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Tacrolimus (FK506) alone or in combination with methotrexate or methylprednisolone for the prevention of acute graft-versus-host disease after marrow transplantation from HLA-matched siblings: a single-center study.

Publication ,  Journal Article
Nash, RA; Etzioni, R; Storb, R; Furlong, T; Gooley, T; Anasetti, C; Appelbaum, FR; Doney, K; Martin, P; Slattery, J
Published in: Blood
June 15, 1995

The pharmacokinetics, safety, and efficacy in marrow transplantation of FK506-based immunosuppression for graft-versus-host disease (GVHD) prophylaxis was evaluated in an open label pilot study of 18 patients. Patients more than 12 years of age (median, 35 years; range, 15 to 50 years) with advanced hematologic malignancies receiving HLA-matched sibling marrow grafts were randomized to receive FK506 alone, FK506 and methotrexate (MTX), or FK506 and methyl-prednisolone. Of 17 evaluable patients, all had evidence of sustained marrow engraftment. The median time to an absolute neutrophil count of greater than 500/microL was 15 days for patients receiving FK506 alone or FK506 plus methylprednisolone and 23 days for FK506 plus short MTX. Pharmacokinetic studies did not show any significant difference in clearance of FK506 when administered alone or in combination with methylprednisolone or MTX. The mean bioavailability after oral administration in these same three groups was 0.49 +/- 0.1, 0.27 +/- 0.12, and 0.16 +/- 0.08, respectively (P = .003). The decrease in bioavailability may have resulted from an exacerbation of radiation-induced gastroenteritis by MTX. The most significant adverse effect associated with the administration of FK506 was nephrotoxicity, which occurred in 14 of 18 patients (78%). The mean glomerular filtration rate, determined by clearance of (99MTc)DTPA, decreased to 56% (+/- 18%) of the pretransplant baseline level by week 8 (P = .002). Eight of 18 patients (44%) developed grades II-IV acute GVHD, predominantly of the skin and gastrointestinal tract. The actuarial probability of transplant-related mortality during the first 100 days was 24%. The actuarial probability of 1-year disease-free survival was 39%. In conclusion, although bioavailability of FK506 may be affected in patients receiving MTX, this study suggests that FK506 may have a role in the management of patients after allogeneic marrow transplantation.

Duke Scholars

Published In

Blood

ISSN

0006-4971

Publication Date

June 15, 1995

Volume

85

Issue

12

Start / End Page

3746 / 3753

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Tacrolimus
  • Survival Analysis
  • Pilot Projects
  • Middle Aged
  • Methylprednisolone
  • Methotrexate
  • Male
  • Kidney
  • Immunology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Nash, R. A., R. Etzioni, R. Storb, T. Furlong, T. Gooley, C. Anasetti, F. R. Appelbaum, K. Doney, P. Martin, and J. Slattery. “Tacrolimus (FK506) alone or in combination with methotrexate or methylprednisolone for the prevention of acute graft-versus-host disease after marrow transplantation from HLA-matched siblings: a single-center study.Blood 85, no. 12 (June 15, 1995): 3746–53.
Nash RA, Etzioni R, Storb R, Furlong T, Gooley T, Anasetti C, Appelbaum FR, Doney K, Martin P, Slattery J. Tacrolimus (FK506) alone or in combination with methotrexate or methylprednisolone for the prevention of acute graft-versus-host disease after marrow transplantation from HLA-matched siblings: a single-center study. Blood. 1995 Jun 15;85(12):3746–3753.

Published In

Blood

ISSN

0006-4971

Publication Date

June 15, 1995

Volume

85

Issue

12

Start / End Page

3746 / 3753

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Tacrolimus
  • Survival Analysis
  • Pilot Projects
  • Middle Aged
  • Methylprednisolone
  • Methotrexate
  • Male
  • Kidney
  • Immunology