoint was time to first episode of acute cellular rejection (ISHLT grade 2R or above). Secondary endpoints were survival, episodes of treated rejection, episodes of infection or a diagnosis of post-transplant lymphoproliferative disorder (PTLD). Results: There were significant differences in baseline characteristics and post-operative adverse events. Patients in group B were older (P = 0.03), had a higher percentage of female donors (P = 0.02), greater need for postoperative mechanical circulatory support (P = 0.01), greater need for postoperative CVVH (P < 0.01) and more frequent re-operation for bleeding (P = 0.02). The median time to first episode of rejection was 45 days in group A and 45.5 days in group B (P = 0.98). There was no difference in freedom from rejection at 1 month, 6 months and 1 year between group A (80%, 54%, 48%) and group B (82%, 61%, 61%, P = 0.32). There was no difference in the incidence of infection between groups (P = 0.62). There were no diagnoses of PTLD in either group. Survival at 1 year was 97% in group A and 80% in group B (P = 0.02). All deaths were due to primary graft dysfunction and none due to acute rejection. Conclusion: We observed no difference in the incidence of rejection in patients that were unable to complete induction with rATG and instead received Basiliximab, compared with those who completed induction with rATG. Survival was lower in patients that were received Basiliximab, probably due confounding by baseline characteristics and post-operative adverse events. Use of Basiliximab may be a safe option in patients who develop thrombocytopenia and are unable to complete induction with rATG.

RATIONALE:

Monoclonal antibodies, such as basiliximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Vaccines may help the body build an effective immune response to kill tumor cells. Giving these treatments together may kill more tumor cells. Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) is a powerful adjuvant capable of stimulating macrophage function, inducing proliferation and maturation of DCs, and is able to enhance T-lymphocyte stimulatory function. Intradermal administration of GM-CSF enhances the immunization efficacy at the site of administration

PURPOSE:

This clinical trial is studying how well basiliximab works in treating patients with newly diagnosed glioblastoma multiforme and temozolomide-caused lymphopenia who are undergoing targeted immunotherapy.