Abstract
We conducted a study to evaluate the efficacy of the combination of tacrolimus and short-course methotrexate for the prevention of acute GVHD in patients with hematologic malignancies. Patients received preparative regimens specific for their disease category. Twenty-six out of 28 received HLA-identical sibling transplants and the two remaining patients received one-antigen mismatched transplants from a family member. With a median follow-up of 14 months, the Kaplan–Meier estimate of event-free survival was 50 ± 9%. The probability of grade II–IV GVHD was 15 ± 7%. Four patients developed GVHD: two had grade II and one each developed grade III and IV GVHD. Administration of methotrexate was associated with severe mucositis and there was no correlation between the distribution of the GVHD grade and the cumulative dose of methotrexate given. Thirteen patients have died; nine from transplant-related complications and four from relapse. The major toxicity of tacrolimus was renal. Nine out of 28 patients (32%) developed renal dysfunction attributed to tacrolimus. The combination of tacrolimus and methotrexate is an effective regimen for GVHD prophylaxis but associated with significant renal and mucosal toxicity. Further studies of tacrolimus as a single agent or in combination with either steroids or with a lower dose of methotrexate or with other antiproliferative drugs to modify the adverse events may improve the therapeutic index of this useful and promising agent.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Uberti, J., Silver, S., Adams, P. et al. Tacrolimus and methotrexate for the prophylaxis of acute graft-versus-host disease in allogeneic bone marrow transplantation in patients with hematologic malignancies. Bone Marrow Transplant 19, 1233–1238 (1997). https://doi.org/10.1038/sj.bmt.1700813
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1700813
Keywords
This article is cited by
-
Pharmacokinetic comparison of cyclosporin A and tacrolimus in graft-versus-host disease prophylaxis
Annals of Hematology (2017)
-
Intestinal thrombotic microangiopathy induced by FK506 in rats
Bone Marrow Transplantation (2007)
-
Tacrolimus as monotherapy or combined with minidose methotrexate for graft-versus-host disease prophylaxis after allogeneic peripheral blood stem cell transplantation: long-term outcomes
Bone Marrow Transplantation (2004)
-
Factors affecting the pharmacokinetics of tacrolimus (FK506) in hematopoietic cell transplant (HCT) patients
Bone Marrow Transplantation (2001)
-
Assessment of myocardial hypertrophy by echocardiography in adult patients receiving tacrolimus or cyclosporine therapy for prevention of acute GVHD
Bone Marrow Transplantation (2001)