Tacrolimus and methotrexate for the prophylaxis of acute graft-versus-host disease in allogeneic bone marrow transplantation in patients with hematologic malignancies

J. P. Uberti, S. M. Silver, P. T. Adams, P. Jacobson, A. Scalzo, V. Ratanatharathorn

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1233-1238
Number of pages6
JournalBone marrow transplantation
Volume19
Issue number12
DOIs
StatePublished - Jun 2 1997

Keywords

  • Acute-graft-versus host disease
  • Allogeneic bone marrow transplantation
  • Hematologic malignancies
  • Methotrexate
  • Tacrolimus

Fingerprint

Dive into the research topics of 'Tacrolimus and methotrexate for the prophylaxis of acute graft-versus-host disease in allogeneic bone marrow transplantation in patients with hematologic malignancies'. Together they form a unique fingerprint.

Cite this