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)

The IBM 2991 Blood Cell Processor has been used to isolate a mononuclear cell (MNC) fraction from the marrow of 31 allogeneic donors. The MNC fraction was then incubated with a combination of two murine monoclonal antibodies MBG6 (CD6) and RFT8 (CD8) followed by two rounds of treatment with rabbit complement resulting in a marrow inoculum significantly reduced in the number of T-lymphocytes. We report here new specifications for the use of Ficoll-Metrizoate, the method used to calculate T-lymphocyte depletion and the details of our attempts to improve T-depletion. Following marrow transplantation with this T-depleted fraction, 29 patients are evaluable for engraftment, one patient failed to engraft and one died too early for evaluation. Twenty-two had no acute graft-versus-host disease (aGvHD), at a minimum of 60 d, six had grade I acute GvHD and one grade III. No correlation was found between the absolute number of MNC infused and time to engraftment, nor any relationship between the number of residual viable T-lymphocytes in the infused marrow and the incidence of GvHD, but the patient with the most severe aGvHD also had the highest number of T-lymphocytes infused.
 ...
PMID:Standardization of T-cell depletion in HLA matched bone marrow transplantation. 353 Mar 16

The technique using the IBM 2991 blood cell processor is an effective technique for the concentration of mononuclear cells from large volumes of bone marrow. The marrow cells are layered on to Ficoll Metrizoate using the IBM processing set. The mononuclear cells and CFU-GM recoveries are in close relationship with the hematocrit of the cell suspension processed. Twenty two bone marrows have been collected and purified according to this protocol. The mononuclear cell recovery is an average of 78,3% (range: 44-92%) and the CFU-GM recovery is in average of 67,5% (range: 40-89%). At the end of the procedure the cell viability is satisfying (97,1% +/- 1,7 are trypan blue negatives). When it is necessary to remove from the bone marrow collected either malignant cells prior autologous bone marrow graft or T lymphocytes in an attempt to prevent GVHD in allogeneic BMT, the purity of marrow cell suspension become a fundamental parameter.
 ...
PMID:[Method for concentrating marrow stem cells using the IBM 2991 washer. Necessary preparation before in vitro treatment of bone marrow by pharmacologic or immunologic means]. 634 24

Marrow from seven normal donors and patients has been layered onto Ficoll-Metrizoate (FM) under pressure in the IBM 2991 blood cell processor to isolate the mononuclear cell (MNC) population prior to allogeneic transplantation or cryopreservation. This separation method, which takes less than 90 min, is a further development since our previous report detailing the use of the IBM 2991 to produce a concentrated marrow 'buffy coat' for infusion (Gilmore & Prentice, 1981). By adding FM to the system, marrow stem cells are further concentrated in a small volume with removal of unwanted granulocytes and red blood cells. This facilitates in in vitro treatment of marrow with monoclonal antibodies (Granger et al. 1982) or drugs, for either the selective elimination of malignant cells prior to autologous bone marrow transplantation (BMT), or T lymphocytes in an attempt to prevent graft versus host disease (GvHD) in allogeneic BMT. Five of the seven marrows processed by this procedure have thus far been infused into lethally irradiated recipients with engraftment (allogeneic); the other two marrows have been cryopreserved.
 ...
PMID:A technique for rapid isolation of bone marrow mononuclear cells using Ficoll-Metrizoate and the IBM 2991 blood cell processor. 703 61

Using various autoimmune-prone mice, we have previously shown that conventional allo BMT can be used to treat a range of autoimmune diseases. These findings have recently been confirmed even in humans. However, in humans, the success rate of BMT across major histocompatibility complex(MHC) barriers is lowered by graft-versus-host disease(GvHD), graft rejection, and incomplete T-cell recovery. We have just established a new BMT method in which bone marrow cells(BMCs) are directly injected into the intra-bone marrow(IBM-BMT). We here show that 'IBM-BMT' is the best strategy for allo BMT and also organ allografts to induce persistent tolerance.
 ...
PMID:[New strategies for BMT]. 1251 Mar 55

In humans, the success rate of BMT across major histocompatibility complex (MHC) barriers is lowered by graft-versus-host disease (GvHD), graft rejection and incomplete T-cell recovery. To prevent GvHD, we attempted to minimize the contamination of bone marrow cells (BMCs) with T cells from the peripheral blood when donor BMCs were collected, finally establishing a new 'Perfusion Method' using cynomolgus monkeys. There was significantly less contamination of BMCs with T cells in this method (<6%) than in the conventional 'Aspiration Method' (>20%) consisting of multiple aspirations of BMCs from the iliac crest. Using radio-sensitive and chimerism-resistant MRL/lpr mice, we also established a new method for allogeneic (allo) BMT and organ allografts. In this method, whole BMCs, containing a small number of T cells and mesenchymal stem cells (MSCs), were directly injected into the bone marrow cavity (intrabone marrow [IBM]-BMT). MRL/lpr mice treated with IBM-BMT survived more than 2 years without showing the symptoms of autoimmune diseases. IBM-BMT thus has several advantages: (i) no GvHD develops even if T cells are not depleted from BMCs; (ii) no graft failure occurs even if the dose of radiation as the conditioning regimen for allo BMT is reduced to 5Gy x 2; (iii) hemopoietic recovery is rapid; and (iv) the restoration of T-cell functions is quick and complete even in donor-recipient combinations across MHC barriers. We believe that these strategies for allo BMT and organ allografts herald a new era in transplantation, and that they would be helpful in allogeneic HSCT of autoimmune diseases.
 ...
PMID:New strategies for allogeneic BMT. 1293 Dec 48

Donor lymphocyte infusion (DLI) is clinically used for the treatment of malignant tumors. We have found recently that intra-bone marrow-bone marrow transplantation (IBM-BMT) can be used to treat various autoimmune diseases, even when radiation doses are reduced. In addition, recently we have found that IBM-BMT can prevent not only graft failure but also graft-versus-host disease (GvHD). Based on these findings, we attempted to prevent and treat the progression of a tumor (Meth-A cell line: BALB/c-derived fibrosarcoma) by DLI plus IBM-BMT. When the tumors had grown to approximately 10 x 10 mm, the tumor-bearing BALB/c (H-2(d)) mice were irradiated with 5 Gy, and whole spleen cells from C57BL/6J (B6) (H-2(b)) mice (as DLI) were then intravenously injected into the BALB/c mice. Simultaneously, bone marrow cells (BMCs) from B6 mice were injected directly into the bone marrow cavity of the BALB/c mice (IBM-BMT). The tumors decreased in size, but the mice died of GvHD. However, when CD4(+) T-cell-depleted spleen cells were used for DLI, the recipients showed only mild GvHD and survived longer, due to the slow growth of the tumor. In contrast, when CD8(+) T-cell-depleted spleen cells were used for DLI, the recipients showed more severe GvHD than those injected with whole spleen cells. These results suggest that IBM-BMT plus DLI (the depletion or reduction of a certain cell population like CD4(+) T cells) could be helpful to suppress both GvHD and tumor growth.
 ...
PMID:A new strategy for treatment of malignant tumor: intra-bone marrow-bone marrow transplantation plus CD4- donor lymphocyte infusion. 1574 31

The purpose of hematopoietic stem cell transplantation by intra-bone marrow injection (IBM-HSCT) is to facilitate the homing of HSC. It has been recently proven in many animal experiments that different kinds of donor cells could efficiently home and engraft into the bone marrow by IBM-HSCT, which led to the rapid hemopoietic and immune recovery of recipients, preventing the development of GVHD, inducing the donor-specific tolerance in allogeneic organ transplantation, and promoting the survival rate of recipients. In this review, the effect of IBM-BMT and IBM-UCBT, the application of IBM injection technique in the study on HSC's biological characteristics, and its prospect for clinical HSCT were summarized.
 ...
PMID:[Progress of research and application on hematopoietic stem cell transplantation by intra-bone marrow injection--review]. 1658 20

Using small animals (mice and rats) and monkeys, we have found that the combination of bone marrow collection using the perfusion method (PM) and intra-bone marrow-bone marrow transplantation (IBM-BMT) of the collected cells is safe and effective in treating various intractable diseases. Based on these findings, we attempted to apply this method to humans. We report here the first case of a patient (6 years old) with beta-thalassemia major who underwent allogeneic BMT using this new PM + IBM-BMT method. The white blood cell counts of the patient gradually increased to more than 1500/microL by day 47 and continued to increase, reaching the highest level (8600/microL) on day +55. Fluorescence in situ hybridization data on day +33 showed that 98% of the peripheral blood cells were from the donor. Notably, there were no symptoms of graft-versus-host disease (GvHD). However, on day +56, the patient regrettably died of asphyxia resulting from sticky sputum. There was no evidence of infection (in the lung or liver) or GvHD (in the skin) by necropsy. We hope that this case report will help make our new strategies more readily available for the treatment of patients with various intractable diseases.
 ...
PMID:An innovative approach to bone marrow collection and transplantation in a patient with beta-thalassemia major: marrow collection using a perfusion method followed by intra-bone marrow injection of collected bone marrow cells. 1726 5

We have recently found that allogeneic intrabone marrow-bone marrow transplantation (IBM-BMT) + donor lymphocyte infusion (DLI) using CD4(+) cell-depleted spleen cells (CD4(-) cells) can prevent graft-versus-host disease (GvHD) but suppress tumor growth (Meth A: fibrosarcoma) in mice. In the present study, we show that allogeneic IBM-BMT + DLI using CD4(-) cells also has suppressive effects on the growth of colon cancer cells implanted not only in the skin but also in the liver of rats. First, we examined the effects of allogeneic IBM-BMT + DLI on the subcutaneously inoculated ACL-15 (rat colon cancer cell line). Lethally irradiated Fischer rats (F344 rats) were transplanted with T-cell-depleted bone marrow cells (BMCs) from Brown Norway (BN) rats. Simultaneously, DLI was performed using whole spleen cells (whole cells), CD4(+) cell-depleted spleen cells (CD4(-) cells) or CD8(+) cell-depleted spleen cells (CD8(-) cells) of BN rats. Although allogeneic IBM-BMT + DLI suppressed tumor growth, a considerable number of rats treated with allogeneic IBM-BMT + DLI using whole cells or CD8(-) cells died due to GvHD. In contrast, allogeneic IBM-BMT + DLI using CD4(-) cells also suppressed tumor growth, but there was no GvHD. Based on these findings, we next examined the effects of allogeneic IBM-BMT + DLI using CD4(-) cells on the cancer cells implanted in the liver. Allogeneic IBM-BMT + DLI using CD4(-) cells via the portal vein significantly prolonged the survival. These results suggest that allogeneic IBM-BMT + DLI using CD4(-) cells could become a new strategy for the treatment of solid tumors.
 ...
PMID:Allogeneic intrabone marrow-bone marrow transplantation plus donor lymphocyte infusion suppresses growth of colon cancer cells implanted in skin and liver of rats. 1728 50

We have recently found that intra-bone marrow-bone marrow transplantation (IBM-BMT) can be used to prevent graft-versus-host disease (GvHD), even when intensive donor lymphocyte infusion (DLI) is carried out. In the present study, in conjunction with IBM-BMT, allogeneic splenic T cells as DLI were also injected into the bone marrow cavity of lethally irradiated (8.5 Gy) recipients. The extent of GvHD was compared with that of recipients that had received allogeneic IBM-BMT plus i.v. injection of allogeneic T cells (intravenous DLI [IV-DLI]). GvHD in recipients treated with allogeneic IBM-BMT plus IBM-DLI was far milder than in those treated with allogeneic IBM-BMT plus IV-DLI. This was confirmed macroscopically and histopathologically. The frequency of regulatory T cells (Tregs) detected as CD4(+)CD25(+) and CD4(+)Foxp3(+) cells was significantly higher in recipients treated with IBM-BMT plus IBM-DLI than in those treated with IBM-BMT plus IV-DLI. Donor-derived helper T (Th) cells polarized to Th2 type in recipients treated with IBM-BMT plus IBM-DLI, whereas Th1 cells were dominant in recipients treated with IBM-BMT plus IV-DLI. Furthermore, the production of transforming growth factor-beta and hepatocyte growth factor from bone marrow stromal cells was enhanced after IBM-DLI. Thus, IBM-BMT plus IBM-DLI seem to preferentially induce Tregs and Th2, resulting in the prevention of GvHD. Disclosure of potential conflicts of interest is found at the end of this article.
 ...
PMID:Prevention of graft-versus-host disease by intra-bone marrow injection of donor T cells. 1744 64


1 2 Next >>