Biomaterial Database

FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors. 1996

R A Nash, and L A Piñeiro, and R Storb, and H J Deeg, and W E Fitzsimmons, and T Furlong, and J A Hansen, and T Gooley, and R M Maher, and P Martin, and P A McSweeney, and K M Sullivan, and C Anasetti, and J W Fay

Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.

The safety and potential efficacy of FK506 in combination with a short course of methotrexate (MTX) for the prevention of acute graft-versus-host disease (GVHD) after marrow transplantation from HLA-matched unrelated donors was evaluated in a single-arm Phase II study conducted at two centers. Forty-three patients, 15 to 54 (median 41) years of age, were transplanted for hematologic malignancies. Thirty-seven of 43 evaluable patients had evidence of sustained marrow engraftment. Five patients died before day 17 after transplantation. The median time to an absolute neutrophil count of > 0.5 x 10(5)/L was 21 (range, 14 to 30) days. Nephrotoxicity (serum creatinine concentration > 2 mg/dL or doubling of baseline) occurred in 32 patients (74% cumulative incidence during the first 100 days after transplant). Other adverse effects included hypertension (n = 27), hyperglycemia (n = 27), neurotoxicity (n = 9) and thrombotic thrombocytopenic purpura (n = 2). Severe veno-occlusive disease of the liver occurred in 9 (21%) of the 43 patients. Eighteen patients (42%) developed grades II to IV acute GVHD and five (12%) developed grades III to IV acute GVHD. Twelve of 25 evaluable patients developed extensive chronic GVHD within 1 year of marrow transplantation resulting in an estimate of the probability of developing this complication of 48%. The cumulative incidence of transplant-related mortality during the first 100 days was 37%. Kaplan-Meier estimates of disease-free survival at 2 years for good-risk, poor-risk, and all patients were 65%, 4%, and 32%, respectively. FK506 in combination with a short course of MTX appears active in preventing acute GVHD after marrow transplantation from unrelated donors. Further studies comparing the combination of FK506 and MTX with cyclosporine and MTX for the prevention of acute GVHD are warranted.

UI	MeSH Term	Description	Entries
D007166	Immunosuppressive Agents	Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.	Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D007262	Infusions, Intravenous	The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.	Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D008297	Male		Males
D008727	Methotrexate	An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.	Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D004359	Drug Therapy, Combination	Therapy with two or more separate preparations given for a combined effect.	Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D005260	Female		Females
D006085	Graft Survival	The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.	Graft Survivals,Survival, Graft,Survivals, Graft
D006086	Graft vs Host Disease	The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION.	Graft-Versus-Host Disease,Homologous Wasting Disease,Runt Disease,Graft-vs-Host Disease,Disease, Graft-Versus-Host,Disease, Graft-vs-Host,Disease, Homologous Wasting,Disease, Runt,Diseases, Graft-Versus-Host,Diseases, Graft-vs-Host,Graft Versus Host Disease,Graft-Versus-Host Diseases,Graft-vs-Host Diseases
D006650	Histocompatibility Testing	Identification of the major histocompatibility antigens of transplant DONORS and potential recipients, usually by serological tests. Donor and recipient pairs should be of identical ABO blood group, and in addition should be matched as closely as possible for HISTOCOMPATIBILITY ANTIGENS in order to minimize the likelihood of allograft rejection. (King, Dictionary of Genetics, 4th ed)	Crossmatching, Tissue,HLA Typing,Tissue Typing,Crossmatchings, Tissue,HLA Typings,Histocompatibility Testings,Testing, Histocompatibility,Testings, Histocompatibility,Tissue Crossmatching,Tissue Crossmatchings,Tissue Typings,Typing, HLA,Typing, Tissue,Typings, HLA,Typings, Tissue