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)

A 5-month-old Amish infant boy with chronic granulomatous disease underwent bone marrow transplantation from his 5-year-old, histocompatible brother after a preconditioning regimen of busulfan 2 mg/kg/day for 4 days, followed by cyclophosphamide 50 mg/kg/day for 4 days. At the time of bone marrow transplantation, he was free of infection, and remained so throughout the course of the transplant. He was engrafted promptly, with complete reversal of the neutrophil function defect and no sign of graft-versus-host disease. This was followed by loss of the erythroid graft and deterioration in neutrophil function over a period of 9 months. Sixteen months after transplantation, he is free of infection and growing normally, with essentially no evidence for neutrophil engraftment.
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PMID:Bone marrow transplantation in chronic granulomatous disease. 637 46

We describe a family of six rat monoclonal antibodies which appear to recognize identical or closely related determinants present on virtually all mature human lymphocytes and monocytes, but absent from other blood cells including myeloid and erythroid colony-forming cells. Four IgM antibodies and one IgG2a fix human complement; one IgG2c antibody does so only poorly. All of the antibodies react with lymphocytes from baboons, rhesus and cynomolgus monkeys. However, in all baboons and rhesus monkeys tested, and some cynomolgus monkeys, they also recognize red cells. Nevertheless, in other cynomolgus monkeys reactivity is with lymphocytes only, so these animals will be suitable models for testing the effects of the antibodies in vivo. The antibodies described here could be useful for in vitro removal of lymphocytes from allogeneic marrow grafts (to prevent graft-versus-host disease) or malignant lymphoid cells from autologous grafts (for treatment of leukaemia) and may also find application as general immunosuppressants and for immunotherapy of leukaemia.
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PMID:Removal of T cells from bone marrow for transplantation. Comparison of rat monoclonal anti-lymphocyte antibodies of different isotypes. 639 85

Human bone marrow was fractionated by counterflow centrifugation into 16 fractions with increasing cell size. Three distinct subpopulations could be recognized: small lymphocytic cells, medium-sized nucleated erythroid cells and large myeloid elements. DNA-flowcytometry and 3H-thymidine uptake showed that within the erythroid and myeloid cell populations counterflow centrifugation separates each population according to the cell cycle phase. Hypotonic treatment of bone marrow for removal of the erythroid nucleated cells resulted in a complete abrogation of the proliferating erythroid cell population. Counterflow centrifugation also separates the small non-proliferating myeloid and erythroid committed stem cells from the larger proliferating stem cells. It appeared feasible to separate the small lymphocytic cells from the majority of BFU-E and CFU-GM, due to the larger size of the proliferating normoblasts and the committed progenitor cells. Elimination of the mature lymphocytes from the haematopoietic stem cells by counterflow centrifugation may offer an alternative approach to the prevention of graft versus host disease (GvHD).
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PMID:Separation of human bone marrow by counterflow centrifugation monitored by DNA-flowcytometry. 647 34

Noninbred rabbits that were characterized for antigens of the major histocompatibility complex (MHC) by serological (RLA) typing were used as adult donors and newborn recipients of lymphoid cells. The majority of RLA-heterozygous (CE) animals transplanted with homozygous type C cells died before 7 weeks of age with clinical and histological signs of graft-versus-host disease, but a small proportion survived with their lymphoid and erythroid systems completely converted to phenotypes of the donors. Takeover of the host's hematopoietic system was associated with a transient hyperimmunoglobulinemia, mostly of donor origin, and with a striking and permanent abrogation of allotype suppression on the part of donor lymphocytes. In contrast, as shown in this and in earlier publications, recipients of RLA-compatible cells become stable B lymphocyte chimeras without detectable T cells or erythrocytes of donor type. In the latter case allotype suppression is neither established in the recipient nor abrogated in the donor's cells.
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PMID:Graft-versus-host reactions and abrogation of allotype suppression following histoincompatible lymphoid cell transfers in rabbits. 661 Feb 34

The complement-dependent cytotoxicity of monoclonal T-cell antibody (T101) for normal and abnormal hemopoietic progenitors was assessed. T101 demonstrated toxicity for normal T-colony-forming cells from peripheral blood and bone marrow. Cytotoxicity was absent for normal peripheral blood and bone marrow granulocytes/macrophage (CFU-C) and erythroid (BFU-E) progenitors. The antibody was also not toxic for peripheral blood blast progenitors from patients with acute myelogenous leukemia (AML). These studies indicate the absence of the antigen defined by T101 (T65) from normal progenitor cells and from blast progenitors in patients with AML. T101 may be used in the treatment of T-cell malignancies and in the prevention of graft-versus-host disease (GVHD) without damage to normal progenitor cells.
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PMID:Human T-cell antigens defined by monoclonal antibodies. Absence of T65 on committed myeloid and erythroid progenitors. 696 3

Complement-mediated cytolysis has been used to remove T-lymphocytes from suspensions of human peripheral blood and bone marrow. Selective T-cell removal was investigated by three monoclonal antibodies. OKT3, MBG6 and OKT11A. All three removed greater than 90% of T-cells but combinations were necessary to kill greater than 99% of T-cells in vitro. The macrophage-granulocyte and erythroid colony forming cells of the bone marrow were spared. The method can be applied on bulk BM samples during clinical BM transplantation and will be useful to establish whether the virtually complete removal of T-lymphocytes totally prevents transplant associated graft-versus-host disease in man.
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PMID:Elimination of T-lymphocytes from human bone marrow with monoclonal T-antibodies and cytolytic complement. 697 74

We studied the role of ABH antigens in determining graft outcome in 104 patients who received HLA-identical bone marrow transplants for aplastic anaemia and acute leukaemia. ABH compatibility had no significant effect on incidence of graft rejection or graft-versus-host disease. Fifteen recipients ahd pre-transplant antibodies against donor ABH antigens. In 14, large volume plasma exchange and transfusion of donor-type erythrocytes was successful in reducing the antibody titre to low or undetectable levels. In one patient, plasma exchange was unsuccessful and red cells were removed from the marrow inoculum by unit gravity sedimentation. This approach prevented transfusion reaction, and permitted engraftment of all haematopoietic cell lines despite persistently elevated antibody titres. Parallel in vitro studies revealed that antibodies to ABH antigens failed to inhibit the growth of progenitor cells committed to both granulocyte-macrophage (CFU-C) and erythroid (BFU-E) development. These findings indicate that ABH-antigens are not clinically important transplantation antigens and suggest that ABH antigens are not operationally present on hematopoietic stem cells.
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PMID:ABH antigens and bone marrow transplantation. 699 Sep 58

Fifteen S/S children with severe SCD were transplanted with marrow from HLA identical siblings. All developed frequent (> 3/y) vaso-occlusive crises (VOC) associated with recurrent acute chest syndrome episodes (n = 10), osteitis (n = 3), osteonecrosis (n = 3), strokes (n = 3) or frequent massive deglobulisation (n = 2). Two children undergone splenectomy, two were chelated and two had an erythroid allo-immunization. Ethnic origins were from various countries in Africa (n = 11), North-Africa (n = 3) or West Indies (n = 1). At BMT, they were 2y 3m to 14y 9m old (mean: 8y 7m). Donors were AS (n = 11) or AA (n = 4). At first, various conditioning regimens were used consisting of busulfan (BU) plus Cyclophosphamide (CY) at different doses: CY:200 mg/kg (n = 13) or 260 mg/kg (n = 2); BU: 14 mg/kg (n = 1), 16 mg/kg (n = 9), > 16 mg/kg (n = 5); one patient received also TLI and the last two anti-thymoglobulin (ATG): 20 mg/kg. GVHD prophylaxis was CSA alone (n = 4) or CSA plus short-term MTX (n = 11). Median follow-up is 28 months (5 m to 53 m). All patients had an engraftment (d12 to d32) with a stable total chimerism in 10/14 patients. In the 4 others, partial chimerism was observed: one patient had a early and progressive rejection of his graft but is doing very well (35 m follow-up) without any manifestation of SCD, with a high stable 22% Hb F level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of severe forms of sickle cell anemia with bone marrow allograft: French experience (15 cases). SFGM]. 833 53

9-beta-D-Arabinofuranosylguanine (araG), an analog of deoxyguanosine which is not degraded by purine nucleoside phosphorylase, has been previously shown in in vitro studies by our laboratory to be effective in purging malignant T cells from human bone marrow (1). We now describe studies in a murine model of T-cell acute lymphoblastic leukemia (ALL) in which we tested whether bone marrow, contaminated with malignant T cells and purged ex vivo with araG, could reconstitute both the lymphoid and myeloerythroid lineages in the absence of leukemic relapse. The model utilized 6C3HED tumor cells, derived from a Thy 1.2+ malignant murine T-cell line, which were shown to cause lethal leukemia in C3H/HeN mice. Intravenous injection of 10(6) 6C3HED cells resulted in 100% mortality within 18 days, with autopsy revealing tumor infiltration of multiple organs. 100% of non-leukemia bearing lethally irradiated C3H/HeN mice transplanted with syngeneic bone marrow, treated ex vivo with 100 microM of araG for 18 hours, survived > 365 days post-transplant with full lymphohematopoietic reconstitution. Evidence of araG's ability to purge bone marrow of malignant tumor cells without causing significant toxicity to normal marrow derived hematopoietic progenitor cells was documented in experiments in which 75% of lethally irradiated mice transplanted with syngeneic bone marrow, contaminated with 6C3HED tumor cells and treated ex vivo with 100 microM araG for 18 hours, survived for > 250 to > 400 days. Death in 25% of mice was secondary to infection which developed before marrow reconstitution occurred. Reconstitution of the lymphoid, myeloid, and erythroid lineages with donor cells in surviving mice was documented. The data presented indicate that araG may effectively purge bone marrow of malignant T cells without irreversible toxicity to hematopoietic stem cells. This purging regimen is recommended for consideration for clinical trials in patients with T-cell malignancies undergoing autologous bone marrow transplantation and may also be a viable option for T-cell depletion as a strategy to prevent graft-versus-host disease.
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PMID:Efficacy and toxicity of 9-beta-D-arabinofuranosylguanine (araG) as an agent to purge malignant T cells from murine bone marrow: application to an in vivo T-leukemia model. 835 Jun 27

Arabinosylguanine (araG) is a nucleoside analogue that is rapidly converted by cells of the T lymphoid lineage to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in inhibition of DNA synthesis and selective in vitro toxicity to T lymphoblastoid cell lines as well as to freshly isolated leukemia cells from patients with T cell acute lymphoblastic leukemia (ALL). We have previously demonstrated that araG is an effective agent to use for chemoseparation of malignant T lymphoblasts from human bone marrow. When freshly isolated human T leukemia cells or T lymphoblastoid cells were treated with 100 microM araG for 18 hours, up to 6 logs of clonogenic T cells are eliminated without appreciable toxicity to the normal myeloid, erythroid, and megakaryocytoid clonal progenitor cells. We subsequently described studies in a murine model of T cell acute lymphoblastic leukemia (ALL) in which we tested whether bone marrow contaminated with malignant T cells and purged ex vivo with araG, could reconstitute both the lymphoid and myeloerythroid lineages in the absence of leukemic relapse. The model utilized 6C3HED tumor cells, derived from a Thy 1.2+ malignant murine T cell line, which were shown to cause lethal leukemia in C3H/HeN mice. Intravenous injection of 10(6) 6C3HED cells resulted in 100 percent mortality within 18 days, with autopsy revealing tumor infiltration of multiple organs. Evidence of araG's ability to purge bone marrow of malignant tumor cells without causing significant toxicity to normal marrow-derived hematopoietic progenitor cells was documented in experiments in which 75 percent of lethally irradiated mice receiving transplants of syngeneic bone marrow contaminated with 6C3HED tumor cells and treated ex vivo with 100 mM araG for 18 hours survived for 250 to > 400 days. Reconstitution of the lymphoid, myeloid, and erythroid lineages with donor cells in surviving mice was documented. The data presented indicate that araG may effectively purge bone marrow of malignant T cells without irreversible toxicity to hematopoietic stem cells. This purging regimen is recommended for consideration for clinical trials in patients with T cell malignancies undergoing autologous bone marrow transplantation and may also be a viable option for T cell depletion as a strategy to prevent graft versus host disease.
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PMID:Guanine arabinoside as a bone marrow-purging agent. 836 26


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