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)

We have previously reported the successful development of hematopoietic chimerism after the in utero transplantation of fetal hematopoietic stem cells (HSC) in rhesus monkeys (Macaca mulatta). These animals exhibit sustained engraftment without immunosuppression or graft-versus-host disease (GVHD). To assess the functional response of the donor-derived erythropoietic population, we assayed the relative expression of donor and recipient hematopoietic progenitors in chimeric monkeys before and after anemic stress. Anemia in our chimeric animals resulted in increased erythropoietin (EPO) production comparable to controls. This was accompanied by changes in erythroid progenitor profiles, again similar to controls. Chimeric animals demonstrated normal reticulocytosis and reconstituted their hematocrit after hemorrhage at the same rate as controls. The donor-derived erythropoietic population exhibited normal responses to recipient regulatory signals and did not seem to expand at the expense of other hematopoietic lineages. Thus the proportions of engraftment for the myeloid and erythroid precursors in bone marrow and for blood lymphocytes remained stable. Our results demonstrate that the in utero transplantation of fetal HSC results in stable engraftment of donor erythropoietic progenitors, which appear to be fully integrated within the recipient's regulatory system. The abnormalities reported in the postnatal transplantation setting can then be attributed to immunologic reactions requiring conditioning myeloablative regimens. Fetal transplantation bypasses all these factors.
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PMID:Effect of erythropoietic stress on donor hematopoietic cell expression in chimeric rhesus monkeys transplanted in utero. 134 81

Bone marrow transplantation was performed on a 15 year old girl with chronic myelogenous leukemia. The bone marrow was obtained from her younger sister, who was human leukocyte antigen haplo-identical but major ABO incompatible. As a result, the condition of pure red cell aplasia (PRCA) persisted over a long period of time. In order to overcome major ABO incompatibility, erythrocytes were eliminated from the bone marrow graft before transplantation, and methotrexate and cyclosporine (CsA) were used to prevent graft-versus-host disease (GVHD). Administration of erythropoietin proved ineffective. B19 parvovirus infection could not be detected during that time. Agglutinin titers decreased to less than fourfold in parallel with the recovery of erythrocytes. Reports on similar PRCA have been limited to cases of transplantation with ABO incompatibility and cases where CsA was administered to prevent GVHD. This suggests that ABO incompatibility and CsA might be related to the development of PRCA.
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PMID:Long duration of erythrocyte hypoplasia after bone marrow transplantation. 141 39

Delayed erythroid recovery is common after bone marrow transplantation (BMT), with some patients continuing to require red blood cell (RBC) transfusion support for as long as 1 year. While the etiology is multifactorial, inadequate stimulation of erythroid progenitors by the erythroid growth factor, erythropoietin, may play a role. In this study, the erythropoietin response to anemia of 70 consecutive patients undergoing BMT at the Johns Hopkins Oncology Center was compared with the erythropoietin response in uncomplicated iron deficiency anemia. Erythropoietin levels were elevated for the degree of anemia early after BMT; however, at the time of marrow recovery, erythropoietin levels were significantly suppressed in both allogeneic and autologous BMT patients compared with the iron-deficient patients. Patients with acute graft-versus-host disease (GVHD) had a more marked suppression of the erythropoietin response to anemia. In the patients who remained anemic for extended periods of time (up to 12 months after BMT), an inadequate erythropoietin response to anemia persisted. Delayed erythroid recovery after BMT is associated with inadequate erythropoietin levels. Therefore, recombinant human erythropoietin may be useful in the treatment of the anemia associated with both autologous and allogeneic BMT.
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PMID:Impaired erythropoietin response to anemia after bone marrow transplantation. 142 81

Serial serum erythropoietin levels were measured in 10 consecutive patients undergoing allogeneic bone marrow transplantation. Observed erythropoietin levels are compared with those predicted from a large control population of anaemic patients not receiving chemotherapy. There was an initial acute rise in serum erythropoietin, peaking between days 1 and 4 after marrow transfusion, which was unrelated to changes in haemoglobin concentration. Patients maintained serum erythropoietin concentrations at around twice the predicted level for the first 2 weeks following transplantation, with a gradual fall into the expected range by wk 3. Erythropoietin levels did not change with episodes of bacterial infection or acute graft-versus-host disease. A patient with severe aplastic anaemia had initial successful engraftment with normalisation of erythropoietin levels, but showed a marked and amplified rise in erythropoietin 2 wk before falling peripheral blood counts indicated failure of the bone marrow graft.
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PMID:Changes in serum erythropoietin levels during allogeneic bone marrow transplantation. 188 86

Serum erythropoietin (EPO) levels were measured by radioimmunoassay in 36 patients undergoing allogeneic bone marrow transplantation (BMT). Serum EPO levels before conditioning treatment for BMT were generally higher than the levels obtained from healthy controls (49 +/- 17 (SEM) and 17 +/- 0.6, respectively). One day prior to BMT, after conditioning by chemotherapy with or without total body irradiation, the mean EPO level was markedly elevated (218 +/- 23 U/l, p less than 0.001) and reached to its highest level at 1 week post-BMT (269 +/- 40 U/l). Although, the EPO levels were significantly lower at 1 month (98 +/- 24 U/l, p less than 0.001), they were still elevated up to 3 months post-BMT, after which they gradually normalized. Patients given methotrexate and cyclosporine for prophylaxis against graft-versus-host disease (GVHD) had significantly lower EPO levels during the first 3 months post-BMT than patients transplanted with T cell-depleted marrow (p less than 0.05). Patients with post-transplant nephrotoxicity had lower, though not statistically significant, EPO levels than patients with normal renal function (p = 0.07). Acute GVHD and number of blood transfusions had no influence on serum EPO levels after BMT.
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PMID:Markedly increased serum erythropoietin levels following conditioning for allogeneic bone marrow transplantation. 220 49

Sequential changes in serum erythropoietin (sEPO) levels were measured by radioimmunoassay in six patients receiving autologous rescue (AR) and 11 patients receiving an allogeneic bone marrow transplant (BMT) for malignant disease. Longitudinal studies showed an inverse relationship between sEPO and haemoglobin levels in the autologous rescue and allogeneic transplant patients throughout the 130 d post-transplant study period. Early post-conditioning EPO responses were normal for the haemoglobin level in both groups, but after day 14 post-transplant, erythropoietin production in response to anaemia became impaired in one autologous rescue patient and eight of the 11 allogeneic transplant patients. There was no clear association between late impairment of sEPO production and conditioning therapy, infection, graft-versus-host disease, immunosuppressive therapy or serum creatinine. Blood transfusion requirements were similar for both groups in the first month after transplantation, but from days 31 to 90 post-transplant, BMT patients required an average of 5.5 units per patient compared with 1 unit per patient for the autologous group. Marrow transplant procedures do not affect early EPO responses but may diminish late responses. The potential value of exogenous rHuEPO in hastening engraftment and decreasing transfusion requirements, particularly for those patients who appear to have impaired EPO responses, remains to be shown by clinical trials.
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PMID:Serum erythropoietin changes in autologous and allogeneic bone marrow transplant patients. 222 32

Highly purified and cloned preparations of interleukin-1 (IL-1) were found to antagonize the capacity of erythropoietin (Epo) to stimulate the proliferation of mouse spleen and bone marrow erythroid precursor cells (EPC) in culture. Cloned murine IL-1 and purified and cloned human IL-1 alpha and IL-1 beta were approximately equipotent in this assay. IL-1 inhibited the proliferation response of EPC even when added as long as 17 h after Epo, suggesting that IL-1 does not affect binding of Epo to receptors or biochemical events following shortly thereafter. Indomethacin did not influence the inhibitory effect of IL-1 on Epo-induced proliferation, and PGE2 had no demonstrable effect on the process. Tumor-necrosis factor-alpha and interferons beta 1, and gamma did not affect Epo-induced proliferation. It is suggested that IL-1 mediated antagonism of the effects of Epo on erythroid precursors is a factor in the pathogenesis of many types of hypoplastic anaemia, including those associated with infections, rheumatoid arthritis and systemic lupus erythematosus, giant-cell arteritis, graft-versus-host disease and disorders associated with lymphocyte-mediated suppression of erythropoiesis.
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PMID:Inhibition by interleukin-1 of the action of erythropoietin on erythroid precursors and its possible role in the pathogenesis of hypoplastic anaemias. 349 70

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

Allogeneic peripheral blood progenitor cells (PBPCs) were transplanted after immunoselection of CD34+ cells. Two patient groups were studied: group I patients received immunoselected blood CD34+ cells and unmanipulated marrow cells from the same donor. Group II patients were given immunoselected blood and bone marrow (BM) CD34+ cells. One to 6 weeks before bone marrow transplantation (BMT), PBPCs from HLA-identical and MLC- sibling donors were mobilized with granulocyte colony-stimulating factor (G-CSF) (5 micrograms/kg twice daily subcutaneously) for 5 days. Aphereses were performed at days 4 and 5 of G-CSF application. CD34+ cells were separated from the pooled PBPC concentrates by immunoadsorption onto avidin with the biotinylated anti-CD34 monoclonal antibody 12.8 and then stored in liquid nitrogen. BM was procured on the day of transplantation. Patients were conditioned with either busulfan (16 mg/kg) or total body irradiation (12 Gy) followed by cyclophosphamide (120 mg/kg). Cyclosporin A and short methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. After transplantation, all patients received 5 micrograms G-CSF/kg/d from day 1 until greater than 500 neutrophils/microL were reached and 150 U erythropoietin/kg/d from day 7 until erythrocyte transfusion independence for 7 days. Group I consisted of patients with acute myeloid leukemia (AML) (n = 2), chronic myeloid leukemia (CML) (n = 2), and T-gamma-lymphoproliferative syndrome and BM aplasia (n = 1). The patients received a mean of 3.3 x 10(6) CD34+ and 3.7 x 10(5) CD3+ cells/kg body weight of PBPC origin and 4.5 x 10(6) CD34+ and 172 x 10(5) cells/kg body weight of BM origin. Group II consisted of five patients (two AML, two CML, one non-Hodgkin's lymphoma). They received a mean of 3.3 x 10(6) CD34+ and 3.2 x 10(5) CD3+ cells/kg from PBPC and 1.4 x 10(6) CD34+ and 0.6 x 10(5) CD3+ cells from BM. A matched historical control group (n = 12) transplanted with a mean of 5.2 x 10(6) CD34+ and 156 x 10(5) CD3+ cells/kg from BM alone was assembled for comparison. In group I, the median time to neutrophil recovery to > 100, > 500, and > 1,000/microL was 12, 15, and 17 days, respectively. Patients from group II reached these neutrophil levels at days 13, 15 and 17 post BMT. Neutrophil recovery in the control patient group occurred at days 17, 18, and 20 respectively. Group I patients were given platelet transfusions within 18 days and red blood cells within 10 days, whereas for group II patients, these time points were 26 and 17 days, respectively. These same transfusions could be ceased within 38 and 24 days, respectively, in control patients. The addition of about 2% more peripheral blood CD3+ cells (group I patients) did not result in higher grades of acute GVHD (median grade II) as compared with the controls (median grade II). Four of five group II patients showed no signs of acute GVHD. These data suggest that the addition of immunoselected allogeneic CD34+ progenitor cells to BM cells may accelerate hematopoietic recovery.
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PMID:Combined transplantation of allogeneic bone marrow and CD34+ blood cells. 754 59

Recombinant human erythropoietin (rHuEPO) stimulates erythropoietic bone marrow cells and increases erythrocyte production. This prospective study was designed to evaluate the effects of rHuEPO on regeneration of erythropoiesis after allogeneic or autologous bone marrow transplantation (BMT). Seventeen centers participated in this randomized, double-blind, placebo-controlled multicenter trial. The randomization was performed centrally for each center and stratified according to allogeneic or autologous BMT and major ABO-blood group incompatibility. One hundred and six patients received rHuEPO after allogeneic BMT and 109 patients received placebo. After autologous BMT, 57 patients were treated with rHuEPO and 57 with placebo. Patients received either 150 IU/kg/day C127 mouse-cell-derived rHuEPO or placebo as continuous intravenous infusion. Therapy started after bone marrow infusion and lasted until independence from erythrocyte transfusions for 7 consecutive days with stable hemoglobin levels > or = 9 g/100 mL or until day 41. After allogeneic BMT, the reticulocyte counts were significantly higher with rHuEPO from day 21 to day 42 after BMT. The median time (95% confidence intervals) to erythrocyte transfusion independence was 19 days (range, 16.3 to 21.6) with rHuEPO and 27 days (range, 22.3 to > 42) with placebo (P < .003). The mean (+/- SD) numbers of erythrocyte transfusions until day 20 after BMT were 6.6 +/- 4.8 with rHuEPO and 6.0 +/- 3.8 with placebo. However, from day 21 to day 41, the rHuEPO-treated patients received 1.4 +/- 2.5 (median, 0) transfusions and the control group received 2.7 +/- 4.0 (median, 2) transfusions (P = .004). In the follow-up period from day 42 up to day 100, 2.4 +/- 5.6 transfusions were required with rHuEPO and 4.5 +/- 9.6 were required with placebo (P = .075). A multivariate analysis (ANOVA) showed that acute graft-versus-host disease (GVHD), major ABO-blood group incompatibility, age greater than 35 years, and hemorrhage significantly increased the number of transfusions. However, after day 20, rHuEPO significantly reduced the number of erythrocyte transfusions in these patient groups, as well as reducing incompatibility in the major ABO-blood group. For the whole study period, rHuEPO reduced the transfusion requirements in GVHD III and IV from 18.4 +/- 8.6 to 8.5 +/- 6.8 U (P = .05). After autologous BMT, there was no difference in the time to independence from erythrocyte transfusions and in the regeneration of reticulocytes. Marrow purging strongly increased the requirement for transfusions as well as the time to transfusion independence.
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PMID:A controlled trial of recombinant human erythropoietin after bone marrow transplantation. 794 88


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