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)

Retrospectively we analyzed the histocompatibility data and clinical results of bone marrow transplantation in 51 patients who received marrow from unrelated donors (UD) from 1977 to 1987 at one of four UK BMT centers. We compared the results with those obtained in 51 transplants carried out at the same centers using HLA-identical (ID) sibling donors. Of the UD/recipient pairs 32 (63%) were serologically identical for HLA A, B, and DR antigens, and 37% showed varying degrees of mismatch. UD-BMT primary diagnoses were: severe aplastic anemia or Fanconi's anemia (n = 17), acute leukemia (n = 11), chronic myeloid leukemia (n = 21), and other conditions (n = 2). T cell depletion of the graft was associated with a significant improvement in survival in both UD and ID-BMT. Graft failure was more common in recipients of UD than of ID transplants (13 [25%] vs. 5 [10%] P = 0.05) but there was no significant difference in the frequency of acute or chronic graft-versus-host disease. Actuarial survival was superior for recipients of ID transplants (UD vs. ID: 49% vs. 78%, respectively, at 3 months; 32% vs. 63% at one year). Reduced survival for recipients of UD-BMT was confirmed in case control regression analysis (relative risk 3.0, P = 0.01). Nevertheless in patients whose only alternative is a partially mismatched family donor we think that UD-BMT is justified.
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PMID:Unrelated donor marrow transplantation between 1977 and 1987 at four centers in the United Kingdom. 218 Jan 50

Bone marrow transplantation is the only treatment that can result in long-term disease-free survival and possible cure in a significant number of patients with CML. Several prognostic features influence relapse and survival following allogeneic BMT for CML. The most important factor is treatment of patients during chronic phase. The timing of BMT in chronic phase CML remains controversial, because the Seattle findings that BMT done within a shorter interval from diagnosis to transplant was associated with improved survival has not been confirmed by the IBMTR. No factor can predict in the individual patient the timing of transformation, even in patients with low-risk chronic phase CML, but we believe that allogeneic BMT should be offered as soon as possible for newly diagnosed patients who have histocompatible siblings. More widespread application of BMT in CML is possible because of effective methods for preventing GVHD, the major cause of morbidity after allogeneic BMT. However, in vitro techniques for the depletion of donor marrow T cells have resulted in higher graft failure and relapse rates. More precise understanding of the immune mechanisms involved may permit more selective depletion techniques which not only abrogate GVHD but also permit sustained engraftment and preserve GVL effect. This may extend application of BMT for patients with mismatched related or histocompatible unrelated donors. It is of interest that cytogenetic relapse after BMT is not invariably followed by hematologic relapse. It is likely that the use of polymerase chain reaction techniques which detect the bcr-abl rearrangement at a very low level will identify the persistence of the malignant clone after allogeneic BMT in even more patients. At present, the significance of such findings is unclear, but further study of the kinetics of disappearance of the CML clone post-BMT may increase our understanding of the immune mechanisms involved in suppression of the malignant clone and determine whether in fact CML can be cured using BMT approaches.
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PMID:The evolving role of bone marrow transplantation in the treatment of chronic myelogenous leukemia. 218 97

BMT is the only curative therapy for CML, a uniformly lethal malignant disorder of the hematopoietic stem cell. Younger patient age and transplant in CP are associated with better outcome. Transplant within 1 year of diagnosis may provide a greater chance of survival than transplant at a longer interval from diagnosis. T-cell depletion of donor BM significantly reduces the incidence of acute and chronic GVHD, but is associated with an increased risk of graft failure and a marked increase in rate of relapse. Early results suggest that HLA-matched or partially HLA-mismatched unrelated donors may be used successfully in cases in which a suitably matched related donor is not available. Autologous transplantation of BM or PB stem cells can result in successful engraftment and possibly prolonged survival in some patients with CML. Following allogeneic BMT, some patients relapse cytogenetically without progressing to hematologic relapse. The use of PCR methodology to amplify bcr-abl transcripts has revealed persistence of the malignant clone in a substantial number of patients who are in hematologic and cytogenetic remission. The clinical significance and biologic mechanism(s) of this form of molecular relapse remain to be defined.
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PMID:Treatment of chronic myelogenous leukemia with bone marrow transplantation. 219 13

A group of 466 leukemic bone marrow transplanted patients were reported from 17 European bone marrow transplantation teams. Of these, 285 survived more than 3 months and could be evaluated for chronic GVHD. The cumulative incidence of chronic GVHD was 32% two years after BMT. The following factors were statistically significantly associated with chronic GVHD in bivariate analysis: high donor and recipient age, splenecacute GVHD, pretransplant seropositivity to CMV among the recipients and the donors, and donor seropositivity to 3 or 4 different herpesviruses, compared with 0-2, prior to BMT. In multivariate analysis pretransplant recipient CMV seropositivity in combination with donor CMV seropositivity prior to BMT (P = 0.0006), a previous grade II-IV acute GVHD (P = 0.001), and splenectomy (P = 0.01) were significantly associated with chronic GVHD. Thus, in addition to acute GVHD, CMV immune donor cells may be triggered by latent CMV in the recipient, which may play a role in the triggering of chronic GVHD. The possible role of splenectomy in GVHD is also discussed.
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PMID:A European multicenter study of chronic graft-versus-host disease. The role of cytomegalovirus serology in recipients and donors--acute graft-versus-host disease, and splenectomy. 219 43

Fourteen patients with T-cell-derived leukemia and lymphoma underwent high-dose chemoradiotherapy and anti-T-cell monoclonal antibody-treated autologous bone marrow transplantation (ABMT). All patients were either in sensitive relapse or had adverse prognostic features, and five patients had a history of bone marrow involvement with disease. Patients received a median of 2 (1 to 3) prior chemotherapy regimens; 10 patients received local radiotherapy. After high-dose ablative therapy, greater than 500/mm3 granulocytes and greater than 20,000 untransfused platelets/mm3 were noted at a median of 23 (13 to 48) and 26 (15 to 43) days post-ABMT, respectively. Natural killer (NK) cells, T cells (predominantly T8+), and monocytes were noted within the first 1 to 2 months post-AMBT, as seen in other series. Disease-free survival was a median of 10.1 months, 5.9 months for patients with T acute lymphoblastic leukemia or lymphoblastic lymphoma and 25.6 months for patients with T non-Hodgkin's lymphoma (NHL). Toxicities were common and severe. Thirty-six percent of patients developed bacteremias early post-BMT. Late complications included a skin rash consistent with graft versus host disease; infections with Herpes zoster, hepatitis, and Pneumocystis carinii; and the development of Epstein-Barr virus associated lymphoproliferative syndrome. Our findings suggest that patients who have undergone T-depleted ABMT have a profound immunodeficiency not reflected in the phenotypic reconstitution of the T and NK cells. Characterization of the functional deficiency may facilitate the development of methods to reduce the long-term toxicity of AMBT in these patients.
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PMID:T-cell-depleted autologous bone marrow transplantation therapy: analysis of immune deficiency and late complications. 219 91

An enzyme-linked immunosorbent assay was used to quantify soluble interleukin 2 receptor (IL2R) in the serum of 25 patients prior to allogeneic or autologous bone marrow transplantation and in the early post-transplantation period. A significant correlation between IL2R and the occurrence of fever and/or graft-versus-host disease (GVHD) could be shown. Patients with moderate to severe GVHD (grade II-IV) had significantly higher IL2R levels (median 480 U/ml) than patients without or with acute GVHD grade I (median 139 U/ml). In patients without or with acute GVHD grade I, significant differences in the maximum IL2R levels depended on the duration of fever greater than or equal to 38 degrees C. Evaluation of the peak IL2R levels in patients with fever lasting longer than 6 days led to a median of 260 U/ml and in patients with fever lasting less than 6 days to a median of 118 U/ml. In patients without or with acute GVHD grade I, who developed fever lasting longer than 6 days, IL2R levels started to rise with the onset of fever, reached peak values during temperature maximum and declined parallel with temperature normalization. In patients without or with acute GVHD grade I who developed fever lasting for only 6 days or less IL2R levels remained within the normal range. In patients with acute GVHD grade II-IV, IL2R levels began to rise with the onset of fever, and then continued to rise despite temperature normalization. The peak levels were reached in the early period of acute GVHD. Our observations in BMT patients show that severe infections and acute GVHD are associated with a stimulation of the immune system leading to elevated IL2R serum levels.
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PMID:Soluble interleukin 2 receptors in patients after bone marrow transplantation. 220 58

A 36-year-old man was diagnosed as having RAEB in 1986, and required blood transfusion regularly because of severe anemia. He received the first bone marrow transplantation following total-body irradiation and etoposide infusion in October 1987. He was found to be relapsed into RAEB on 106th day after BMT. And the second BMT was planned. According to the conditioning regimen of Tutschka, et al, we administrated busulfan and cyclophosphamide before re-transplantation. On 26th day after BMT, the WBC count exceeded 1,000/microliters and anemia was improved, while thrombocytopenia persisted until 50th day. Normal hematopoiesis in the bone marrow was confirmed on the 29th day. No severe side effect except for a little fevering and bleeding was found during the clinical course. Unfortunately he died of pneumonia following graft versus host disease on the 166th day after re-BMT. This new conditioning regimen is considered to be a choice for the high risk patients on re-transplantation.
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PMID:[Bone marrow re-transplantation following a busulfan and cyclophosphamide regimen]. 221 94

Fanconi anemia is characterised by pancytopenia, malformations and chromosomal breaks probably related to a congenital defect of DNA repair mechanisms. The evolution is always fatal unless, the patient receives a bone marrow transplant from an HLA identical sibling. According to preliminary work on sensitivity of FA cells to alkylating agents and to in vivo radiosensitivity tests, we used a modified conditioning regimen with cyclophosphamide 20 mg/kg and 5 Grays thoraco-abdominal irradiation. Nineteen patients are reported. The actuarial survival is 74% with a median follow-up time of 4 years (range 6 months to 6 years). GVH was the main complication (58%). It was responsible directly or indirectly for 4 deaths. These results show that BMT in FA is successful in the large majority of cases. The decrease of the dose cyclophosphamide allowed a good engraftment without major toxicity. Studies are in progress for using this type of protocol in situations without a HLA matched sibling donor.
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PMID:Radiosensitivity in Fanconi anemia: application to the conditioning for bone marrow transplantation. 224 53

The liver is a major target organ of graft-versus-host disease. We have induced graded intensities of acute GVHD to minor histocompatibility antigens in a well-characterized murine bone marrow transplant model and analyzed hepatic pathology one month after BMT. Nuclear-magnetic-resonance relaxation times and proton spectra were compared to systemic clinical disease, serum biochemistries, and histologic findings. T2 relaxation times correlated directly with the intensity of histologic abnormalities, but the hepatic histology remained mild even in animals with moderate GVHD. In contrast, NMR proton spectra of hepatic tissue showed large decreases in metabolite levels (acetate and glycogen) in animals with moderate systemic disease despite mild hepatic histology. We conclude that NMR of the liver can be used to differentiate hepatic from systemic GVHD in this model and may help to elucidate the differential effects of GVHD in various target organs.
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PMID:Nuclear magnetic resonance of hepatic graft-versus-host disease in mice. 225 43

A 31-year-old woman with Philadelphia (Ph) chromosome-positive chronic myeloid leukaemia (CML) underwent allogenic bone marrow transplantation during accelerated phase. Non-T-cell-depleted marrow from a male sibling mismatched at one Class 2 histocompatibility locus was infused after conditioning with total body irradiation and intravenous cyclophosphamide. Cyclosporin and methotrexate were given for prevention of graft-versus-host disease (GVHD). Prompt engraftment occurred with donor karyotype cells, followed by transient moderate acute GVHD. However, by day 60 after BMT, haematological relapse occurred with increasing splenomegaly, leucocytosis, increasing marrow fibrosis, and cytogenetic mosaicism, consisting of 47% donor metaphases with 53% Ph-positive host metaphases, some containing additional structural changes. Thirty days later further cytogenetic progression was evident. A slowly progressive fungal pneumonia concurrently present was treated with intravenous amphotericin and gradual reduction of cyclosporin. Subsequently, without further cytotoxic chemotherapy, pancytopenia and bone marrow hypoplasia developed, and on day 144 only donor karyotype marrow cells were seen. Chromosomes have remained of donor type on subsequent occasions, and the patient has a normal performance status 25 months after BMT. The patient's course illustrates that factors operating after allogeneic BMT contribute to longterm control of CML. The factors potentially responsible for this spontaneous remission, after early relapse, are discussed.
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PMID:Spontaneous complete remission of chronic myeloid leukaemia following haematological relapse after allogeneic bone marrow transplantation. 228 87


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