Tacrolimus (FK506) and methotrexate as prophylaxis for acute graft-versus-host disease in pediatric allogeneic stem cell transplantation.
Currently, limited data exist on the role of tacrolimus (FK506) in pediatric allogeneic marrow transplantation. Forty-one patients who received tacrolimus as prophylaxis were reviewed, with a median age of 9 years (range 0.2-16 years). Twenty-one patients underwent related donor transplants and 20 underwent unrelated donor transplants. All patients received tacrolimus beginning the day prior to transplant at a dose of 0.03 mg/kg/day by continuous i.v. infusion. When clinically possible, patients were switched to oral therapy in two divided doses, at four times the intravenous dose. Tacrolimus levels were monitored twice a week, and dosages adjusted to maintain serum levels 5-15 ng/ml. Common adverse effects included hypomagnesemia (98%), hypertension (49%), nephrotoxicity (34%), and tremors (32%). Less common side-effects (<10% cases) included seizures and hyperglycemia. The median time to ANC recovery (ANC >500 x 106/l) was 15 days. For the related donor group, the incidence of grade II-IV acute GVHD was 33%, and grade III-IV GVHD 19%. For the unrelated donor group, the incidence of grade II-IV acute GVHD was 55%, and grade III-IV GVHD 30%. Overall, tacrolimus therapy was well tolerated as prophylaxis for acute GVHD in pediatric patients undergoing allogeneic transplantation.
Blood and Marrow Stem Cell Transplantation Program, Divisions of Hematology/Oncology, Department of Pediatrics, University of Michigan Medical Center, Ann Arbor 48109, USA.
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Yanik
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Levine
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Ratanatharathorn
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Dunn
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Ferrara
R J
RJ
Hutchinson
D000206:Actuarial Analysis; D000208:Acute Disease; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use / Q000633:toxicity; D007223:Infant; D007239:Infections / Q000139:chemically induced; D017093:Liver Failure / Q000139:chemically induced / Q000628:therapy; D008275:Magnesium Deficiency / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000633:toxicity; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000633:toxicity*; D013997:Time Factors; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000139:chemically induced
D007166:Immunosuppressive Agents; D016559:Tacrolimus; D008727:Methotrexate