The effect of different immunoprophylaxis regimens on post-transplant cytomegalovirus (CMV) infection in CMV-seropositive liver transplant recipients.

BACKGROUND: The effects of different immunoprophylaxis regimens on cytomegalovirus (CMV) infection in liver transplant recipients (LTRs) have not been compared. METHODS: In a cohort, we studied 343 CMV-seropositive recipient (R+) and 83 seronegative donor/recipient (D-/R-) consecutive LTRs from 2004 to 2007. Immunoprophylaxis regimens included steroid-only, steroids plus rabbit anti-thymocyte globulin (rATG), and steroids plus basiliximab. Logistic regression analysis, Cox proportional hazards regression model, and log-rank test were performed for multivariate analysis as appropriate. RESULTS: In total, 164 (39%), 69 (16%), and 193 (45%) patients received steroid-only, basiliximab, and rATG immunoprophylaxis, respectively. CMV infection rates were 15.7% (54/343) in CMV R+ LTRs and 2.4% (2/83) in CMV R- LTRs. Among CMV R+ LTRs who received rATG, the use of at least 6 weeks of CMV prophylaxis reduced the rate of CMV infection from 24.4% (19/78) to 11.7% (9/77). In multivariate analysis, CMV R+ vs D-/R- (odds ratio [OR]=13.1, 95% confidence interval [CI]: 1.8-97.2), rATG >3 mg/kg vs steroid-only induction (OR=1.6, 95% CI: 1.1-2.3), and CMV prophylaxis <6 weeks vs ≥6 weeks (OR=2.7, 95% CI: 1.2-6.4) were independently associated with CMV infection. Subgroup analysis in CMV D-/R+ group who received rATG showed that ≥6 weeks of CMV prophylaxis significantly decreased the risk of CMV infection (OR=1.9, 95% CI: 1.1-3.9; P=.03). CONCLUSION: The use of rATG immunoprophylaxis increases the risk of CMV infection in CMV-seropositive LTRs, specifically in the CMV D-/R+ group. Prophylaxis with valganciclovir in this group for at least 6 weeks decreases the risk of CMV infection.

ATG-Fresenius increases the risk of red blood cell transfusion after kidney transplantation.

Introduction: In sensitized deceased donor kidney allograft recipients, the most frequent induction therapy is anti-thymocyte globulins (ATG), including Thymoglobulin® (Thymo) and ATG-Fresenius (ATG-F). Methods: We conducted a 3-year monocentric observational study to compare the impact of ATGs on hematological parameters. We included adult kidney transplant recipients treated with ATG induction therapy, either Thymo or ATG-F, on a one-in-two basis. The primary endpoint was red blood cell (RBC) transfusions within 14 days after transplantation. Results: Among 309 kidney allograft recipients, 177 (57.2%) received ATG induction, 90 (50.8 %) ATG-F, and 87 (49.2%) Thymo. The ATG-F group received significantly more RBC transfusions (63.3% vs. 46% p = 0.02) and in bigger volumes (p = 0.01). Platelet transfusion was similar in both groups. Within 14 and 30 days after transplantation, older age, ATG-F induction, and early surgical complication were independently associated with RBC transfusion. Patient survival rate was 95%, and the death-censored kidney allograft survival rate was 91.5% at 12 months post-transplantation. There was no difference in the incidence of acute rejection and infections or in the prevalence of anti-HLA donor-specific antibodies. Discussion: In conclusion, after kidney transplantation, ATG-F is an independent risk factor for early RBC transfusion and early thrombocytopenia without clinical and biological consequences. These new data should be clinically considered, and alternatives to ATG should be further explored.

Immune reconstitution with two different rabbit polyclonal anti-thymocytes globulins.

Broad T cell depletion by polyclonal anti-thymocyte globulins (ATG) has been used for many years as a part of immunosuppressive treatment in transplantation. Currently, two different ATG are used in clinical practice, Thymoglobulin and Grafalon. Due to differences in the immunization source, these products contain different specificities and quantity of antibodies. These differences may have clinical consequences. We conducted a nested study in a large prospective multicentric cohort of kidney transplant to determine whether Grafalon-treated and Thymoglobulin-treated patients experience different lymphocyte reconstitution and clinical outcomes. 182 patients matched for age, gender, CMV status, CMV prophylaxis, number of previous transplantation, and maintenance immunosuppressive treatment were included (Thymoglobulin, [n=91]; Grafalon®, [n=91]). One-year post-transplant, recent thymic emigrants were significantly decreased (12±10% vs 21±12%; p<0.001) in Grafalon-treated patients. By contrast, T cell activation (CD38+DR+Ki67+) and senescence (CD8+CD57+CD28-) was increased in Thymoglobulin-treated patients. Compared to Grafalon, Thymoglobulin was not associated with a significantly different rate of acute rejection. CMV disease (p=0.013) was more frequent in Thymoglobulin-treated patients. Grafalon and Thymoglobulin seem to be equivalent to prevent acute rejection. CMV disease is more frequent in Thymoglobulin-treated patients. One year post-transplant immune profile profoundly differs according to the type of ATG.

Induction by anti-thymocyte globulins in kidney transplantation: a review of the literature and current usage.

CONTEXT: Preventing acute rejection (AR) after kidney transplantation is of utmost importance because an AR can have a negative impact on long-term allograft survival. EVIDENCE ACQUISITION: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO, and Web of Science have been searched. RESULTS: At the moment this can be done by using rabbit anti-thymocyte globulins (rATGs) as an induction therapy. However, because rATGs are associated with some deleterious side-effects, such as the opportunistic infections cytomegalovirus (CMV) and de novo post-transplant cancer, it is very important they are used optimally, i.e., at minimal doses that avoid many side-effects but still retain optimal treatment efficacy. Recent data show that the risk of CMV infection can be minimized using tacrolimus plus everolimus, and not tacrolimus plus mycophenolic acid, as the maintenance immunosuppression. The use of rATG is particularly valuable in; (a) sensitized patients; (b) in recipients from an expanded-criteria donor, thus enabling the introduction of calcineurin inhibitors at reduced doses; and (c) for patients where steroid avoidance is contemplated. However, we also need to consider that rATG may increase the risk of de novo cancer, even though recent data indicate this is unlikely and that any risk can be reduced by using mammalian target of rapamycin (mTOR) inhibitors instead of mycophenolic acid combined with low-dose calcineurin inhibitors. CONCLUSIONS: Even though rATGs do not improve long-term kidney-allograft survival, they may help reduce calcineurin-inhibitor dosage during the early post-transplant period and minimize the risk of AR.

Anti-thymocyte globulins for post-transplant graft-versus-host disease prophylaxis-A systematic review and meta-analysis.

BACKGROUND: Despite advances made in allogeneic hematopoietic stem cell transplantation (alloSCT), graft versus host disease (GvHD) remains a major problem. The main strategy to combat GvHD is prophylaxis and ATG plays a major role in this arena. Conflicting reports on the effectiveness of ATG on GvHD prevention prompted us to address this question by means of a systematic review and meta-analysis. METHODS: Six prospective randomized controlled trials (RCT) comparing the addition of ATG to standard immunosuppressive regimen as GvHD prophylaxis were analyzed. All ATG preparations were considered but homogeneity in type of preparation and dosage had to be observed within each trial. RESULTS: Our meta-analysis reveals that the incidence of grade II-IV GvHD was significantly lower in patients receiving ATG. Addition of ATG had no impact on overall survival, relapse or non-relapse mortality. CONCLUSIONS: Based on the current level of the data analyzed in this systematic review, we cannot conclude a general recommendation for the use of ATG for GvHD prophylaxis in alloSCT. In patients who are at high risk for severe GvHD it should be considered individually. However, due to the heterogeneity of the analyzable studies it seems likely that future studies might change the results of the pooled data of this meta-analysis. In order to improve the current level of data, further randomized studies in this topic are therefore urgently warranted.