Comparison of different rabbit ATG preparation effects on early lymphocyte subset recovery after allogeneic HSCT and its association with EBV-mediated PTLD

Mensen, Angela; Na, Il‐Kang; Häfer, Ralf; Meerbach, Astrid; Schlecht, Maria T.; Pietschmann, Marie-Luise; Gruhn, Bernd

doi:10.1007/s00432-014-1742-z

Cited by 20 publications

(17 citation statements)

References 33 publications

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“…Patients receiving 15 mg/kg ATG showed a delay of CD19+ cells, but also of CD3+ and CD4+ cells compared to patients receiving ATG at a dosage of 7.5 mg/kg. A recently published study in pediatric patients comparing the influence on immune reconstitution of ATG-G (Thymoglobuline) and ATG-F (Fresenius) found decreased B-cell numbers at day 100 post-transplantation with no significant differences between the 2 ATG preparations (31). The decreased numbers of transitional and na€ ıve B cells at days 15 and 30 may seem to also be related to the B cell activity of ATG-F, as the rabbit IgG persists for more than 100 days after transplantation and correlates with pregraft doses (32).…”

Section: Discussionmentioning

confidence: 99%

Effect of ATG‐F on B‐cell reconstitution after hematopoietic stem cell transplantation

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Muhammad

Stuhler

et al. 2015

European J of Haematology

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Antithymocyte globulin Fresenius (ATG-F) is used before hematopoietic stem cell transplantation to prevent graft rejection and graft-versus-host disease in patients with HLA-matched unrelated donors or mismatched volunteers. However, little is known about the effect of ATG-F on the reconstitution of B-cell subsets. Sixty-seven patients were longitudinally studied at day 15, day 30, and then monthly after hematopoietic stem cell transplantation. Conditioning regimes included ATG-F, which was infused at days 3, 2 and 1 at a dosage of 10 mg/kg/d. Twenty-seven patients received conditioning regimes without ATG. ATG-treated patients showed a significant delay of CD19+ B cells in the early recovery period. The absolute numbers of circulating CD19+ B cells were significantly lower (P < 0.05) up to 5 months post-transplantation compared to non-ATG patients. The recovery of the memory compartment was delayed in both groups and did not reach normal values 1-year post-transplantation. ATG-treated patient showed significantly lower absolute numbers of circulating CD27+ memory B cells in the first-month after transplantation compared to non-ATG patients. In conclusion, treatment with ATG in the conditioning regime of patients undergoing allogeneic hematopoietic stem cell transplantation leads to a significant delay of CD19+ B cells. Thus, ATG seems also to negatively influence B-cell immune reconstitution.

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Section: Discussionmentioning

confidence: 99%

Effect of ATG‐F on B‐cell reconstitution after hematopoietic stem cell transplantation

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Muhammad

Stuhler

et al. 2015

European J of Haematology

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“…In 1 Thymo trial [21], 33.0% of the patients in the ATG arm had Epstein-Barr virus reactivation, compared with 3.0% in the non-ATG arm, whereas these rates were similar in 1 ATLG trial (3.6% compared with 1.4%) [20]. A specifically designed trial with adequate numbers of patients is needed to resolve these controversial questions [27]. The evidence synthesized in this NMA is supported using HR in most efficacy endpoints as an effect measure, which is assumed to suffer somewhat less from selection bias than RR with respect to the endpoints chosen and can indicate risks occurring before the endpoint [28].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Different Rabbit Anti-Thymocyte Globulin Formulations in Allogeneic Stem Cell Transplantation: Systematic Literature Review and Network Meta-Analysis

Gagelmann

Ayuk

Wolschke

2017

Biology of Blood and Marrow Transplantation

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Since 2000, various phase III randomized controlled trials (RCTs) have investigated the efficacy of rabbit antithymocyte globulin (ATG) in patients following allogeneic stem cell transplantation (allo-SCT). Comparisons of different ATG formulations are lacking, however. Our aim was to synthesize all published efficacy evidence to enable a comparison of all available formulations of rabbit ATG in the allo-SCT setting. We performed a systematic literature review to identify all available phase III RCT evidence. We searched the Cochrane Library, MEDLINE, MEDLINE In-Process, and the website www.ClinicalTrials.gov. In addition, a trial presented at the Annual Meeting of the American Society of Hematology 2016 was added to include the most recent evidence. We identified a total of 6 RCTs, including 2 formulations: anti-T lymphocyte globulin (ATLG; Grafalon, Neovii Biotech, Lexington, MA) and polyclonal globulin immunized with human thymocytes (Thymoglobulin [Thymo]; Genzyme-Sanofi, Cambridge, MA). The evidence was synthesized using a conventional network meta-analysis (NMA). The best treatment for preventing graft-versus-host disease (GVHD) was ATLG, which had a more favorable hazard ratio (HR) compared with standard treatment (chronic GVHD: HR, .42; 95% confidence interval [CI], .31 to .56; acute GVHD grade II-IV: HR, .54; 95% CI, .39 to .73; acute GVHD grade III-IV: HR, .50; 95% CI, .29 to .86), whereas both ATLG and Thymo were at least similarly effective in terms of transplantation-related mortality (TRM) (ATLG: HR, .90; 95% CI, .61 to 1.32; Thymo: HR, .90; 95% CI, .56 to 1.44). Thymo tended to be the better treatment option regarding overall survival (OS) (HR, .86; 95% CI, .59 to 1.26). Our NMA provides the first report of the relative efficacy of all available rabbit ATG formulations in patients undergoing allo-SCT. Until additional data from randomized head-to-head comparisons are available, based on the present analysis, ATLG seems to be the best option to prevent chronic and acute GVHD. Both formulations show similar efficacy in terms of TRM, whereas Thymo appears to be the better treatment option in terms of OS.

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“…It was shown by Höcker et al that VGC in EBV high risk patients (D+/R-) is reducing the incidence of EBV primary infection and in case of primary infection patients with VGC have significant lower EBV viral load [18]. Early EBV reactivation after ATGs is widely described in patients after induction treatment for bone marrow transplantation [19;20]. Mensen et al found a similar incidence of EBV-reactivation in patients who received ATG-F or Thymo for induction treatment for allogenic bone marrow transplantation but significant higher copies in patients who received Thymo.…”

Section: Discussionmentioning

confidence: 99%

A Comparison of Two Types of Rabbit Antithymocyte Globulin Induction Therapy in Immunological High-Risk Kidney Recipients: A Prospective Randomized Control Study

et al. 2016

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BackgroundInduction treatment with rabbit polyclonal antithymocyte globulins (ATGs) is frequent used in kidney transplant recipients with donorspecific HLA antibodies and shows acceptable outcomes. The two commonly used ATGs, Thymoglobulin and ATG-F have slightly different antigen profile and antibody concentrations. The two compounds have never been directly compared in a prospective trial in immunological high-risk recipients. Therefore we performed a prospective randomized controlled study comparing the two compounds in immunological high-risk kidney recipients in terms of safety and efficacy.MethodsImmunological high-risk kidney recipients, defined as the presence of HLA DSA but negative CDC-B and T-cell crossmatches were randomized 1:1 to receive ATG-F or Thymoglobulin. Maintenance immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil and steroids.ResultsThe per-protocol analysis included 35 patients. There was no immediate infusion reaction observed with both compounds. No PTLD or malignancy occurred during the follow-up in both groups. The incidence of viral and bacterial infections was similar in both groups (p = 0.62). The cumulative incidence of clinical and subclinical antibody mediated allograft rejection as well as T-cell mediated allograft rejection during the first year between ATG-F and Thymoglobulin was similar (35% versus 19%; p = 0.30 and 11% versus 18%; 0.54 respectively). The two-year graft function was similar with a median eGFR of 56 ml/min/1.73m2 (range 21–128) (ATG-F-group) and 51 ml/min/1.73m2 (range 22–132) (Thymo-group) (p = 0.69).ConclusionWe found no significant differences between the compared study drugs for induction treatment in immunological high-risk patients regarding safety and efficacy during follow-up with good allograft function at 2 years after transplantation.

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Comparison of different rabbit ATG preparation effects on early lymphocyte subset recovery after allogeneic HSCT and its association with EBV-mediated PTLD

Cited by 20 publications

References 33 publications

Effect of ATG‐F on B‐cell reconstitution after hematopoietic stem cell transplantation

Effect of ATG‐F on B‐cell reconstitution after hematopoietic stem cell transplantation

Comparison of Different Rabbit Anti-Thymocyte Globulin Formulations in Allogeneic Stem Cell Transplantation: Systematic Literature Review and Network Meta-Analysis

A Comparison of Two Types of Rabbit Antithymocyte Globulin Induction Therapy in Immunological High-Risk Kidney Recipients: A Prospective Randomized Control Study

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