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)

A male patient with CML received a BMT from his sister and developed chronic GVHD. The host-origin normal karyotype (46,XY) was identified for the first time in the 60th month after BMT. Detection of Y-chromosome-specific DNA in BM and peripheral blood (PB) showed that all BM samples obtained 6 months from BMT were positive for Y-specific DNA, while PB became positive in the 60th month after BMT. The BCR-ABL mRNA derived from leukemic cells was detected in the 36th month post-BMT, but not in the 60th month or thereafter. Fluorescence in situ hybridization revealed that 1.5% and 0.6% in BM and PB cells were Y-positive in the 70th month post-BMT, respectively. DNA analysis of hematopoietic progenitor colonies revealed 1 of 42 erythroid colonies to be host derived. These results indicate that host-origin hematopoietic cells survive chronic GVHD, while the Ph1 clone was eliminated.
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PMID:Hematopoietic recovery from host progenitors with normal karyotype devoid of Philadelphia chromosome in a patient with CML after allogeneic BMT. 837 40

Fourteen S/S children with severe SCD were transplanted with marrow from HLA identical siblings. All developed frequent (> 4/y) vasoocclusive crises (VOC) and 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, 2 were chelated and 2 had erythroid allo-immunization. Ethnic origins were from various countries in Africa (n:10), 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:3). At first, various conditioning regimens were used consisting of busulfan (BU) plus Cyclophosphamide (CY) at different doses: CY:200 mg/kg (n:12) or 260 mg/kg (n:2); BU:14 mg/kg (n:1), 16 mg/kg (n:9), > 16 mg/kg (n:4); 1 patient received also TLI and one other antithymoglobulin (ATG): 20 mg/kg. GVHD prophylaxis was CSA alone (n:4) or CSA plus short-term MTX (n:10). Median follow-up was 23 months (8 m. to 48 m.). All patients had an engraftment (d13 to d32) with a stable total chimerism in 10/14 patients who are cured. In the 4 others, partial chimerism was observed: one patient had a early and progressive rejection of his graft but is doing very well (28 m. follow-up) without any manifestation of SCD, with a high stable 22% Hb F level. One patient developed an aplastic anaemia 15 m after BMT: a second BMT was achieved 21 m after the first one with engraftment and total chimerism. Two patients have a relatively stable partial chimerism with still undergoing CSA therapy (11 m. and 23 m. follow-up).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone marrow transplantation (BMT) in 14 children with severe sickle cell disease (SCD): the French experience. GEGMO. 837 51

We performed chromosome studies on 121 paired samples of phytohaemagglutinin-stimulated blood and unstimulated bone marrow cells from 57 recipients of lymphocyte depleted grafts using counterflow centrifugation. The paired samples were drawn simultaneously 6-108 months after transplantation. The incidence of mixed chimaerism was higher in blood than in bone marrow cells, both in patients who relapsed and in patients in continuous complete remission. The higher number of mixed lymphoid chimaeras is caused by autologous T lymphocytes which have survived the conditioning regimen and/or by donor lymphocytes which persisted after disappearance of the marrow graft. The type of blood and bone marrow chimaerism had no significant impact on the incidence of chronic GVHD but the overall incidence of chronic GVHD was too low to allow an accurate assessment. Cytogenetic analysis is a useful method for assessing chimaerism after bone marrow transplantation. Apart from its limited sensitivity for the demonstration of a minor cell population, discrepancies between chromosome studies of blood cells (lymphoid chimaerism) and bone marrow cells (myeloid/erythroid chimaerism) have to be taken into consideration.
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PMID:Comparison of chromosome studies on PHA-stimulated blood and unstimulated bone marrow cells in recipients of lymphocyte depleted grafts using counterflow centrifugation. 843 69

The suppressed lymphocyte proliferative responses characteristic of graft-versus-host disease (GVHD) are due, in part, to production of nitric oxide (NO). In order to more fully elucidate the role of NO during GVHD, an NO synthesis inhibitor, aminoguanidine (AG), was administered to unirradiated (C57BL/6J X DBA/2J)F1 mice injected with 5 X 10(7) C57BL/6J splenocytes. Administration of AG resulTed in abrogation of the elevation in serum NO2- + NO3- levels characteristic of GVHD. A significantly increased percentage of splenocytes of host phenotype (H2b/d, B220+, and THY1.2+) and a significantly higher hematocrit value were detected in GVHD animals receiving AG therapy. Additionally, the Con A-induced proliferative response of splenocytes obtained from GVHD mice receiving AG therapy was increased compared with the responses of splenocytes from animals that did not receive AG therapy. Parameters not affected by AG therapy included NO synthesis by recovered peritoneal macrophages, donor antihost cytolytic activity in splenocyte populations, serum GM-CSF levels and long-term engraftment of donor cells. These data indicate that NO may play a role in the destruction of both lymphoid and erythroid host tissue as well as the reduced lymphoproliferative responses associated with the acute phase of GVHD.
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PMID:Bystander injury of host lymphoid tissue during murine graft-verus-host disease is mediated by nitric oxide. 861 Mar 89

A 4-year-old boy with Diamond-Blackfan anemia and a history of multiple transfusions underwent umbilical cord blood transplantation from his HLA-identical female sibling born by vaginal delivery at 38 weeks. The patient was prepared with busulfan, cyclophosphamide and antilymphocyte globulin. Methotrexate and cyclosporin A were given for the prophylaxis of GVHD. Regimen-related toxicity was not observed and successful engraftment occurred, including the erythroid series. No evidence of acute or chronic GVHD has been observed for 14 months after transplantation. This is the first case of successful umbilical cord blood transplantation to a patient with Diamond-Blackfan anemia.
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PMID:Successful hematopoietic reconstitution by transplantation of umbilical cord blood cells in a transfusion-dependent child with Diamond-Blackfan anemia. 961 95

After allogeneic bone marrow transplantation (BMT), the beneficial graft-versus-leukemia (GVL) effect but also the life-threatening graft-versus-host disease (GVHD) are mediated by T cells of the grafted marrow. The identification of leukemia cell-reactive T cells and their ligands are, therefore, crucial for the development of new anti leukemia strategies. Here we describe a leukemia-reactive allo-HLA class II restricted CD4+ T-cell clone, 6.2, isolated from a healthy individual after stimulation with allogeneic leukemic cells. Clone 6.2 recognizes leukemic cells from several AML patients without showing reactivity to unfractioned peripheral blood mononuclear cells, monocytes, B cells, T-cell blasts, and proximal tubulus epithelial cells. Interestingly, clone 6.2 also recognizes BM cells derived from healthy individuals and inhibits the colony formation of myeloid and erythroid cell lineages. In the BM, clone 6.2 recognizes only CD34+ early precursor cells but not CD34-, more differentiated cells. Thus, the target antigen of clone 6.2 is developmentally regulated and expressed only by leukemic cells and CD34+ early progenitor cells in the hematopoietic system. We suggest that targeting the T-cell immune response to leukemia-associated, developmentally regulated antigens of the hematopoietic system can provide a basis for the separation of GVL from GVHD, and may lead to new therapeutic approaches for residual and relapsed leukemia.
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PMID:HLA class II restricted T-cell reactivity to a developmentally regulated antigen shared by leukemic cells and CD34+ early progenitor cells. 924 39

Recombinant human erythropoietin (rHu EPO) has been reported to accelerate early erythroid reconstitution after bone marrow transplantation (BMT). We conducted a pilot study on rHu EPO for late-onset anemia in 9 patients after allogeneic BMT. The patients achieved initial erythropoietic recovery (hemoglobin (Hb) range 9.1-13.4, mean 10.8 g/dl), but then developed transplant-related anemia (Hb range 6.3-9.7, mean 8.2 g/dl) more than 50 days after BMT. This type of anemia was related to graft-versus-host disease (GVHD), cytomegalovirus infection, and/or impaired EPO secretion. The patients received 3,000 or 12,000 U of rHu EPO subcutaneously three or seven times weekly. Hb levels increased by more than 2 g/dl in 6 of the 9 patients, but were unchanged in the 3 patients with severe GVHD. These findings suggest that in some cases rHu EPO is effective for the treatment of late-onset anemia after BMT.
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PMID:Recombinant human erythropoietin for late-onset anemia after allogeneic bone marrow transplantation. 963 79

Graft-versus-host disease (GVHD) is currently one of the major obstacles for successful allogeneic bone marrow transplantation (BMT). GVHD results from a complex set of interactions between donor T cells and a variety of target tissues from the host. To gain a better understanding of the biology of the human hematopoietic system in GVHD patients, in the present study we have determined the progenitor cell content in bone marrow (BM) samples from BMT recipients, with and without GVHD, and followed their growth kinetics in Dexter-type long-term marrow cultures (LTMC). We have also assessed some aspects regarding the composition of the hematopoietic microenvironment developed in vitro. As compared to normal subjects, BMT recipients showed decreased numbers of myeloid, erythroid, and multipotent progenitor cells. Interestingly, progenitor levels were significantly lower in GVHD patients (7% of the levels in normal marrow) than in those without GVHD (44% of the levels in normal marrow). When marrow cells from BMT recipients were cultured in LTMC, hematopoiesis was sustained at lower levels and for shorter periods of time, as compared to cultures from normal subjects. The hematopoietic deficiencies observed in this in vitro system were also more pronounced in GVHD patients. In terms of the microenvironment elements, reduced numbers of fibroblastic progenitors and adherent stromal cells were observed in BMT recipients, as compared to normal subjects, who showed 7 colony-forming unit fibroblast (CFU-F)/10(5) marrow cells and 320,000 adherent cells in LTMC. Again, GVHD patients showed more severe deficiencies (0.16 CFU-F/10(5) marrow cells and 34,000 adherent cells in LTMC) than patients without GVHD (2 CFU-F/10(5) marrow cells and 122,000 adherent cells in LTMC). Our results demonstrate that the hematopoietic system of BMT recipients is impaired, both in terms of its in vitro composition and function, and that these deficiencies are clearly more pronounced in patients with GVHD than in those without GVHD. Finally, although the evidence is still preliminary, our results also indicate that the severity of the hematopoietic alterations may be greater in acute GVHD than in chronic GVHD.
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PMID:Severe hematopoietic alterations in vitro, in bone marrow transplant recipients who develop graft-versus-host disease. 1145 10

A novel IFN-like molecule, limitin, was recently identified and revealed to suppress B lymphopoiesis through the IFN-alphabeta receptor, although it lacked growth suppression on myeloid and erythroid progenitors. Here we have studied diverse effects of limitin on T lymphocytes and compared limitin with previously known IFNs. Like IFN-alpha and -beta, limitin modified immunity in the following responses. It suppressed mitogen- and Ag-induced T cell proliferation through inhibiting the responsiveness to exogenous IL-2 rather than suppressing the production of IL-2. In contrast, limitin enhanced cytotoxic T lymphocyte activity associated with the perforin-granzyme pathway. To evaluate the effect of limitin in vivo, a lethal graft-versus-host disease assay was established. Limitin-treatment of host mice resulted in the enhancement of graft-versus-host disease. Limitin did not influence thymocyte development either in fetal thymus organ cultures or in newborn mice injected with limitin-Ig, suggesting that limitin is distinguishable from IFN-alpha and -beta. From these findings, it can be speculated that the human homolog of limitin may be applicable for clinical usage because of its IFN-like activities with low adverse effects on, for example, T lymphopoiesis, erythropoiesis, and myelopoiesis.
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PMID:A new IFN-like cytokine, limitin, modulates the immune response without influencing thymocyte development. 1154 1

Autoimmune thrombocytopenia (AITP) after bone marrow transplantation (BMT) was suggested to occur by immune dysregulation mainly in association with graft-versus-host disease (GVHD). Here we present a patient who developed severe AITP after BMT. A 40-year-old woman with severe aplastic anemia received a BMT from a partially HLA-matched brother. Despite myeloid and erythroid engraftments, platelet recovery was delayed. All bone marrow cells were 46,XY and were derived from the donor. Grade I acute GVHD involving skin developed from day 34 posttransplantation, but promptly responded to prednisolone in addition to a prophylactic dose of tacrolimus. With the tapering of prednisolone, thrombocytopenia progressed without substantial changes in the white blood cell count, hemoglobin concentration, or reticulocyte count. On day 188, the patient developed chronic GVHD involving skin and liver, which promptly responded to the readministration of prednisolone and increased tacrolimus. However, the patient's platelet count decreased to 9 x 10(9) cells/L on day 222. The platelet-associated immunoglobulin G (PAIgG) values were elevated. Bone marrow examination showed hypercellularity with plentiful megakaryocytes. The number of colony-forming units-megakaryocyte was within the normal range. The elevated PAIgG values and a correlation between thrombocytopenia and the intensity of the immunosuppressive agents strongly suggested a causative role of the autoimmune mechanisms for thrombocytopenia in this patient.
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PMID:Severe autoimmune thrombocytopenia after allogeneic bone marrow transplantation for aplastic anemia. 1159 27


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