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)

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

Bone marrow transplantation to reconstitute defective hematopoietic cell lines in children with congenital defects is limited by donor availability, graft rejection, and graft-versus-host disease (GVHD). These problems can be eliminated by transplanting normal preimmune fetal hematopoietic stem cells (HSC) into an unrelated preimmune fetal recipient. We show here that injections of allogeneic fetal stem cells into preimmune fetal lambs and monkeys result in long-term stable hematopoietic chimerism. HSCs harvested from the livers of preimmune fetal sheep and monkeys when injected into the peritoneal cavity of young unrelated fetal sheep and monkey recipients results in stable, long-term postnatal hematopoietic chimerism involving lymphoid, erythroid, and myeloid cells of donor origin. Donor cell engraftment was achieved without the use of cytoablative procedures and without the development of GVHD.
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PMID:Hematopoietic chimerism in sheep and nonhuman primates by in utero transplantation of fetal hematopoietic stem cells. 168 May 4

Human fetal liver hemopoietic stem cells were transplanted into preimmune fetal sheep. Significant numbers of recipient fetuses showed evidence of engraftment of human stem cells which responded in vivo to human-specific hemopoietic growth factors. The chimerism has persisted now for > 2 years without significant graft loss. No evidence of GVHD has been noted. Successful engraftment was associated with the expression of human erythroid, myeloid, and lymphoid differentiation. This xenograft model offers useful possibilities for the study of the biology of human hemopoiesis in vivo.
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PMID:Successful stable xenograft of human fetal hemopoietic cells in preimmune fetal sheep. 168 60

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

Cyclosporin A is used to prevent graft-versus-host disease (GvHD) following bone marrow transplantation (BMT) and it has been implicated in reducing the time to engraftment for leukaemia and aplastic anaemia patients. To evaluate the effect of cyclosporin A on engraftment, the proliferative capacity of bone marrow progenitors (CFU-E, CFU-F and CFU-C) was assessed both in vitro and following treatment with cyclosporin A over a 9-week period using an animal model. Cyclosporin had a differential effect on the haemopoietic progenitors, with the myeloid series unaffected at therapeutic concentrations. Both erythroid and stromal progenitors were significantly inhibited at similar concentrations. The mechanism by which cyclosporin A enhances engraftment remains unclear; however, it is not mediated by enhancing any of the haemopoietic progenitors.
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PMID:Inhibitory effect of cyclosporin A on erythroid and stromal colonies. 195 87

We report a patient who had abrupt onset of pure red cell aplasia (PRCA) induced by B19 parvovirus during allogeneic bone marrow transplantation (BMT). A 14-year-old girl with APL in complete remission was admitted in February 1988, for the purpose of BMT. She was received marrow from HLA identical sister on March 17, 1988 (day 0). She received 120 mg/kg cyclophosphamide and 12 Gy total body irradiation for conditioning of BMT. For graft-versus-host disease (GVHD) prophylaxis she was given cyclosporine and short term methotrexate. She did not develop acute GVHD after BMT, but on the day 28 a bone-marrow aspirate revealed findings of PRCA. During this course the number of white blood cell and platelet favorably recovered. B 19 parvovirus DNA was detected in the serum of the day 30 and day 42. Antihuman B 19 parvovirus (HPV) antibody titers were increased: the values of anti-HPV IgM were suddenly elevated and those of anti-HPV IgG were elevated. Serum on the day 42 inhibited erythroid progenitors (CFU-E, BFU-E) but not inhibited myeloid progenitors (CFU-C). A reticulocyte count recovered on the day 50. As the patient was HPV-IgG negative prior to BMT and the donor was HPV-IgG seronegative, the source of infection may be platelet transfusion (day 7 through 14).
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PMID:[Pure red cell aplasia induced by B19 parvovirus during allogeneic bone marrow transplantation]. 217 87

To evaluate the potential of in-utero transplantation of fetal haemopoietic stem cells (HSCs) for permanent engraftment as a treatment of congenital haemoglobinopathies, fetal rhesus monkeys were transplanted with HSCs derived from fetal livers. Five pregnant monkeys (60-62 days' gestation) were given an in-utero intraperitoneal injection of fetal liver cells (10(8)-10(9) cells/kg estimated fetal recipient body weight) derived from opposite sex donors at 59-68 days' gestation. Engraftment was confirmed by karyotype analysis of peripheral blood leucocytes and bone marrow; cells of donor sex were found among the recipient cells. Donor cell engraftment was apparent in four of five in-utero HSC transplant recipients at birth. Engraftment involved lymphoid (2.9-8.0% donor cells), erythroid (5.3-12.5%), and myeloid (8.5-15.4%) lineages and has persisted for up to 2 years without evidence of graft-versus-host disease.
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PMID:In-utero transplantation of fetal liver haemopoietic stem cells in monkeys. 257 63

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

Six patients underwent allogeneic bone marrow transplantation (BMT) for treatment of acute non-lymphocytic leukemia. Hemopoietic reconstitution after BMT was monitored by peripheral blood counts, counts of bone marrow cellularity, bone marrow pictures, and clonal assays for myeloid progenitors (CFU-GM). Although bone marrow samples were markedly hypocellular on day 7 posttransplant, myeloid and erythroid elements were seen in 5 of 6 patients. Peripheral blood recovery of these 5 patients was achieved by third weeks posttransplant. The values of (CFU-GM) per 1 X 10(5) marrow mononuclear cells reached normal values on day 7 in two patients and significantly increased by day 28 in a patient. After day 84 the values of (CFU-GM) were remained almost normal and they had no relation to the occurrence of chronic graft-versus-host disease (GVHD). But in patients with chronic GVHD, marrow (CFU-GM) values were significantly increased on day 7 and day 14. These results suggest that marrow (CFU-GM) values by day 28 may predict the occurrence of chronic GVHD.
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PMID:[Recovery of marrow myeloid progenitors (CFU-GM) after bone marrow transplantation, especially associated with chronic graft-versus-host disease (GVHD)]. 267 38

The transfer of lpr BM stem cells into lethally irradiated non-lpr recipients (including the congenic MRL/+ differing only at the lpr locus) causes GVHD characterized by a wasting syndrome. In this study we investigated the interaction between the autoimmune (lpr) and normal (A-Thy) B, T, and RBC cell lineages in two types of radiation chimeras: MRL/lpr plus A-Thy----(MRL/lpr X A-Thy)F1 and MRL/+ plus A-Thy----(MRL/lpr X A-Thy)F1. Analysis of B cell repopulation by competitive RIA of serum Igh-1 allotype showed that both the MRL and the A-Thy donor cells initially engrafted. However, by 2 to 4 mo post-transplantation the normal A-Thy allotype was barely detectable (reduced greater than 2 orders of magnitude), whereas the autoimmune MRL/lpr allotype persisted at normal levels. Similarly, investigation of the donor origin of peripheral blood T cells by two-color flow cytometry showed that by 8 mo post-transplantation normal A-Thy T cells had been eliminated and only MRL/lpr T cells were present in the circulation. In contrast, erythrocytes from both the MRL/lpr and A-Thy donor strains successfully engrafted the F1 recipients and persisted until the termination of the study. Control chimeras transplanted with a mixture of MRL/+ plus A-Thy BM were stably engrafted with both donor strains in both the erythroid and lymphoid populations. Additional experiments in which either B6/lpr or MRL/lpr (and B6/+ or MRL/+ control) BM cells were transferred into (MRL/lpr X B6/+)F1 and (MRL/lpr X B6/lpr)F1 recipients demonstrated that the development of GVHD was not simply due to increased alloreactivity by the lpr donor cells. In these chimeras only the recipients heterozygous (but not homozygous) for the lpr gene developed lpr-GVHD, although both types of recipients had identical genotypes except at the lpr locus.
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PMID:Selective elimination of non-lpr lymphoid cells in mice undergoing lpr-mediated graft-vs-host disease. 288 17


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