Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021933 (intussusception)
 3,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of trimetrexate following marrow transplantation were studied in a dog model. Four animals were given 9.2 Gy total body irradiation (TBI), autologous marrow, and either trimetrexate alone (0.4 mg/kg on days 1, 3, 6, and 11) or combined with cyclosporine (CSP) (15 mg/kg per day i.m. on days 1-7, then orally until day 25, then taper). All four animals engrafted normally, demonstrating that trimetrexate at this dose is tolerable. Ten additional animals were given a similar dose of TBI followed by marrow and buffy coat cells from littermate donors differing for one DLA haplotype. Trimetrexate and CSP were given as noted above. Four of the 10 animals died, one with septicemia prior to engraftment (day 14), one with intussusception (day 28), one with graft failure (day 32) and one with a tracheal abscess without graft-versus-host disease (GVHD) (day 67). Six dogs survived in excess of 100 days; one of the six developed chronic GVHD. These results are superior to those previously achieved with either methotrexate or CSP as single agents and are roughly equivalent to results achieved with a combination of methotrexate and CSP in similarly mismatched donor-recipient pairs.
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PMID:Use of trimetrexate for the prevention of graft-versus-host disease. 252 87

We previously reported an synergism between methotrexate and tacrolimus (FK506) in preventing graft-versus-host disease (GVHD) in dogs given DLA-nonidentical unrelated marrow grafts after 9.2 Gy of total body irradiation (TBI). Methotrexate was given at 0.4 mg/kg i.v. on days 1, 3, 6 and 11 and FK506 at 0.15 mg/kg/day i.m. on days 0-8 and 0.5 mg/kg/day orally on days 9-90. Half of the dogs became long-term survivors. A major toxicity was gastrointestinal, and 25% of dogs died with intussusception. The current study addresses the problem of intussusception by making changes in drug doses used. In one group of dogs, FK506 was reduced to 0.075 mg/kg i.m. on days 1-8, while methotrexate was administered per original schedule. In a second group, methotrexate was reduced to a single dose on day 7, while FK506 was either administered per the original or reduced-dose schedule. None of the 17 current dogs developed intussusception, however, all but two dogs died with GVHD (n = 12) or graft failure (n = 3). Only two dogs survived after transient GVHD. Results show that there is little room for maneuvering FK506 or methotrexate doses, and hopes of reducing gastrointestinal toxicity by dose modifications while retaining the ability to prevent GVHD were not fulfilled.
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PMID:Tacrolimus (FK506) and methotrexate regimens to prevent graft-versus-host disease after unrelated dog leukocyte antigen (DLA) nonidentical marrow transplantation. 872 70

Mycophenolate mofetil (MMF) was evaluated either alone or combined with cyclosporine (CSP) for preventing graft-versus-host disease (GVHD) in dogs given 9.2 Gy total body irradiation and DLA-nonidentical unrelated marrow grafts. Marrow autograft studies showed gut toxicity as limiting MMF side effects. Four groups were studied for GVHD prevention: six dogs in group 1 received MMF 10 mg/kg twice daily subcutaneously (SC) on days 0 to 27. They died between 8 to 28 days from infection or GVHD; survival was better than that of 72 controls given no immunosuppression (P = .04), but not different from 19 dogs given CSP. Four dogs in group 2 received MMF as described, along with CSP at 10 to 15 mg/kg twice daily on days 0 to 27. They died at 6 to 98 days from CSP-associated toxicity, weight loss, or infection. Nine dogs in group 3 received MMF SC twice daily 6 mg/kg/d for 3 days, followed by 10 mg/kg twice daily until day 27, along with CSP as described; four died between 7 to 106 days with intussusception, infection, or GVHD, and five became long-term survivors. Six dogs in group 4 received shortened MMF (21 days) and reduced doses of CSP given through day 100. Three died with GVHD or infection between days 38 to 119, and three became long-term survivors. Results support the notion of synergism between MMF and CSP, as evidenced by stable graft-host tolerance in greater than 50% of dogs.
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PMID:Synergism between mycophenolate mofetil and cyclosporine in preventing graft-versus-host disease among lethally irradiated dogs given DLA-nonidentical unrelated marrow grafts. 951 60