Este artículo no tiene resumen

Este artículo no tiene resumen

Este artículo no tiene resumen

Management of steroid-refractory acute graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation continues to be a major challenge; however, no standard second-line therapy exists. IL2 plays a crucial role in the pathogenesis of acute GVHD. Basiliximab is a chimeric monoclonal antibody that blocks the alpha-chain of the interleukin-2 (IL-2) receptor complex. We report our clinical experience with basiliximab in the second line management of steroid refractory acute GVHD. Thirty-eight patients were retrospectively studied from June 2012 to March 2015. Basiliximab 20 mg was given intravenously on days 1 and 4 to patients unresponsive after 5 to 7 days or progressing within 3 days on high dose corticosteroids. A second course of basiliximab was given to patients with continued symptoms after 7-10 days. Response was assessed at day 28 following initiation of basiliximab. Table 1 describes patient characteristics. Acute GVHD was diagnosed at a median of 110 days (range 11-474) and basiliximab was given at a median of 102 days (18- 290) after transplant. Acute GVHD organ involvement included: 45% gastrointestinal (GI), 13% skin, and 3% liver with 40% of patients having multi-organ involvement. On average, patients were on high dose steroid therapy (2mg/kg) for 11 days (4-28) before being declared steroid refractory and initiated on basiliximab. At day 28 after basiliximab overall response rate was 42% with 21% of patients achieving a complete response, 13% with a partial response, 8% with a mixed response and 58% with no response or disease progression. Fortytwo percent of patients required utilization of a third agent for steroid refractory GVHD. Overall survival at day 28 post basiliximab was 63%, average time to death after dose of basiliximab was 59 days (6-188). Nine of 38 patients (23%) remain alive at a median follow up of 16.5 months. Primary causes of death include progressive GVHD (55%), infection (27%) and other treatedrelated mortality (17%). Basiliximab is a reasonable option for patients with steroid refractory GVHD, however better therapeutic options for SR GVHD are needed. Prospective and preferably randomized studies are needed in this setting.

BACKGROUND.: Retrospective comparison of treatment-related kidney transplant outcomes may be facilitated by multivariable statistical adjustments and case-matching. METHODS.: We studied Organ Procurement and Transplantation Network registry data for kidney transplants in 2001 to 2005 managed with thymoglobulin, basiliximab, or no antibody induction and discharge maintenance immunosuppression regimens of tacrolimus and mycophenolate mofetil. The primary outcome was the 6 month, Food and Drug Administration-approved composite endpoint of rejection, graft failure, or death. Outcomes according to induction exposure were compared using logistic regression analysis, exposure likelihood matching, and outcome risk score matching. RESULTS.: All statistical approaches demonstrated lower rates of the 6-month triple endpoint with thymoglobulin compared with basiliximab when steroids were present, with approximately 22% adjusted, relative reduction by logistic regression analysis and 3% absolute reductions by matching approaches. When steroids were absent, risk reduction among thymoglobulin versus basiliximab-treated patients was of larger magnitude but borderline statistical significance. Triple endpoint incidence was lower with both induction regimens compared with no induction across methods. Estimated sample sizes necessary to detect the observed differences between induction types in the presence of steroids in a prospective trial ranged from 1600 to nearly 7000 patients. CONCLUSIONS.: Consistency across statistical approaches suggests superiority of thymoglobulin compared with basiliximab or no antibody induction therapy for 6-month kidney transplant outcomes in the modern immunosuppression era. As the sample sizes necessary to power a prospective superiority trial are likely prohibitive, studies such as these provide clinically relevant information that may not be otherwise attainable. © 2009 by Lippincott Williams & Wilkins.

Induction with the use of interleukin-2 receptor monoclonal antibodies may avoid many of the adverse events associated with polyclonal antibodies and significantly impact on rejection-free long-term survival in orthotopic liver transplantation (OLTx). We describe our experience with the use of basiliximab induction therapy in adult OLTx recipients on tacrolimus-based immunosuppression. Forty-six consecutive deceased donor primary OLTx were analyzed. All patients received standard doses of basiliximab, tacrolimus, and steroids. Mycophenolate mofetil was also used as indicated. The mean follow-up period was 17.9 months. Forty-three patients remained rejection-free during follow-up. The actuarial patient and graft survival rate at 2 years was 93%. The rate of histology-proven hepatitis C virus (HCV) recurrence was 24%, with two progressing to severe cholestatic recurrent HCV. None of the study patients developed (cytomegalovirus (CMV) infection or posttransplant lymphoproliferative disease (PTLD). Results were compared to a historical group of 46 OLTx recipients on tacrolimus-based immunosuppression without basiliximab induction. The historical group had a rejection rate of 34% with lower patient and graft survival rates of 71.74% and 69.5%, respectively, at 24 months as well as a higher histological HCV recurrence rate of 77% (17/22), with three patients progressing to graft failure within 2 years. CMV infection and disease developed in 4.5% of the patients. Although PTLD was not observed, three recipients with hepatocellular carcinoma (HCC) developed and died of metastatic HCC. Induction with basiliximab in combination with tacrolimus-based immunosuppressive regimen reduces the incidence of rejection and improves rejection-free survival rate after OLTx without increasing the incidence of CMV, PTLD, or HCV recurrence.

AIMS:

We aim to evaluate the efficacy and safety of basiliximab in liver transplantation (LT) for patients with hepatitis B virus-related diseases.

METHODS:

A total of 268 patients with hepatitis B virus-related diseases undergoing LT were enrolled and divided into two groups according to the usage of basiliximab. Total survival, the survival of high-risk patients defined by the posttransplant model for predicting mortality, acute rejection rate, biochemical parameters and other follow-up data were compared between the two groups.

RESULTS:

Group Bas was composed of 131 patients who received basiliximab, and Group Triple enrolled the other 137 patients who did not. Between the two groups, there was no significant difference in the cumulative survival of patients without hepatocellular carcinoma (HCC) or in the cumulative survival of patients with HCC. For patients with benign end-stage liver diseases, Group Bas had more patients with a high risk of short- and medium-term mortality than Group Triple (22.81% vs. 8.85%, p = 0.017), but the survival curves of the two groups were not significantly different. The 1-year incidence of acute rejection was lower in Group Bas, although the difference was not significant (8.75% vs. 15.33%, p > 0.05). In both Group Bas and Group Triple, the level of serum creatinine (Scr) at 1 week posttransplantation was significantly lower than pretransplantation (61.00 vs. 88.50 μmol/l, p < 0.001; 61.50 vs. 74.00 μmol/l, p < 0.001; respectively). There was a significant difference in the pretransplantation Scr between the two groups (88.50 vs. 74.00 μmol/l, p = 0.005), but the values of Scr decreased to the same level 1 week (61.00 vs. 61.50 μmol/l, p > 0.05) and 4 weeks (61.00 vs. 59.00 μmol/l, p > 0.05) after transplantation. Significantly fewer recipients in Group Bas experienced hepatitis B relapse than in Group Triple (2/131 vs. 13/137, p = 0.006).

CONCLUSIONS:

A basiliximab-induced immunosuppressive protocol is a safe regimen that achieves similar survival without increasing the acute rejection rate for LT recipients with hepatitis B virus-related diseases. For patients with benign end-stage liver diseases, this regimen reduces medium-term mortality in high-risk patients. This regimen remarkably improves renal function in the first month after LT and is correlated with a decreased hepatitis B recurrence rate in adult patients after LT.

Background: CMV is a major cause of morbidity in transplant recipients and manifests as tissue invasive diseaseor CMV viral syndrome. Controversy exists regarding best method for CMV prevention.

AIM OF THE STUDY:

To evaluate incidence of CMV viremia and symptomatic CMV infection in adult KTR with basiliximab or antithymocyte globulin (ATG) induction without the use of valganciclovir prophylaxis.

METHODS:

A prospective; open-label; single centre study. Patients were monitored for CMV DNA-PCR twice a week for month 1 post-transplant; once a week in month2; and then every 2 weeks in month 3; and then once a month from month 4 to 6.Inclusion Criteria:First living related donor (LD) kidney transplant; age > 18yr Exclusion Criteria:second or more transplants; Hepatitis B or C infection; CMV D+/R- and Pregnancy. Induction therapy:ATG 1.5mg/kg:day 0 and 2Basiliximab 20 mg:day 0 and 4 Maintenance:Tac+MMF+steroids in standard doses.Asymptomatic CMV infections: PCR> 2000 copies/ml without organ dysfunctionSymptomatic CMV infection/disease: PCR> 2000 copies/ml with organ involvement Valganciclovir was started if CMV PCR > 2000 copies/mL in ≥ 2 consecutive samples.

RESULTS:

We included 40 patients with low-dose ATG induction (group1) and 20 patients with Basiliximab induction (group2) Mean recipient age was 40.95 and 45.9 yr in group 1 and 2; mean donor age was 49.53 and 51.6 yr resp. Male recipients were 67.5% and 65% in group 1 and 2 respectively; male donors were 22.5% and 20% respectively (not signficant). Average HLA mismatches were 4.1/6 and 3.7/6 (not sign). In group1 average transfusions per patient were 2.3 units (vs 1.7units in group 2) and 24.13% pts in group1 had >3 units transfusion. Mean follow-up was 26.1 and 32.7 months respectively.Incidence of acute rejection was 7.5% (3/40) and 10% (2/20) in group 1 and 2 respectively. (not significant). Incidence of CMV viremia requiring valganciclovir therapy was 1.25% (5/40) and 10% (2/20) in group 1 and 2 respectively. (not significant). No patient developed CMV disease.Mean serum creatinine was 1.12 and 1.09 mg/dL at 1 month and 1.2 and 1.14 mg/dL at 3 months (not sign).

CONCLUSIONS:

The incidence of CMV viremia is low and not significantly different in patients receiving basiliximab or low dose ATG induction in living donor KTR on tacrolimus based immunosuppression.Hence universal prophylaxis with valganciclovir may not be required with basiliximab and low dose ATG induction.

Background: Calcineurin inhibitors (CNI) may delay recovery from acute kidney injury after heart transplantation (HT). Oliguria is common after initiation of CNI and an advantage of antibody induction is that CNI may be avoided until renal function has recovered. When renal recovery is delayed, repeated antibody doses may be used to delay CNI initiation and bridge patients to renal recovery. Aim: The aim was to evaluate renal function and the incidence of rejection, infection and PTLD in patients with delayed renal recovery after HT who receive extended antibody induction in order to delay CNI initiation. Methods. We included 66 consecutive patients who underwent HT between January 2013 and December 2014 at Papworth Hospital. Patients were grouped according to induction received: (A) Standard induction with 3 doses antibody and (B) Extended induction with more than 3 doses antibody due to prolonged renal dysfunction after HT. The primary endpoint was need for renal replacement therapy or estimated glomerular filtration rate (eGFR) of <30 ml/min/1.73 m2 at 1 year post HT. Secondary endpoints were survival at 1 year after HT and episodes of treated rejection (ISHLT grade 2R or above), episodes of infection and development of PTLD during year 1. Results: There were no differences in recipient baseline characteristics. Patients in group B had older donor age (P = 0.02), longer ischaemic time (P = 0.02) and were more likely to have required post-transplant MCS (P < 0.01) and CVVH (P < 0.01). The primary endpoint was reached in 4.8% of group A, but 35.7% of group B despite delayed CNI initiation (P < 0.01). The median serum Creatinine at 1 year was 111 μmol/l in group A and 129 μmol/l in group B (P = 0.06). There was no difference in freedom from rejection at 1 month, 6 months and 1 year after HT (P = 0.32) and incidence of infection between groups (P = 0.62). No patients developed PTLD. Survival at 1 year was 93% in group A and 73% in group B (P = 0.03). All deaths were due to primary graft dysfunction and none due to acute rejection. Conclusion: Although we observed significant renal dysfunction at 1 year in patients with prolonged post-operative acute kidney injury, there was no increase in the incidence of rejection, infection or PTLD with use of extended antibody induction. Survival was lower in these patients, probably due to confounding by baseline characteristics and post-operative adverse events. Extended antibody induction may be a safe option in patients with postoperative renal dysfunction in whom delayed CNI initiation is desirable. (Table Presented).

Corticosteroids withdrawal from immunosuppressive regimens has thus far been associated with increased risk of acute rejection episodes. In this study, basiliximab, a chimeric monoclonal interleukin-2 receptor antagonist, added to a maintenance regimen consisting of cyclosporine microemulsion and mycophenolate mofetil was studied for its effectiveness in allowing early corticosteroid withdrawal in de novo renal allograft recipients. Primary renal transplant recipients receiving basiliximab, cyclosporine-microemulsion, and mycophenolate mofetil, were randomized to either corticosteroid withdrawal at day four post-transplantation (n = 40) or standard steroid therapy (n = 43). The primary endpoint was the incidence of biopsy-proven acute rejection episodes. Randomized subjects who underwent transplantation and received at least one dose of basiliximab were analyzed in an intent-to-treat fashion. The incidence of biopsy-proven acute rejection at 12 months was not significantly different between the steroid withdrawal group (20%) and the standard treatment group (16%). Patient and graft survival was 100% in the steroid withdrawal group while one death in a patient with a functioning graft occurred in the standard steroid group. Seventy-two percent of the steroid withdrawal group remained off steroids at 6 months post-transplant. Allograft function and incidence of adverse events and infections were similar between the two groups. Rapid and early corticosteroid withdrawal among renal transplant recipients receiving basiliximab induction and daily therapy with cyclosporine-microemulsion and mycophenolate mofetil was not associated with an increased risk of acute rejection.