Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rat model of combined pancreas-spleen transplantation (PST) was used in order to characterize the immunologic consequences of PST when compared to pancreas transplantation (PT) alone. Weakly MHC disparate Fischer (F344) PST grafts survived significantly longer in LEW recipients than did F344 PT grafts (17.6 +/- 3.4 vs 12.1 +/- 1.0 days, respectively, P less than 0.001). However, graft versus host disease (GVHD) occurred regularly in the PST recipients. Similarly, in haploidentical LBN to LEW donor-recipient pairs, PST graft survival was also modestly but significantly increased over that of the PT controls (10.6 +/- 1.0 vs 8.5 +/- 0.8 days, respectively, P less than 0.001). Conversely, in the ACI to LEW combination where MCH differences are very strong, PST graft survival was not longer than PT controls (7.5 +/- 0.8 vs 7.0 +/- 0.6 days, respectively, P greater than 0.2). GVHD was not observed in either of the latter two experiments. Short-term immunosuppression with cyclosporine further improved the outcome in LEW recipients of F344 grafts by inducing long-term graft survivals in approximately one-fourth of the PST recipients. Host splenectomy did not improve graft survival in PST recipients but did increase the risk of GVHD in LEW recipients of F344 PST grafts. Graft irradiation prior to transplantation with 500 rad not only abrogated the GVHD potential of the F344 PST graft but also eliminated the graft survival prolonging effect of the donor spleen. Donor spleen cells injected at the time of PT in F344 to LEW transplants resulted in graft prolongation not different from spleen intact PST recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunologic consequences of combined pancreas-spleen transplantation in the rat. 266 20

Relapse remains the major cause of mortality in haematological malignancies treated with autologous stem cell transplantation (ASCT). Graft versus tumour reaction (GVT) associated to autologous graft versus host disease (GVDH) may contribute to eliminate minimal residual disease (MRD) after ASCT. Eighty patients with several diagnostics were submitted to ASCT. After stem cell infusion, patients randomised in 4 groups. Groups were treated as follows: Group A received either a IFN (alpha Interferon--1,000,000 U/d), Cyclosporine A (CSA--1 mg/-kg/d intravencus) for 28 days, and granulocyte-macrophage colony stimulating factor (GM-CSF-250/m2/d) until engraftment; B: CSA (same dose and way) and GM-CSF; C: CSA (1 mg/kg/d orally) and GM-CSF and D: only GM-CSF. Patients were inspected daily and if skin rash was detected, a skin biopsy was obtained at that moment, otherwise biopsies were obtained at day 21 after ASCT. GVHD was positive in 23 patients (13 from group A and 10 from group B). All cases were grades I and II. A majority of CD4+ T lymphocytes was seen in skin infiltrates. No significant differences were seen in WBC and platelets engraftment times, antibiotic administration or hospitalisation days required among the four groups. With a median follow up of 18 months, there were no differences in disease free survival (DFS) or overall survival (OS) between the patients who developed GVHD and the others. However, considering that myeloma cells do not express antigen MCH II, which is necessary for GVT effect, we excluded patients with multiple myeloma (MM) from survival analysis, thus obtaining a significant difference in OS results between patients who developed GVHD and those in whom this reaction was not observed (81% vs 58% p:0.05). We conclude that pharmacological induction of GVHD in ASCT is possible with CSA administration (1 mg/kg/d i.v.). Development of GVHD showed a better outcome for patients in our study except for those patients with MM. This results must be confirmed by a longer follow up of our patients and further studies.
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PMID:Graft versus host disease in autologous stem cell transplantation. 1046 7