The impact of antithymocyte globulin on short-term toxicity after allogeneic stem cell transplantation

Pihusch, Rudolf; Holler, Ernst; Mühlbayer, Dieter; Göhring, Peter; Stötzer, Oliver; Pihusch, Markus; Hiller, Erhard; Hj, Kolb

doi:10.1038/sj.bmt.1703640

Cited by 57 publications

(62 citation statements)

References 25 publications

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“…Other side effects of ATG are induction of intravascular coagulation, hypotension, and liver dysfunction. In a cohort of adult patients who received allogeneic HSCT for different indications, side effects were less frequent if ATG was given over 12 h instead of 4 h and if accompanied by higher doses of steroids (25). ATG has been reported to be associated with an acute respiratory distress syndrome (26).…”

Section: Toxicity Associated With Atg Administrationmentioning

confidence: 99%

Complications of autologous hematopoietic stem cell transplantation for patients with autoimmune diseases

2012

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Section: Toxicity Associated With Atg Administrationmentioning

confidence: 99%

Complications of autologous hematopoietic stem cell transplantation for patients with autoimmune diseases

2012

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“…8,9 Most patients experience significant acute side effects from antithymocyte globulin (ATG). 10 Non-myeloablative conditioning including Campath-1H (alemtuzumab) provides a low risk for GvH with promising overall survival, 11 despite an increased risk for CMV disease. 12 Campath depletes both B-and T-cells, 13 and might thus also reduce the risk for EBV-induced post transplantation lymphoproliferative disease.…”

Section: Introductionmentioning

confidence: 99%

Subcutaneous alemtuzumab vs ATG in adjusted conditioning for allogeneic transplantation: influence of Campath dose on lymphoid recovery, mixed chimerism and survival

Juliusson

Theorin

Karlsson

et al. 2006

Bone Marrow Transplant

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Sixty-nine consecutive patients (median age 54 years) were prospectively enrolled in a single-institution protocol for allogeneic transplantation with adjusted non-myeloablative fludarabine-melfalan-based conditioning including cyclosporin A and MMF, and one of three modes of serotherapy. Thirty-one donors (45%) were unrelated. The first cohort of 29 had ATG (Thymoglobulin 2 mg/kg Â 3 days), the subsequent 26 had Campath 30 mg Â 3 days subcutaneously, and the final cohort of 14 had 30 mg Campath once. The groups were similar as regards age, diagnosis and risk factors. Campath-patients had no acute toxicity, fewer days with fever and antibiotics, and required fewer transfusions than ATG-treated patients. 3-d-Campath patients showed lower lymphocyte counts from day þ 4, and CD4 þ , CD8 þ , CD19 þ and NK cells recovered slower than in ATG-treated patients. More Campath patients developed mixed chimerism that required DLI. 3-d-Campath induced more serious and opportunistic infections than ATG, which resulted in a greater non-relapse mortality and an impaired overall survival despite a low tumor-related mortality. The change of the Campath dosing schedule to one dose abrogated the deleterious effect of 3-d-Campath on immune recovery, severe infections and survival. Subcutaneous Campath is simple and provides strong immune suppression with no early toxicity, but dose limitation to 30 mg once is recommended.

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“…3,4 However, ATG has considerable short-term toxicity. 5 While the efficacy of ATG to prevent GVHD and to reduce nonrelapse mortality after myeloablative HSCT has been demonstrated in several studies, the role of ATG in reduced-intensity conditioning has not been evaluated. [6][7][8][9][10] However, reduced-intensity conditioning with BU and FLU was safe even without ATG in 24 patients as shown by our group.…”

mentioning

confidence: 99%

Reduced-intensity conditioning with busulfan and fludarabine with or without antithymocyte globulin in HLA-identical sibling transplantation – a retrospective analysis

Schetelig

Bornhäuser

Kiehl

et al. 2003

Bone Marrow Transplant

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Summary:It is unknown whether the addition of antithymocyte globulin (ATG) to reduced-intensity conditioning with busulfan (BU) and fludarabine (FLU) is beneficial in HLA-identical sibling transplantation. Therefore, we analyzed retrospectively data on 83 patients, who received peripheral blood stem cells from HLA-identical siblings after conditioning with either 8 mg/kg BU and 150 mg/m 2 FLU (n ¼ 45) or 8 mg/kg BU, 180 mg/m 2 FLU and 40 mg/ kg ATG (n ¼ 38). Graft-versus-host disease (GVHD) prophylaxis consisted of CSA alone (n ¼ 32) or a combination with either MTX or MMF (n ¼ 51). The median age was 52 years. Graft failure occurred in two patients after BU/FLU and in three after BU/FLU/ATG (P ¼ 0.66). After conditioning with BU/FLU, platelet recovery was significantly faster (P ¼ 0.017), and less platelet (Po0.001) and red blood cell (P ¼ 0.002) support was needed. Incidences of acute GVHD grades II and IV were 46 and 49%, respectively. Limited chronic GVHD occurred more often after BU/FLU compared to BU/FLU/ ATG (54 vs 23%, P ¼ 0.02). The overall survival, nonrelapse and relapse mortality did not differ significantly. We conclude that in peripheral blood stem cell transplantation from HLA-identical siblings after reduced-intensity conditioning with BU and FLU, ATG has no major impact on the rate of graft rejection and acute GVHD, but it reduces the incidence of limited chronic GVHD. Reduced-intensity conditioning regimens with busulfan (BU), fludarabine (FLU) and antithymocyte globulin (ATG) are increasingly used in related and unrelated hematopoietic stem cell transplantation (HSCT). 1 While the use of ATG as an additional drug for graftversus-host disease (GVHD) prophylaxis is widely accepted in unrelated transplantation, the application in HLA-identical sibling transplantation is a matter of debate. ATG-Fresenius is a polyclonal IgG antibody raised in rabbits against the Jurkat T cell line. 2 The antibody had been incorporated into dose-reduced conditioning regimens for two reasons: first, ATG given before transplantation exerts T-cell depletion of the recipient, which facilitates donor stem cell engraftment after nonmyeloablative doses of BU and FLU and second, antibody persisting in the recipient beyond transplantation exerts in vivo depletion of donor T cells, thereby possibly reducing the risk for acute and chronic GVHD. 3,4 However, ATG has considerable short-term toxicity. 5 While the efficacy of ATG to prevent GVHD and to reduce nonrelapse mortality after myeloablative HSCT has been demonstrated in several studies, the role of ATG in reduced-intensity conditioning has not been evaluated. [6][7][8][9][10] However, reduced-intensity conditioning with BU and FLU was safe even without ATG in 24 patients as shown by our group. 11 In order to assess the impact of ATG, we retrospectively compared the engraftment, incidence and severity of GVHD and survival after BU-and FLU-based reduced-intensity conditioning with or without ATG in patients who had received peripheral blood stem cell transplantation (PBSCT...

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The impact of antithymocyte globulin on short-term toxicity after allogeneic stem cell transplantation

Cited by 57 publications

References 25 publications

Complications of autologous hematopoietic stem cell transplantation for patients with autoimmune diseases

Complications of autologous hematopoietic stem cell transplantation for patients with autoimmune diseases

Subcutaneous alemtuzumab vs ATG in adjusted conditioning for allogeneic transplantation: influence of Campath dose on lymphoid recovery, mixed chimerism and survival

Reduced-intensity conditioning with busulfan and fludarabine with or without antithymocyte globulin in HLA-identical sibling transplantation – a retrospective analysis

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