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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)

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but lethal disorder caused when viable donor lymphocytes engraft and proliferate in a susceptible transfusion recipient. Patients with immune deficiency disorders, hematologic malignancies and bone marrow transplants are at risk to TA-GVHD, as are premature newborns and transfusion recipients who are HLA heterozygous for an HLA-haplotype that is shared with an HLA homozygous donor. Irradiation of blood components with 2500 cGy will inactivate donor lymphocytes and prevent TA-GVHD. Platelets and granulocytes are not functionally impaired by this radiation dose, but red cells sustain detectable damage. Red cell units irradiated and stored for 42 days have significantly higher supernatant recovery of chromium-51 labeled cells is sub-optimal. Based on these data, the maximum permissible storage time for irradiated red cells has been reduced to 28 days.
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PMID:Transfusion-associated graft-versus-host disease and the irradiation of blood components. 771 2

Questionnaires assessing a range of quality of life (QOL) outcomes were completed by 200 adult bone marrow transplant (BMT) recipients from five BMT treatment centres. Respondents had undergone allogeneic (46%) or autologous BMT (54%) for a haematological malignancy and were disease free and at least 12 months post BMT (mean 43 months). Variability in post-BMT QOL was reported with deficits in physical, sexual and occupational functioning particularly likely. Allogeneic recipients reported poorer QOL than autologous recipients. Greater age at BMT, lower level of education and more advanced disease at BMT were consistent risk factors for poorer QOL. Contrary to previous research, evidence for improved functional status with the passage of time post BMT was obtained. Factors generally not associated with post-BMT QOL included disease diagnosis, dose of total body irradiation, presence of chronic graft-versus-host disease (GVHD), type of GVHD prophylaxis and extent of marrow graft match. In conclusion, while many BMT recipients reported normal QOL, the majority indicated that their QOL was compromised relative to premorbid status. Prospective, longitudinal research will be necessary to further identify risk factors for poor post-BMT QOL and identify the temporal trajectory of post-BMT QOL.
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PMID:Quality of life following bone marrow transplantation: findings from a multicentre study. 777 32

Ten patients with haematological malignancy receiving allogeneic transplants from donors other than HLA-identical siblings were prepared for marrow transplantation with antithymocyte globulin, cyclophosphamide 120 mg/kg and fractionated total body irradiation 12 Gy, and were given cyclosporin, methotrexate and prednisolone as prophylaxis against graft-versus-host disease post-transplant. The harvested T replete donor marrow was incubated with recombinant human (rh) GM-CSF 10 micrograms/ml (supersaturating concentration) for 1 h at 37 degrees C on a gently shaking rocker platform. After incubation the marrow was washed twice in 5% human serum albumin/normal saline and infused into the recipient. Before and after incubation, there was no significant difference in cell viability, the nucleated cell count, the CFU-GM content nor the proportion of cells in S phase of the cell cycle. Compared with a preceding cohort of 16 patients treated on the same protocol but in whom the marrow was not incubated with GM-CSF, there was no difference in the incidence of graft failure or rate of neutrophil recovery.
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PMID:Lack of efficacy of a short ex vivo incubation of human allogeneic donor marrow with recombinant human GM-CSF prior to its infusion into the recipient. 785 31

To increase the cure rate of advanced hematologic malignancies following allogeneic bone marrow transplantation we sequentially evaluated two intensified conditioning regimens. Eleven patients with acute myeloblastic leukemia (AML) beyond the first complete remission or chronic myelogenous leukemia (CML) not in first chronic phase received an association of 13.5 Gy of fractionated total body irradiation (TBI) followed by cyclophosphamide (CY) 120 mg/kg. Following this regimen, the probability of relapse was 47% at 3 years and the non-relapse mortality rate was 27%. Given the acceptable tolerance of this regimen, 13.5 Gy fractionated TBI was associated with intensified chemotherapy consisting of a combination of CY 120 mg/kg, carmustine 300 mg/m2 and etoposide 600 mg/m2 (CBV). This regimen was administered to 22 patients with comparable diseases. Of these patients, 7 received a transplant from a matched unrelated donor and 2 other patients received a second transplant from the original genoidentical donor. For 15 patients with a genoidentical donor, including the 2 second transplant, the 3 year probability of survival, disease-free survival and relapse are 40%, 40% and 14%, respectively. No regimen-related toxic deaths were recorded during the first 100 days. Of 7 patients with matched unrelated donors, 3 died before day 100, one death being directly attributable to the regimen. Early non-fatal regimen-related toxicity consisted mainly in grade II mucositis with no grade III or IV toxicity in recipients of genoidentical marrow. The late deaths were mainly due to chronic GVH-related complications. In conclusion, the association of fractionated 13.5 Gy TBI and CBV carries a high antileukemic activity and an acceptable toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Total body irradiation and high-dose cyclophosphamide, BCNU and VP-16 (CBV) as a new preparatory regimen for allogeneic bone marrow transplantation in patients with advanced hematologic malignancies. 788 8

Supraintensive cytoreductive therapy with hematopoietic stem cell rescue (HSCR) is able to provide curative therapy in a number of hematologic malignancies. Allogeneic HSCR is limited to less than 50% of patients because of the absence of related or unrelated compatible donors. Autologous HSCR is a viable alternative to allogeneic HSCR and is applicable to a greater number of patients. In addition, because of the absence of graft-versus-host disease, it is applicable to older patients. Although the relapse of malignancy is higher following autologous compared with allogeneic marrow, the disease-free survival for autologous HSCR is often equal to or greater than that seen following allogeneic HSCR. A number of posttransplantation immunological based therapies have shown promise for further decreasing the relapse rate following autologous HSCR.
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PMID:The role of autologous hematopoietic stem cell transplantation in hematologic malignancy. 791 7

Bone marrow transplantation is an accepted therapy for hematologic malignancies, aplastic anemia, metabolic disorders, and solid tumors. However, graft-versus-host disease (GVHD) and failure of engraftment have limited the widespread application of this technology to nonmalignant disease states. The use of purified bone marrow stem cells has been suggested as an approach to promote engraftment yet avoid GVHD. Although bone marrow stem cells, purified by cell sorting, engraft and repopulate lethally irradiated genetically identical recipients, they do not engraft in major histocompatibility complex (MHC)-disparate allogeneic recipients. We report for the first time the characterization of a novel cell population of donor bone marrow origin, separate from the hematopoietic stem cell, that facilitates engraftment of purified allogeneic bone marrow stem cells in an MHC-specific fashion without causing GVHD. Although 1,000 purified stem cells (c-kit+/Sca-1+/lineage-) reliably repopulate syngeneic mouse recipients, 10 times that number do not engraft in MHC-disparate allogeneic recipients. The addition of as few as 30,000 facilitating cells (CD8+/CD45R+/TCR-) is sufficient to permit engraftment of purified stem cells in MHC-disparate recipients. The cell surface phenotype of this purified cellular population differs significantly from other characterized lineages of lymphoid or myeloid origin. Based on multiparameter rare-events cell sorting, the facilitating fraction is CD8+, CD3+, CD45R+, Thy 1+, class IIdim/intermediate but alpha beta-TCR- and gamma delta-TCR-. This cellular population comprises approximately 0.4% of the total bone marrow and is separate from the hematopoietic stem cell. The coadministration of purified facilitating cells plus stem cells to optimize engraftment yet avoid GVHD may expand the potential application of bone marrow transplantation to disease states in which the morbidity and mortality associated with conventional BMT cannot be justified.
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PMID:Phenotypic characterization of a novel bone marrow-derived cell that facilitates engraftment of allogeneic bone marrow stem cells. 791 63

A total of 116 consecutive patients, including 82 cases of hematologic malignancies and 34 cases of severe aplastic anemia (SAA), were treated by allogeneic bone marrow transplantation (BMT). The conditioning regimens and post-graft immunosuppressive agents were as described by Thomas in Seattle and Santos in Baltimore. The incidence of grades II-IV acute GVHD in patients with hematologic malignancies with a full HLA match, with one locus and with two loci mismatches was 6.3% (4 of 63), 0% (0 of 11) and 37.5% (3 of 8), respectively. None of SAA patients developed grade II-IV acute GVHD. The low incidence of acute GVHD after BMT among Chinese patients may be associated with the use of isolation in laminar airflow rooms and a relatively low level of genetic diversity in histocompatibility antigens. This is an interesting issue for further study.
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PMID:Bone marrow transplantation in Taiwan: low incidence of acute GVHD in patients with hematologic malignancies and severe aplastic anemia. 792 Feb 99

Comprehensive programmes for BMT started in Hong Kong in 1990. As of September 1993, there are a total of 13 BMT beds in Government-funded University Hospitals performing about 110 transplants per year or 18 transplants per million population per year. So far, 194 transplants were performed: allogeneic BMT (72.2%), autologous BMT (11.8%), matched unrelated donor BMT (8.8%), identical twin BMT (1.5%), mismatched BMT (2.1%) and second BMT (3.6%). The major indication was haematological malignancy (84%). About 40% of the patients were prepared by chemotherapy alone. A combination of CsA and short MTX was the commonest GVHD prophylaxis. The incidence of GVHD was the same as in the Caucasians. Results of transplant outcome were comparable to those reported by the International Bone Marrow Transplant Registry.
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PMID:Bone marrow transplantation in Hong Kong. 792 Mar

Campath-1G is an immunosuppressive monoclonal antibody directed against human lymphocytes. Its effectiveness in preventing graft-versus-host disease (GVHD) by simple opsonisation of bone marrow T-cells has been studied in 36 consecutive allografts: in 17 for leukaemia, one for essential thrombocytosis and four for myeloma this was the sole means of GVHD prophylaxis. A further eight patients with aplastic anaemia received 3 months post-transplantation cyclosporin A (CsA) for this purpose whereas in the ninth and tenth the preparative regimen has been modified with this immunosuppressive agent now discontinued. Nucleated cells were harvested and after quantitative recovery of the mononuclear population on the Cobe 2997 separator they were exposed to 20 mg Campath-1G for 30 min at room temperature and then infused. Following standard conditioning, which included total lymphoid irradiation, the median days to reach 0.5 and 1.0 x 10(9)/l neutrophils were respectively 18 (range 9-34) and 28 (range 10-59); to 25 and 100 x 10(9)/l platelets the corresponding times were 17 days (range 5-32 days) and 27 days (range 13-127 days). In all, the day 14 trephine biopsy showed engraftment. At median follow-up of 20 months (range 5-44 months) only one patient has developed possible grade I cutaneous GVHD that responded promptly to corticosteroids: no chronic GVHD or CMV pneumonitis has been encountered. Of those with haematological malignancy transplanted in remission only two with acute leukaemia have relapsed. In aplastic anaemia graft loss initially occurred but this has been overcome by adding Campath-1G in vivo and omitting CsA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:T cell depletion by exposure to Campath-1G in vitro prevents graft-versus-host disease. 1045 57

Bone marrow manipulation is an essential procedure when bone marrow transplantation (BMT) is used to improve the chances of survival among high risk patients with hematologic malignancies. Ex vivo purging of donor T cells effectively prevents a fatal reaction known as graft-versus-host disease in allogeneic BMT. Ex vivo purging of residual leukemia cells from autologous marrow can virtually eliminate the risk of autograft contamination. Immunotoxins are powerful and selective reagents for these tasks. However, ex vivo purging may be insufficient by itself to overcome the high risk of relapse that confronts many patients undergoing autologous BMT. Bone marrow manipulation may even present problems of its own, such as loss of the graft-versus-leukemia effect when allogeneic marrow is T cell depleted. We are currently evaluating immunotoxins containing pokeweed antiviral protein in clinical trials as in vivo purging reagents that may reduce the risk of relapse for BMT patients.
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PMID:Allograft and autograft purging using immunotoxins in clinical bone marrow transplantation for hematologic malignancies. 792 71


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