Antibodies to glycosylphosphatidyl-inositol anchored proteins (GPI-AP) in antithymocyte and antilymphocyte globulin: possible role for the expansion of GPI-AP deficient cells in aplastic anemia

Breitinger, Heike H.; Rojewski, Markus; Schrezenmeier, Hubert

doi:10.1007/s00277-008-0688-0

Cited by 3 publications

(3 citation statements)

References 29 publications

(32 reference statements)

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“…As a result, the relative concentrations of antibodies recognizing various antigens expressed on T-cells vary between ATG-GENZ and ATG-FRES. For example, ATG-GENZ contains more antibodies recognizing CD8, CD11a, CD18, CD44, CD52, CD99 while ATG-FRES recognizes more CD5, CD98, and CD147 (5, 40), although other studies reported different antigens (41, 42).…”

Section: Discussionmentioning

confidence: 99%

Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation

et al. 2019

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Anti-thymocyte globulin (ATG) is a lymphocyte depleting agent applied in hematopoietic stem cell transplantation (HSCT) to prevent rejection and Graft-vs.-Host Disease (GvHD). In this study, we compared two rabbit ATG products, ATG-Genzyme (ATG-GENZ), and ATG-Fresenius (ATG-FRES), with respect to dosing, clearance of the active lymphocyte binding component, post-HSCT immune reconstitution and clinical outcome. Fifty-eigth pediatric acute leukemia patients (n = 42 ATG-GENZ, n = 16 ATG-FRES), who received a non-depleted bone marrow or peripheral blood stem cell graft from an unrelated donor were included. ATG-GENZ was given at a dosage of 6–10 mg/kg; ATG-FRES at 45–60 mg/kg. The active component of ATG from both products was cleared at different rates. Within the ATG-FRES dose range no differences were found in clearance of active ATG or T-cell re-appearance. However, the high dosage of ATG-GENZ (10 mg/kg), in contrast to the low dosage (6–8 mg/kg), correlated with prolonged persistence of active ATG and delayed T-cell reconstitution. Occurrence of serious acute GvHD (grade III–IV) was highest in the ATG-GENZ-low dosage group. These results imply that dosing of ATG-GENZ is more critical than dosing of ATG-FRES due to the difference in clearance of active ATG. This should be taken into account when designing clinical protocols.

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Section: Discussionmentioning

confidence: 99%

Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation

et al. 2019

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“…While studies in both primates and humans have shown that rATG does deplete T cells 1, 2, several other studies have identified rATG antibodies that might prevent injury due not only to rejection but also to inflammation associated with brain death and/or reperfusion 3, 4, 5, 6.…”

Section: Introductionmentioning

confidence: 99%

“…Although rATG was developed as an agent to deplete T cells, its manufacture results in the generation of multiple antibodies against a myriad of distinct epitopes. While studies in both primates and humans have shown that rATG does deplete T cells (1,2), several other studies have identified rATG antibodies that might prevent injury due not only to rejection but also to inflammation associated with brain death and/or reperfusion (3)(4)(5)(6). and with cardiopulmonary instability, the prescribing information for rATG (in treating kidney rejection) recommends administering a series of small doses spaced at 1-or 2-day intervals (divided-dose rATG [DD-rATG]), along with premedication that includes corticosteroids (7).…”

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confidence: 99%

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation

Stevens

Wrenshall

Miles

et al. 2016

American Journal of Transplantation

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A previous nonblinded, randomized, single‐center renal transplantation trial of single‐dose rabbit anti‐thymocyte globulin induction (SD‐rATG) showed improved efficacy compared with conventional divided‐dose (DD‐rATG) administration. The present multicenter, double‐blind/double‐dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD‐rATG versus DD‐rATG induction for noninferiority in early (7‐day) safety and tolerability. Ninety‐five patients (randomized 1:1) received 6 mg/kg SD‐rATG or 1.5 mg/kg/dose DD‐rATG, with tacrolimus‐mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12‐month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD‐rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD‐rATG induction to be noninferior to DD‐rATG induction in early tolerability and equivalent in 12‐month safety. (Clinical Trials.gov #NCT00906204.)

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Immunosuppressive therapy for transplant-ineligible aplastic anemia patients

Schrezenmeier

Körper²,

Höchsmann³

2015

Expert Review of Hematology

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Aplastic anemia is a rare life-threatening bone marrow failure that is characterized by bicytopenia or pancytopenia in the peripheral blood and a hypoplastic or aplastic bone marrow. The patients are at risk of infection and hemorrhage due to neutropenia and thrombocytopenia and suffer from symptoms of anemia. The main treatment approaches are allogeneic stem cell transplantation and immunosuppression. Here, we review current standard immunosuppression and the attempts that have been made in the past two decades to improve results: review of recent developments also reveals that sometimes not only the advent of new drugs, good ideas and well-designed clinical trials decide the progress in the field but also marketing considerations of pharmaceutical companies. Aplastic anemia experts unfortunately had to face the situation that efficient drugs were withdrawn simply for marketing considerations. We will discuss the current options and challenges in first-line treatment and management of relapsing and refractory patients with an emphasis on adult patients. Some promising new approaches are currently under investigation in prospective, randomized trials.

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Antibodies to glycosylphosphatidyl-inositol anchored proteins (GPI-AP) in antithymocyte and antilymphocyte globulin: possible role for the expansion of GPI-AP deficient cells in aplastic anemia

Cited by 3 publications

References 29 publications

Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation

Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation

Immunosuppressive therapy for transplant-ineligible aplastic anemia patients

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