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)

The effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was evaluated in 37 patients with marrow graft failure after allogeneic (n = 15), autologous (n = 21), or syngeneic (n = 1) bone marrow transplantation. rhGM-CSF was administered by 2-hour infusion at doses between 60 and 1,000 micrograms/m2/d for 14 or 21 days. At doses of less than 500 micrograms/m2, rhGM-CSF was well-tolerated and did not exacerbate graft-versus-host disease in allogeneic transplant recipients. No patient with myelogenous leukemia relapsed while receiving rhGM-CSF. Twenty-one patients reached an absolute neutrophil count (ANC) greater than or equal to 0.5 x 10(9)/L within 2 weeks of starting therapy while 16 did not. None of seven patients who received chemically purged autologous marrow grafts responded to rhGM-CSF. The survival rates of GM-CSF-treated patients were significantly better than those of a historical control group.
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PMID:Use of recombinant human granulocyte-macrophage colony-stimulating factor in graft failure after bone marrow transplantation. 219 92

A randomized, double-blind placebo-controlled phase III clinical trial was performed to study the effects of human urinary macrophage colony-stimulating factor (hM-CSF) after allogeneic and syngeneic bone marrow transplantation (BMT) in 60 hM-CSF treated and 59 placebo control patients. HM-CSF was administered at a daily dose of 2 x 10(5) units/kg from day 1 to day 14 after BMT. Significant differences between hM-CSF and control patient were found in the recovery time to greater than 0.5 x 10(9) granulocytes/l and the survival rate during the initial 120 d without retransplantation. There was no difference in the incidence or grade of graft-versus-host disease (GVHD). There was no difference in the rate of leukaemic relapse at 24-36 months after BMT in patients with acute lymphocytic, acute nonlymphocytic, or monocytic leukaemia. The results of this trial show that human M-CSF improves the outcome of BMT without any influence on the occurrence of leukaemic relapse or GVHD.
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PMID:Double-blind test of human urinary macrophage colony-stimulating factor for allogeneic and syngeneic bone marrow transplantation: effectiveness of treatment and 2-year follow-up for relapse of leukaemia. 226 13

The clonal culture of bone marrow cells is a usefull method for the investigation of the normal and the disturbed haemopoiesis. In the field of bone marrow purging for autologous bone marrow transplantation and T-cell elimination for GVHD-prophylaxis, the bone marrow culture is used to control the bone marrow processing. The use of pure CSF-preparations and cell separators make this technique well reproducible.
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PMID:[The conditions and clinical feasibility of technics of bone marrow stem cell culture]. 248 19

Recently, treatment of leukemia has shown remarkable progress. Development of new antileukemic drugs, improvements in supportive care and rapid progress in bone marrow transplantation have resulted in considerable changes in responses in refractory leukemia. Chemotherapy for Acute leukemia: By the introduction of Mitoxantrone and etoposide and a new combination chemotherapy including them, a high remission rate of acute leukemia is obtained, but because of the high relapse rate the 5-year survival rates in our center were 20% for adult ALL and 18% for ANL. In order to reduce the relapse rate, a new regimen containing intensive consolidation treatments is now being studied in a nation-wide cooperative study. BMT: In 1987, 160 BMTs including 75 acute leukemia and 28 CML, were registered in Japan. The improvements in the management of graft versus host disease (GVHD) and infections in the granulocytopenic period has contributed to the marked increase in the long-term survival rate after BMT. In our center the long-term survival rate rose from 20% before 1984 to 85% after 1985. Colony stimulating factor: Macrophage-colony stimulating factor (M-CSF) and granulocyte colony stimulating factor (G-CSF) were studied in Japan. In the double-blind placebo controlled study of M-CSF, a significantly shorter duration of granulocytopenia, as well as a significantly lower rate of failure of BMT (i.e., death or retransplant) was observed. In the phase II study of G-CSF, a rapid recovery of granulocytes after chemotherapy or BMT and marked efficacy on infection in granulocytopenic patients were observed.
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PMID:[Multidisciplinary treatment of leukemia]. 265 20

The aim of this study was to test whether colony stimulating factors (CSF) and other cytokines facilitate the recovery of a variety of immunohematopoietic functions in lethally irradiated mice undergoing bone marrow transplantation (BMT). Two experimental systems were employed: (a) lethally irradiated mice transplanted with syngeneic or T cell-depleted semi-allogeneic bone marrow (BM) cells (0.1-10 x 10(6)), subsequently treated by multiple doses of cytokines; and (b) lethally irradiated mice transplanted with BM cells that had previously been cultivated with cytokines. The cytokines used were: pure natural mouse interleukin-3 (IL-3); recombinant mouse granulocyte-macrophage CSF (rGM-CSF); recombinant human interleukin-2 (rIL-2); and crude cytokine preparations obtained from the culture supernatants of murine leukemia WEHI-3b cells (containing mainly IL-3), and of phorbol myristate acetate (PMA)-stimulated EL4 leukemia cells and concanavalin A-stimulated rat splenocytes (each containing a multitude of cytokines). For BM cultures (1-9 days), the cytokines were used at a dosage of 1-100 U/ml; for in vivo treatment, 2 x 10(2)-5 x 10(4) units were administered intraperitoneally and subcutaneously at different schedules for varying periods (1-3 weeks). The following parameters were tested 1-10 weeks post-BMT: white blood cell count, colony formation in agar and in the spleen of lethally irradiated mice, proliferative responses to mitogens and alloantigens, allocytotoxicity and antibody production (serum agglutinins and plaque-forming cells) against sheep red blood cells. Under appropriate conditions, cytokine treatment either in vitro or in vivo significantly enhanced (2- to 50-fold compared with controls) most functions tested at 2-8 weeks post-BMT, and shortened the time interval required for full immunohematopoietic recovery by 2-5 weeks. In recipients of semi-allogeneic, T lymphocyte-depleted BM no evidence of graft-versus-host disease was found. It is suggested that judicious application in vitro and/or in vivo of certain pure cytokines (e.g. GM-CSF, IL-3) or cytokine 'cocktails' might be beneficial in enhancing hematopoiesis and in the treatment of immunodeficiency associated with BMT.
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PMID:In vitro and in vivo cytokine-induced facilitation of immunohematopoietic reconstitution in mice undergoing bone marrow transplantation. 304 95

This report reviews the diagnostic significance of immune markers, their relationship to patient outcome, and the therapeutic uses of monoclonal antibodies (MoAbs) in acute leukemia. Immunophenotyping allows for rapid and reproducible diagnosis in the majority of cases of acute leukemia. It is of particular importance in recognizing the major immunologic subclasses of acute lymphoblastic leukemia (ALL), and in identifying subtypes of acute myeloblastic leukemia (AML) which cannot be differentiated by morphology and cytochemistry alone, such as FAB M0 or M7. Immune marker analysis has been used to detect minimal residual disease in patients' bone marrow and CSF after treatment. However, the presence of leukemia-associated phenotypes on small numbers of normal cells may reduce the sensitivity of detection in some cases. The prognostic value of immune markers in AML is limited. In ALL, the prognostic significance of the different immunophenotypic subtypes has been lessened by modern treatment protocols. The relationship of mixed-lineage or biphenotypic antigen expression to patient outcome in both AML and ALL is unclear. Therapeutic applications of MoAbs in acute leukemia include immunologic techniques for purging malignant cells from autografts prior to transplantation, T-lymphocyte depletion from allografts as a strategy to reduce graft-versus-host disease, and the use of flow cytometry to monitor the timing and extent of leukapheresis in peripheral stem cell transplantation. MoAbs have also enabled the recent development of transplantation protocols using positively-selected CD34+ stem cells.
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PMID:Monoclonal antibodies in the management of acute leukemia. 748 80

The effects of rhG-CSF on peripheral blood lymphocytes and lymphocyte populations in the apheresis product has been determined in 13 individuals (11 autografts and 2 normal donors) who had peripheral blood mononuclear cells (PBMCs) collected on days 3, 4, and 5 of administration of rhG-CSF 16 micrograms/kg/day x 5 days. The absolute number of CD34+ cells increased 9 and 25-fold from pretreatment levels after 4 and 5 days of rhG-CSF, respectively. All patients demonstrated an increase in CD3, CD4, CD8, CD19 and CD20 lymphocytes after 3 days of rhG-CSF with T lymphocytes increasing 1.5-2.0 times baseline by day 3 or rhG-CSF administration. All lymphocyte phenotypes returned to below pretreatment levels on days 4 and 5 of rhG-CSF administration. The ratio of CD4/CD8 lymphocytes was not affected by rhG-CSF. Collection of PBMCs on 3 consecutive days yielded a mean of 8.77 x 10(8) CD34 cells, 14.03 x 10(10) total nucleated cells and 3.17 x 10(10) CD3 lymphocytes. These data suggest that rhG-CSF mobilized PBMCs have approximately one log more T cells than marrow and the effect of rhG-CSF on the quantity and phenotype of lymphocytes is minimal. Strategies for coping with an increased incidence of GVHD, if it occurs, could include the utilization of both methotrexate and cyclosporine as immunoprophylaxis, selective T cell depletion or CD34 positive selection.
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PMID:Lymphocyte content in peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor. 751 58

Hematopoietic growth factors have been shown to be effective in reducing the period of neutropenia after autologous bone marrow transplantation (BMT). Initial concerns over potential aggravation of graft-versus-host disease (GVHD) and increase in the incidence of relapse in patients with myeloid leukemias influenced the number of studies using hematopoietic growth factors after allogeneic BMT. We report the experience with 50 patients treated at a single institution using granulocyte colony-stimulating factor (G-CSF) after allogeneic sibling (n = 30) and matched unrelated (n = 20) BMT. The time to an absolute neutrophil count > or = 500/microL was significantly faster in patients who received G-CSF and cyclosporine and prednisone for GVHD prophylaxis when compared with historical control patients receiving the same GVHD prophylaxis (10 v 13 days, P < .01). A similar accelerated myeloid engraftment was observed for those patients who received the addition of methotrexate for GVHD prophylaxis when compared with historical control patients receiving the same GVHD prophylaxis regimen (16 v 19 days, P < .05). The median time to engraftment for patients receiving a matched unrelated BMT and G-CSF was 17 days (range 13 to 26). We did not observe any increase in GVHD or early mortality in the matched related sibling BMT. The incidence of acute GVHD in the matched unrelated BMT recipients was also low at 21%; however, 9 patients (45%) died within 100 days of the date of BMT, similar to the experience reported with granulocyte-macrophage CSF. This study confirms the efficacy of G-CSF in accelerating myeloid engraftment after allogeneic matched sibling BMT. The higher early mortality associated with patients receiving matched unrelated BMT suggests that randomized controlled trials using G-CSF after allogeneic BMT should be performed.
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PMID:Granulocyte colony-stimulating factor after allogeneic bone marrow transplantation. 752 Jul 82

The major immunological reactions after an allogeneic bone marrow transplantation (BMT) are graft rejection and graft-versus-host disease (GVHD). GVHD can be prevented by T-cell depletion of the allogeneic BM graft, but the beneficial effect of T-cell depletion on the incidence of GVHD is counterbalanced by a higher incidence of graft failure. One option for the prevention of graft rejection after T-cell-depleted BM grafts is the administration of cytokines. Before applying cytokines after an allogeneic BMT, we considered it desirable to learn whether cytokines would alter the susceptibility of donor BM cells to host T cells. An in vitro assay was developed to investigate the role of the cytokines interleukin-1 (IL-1), IL-3, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) on the interaction between allosensitized, cytotoxic-T cells (CTLs) and T-cell-depleted BM cells. CTLs primed against the BM donor suppressed the formation of colonies consisting of granulocytes and macrophages (colony-forming unit GM). Colony formation was not inhibited by CTLs sensitized against a third party. Accordingly, the number of colonies scored in cocultures with CTLs sensitized to third party antigens were designated as 0% inhibition. A 66% inhibition of colony formation was observed for untreated BM cells at an effector:target (E:T) ratio of 1:1. Pretreatment of the BM cells with the cytokines G-CSF, GM-CSF, IL-1, and IL-3 resulted in a 38% (P = .001), 53%, 66%, and 68% inhibition of colony formation, respectively, at E:T ratios of 1:1. G-CSF reduced the susceptibility of BM cells over a range from 4:1 to 1:16 (E:T ratios). GM-CSF had only significant influence at the lower E:T ratios (1:4 and 1:16). These in vitro data indicate that G-CSF could protect BM cells from killing by allosensitized CTLs and suggest that administration of these cytokines might potentially reduce the susceptibility of T-cell-depleted allogeneic BM grafts to host T-cell-mediated rejection.
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PMID:Granulocyte colony-stimulating factor (CSF) but not interleukin-1 (IL-1), IL-3, and granulocyte-macrophage CSF protect bone marrow progenitor cells from suppression by allosensitized cytotoxic T cells. 752 93

The use of the recombinant hematopoietic growth factors G-CSF and GM-CSF have shortened the period of neutropenia, or avoided this problem, in many cancer patients who have received cytotoxic therapy. Although these benefits have been particularly striking in the autologous bone marrow and/or autologous peripheral blood progenitor cell transplant setting, most data suggest that the use of G-CSF and GM-CSF only marginally enhance recovery of the neutrophil count when administered after allogeneic bone marrow infusion. Furthermore, in the allograft setting these expensive agents have not provided benefit in the form of enhanced platelet count recovery, lessening the incidence of graft-versus-host disease, or improvement in overall survival. These data do not justify routine widespread use of G-CSF and GM-CSF and suggest that these agents should be reserved for patients who experience delay in engraftment after allogeneic bone marrow infusion. Administration of erythropoietin, on the other hand, may reduce the need for homologous red blood cell transfusions, and may increase the safety margin for both the allogeneic bone marrow recipient and as well as the donor. Recombinant hematopoietic growth factors targetted specifically to enhance platelet recovery after transplantation (such as interleukin-3, interleukin-6, and interleukin-11) have shown promise after autotransplantation and after conventional dose chemotherapy, and likely will be evaluated in the allogeneic transplant patient.
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PMID:Clinical use of hematopoietic growth factors in allogeneic bone marrow transplantation. 752 6


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