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

Migration of hemopoietic stem cells via the blood to sites of stem cell need is a principle that becomes established during the embryonic development of hemopoiesis and can be observed in the adult whenever bone marrow transplantations are being performed. The regular presence of stem cells in the peripheral blood lends itself to the study of their collection, storage, and use for transfusion purposes in cases of bone marrow failure. Both in dog and in man, granulocyte-macrophage progenitor cells (CFU-C) can be collected by leukapheresis from the blood in large quantities, particularly if the yield is increased by the administration of mobilizing agents such as dextran sulfate, and appear to be an indicator for the presence of stem cells. For collection and storage, a closed plastic bag system has been developed that allows the safe handling of the cells. The loss of CFU-C from freezing and thawing with DMSO as a cryoprotective agent is only 10%-20%. If frozen and thawed mononuclear leukocytes are transfused into 1200 rad whole-body X-irradiated autologous or allogeneic recipient dogs, a hemopoietic take is observed when 0.2 X 10(5) CFU-C are present among the mononuclear leukocytes (MNC). Graft-versus-host disease can be avoided in the allogeneic situation when a purified CFU-C rich cell fraction is being transfused. In man collection and storage of MNC including CFU-C is feasible and may eventually become a therapeutic tool.
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PMID:Collection, storage and transfusion of blood stem cells for the treatment of hemopoietic failure. 4 49

Hematopoietic growth factors were found as factors stimulating hematopoietic colony formation in in vitro culture system using bone marrow cells as a source of hematopoietic progenitor cells. Erythropoietin, a growth factor stimulating erythroid lineage has now been clinically used as an therapeutic agent for anemia of chronic renal failure. Macrophage colony-stimulating factor (M-CSF), a growth factor stimulating the production of leukocytes including monocytes and neutrophils has been clinically used as an agent for leukopenic patients after anti-cancer therapy. M-CSF improves a survival rate after bone marrow transplantation (BMT) through the reduction of mortality rate associated with BMT such as bleeding, engraftment failure and GVHD. M-CSF accelerated platelet production when injected to thrombopenic patients with solid tumor after anticancer therapy. Granulocyte CSF (G-CSF) is a most powerful agent for various kinds of neutropenia such as neutropenia after anti cancer therapy, neutropenia after BMT, aplastic anemia, chronic neutropenia of children and myelodysplastic syndrome. However, since G-CSF stimulates growth of leukemic cells in vitro, careful observations should be required when clinically used on leukemic patients. Clinical studies of granulocyte-macrophage CSF (GM-CSF) and interleukin 3 (IL-3) are now in progress, in which a promoting activity of leukocyte production of these factors is evaluated.
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PMID:[Clinical application of hematopoietic growth factor (IL-3, G-CSF, GM-CSF, and EPO)]. 127 40

To characterize immune suppressive and hematopoietic features of enriched subsets of human marrow cells, we separated these cells on Percoll density gradients. CD4+ and CD8+ T cells (CD3+) were enriched in the high-density marrow cell fractions and reduced in low-density fractions. CD4-CD8- (CD3+) T cells expressing the alpha beta T-cell antigen receptor were at least 10 times less numerous than the CD4+ and CD8+ T cells in all fractions. Purified populations of the CD4-CD8- alpha beta + T cells obtained by flow cytometry suppressed the mixed leukocyte reaction (MLR). Another population of suppressor cells that expressed neither T-cell (CD3) nor natural killer cell (CD16) surface markers was also identified. The latter cells had the phenotypic and functional characteristics of "natural suppressor" cells. Suppressor cell activity was enriched in the low-density fractions along with hematopoietic progenitors (colony-forming unit-granulocyte-macrophage and burst-forming unit-erythroid). The progenitor and suppressor cell activities were depleted in high-density fractions. The latter fractions made vigorous responses in the MLR. The low-density fractions, which accounted for less than 10% of the input marrow cells, suppressed the MLR and did not respond. Further evaluation of the low-density fractions may be of value in allogeneic bone marrow transplantation due to the reduction of CD4+ and CD8+ T cells and the enrichment of hematopoietic progenitors as well as immune suppressor cells that may inhibit graft-versus-host disease.
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PMID:T-cell subsets and suppressor cells in human bone marrow. 146 27

In murine models, L-leucyl-L-leucine methyl ester (LLME) is effective as an ex vivo purging agent for the prevention of graft-versus-host disease. However, reduction of progenitor cells by LLME raises concerns about the engraftment potential of LLME-treated marrow. Therefore, the effects of LLME on human marrow were investigated. Concentrations of LLME from 0.005 mM to 5 mM were used to examine the effects of LLME on marrow cells. Concentrations of LLME less than or equal to 0.05 mM had no effect on recovery of nucleated marrow cells, mononuclear cells (MNC), myeloid cells or monocytes. At 0.5 mM, nucleated marrow cell recovery was 25%, and MNC recovery was 93%. As determined by cytochemical stains, 0.5 mM LLME eliminated myeloid cells and monocytes. At 0.005 mM, LLME had little effect on marrow progenitor cells; progenitor cell recovery with 0.05 mM LLME was 35% for granulocyte-macrophage colony forming units (CFU-GM) and 23% for erythroid burst forming units (BFU-E) (p less than 0.05 compared to 0.005 mM). At higher LLME concentrations, recoveries of both CFU-GM and BFU-E were less than 1%. To determine if earlier hematopoietic cells remained after treatment with LLME, progenitor cell experiments were repeated with 0.5 mM LLME using recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) or recombinant human interleukin 3 (rhIL-3) plus or minus recombinant human mast cell growth factor (rhMGF) as sources of colony-stimulating activity. In this system, both IL-3 and GM-CSF induced rare progenitor cells (less than 6/5 x 10(4) cells plated).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of L-leucyl-L-leucine methyl ester on human marrow and protection of progenitor cells by IL-1. 164 32

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) secreted by a hepatoma cell line, HA22T/GVH, was purified and assessed for its effects in vivo on blood leukocytes and bone marrow granulocyte-macrophage progenitor cells (CFU-GM) in ICR mice pretreated with a sublethal dose of cyclophosphamide (cytoxan). The hGM-CSF preparations were natural and had no detectable endotoxin. Five days after the administration of 300 mg/kg cytoxan, severe leukopenia with marked myelopoietic suppression was induced. The cytoxan-treated mice were then injected intraperitoneally with 10,000 units of purified hGM-CSF/mouse daily for three days. Leukopenia was totally abrogated and the leukocyte number greatly increased to a level 2- to 3-fold higher than in GM-CSF-uninjected mice. Differential white cell count showed that the subpopulations of leukocytes responsive to hGM-CSF stimulation were mainly of neutrophils and monocytes, while the lymphocytes remained unaffected. Meanwhile, in the bone marrow, hGM-CSF administration induced an apparent (3-fold) increase in the number of myeloid progenitor cells, CFU-GM. However, the effect in vivo of a single hGM-CSF injection could only maintain for 48 hrs. In addition, the loss in body weight caused by cytoxan was less in the mice with subsequent hGM-CSF than those without CSF. These results suggest that injection of GM-CSF can effectively reconstitute the cytotoxic drug-damaged myelopoiesis without apparent in vivo toxic reaction.
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PMID:In vivo stimulation of myelopoiesis in cyclophosphamide-treated mice by purified human GM-CSF. 165 33

Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.
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PMID:Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. 174 91

There is a well-documented correlation between the number of T-lymphocytes in the bone marrow graft and subsequent development of acute graft-versus-host disease after allogeneic bone marrow transplantation. The incidence of acute graft-versus-host disease may be decreased with elimination of mature T-lymphocytes from the bone marrow graft. We have developed an immunomagnetic separation procedure using an avidin-based magnetic affinity cobalt colloid. Bone marrow cells were incubated with a combination of CD2, CD3, CD4, and CD8 monoclonal antibodies. The cells were washed and then incubated with the biotinylated, affinity-purified IgG fraction of goat anti-mouse immunoglobulins followed by an avidin-based magnetic affinity colloid. The cells were then run through a high-magnetic gradient separation column utilizing an external samarium cobalt magnet. The number of residual T-lymphocytes was assessed by limiting dilution analysis of clonogenic T-lymphocytes. This procedure produces an approximately 1.7-log reduction of antibody-reactive cells with 45% recovery of hematopoietic progenitors (granulocyte-macrophage colony-forming cells, GM-CFC). This causes a reduction of T-lymphocytes in the bone marrow graft to approximately 5 x 10(5) cells/kg body weight.
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PMID:Purging of T-lymphocytes with magnetic affinity colloid. 230 17

Factors which may influence haematopoietic recovery after allogeneic bone marrow transplantation were analysed. Forty-six evaluable patients transplanted with lymphocyte-depleted marrow for acute lymphoblastic leukaemia, acute non-lymphoblastic leukaemia, chronic myeloid leukaemia, myelodysplastic syndrome and severe aplastic anaemia were studied. The median time for platelet recovery to greater than or equal to 20 and to greater than or equal to 50 x 10(9)/l was 21 (9-72) and 26 (11-86) days respectively. The neutrophil recovery to greater than or equal to 0.5 x 10(9)/l and the leucocyte recovery to greater than or equal to 1.0 x 10(9)/l was 19 (8-47) and 18 (6-47) days respectively. No relation was found between the number of infused granulocyte-macrophage colony-forming cells, erythroid burst-forming cells, diagnosis, graft-versus-host disease, antibiotic administration and recovery. Addition of a continuous 6-day infusion of anthracyclines to the conditioning regimen delayed the median recovery of platelets, neutrophils and leucocytes by 7-9 days. Fever during aplasia also inhibited haematopoietic recovery. It is speculated that leakage of intracellular anthracyclines after bone marrow infusion or fever secondary to anthracyclines-induced oromucositis is responsible for the delayed bone marrow recovery.
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PMID:Anthracyclines added to the conditioning regimen for allogeneic bone marrow transplantation are associated with a slower haematopoietic recovery. 265 Jul 86

We have evaluated the transplantation potential of bone marrow stem cell concentrates isolated from the 40/60% interface of discontinuous Percoll gradients. This mononuclear fraction is free from platelets and depleted of granulocytes, and contains the majority of granulocyte-macrophage colony-forming cells (GM-CFC), erythroid burst-forming units (BFU-E), and granulocyte, erythroid, macrophage, megakaryocyte colony-forming cells (GEMM-CFC) in less than 10% of the cell number of the original buffy coat. This preparation allows further manipulation without the clumping and cell loss associated with buffy coat cell preparations. Cells isolated by this technique were evaluated for hematopoietic restoration potential in 14 patients who received allogeneic bone marrow transplants as supportive therapy after high dose cytoreduction to treat leukemias or lymphoma. The number of nucleated cells infused varied from 1.6-5.5 X 10(7)/kg, and the number of GM-CFC infused ranged from 0.4 to 3.7 X 10(5)/kg. There was an inverse relationship between the time to recovery of granulocytes and platelets and the number of GM-CFC infused when fewer than 10(5) GM-CFC/kg were transplanted. Above this dose, there was recovery within 10-15 days after transplantation. The stem cell-enriched fraction contained 30-40% of the original number of T lymphocytes, and acute graft-versus-host disease was observed in seven of these patients.
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PMID:Clinical application of Percoll gradient-separated bone marrow. 290 72

Fetal liver transplants (FLT) were carried out in 25 beagles under various conditions. Graft recipients were prepared with fractionated total body x-irradiation (TBI) of 3 X 6 Gy or 2 X 6 Gy and rescued with cryopreserved fetal liver cells (FLC) from 51- to 52-day-old or 43- to 46-day-old, DLA-identical siblings or DLA-haploidentical, homozygous half-siblings. In all groups, FLC grafts contained comparable numbers of granulocyte-macrophage progenitor cells. Initial engraftment was achieved in all dogs. However, low TBI dose and DLA haplotype disparity between donor and recipient were associated with graft failure in 1/3 and 2/9 recipients, respectively, within 10-16 days of treatment. Lectin-responsive host type lymphocytes circulated for more than 5 weeks, whereas bone marrow metaphases were always of donor sex. Reduced TBI dose and young donor age were associated with delayed granulocyte recovery. Moreover, circulating platelets and total lymphocytes as well as T and B-cell numbers and rose more slowly in recipients of immature FLC grafts than in the other groups. Delayed cutaneous hypersensitivity reactions were normal one year after FLT, whereas the IgM component of the hemagglutinin response to sheep red blood cells was depressed. In mixed leukocyte culture, chimeric lymphocytes were tolerant to host antigens. Nonetheless, clinical and histological signs compatible with low-grade graft-versus-host disease were recorded in 10 or 25 animals. Thus FLT in dogs could be carried out, even across DLA barriers, without severe graft-versus-host disease. However, a low pretransplant TBI dose, incomplete DLA match and young age of the fetal donor were associated with graft rejection and protracted restoration of hemopoiesis and immune functions.
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PMID:Variation of treatment conditions alters the outcome of fetal liver transplantation in dogs. 296 15


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