ATG induction therapy: long-term effects on Th1 but not on Th2 responses

Weimer, Rolf; Staak, A.; Süsal, Caner; Streller, Sabine; Yildiz, S.; Pelzl, Steffen; Renner, Fritz; Dietrich, Hartmut; Daniel, Volker; Rainer, L.; Kamali-Ernst, S.; Ernst, Wolfgang; Padberg, Winfried; Opelz, Gerhard

doi:10.1111/j.1432-2277.2004.00047.x

Cited by 35 publications

(26 citation statements)

References 40 publications

(60 reference statements)

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“…Our study furthermore demonstrates that Tacrbased regimens are more effective in suppressing sCD30 levels and thus might be the appropriate treatment in patients with pretransplant elevated sCD30. Rabbit ATG induction therapy, on the other hand, did not have a similar effect, a finding which was not unexpected since we found no effect of ATG induction therapy on Th2 responses (CD4 helper activity, IL-4 or IL-10 responses) in a previous study (18). Another option in patients with pretransplant elevated sCD30 levels is to transplant HLA compatible grafts since a strong HLA matching effect was evident in these recipients (4).…”

Section: Post-transplant Scd30 and Canmentioning

confidence: 58%

Post-Transplant sCD30 and Neopterin as Predictors of Chronic Allograft Nephropathy: Impact of Different Immunosuppressive Regimens

Weimer

Süsal

Yildiz

et al. 2006

American Journal of Transplantation

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Section: Post-transplant Scd30 and Canmentioning

confidence: 58%

Post-Transplant sCD30 and Neopterin as Predictors of Chronic Allograft Nephropathy: Impact of Different Immunosuppressive Regimens

Weimer

Süsal

Yildiz

et al. 2006

American Journal of Transplantation

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“…Thymoglobulin Ò (Thymo; Genzyme, Cambridge, MA, USA), a rabbit-derived polyclonal antibody, contains a variety of antibodies specific for T-cell epitopes, including CD2, CD3, CD4, CD8 + , CD11a, CD18, CD25, HLA-DR and HLA class I [7,8]. Anti-thymocyte globulin treatment induces a dose-dependent lymphocytopenia in blood as well as T-cell depletion in spleen and lymph nodes [9].…”

Section: Introductionmentioning

confidence: 99%

Comparison of two dosages of thymoglobulin used as a short-course for induction in kidney transplantation

et al. 2006

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Summary Thymoglobulin is used effectively as an induction agent in kidney transplantation, but the optimal dose is not well established. We evaluated the degree and durability of T‐cell clearances with two different thymoglobulin regimens in adult kidney transplant recipients (KTR). Seven KTR received a 3‐day thymoglobulin‐based induction of 1.0 mg/kg/day while nine received 1.5 mg/kg/day, in addition to maintenance immunosuppression. Lymphocyte subsets were monitored for 6 months. Renal function, infections and malignancies were monitored for 24 months. T‐cell subsets were significantly lower by day 30 with the thymoglobulin 1.5 mg/kg/day regimen when compared with the 1.0 mg/kg/day regimen; this trend was sustained at 6‐month (CD3+: 438 ± 254 vs. 1001 ± 532 cells/mm3, P = 0.016). Renal function between the two groups was not significantly different at 6‐ and 24‐months post‐transplant. One case of BK Virus viremia in the 1.5 mg/kg/day thymoglobulin group was detected. No acute rejection episodes, cytomegalovirus infections, or malignancies were noted in either group. Thymoglobulin induction was efficacious in both groups, but with a significantly sustained T‐cell clearance in the 1.5 mg/kg/day regimen. A more profound T‐cell clearance within the first 6 months postinduction therapy may translate into a decreased risk of immunological injury and improved long‐term outcome after kidney transplantation.

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“…We did not use antithymocyte globulin because of its long half-life and its potential to suppress T cells and natural killer (NK) cells, resulting in a high risk of infection and reduced GVL. 5 Clinical GVL effect has been associated with a fast recovery of alloreactive effector cells, such as NK cells in HP settings and T cells in MUD settings. 6,7 A recent report has described a delay in T-cell reconstitution using CD3/CD19-depleted grafts and RIC in the HP setting.…”

Section: Introductionmentioning

confidence: 99%

Early evaluation of immune reconstitution following allogeneic CD3/CD19-depleted grafts from alternative donors in childhood acute leukemia

Pérez‐Martínez

González‐Vicent

Valentín

et al. 2012

Bone Marrow Transplant

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Graft engineering procedures for hematopoietic SCT (HSCT) may improve the chance of success in matched unrelated donor (MUD) and haploidentical donor transplantations. Successful donor immune reconstitution is important to mediate GVL effects in reduced-intensity conditioning (RIC) HSCT. We prospectively investigated early immune reconstitution and clinical outcome in 30 CD3/CD19-depleted MUD (n ¼ 15) or HP (n ¼ 15) HSCTs for high-risk childhood leukemia using a fludarabine-based RIC without serotherapy. The graft consisted of a mean of 10.5 Â 10 6 /kg CD34 þ , 77 Â 10 3 /kg CD3 þ and 39 Â 10 6 /kg CD56 þ cells. After transplantation, 86% of the patients engrafted. In all, 13% of patients had 4grade 3 acute GVHD. Natural killer (NK) cell, DC and T-cell recovery achieved normal values within the first 60 days after transplantation. DC recovery was dominated by the DC2 À subset. NK-cell phenotype was altered and cytotoxicity was lower compared with their donors. EFS was 50 ± 9% (73 ± 11% for those in CR1 and 26 ± 11% for those with advanced disease). Faster DC2 À recovery was associated with better outcome, especially in the MUD setting. In summary, CD3/CD19-depleted HSCT with fludarabine-based RIC without serotherapy resulted in favorable patient survival, and rapid NK, DC and T-cell recovery. T-cell-depleted grafts have been proposed as a strategy to avoid GVHD. For example, CD34-selected HSCT followed by DLI has been proposed to maximize the effects of GVL with low rates of GVHD in HLA-matched HSCT. 3 However, secondary graft rejection is an important problem, especially in the MUD transplant setting. To facilitate engraftment, CD3/CD19-depleted grafts containing different pools of cells have been proposed to be preferable to T-cell-depleted grafts in MUD and HP HSCT in our unit. 4 In addition to T-cell depletion, B-cell depletion was used to prevent EBV-related lymphoproliferative disease. To reduce toxicity, we developed a reduced intensity conditioning (RIC) with i.v. BU, fludarabine and thiotepa. In addition, a high-dose steroid was used to further suppress recipient T-cell function to prevent graft rejection. We did not use antithymocyte globulin because of its long half-life and its potential to suppress T cells and natural killer (NK) cells, resulting in a high risk of infection and reduced GVL. 5 Clinical GVL effect has been associated with a fast recovery of alloreactive effector cells, such as NK cells in HP settings and T cells in MUD settings. 6,7 A recent report has described a delay in T-cell reconstitution using CD3/CD19-depleted grafts and RIC in the HP setting. 8 Furthermore, Dulphy et al. 9 have described an immature NK-cell population during the early post-transplant period following unmanipulated HLA-matched HSCTs. Apart from effector cells, the reconstitution of other immune cells such as DCs has not been systematically studied after T-cell-depleted HSCTs.

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ATG induction therapy: long-term effects on Th1 but not on Th2 responses

Cited by 35 publications

References 40 publications

Post-Transplant sCD30 and Neopterin as Predictors of Chronic Allograft Nephropathy: Impact of Different Immunosuppressive Regimens

Post-Transplant sCD30 and Neopterin as Predictors of Chronic Allograft Nephropathy: Impact of Different Immunosuppressive Regimens

Comparison of two dosages of thymoglobulin used as a short-course for induction in kidney transplantation

Early evaluation of immune reconstitution following allogeneic CD3/CD19-depleted grafts from alternative donors in childhood acute leukemia

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