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)

Using a mouse model for MHC-matched unrelated donor transplantation, the relative influences of the CD4 and CD8 T cell subtypes on graft-versus-leukemia (GVL) were examined in a murine erythroleukemia induced in SJL/J mice by the injection of Rauscher virus. Following leukemia induction, the mice were given 9.5 Gy of total body irradiation (TBI) and injected with mixed marrow and spleen cells from normal MHC-matched--but minor histocompatibility mismatched--B10.S donors. Prior to their injection these donor cells were selectively depleted ex vivo for either CD4, CD8 or Thy-1 by exposure to the appropriate monoclonal antibody (MoAb) plus complement. Following transplant the recipients were observed for 20 weeks, along with parallel control groups, for survival, leukemia relapse, graft failure and graft-versus-host disease; 98% of the controls receiving no transplantation therapy died of leukemia. Among the controls that received TBI plus undepleted B10.S cells 30.9% died of leukemia relapse, but another 34.2% survived free of any clinical evidence of their leukemia. Donor cell depletion for Thy-1 increased the relapse to 68.8%, while survival fell to 10.4%. CD8 depletion resulted in a relapse of 55.6%, with a survival of 19.4%. By contrast, CD4 depletion had no effect on relapse, but did significantly increase the incidence of graft failure. At the end of the 20 weeks additional tests were run to determine whether those transplant survivors that had remained leukemia-free were also free of any residual Rauscher virus. Those tests showed that they were not.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The role of CD4 and CD8 T cells in the graft-versus-leukemia response in Rauscher murine leukemia. 168 16

We performed an HLA-mismatched T cell non-depleted bone marrow transplant on a 53-year-old man with acute erythroleukemia that was highly resistant to conventional remission-induction chemotherapy. After conditioning that included total body irradiation, the patient received a two-HLA-antigen-mismatched bone marrow graft harvested from his sister using tacrolimus and methotrexate for graft-versus-host disease (GVHD) prophylaxis. He successfully established rapid engraftment accompanied by steroid-responsive GVHD localized to the skin. Although bone marrow samples on day 31 and day 66 disclosed a complete remission with full donor chimerism, the patient relapsed and died of pulmonary infection on day 154. There is evidence that tacrolimus is effective in alleviating GVHD. Selected patients who have partially mismatched related donors with less HLA disparity may benefit from tacrolimus-based T cell non-depleted bone marrow transplants because of the more potent graft-versus-leukemia effect that can be expected compared to transplants using T cell depleted inoculum.
 ...
PMID:[T cell non-depleted bone marrow transplantation for primary refractory erythroleukemia using a partially HLA-mismatched related donor]. 1048 42

De novo erythroleukemia (EL) is a rare disease. Reported median survival are poor and vary from 4 to 14 months. The value of hematopoietic stem cell transplantation (HSCT) for EL is unknown. This EBMT registry study reports on the largest series of patients with EL treated with HSCT in first complete remission-103 autologous and 104 HLA identical sibling allogeneic HSCT. Outcome and identification of prognostic factors for each type of transplantation were evaluated. For autologous HSCT, outcome at 5 years showed a leukemia-free survival (LFS) of 26% +/- 5%, a relapse incidence (RI) of 70% +/- 6%, and a transplant-related mortality (TRM) of 13% +/- 4%. By multivariate analysis, the only prognostic factor was age. For allogeneic HSCT, outcome at 5 years showed an LFS of 57% +/- 5%, an RI of 21% +/- 5%, and a TRM of 27% +/- 5%. By multivariate analysis, prognostic factors were graft-versus-host disease and age. This study represents the largest series of de novo EL treated with HSCT and shows that allogeneic HSCT is by far the most effective treatment.
 ...
PMID:Hematopoietic stem cell transplantation for de novo erythroleukemia: a study of the European Group for Blood and Marrow Transplantation (EBMT). 1238 10

This study was undertaken to explore whether the graft-versus-host-disease could be decreased and graft-versus-leukemia effect be retained by transplantation of allogeneic T helper-2 (Th2) cells. T cells from C57BL/6(H-2b) mice were incubated and polarized with rmIL-4, Con A and ionomycin in vitro, and then, the T cells were mixed with marrow cells and transplanted into recipient BALB/c(H-2d) mice bearing erythroleukemia cells. The occurence of GVHD and GVL effect was observed. The results showed that the mean survival time in the groups of untreated control, cyclophosphamide treatment, marrow and spleen T cell transplantation and marrow and Th2 cell transplantation was 10.6 +/- 1.3, 18.7 +/- 4.2, 22.7 +/- 7.4 and 36.9 +/- 10.8 days, respectively. In untreated control and cycophosphamide treatment groups, all of ten mice died from leukemia. Nine of ten mice died from GVHD in marrow and spleen T cells transplantation group. In marrow and spleen Th2 cell transplantation group, three of ten mice died from GVHD, and GVHD was not occurred in the other seven mice, and there was no any evidence of leukemia in two mice on 50 days after transplantation. It was concluded that tranplantation with polarized Th2 cells could relieve GVHD, and at the same time retain the GVL effect.
 ...
PMID:[Effects of Allogeneic Transplantation of T Helper-2 Cells on Graft-versus-Host Disease and Graft-versus-Leukemia Effect] 1257 20

The aim of study was to investigate the effectiveness of allogeneic natural killer (NK) cells in haploidentical bone marrow transplantation (BMT) for leukemia mice. CB6F(1)(H-2b/d) murine model of EL9611 (H-2d) erythroleukemia was established by intravenous injection of EL9611 (H-2(d)) cells. CB6F(1)(H-2b/d) mice were transplanted with bone marrow (BM) cells from C57BL/6(H-2b) mice. Seventy CB6F(1)(H-2b/d) mice were randomly divided into 7 groups with 10 mice per group. 5 control groups were: group 1, in which no treatment was performed; group 2, in which mice were lethally irradiated (9 Gy); group 3, in which mice were treated with cytarabine with dose of 50 mg/kg for 6 days followed by the infusion of EL9611 (H-2(d)); group 4, in which mice were transplanted with BMT and group 5-the GVHD-control group, in which mice were transplanted with BM and spleen cells from C57BL/6(H-2b) mice 4 hours after irradiation. Experimental groups were divided into 2 groups: group A, in which mice were injected with C57BL/6(H-2b) NK cells (1 x 10(6)) after irradiation and were transplanted with BM from C57BL/6(H-2b) 4 hours later, and group B, in which mice were transplanted with BM cells and spleen cells from C57BL/6(H-2b) 4 hours after irradiation. The effect was assessed and compared by blood picture, survival time, body weight, and histopathology in the recipients. The results showed that the survival times in control group 1, 2, 3 and 5 were (10.10 +/- 0.88), (9.80 +/- 0.92), (22.70 +/- 3.23) and (20.10 +/- 1.73) days respectively. The survival time of control group 4 was (30.10 +/- 15.95) days and was over 30 days in 2 mice. The survival times in experimental group A and B were (39.10 +/- 18.11) and (49.30 +/- 17.24) days respectively. 4 mice in experimental group 1 and 7 mice in group 2 survived over 30 days. The survival time of experimental group 1 was significantly longer than that of control group 1, 2, 3 and 5 (p < 0.01). The survival time of experimental group 2 was significantly longer than that of other groups (p < 0.05). Histopathologic examination showed that splenohepatomegalia and disorganization of liver and spleen with infiltration of a large amount of leukemia cells in mice dead of leukemia. Chimerism of Y chromosome was shown in mice of experimental groups with long survival time. It is concluded that the injection with donor-derived NK cells can both eliminate leukemia cells and decrease the severity of GVHD after haploidential BMT.
 ...
PMID:Effectiveness of allogeneic NK cells in haploidentical bone marrow transplantation for leukemic mice. 1969 48