Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transplantability of mouse tumors superinfected with various kinds of membrane viruses was investigated in syngeneic hosts. Methylcholanthrene-induced fibrosarcomas in BALB/c mice, Meth A, and in C57BL/6 mice, BMT-, superinfected with Friend lymphatic leukemia virus in mice given neonatal injection of the virus, grew more slowly than uninfected tumors. The retardation of growths was not observed in mice that had been given injections of the virus at birth. Similarly, Meth A and a hepatoma in C3H/He mice, MH134, superinfected with Moloney murine sarcoma virus in nu/nu mice, had reduced their transplantability in respective syngeneic mice. Further, Meth A and MH134 superinfected with endogenous rat leukemia virus and human measles virus, respectively, in nu/nu mice also showed reduced transplantability, and some of the former were actually rejected by normal syngeneic hosts. On the other hand, the reduced transplantability was not found in irradiated mice, suggesting that the phenomenon was due to immunological events. However, a myelogenous leukemia in C57BL/6 mice, C1498, superinfected with Moloney sarcoma virus in nu/nu mice grew like uninfected tumor and did not show reduced transplantability at all.
 ...
PMID:Reduced transplantability of syngenic mouse tumors superinfected with membrane viruses in nu/nu mice. 100 77

Bone marrow transplantation has become the accepted treatment for several hematologic disorders. We have done 3 autologous and 6 allogeneic bone marrow transplantations at Ramathibodi Hospital since July 1989 in patients with acute lymphoblastic leukemia, acute non-lymphocytic leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma and severe aplastic anemia. Only one patient with aplastic anemia had late graft rejection, but the rest of them engrafted and did well during the median follow up period of 317 days (range: 39 to 962 days) post transplantation. None of the allogeneic BMT had graft-versus-host disease. We use cyclosporin and short course methotrexate for post transplantation immunosuppression.
 ...
PMID:Bone marrow transplantation in Ramathibodi Hospital: progress report. 130 13

Results from phase I/II studies of Granulocyte-colony stimulating factor (G-CSF) for bone marrow transplantation were reported. G-CSF in 200-800 micrograms/m2 was administered from day 3 or 5 daily for 14 days. A very rapid recovery of granulocytes was observed in most cases. Stem cell exhaustion was considered not serious. Stimulation on myeloid leukemic cells was observed in vitro tests, but relapse was observed in only 2 out of 17 myeloid leukemia patients. There was no marked difference in the grade and incidence of GVHD from historical control patients. As side effects, 3 cases of bone pain and 2 of skin rash were observed. All these symptoms were slight, reversible and tolerated for further administration. As a whole, courses of BMT with G-CSF seemed very smooth and uneventful with very rapid and steady recovery of granulocytes. G-CSF seemed promising for bone marrow transplantation in which the severe granulocytopenic stage is inevitable and normal stem cells without contact with cytostatic agents are procured.
 ...
PMID:[Granulocyte colony stimulating factor for bone marrow transplantation]. 247 38

Recombinant human glycosylated G-CSF (rhG-CSF) may stimulate proliferation of myeloid leukemia cells and thereby increase their susceptibility to anti-cancer agents. By in vitro colony assay, the rhG-CSF-responsive NFS-60 leukemic cell clones are more effectively killed by Ara C in the presence of rhG-CSF than in the absence of rhG-CSF, while the killing of the rhG-CSF-unresponsive HL-60 cell clones is unaffected by rhG-CSF. Leukemia cell colony forming units (L-CFU) derived from most AML patients demonstrate similar results to those of the NFS-60 cell clone when treated in vitro. Encouraged by these in vitro results, we used rhG-CSF as a component of a conditioning regimen for 15 relapsed AML patients who were receiving allogeneic BMT. The patients were conditioned with total body irradiation (TBI) and high-dose Ara C. rhG-CSF was infused continuously at a dose of 5 micrograms/kg/day from 24 h before the beginning of TBI to the end of Ara C therapy. Proliferation of the leukemia cells in vivo in response to rhG-CSF was confirmed in 7 of 14 patients tested and the combined use of rhG-CSF had no additional adverse effects. After BMT, four patients died of non-leukemic causes and three patients had leukemic relapse: the other eight patients have remained disease-free for 200-1600 (median 417) days. The actuarial probabilities of relapse and disease-free survival (DFS) at 4.4 years after BMT were 43.2% and 41.7%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Recombinant human glycosylated granulocyte colony-stimulating factor (rhG-CSF)-combined regimen for allogeneic bone marrow transplantation in refractory acute myeloid leukemia. 751 98

The use of an ABO-incompatible donor for BMT after total body irradiation (TBI) has no adverse effect on engraftment, incidence of GVHD or survival when donor erythrocytes and plasma are depleted from the infused marrow. The outcome of ABO-incompatible BMT following a non-TBI-containing preparative regimen has not been as well studied. We therefore performed a retrospective review of consecutive patients undergoing allogeneic BMT for myeloid leukemia after treatment with high-dose busulfan and cyclophosphamide (BUCY) between January 1984 and January 1993. Of the 199 evaluable patients, 100 had AML or myelodysplastic syndrome, 30 of which were ABO-incompatible, and 99 had CML, 35 of which were ABO-incompatible. All patients undergoing transplant received erythrocyte and plasma-depleted marrow but 14 major ABO-incompatible patients also underwent plasma exchange before transplant. T cell-depletion and purging techniques were not employed. All records were reviewed for prognostic factors including patient age, sex, diagnosis, remission status at the time of transplant, and incidence and severity of acute and chronic GVHD. Compatible and incompatible patients with myeloid leukemia did not differ with respect to age, sex, remission status of disease at the time of transplant or incidence of GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Survival after ABO-incompatible allogeneic bone marrow transplant after a preparative regimen of busulfan and cyclophosphamide. 774 42

A model for investigating graft-versus-leukemia (GVL) activity following syngeneic and MHC-compatible allogeneic BMT has been developed in C57BL/6 (B6) mice with use of the c-myc retrovirus-transformed MMB3.19 myeloid leukemia line. The MMB3.19 line was derived from a B6 mouse and expresses monocyte/macrophage markers, including Mac-1, Mac-2, F4/80, and LFA-1, in addition to H-2 class I and class II molecules. A challenge dosage of 10(5) of these leukemia cells was found to be completely lethal when injected into irradiated (850 cGy) B6 recipients, 1 day after the transplantation of syngeneic donor T cell-depleted-bone marrow. The addition of T lymphocytes to the donor inoculum prolonged recipient survival, and both CD4+ and CD8+ subsets were found to be capable of mediating this GVL activity. For the MHC-compatible allogeneic model, the C3H.SW-->B6 (850 cGy) strain combination was utilized, in which CD8+ T cells are known to cause graft-versus-host disease directed to minor histocompatibility antigens expressed by the recipient. In this case, both CD(4+)- and CD(8+)-enriched T cells were found to be capable of mediating GVL activity to MMB3.19 challenge, particularly if donor mice were presensitized with leukemia cells. Of most significance, only the donor CD4+ T cells mediated a GVL effect without the apparent induction of graft-versus-host disease.
 ...
PMID:Graft-versus-myeloid leukemia responses following syngeneic and allogeneic bone marrow transplantation. 791 87

New understanding of the alloresponse following bone marrow transplantation supports the possibility that the graft-versus-host disease (GVHD) response can be separated from a favorable graft-versus-leukemia (GVL) effect. We used chronic myeloid leukemia (CML) cells to generate 122 recipient-reactive T cell clones from a closely HLA-matched sibling responder. Clones were tested for their proliferative response to stimulator CML cells or PHA-transformed (non-leukemic) lymphoblasts. Of 78 clones tested, 32 recognized both leukemia cells and PHA blasts, 19 only CML and four only PHA blasts. The remainder were non-specific responders. This functional specificity corresponded to distinct patterns of T cell receptor (TCR) V beta usage: clones recognizing CML cells preferentially used V beta 5, V beta 6/7 while clones recognizing both CML and PHA blasts or only PHA blasts preferentially used V beta 3 and V beta 8. It may therefore be possible to identify in vitro-generated myeloid leukemia-restricted donor T cells by their pattern of V beta usage. TCR V beta antibodies could thus be used to select and expand leukemia-restricted donor T cells for transfusion after BMT to specifically enhance the GVL response.
 ...
PMID:Preferential usage of T cell receptor (TCR) V beta by allogeneic T cells recognizing myeloid leukemia cells: implications for separating graft-versus-leukemia effect from graft-versus-host disease. 915 63

Donor CD4+ and CD8+ T cells mediate graft-vs.-leukemia (GVL) responses in the allogeneic bone marrow transplantation (alloBMT) setting. To evaluate the role of functional T cell subsets in the mediation of GVL, alloreactive donor CD4+ (Th1/Th2) and CD8+ (Tc1/Tc2) T cells of defined cytokine phenotype were generated by in vitro culture. A leukemia/transplantation model (B6 into B6C3F1; 1050 cGy host irradiation) was established using the bcr/abl-transfected myeloid leukemia line, 32Dp210 (P210; H-2k). Leukemia control mice (1X10(4) P210 cells per recipient) died at day 12.0 post-BMT. Recipients of the CD4+, Th1-type or CD8+, Tc1-type populations were conferred a survival advantage (death at 20.7 and 23.5 days post-BMT, respectively). In contrast, the CD4+, Th2-type population did not mediate GVL (death at 12.3 days). Furthermore, cell mixing experiments demonstrated that the Th2 subset abrogated both Th1- and Tc1-mediated GVL. The CD8+, Tc2 population, which secreted type II cytokines and lysed the P210 leukemia target in vitro, mediated GVL in some experiments; interestingly, the magnitude of Tc2-mediated GVL was inversely related to the level of interleukin-10 (IL-10) secreted in vitro by the Tc2 population. These studies therefore indicate that alloreactive T cells of type I phenotype maximally generate GVL, and that type I/type II interactions are an important consideration for allogeneic transplantation in the setting of leukemic hosts.
 ...
PMID:Allospecific CD4+, Th1/Th2 and CD8+, Tc1/Tc2 populations in murine GVL: type I cells generate GVL and type II cells abrogate GVL. 919 54

We examined the antileukemic activity and the toxicity of HPC transduced with human tumor necrosis factor (TNF) cDNA. Both clonal (32Dcl3) and BM-derived primary hematopoietic progenitors (BM-Prog) expressing hTNF-alpha gene (32DTNF-alpha and BMTNF-alpha cells, respectively) inhibited the development of leukemia in mice with a small dose of 32Dp210 cells, a myeloid leukemia cell line. Whether the trans-gene expressing 32DTNF-alpha cells produce toxicities commonly associated with systemic TNF-alpha therapy was determined by examining the effect of TNF-alpha-secreting progenitor cells on body weight, tissue histology, growth of HPC, and engraftment of BMT. Administration of a low or high dose of TNF-alpha-secreting 32DTNF-alpha cells to mice failed to produce loss in body weight, a measure of TNF-alpha-related cachexia. There was also no evidence of tissue necrosis or mononuclear cell (MNC) infiltration in lung, liver, kidney, or intestine of mice injected with transduced progenitor cells. Furthermore, 32DTNF-alpha cells showed no effect on the clonal growth of HPC in colony-forming assays or loss of cellularity in BM, spleen, or blood. Finally, TNF-alpha-secreting cells were found not to interfere with the engraftment of BM transplant and hematopoietic reconstitution thereafter. We conclude from these findings that unlike systemic administration of TNF-alpha, TNF-alpha gene therapy with transduced HPC is nontoxic and may have a role in eradicating residual leukemia after BMT.
 ...
PMID:TNF-alpha gene therapy with myeloid progenitor cells lacks the toxicities of systemic TNF-alpha therapy. 1041 46

The purpose of study was to investigate the impact of killer immunoglobulin-like receptor (KIR) and its ligand on haploidentical bone marrow transplantation. 74 cases were analyzed for the distribution frequencies and characteristics of KIR and its ligand as well as the impact of KIR ligand for the haploidentical bone marrow transplantation in terms of the overall survival, disease-free survival (DFS), GVHD and relapse. The results showed that among the 19 KIR genotypes currently nominated KIR2DL1, KIR2DL4 and KIR3DL2-3 could be detected in all the cases. Other high frequency genotypes included KIR3DP1 (98.6%), KIR2DP1 (98.6%), KIR3DL1 (97.3%) and KIR2DL3 (97.3%). Inhibitory receptor genotypes were 1.37-fold of activating receptor genotypes. KIR2DL1, KIR3DL2, KIR3DL3 and KIR2DL4 were found in all haplotypes and at least one genotype of KIR2DL2 and/or KIR2DL3 existed in all haplotypes. Among the 14 genotypes found in the test, the HLA-Cw7 was the most popular (37.8%) and the group 2 (HLA-Cw1, 3, 7, 8, 13, 14) recognized by KIR2DL2/2DL3 counted for 43.2%. The incompatibility of KIR for 32 cases of haploidentical BMT was 43.8%, of which 9/14 were KIR2DL incompatible, 5/14 were KIR2DL2 or KIR3DL1 incompatible. Among the 46 cases of haploidentical BMT, 29 cases were HLA-Cw matched and 14 cases were mismatched. The completed mismatch ratio of HLA-Cw was 30.4% and the match ratio was 63.4%. The survival rate was higher for the 14 cases of KIR genotype compatible group than the 13 cases of KIR genotype incompatible group (p = 0.032). The disease-free survival was significantly higher for the 17 cases of mismatched KIR ligands (HLA-Cw) group than the matched group (p = 0.024). The survival rate was higher in GVHD group than that in non-GVHD group when the KIR ligand was missing. The acute and severe GVHD was related to the existence of activating receptor of KIR2DS1/2DS2. The incompatibility group was accompanied with frequent acute and severe GVHD and less relapse and vice versa for the compatibility group. One patient died after BMT among the 14 mismatched KIR ligand group suffering from myelogenous leukemia while 4 patients out of 12 patients died in the matched group. It is concluded that the haploidentical BMT is characterized by mismatch between donor and recipient and its immunological reactions also features by the incompatibility of KIR genotype and missing ligand. The missing ligand for the donor KIR has strong effect on the outcome of BMT and it means a lot to analyze the KIR genotype and its ligand for the selection of best donor and prognostic evaluation in haploidentical BMT.
 ...
PMID:Impact of incompatible killer cell immunoglobulin-like receptor and its ligand on the outcome of haploidentical bone marrow transplantation. 1770 9


1