Limited tolerance of intensified conditioning regimens in children receiving methotrexate/cyclosporin A for graft-versus-host disease prophylaxis.
Twenty-one patients with a median age of 9 years (0.5-19) underwent intensified myeloblative therapy: 1800 mg/m2 etoposide (VP) was added to 120 mg/kg cyclophosphamide (CY) and 12 Gy fractionated total body irradiation (FTBI) or 12-16 mg/kg busulfan (BU) for treatment of acute lymphoblastic leukemia (11 patients), acute myeloid leukemia (8 patients), non-Hodgkin's lymphoma (1 patient), or myelodysplastic syndrome (1 patient). Severe liver toxicity occurred in 5 of 7 children (71%) receiving short-term methotrexate (MTX) and additional cyclosporin A (CSA) for prophylaxis of graft-versus-host disease (GVHD). Three of them died of subsequent acute renal failure on days 8, 13, and 34. In contrast, acute severe organ toxicity occurred in only 1 of 14 children (7%) receiving the same intensified regimens who were autografted (7 pts) or received MTX alone for GVHD prophylaxis (7 pts). These observations suggest that GVHD prophylaxis with MTX and CSA may adversely influence the tolerance of intensified antileukemic regimens in children.
Emminger
W
W
St. Anna Children's Hospital, Vienna, Austria.
Emminger-Schmidmeier
W
W
Peters
C
C
Hawliczek
R
R
Höcker
P
P
Gadner
H
H
D000293:Adolescent; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007223:Infant; D008099:Liver / Q000187:drug effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D009092:Mucous Membrane / Q000187:drug effects
D016572:Cyclosporine; D008727:Methotrexate