Antithymocyte globulin pharmacokinetics in pediatric patients after hematopoietic stem cell transplantation.
To analyze the dose effects of rabbit-derived antithymocyte globulin (ATG) in children after allogeneic hematopoietic stem cell transplantation (HSCT), ATG serum levels were monitored in 32 children and adolescents (median age 3.42 years, range 0.34-18.67 years) and the incidence of acute and chronic graft-versus-host disease, rejection, viral infections, EBV-lymphoproliferative disease, and survival was correlated with the ATG dose used. Cumulative doses from 7.5 to 20 mg/kg showed a constant half-life and linear correlation between dose and Cmax, whereas higher doses (30-40 mg/kg) accumulated in the body. High-dose ATG is of no benefit for preventing graft-versus-host disease but is associated with a significant increase in EBV-linked disease, and it appears to enhance the susceptibility to fatal viral infections and rejection. These data strongly support the use of a low-dose ATG regimen in pediatric HSCT.
Seidel
Markus G
MG
St. Anna Children's Hospital and Children's Cancer Research Institute (CCRI), Vienna, Austria. Markus.Seidel@stanna.at
Fritsch
Gerhard
G
Matthes-Martin
Susanne
S
Lawitschka
Anita
A
Lion
Thomas
T
Pötschger
Ulrike
U
Rosenmayr
Agathe
A
Fischer
Gottfried
G
Gadner
Helmut
H
Peters
Christina
C
D000293:Adolescent; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020031:Epstein-Barr Virus Infections / Q000209:etiology / Q000473:pathology; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000188:drug therapy; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood*; D015994:Incidence; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000473:pathology*; D008297:Male; D011817:Rabbits; D012189:Retrospective Studies; D019172:Transplantation Conditioning
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine