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)

The outcomes of 39 patients with hematological disorders who had undergone allogeneic bone marrow transplantation (BMT) from September 1986 to March 1992 were reported. The length of follow-up was six to 50 months. Twenty patients with acute leukemia, eight patients with aplastic anemia, seven patients with chronic myelogenous leukemia, two patients with non-Hodgkin's lymphoma, and two patients with myelodysplastic syndrome were included. Major complications were acute graft-versus-host disease (GVHD) (17 cases out of 36 evaluable cases; 47 percent), chronic GVHD (13/25; 52 percent), sepsis (20/41; 49 percent), interstitial pneumonitis (IP) (10/30; 33 percent), and veno-occlusive disease (VOD) of the liver (5/41; 12 percent). Acute and chronic GVHD were well managed with cyclosporin, methotrexate, and steroids. VOD of the liver seemed to be associated with the pretransplant regimen including busulfan and cyclophosphamide. The overall probability of disease free survival of 39 patients who had undergone allogeneic BMT was 0.56. This includes nine high risk cases such as HLA antigen mismatch between the donor and the recipient, and as in the second or subsequent remission or in relapsed cases. The probability of disease free survival in patients with acute leukemia, chronic myelogenous leukemia, and aplastic anemia including high risk cases was 0.55 (n = 20), 0.71 (n = 7), and 0.50 (n = 8) respectively. These results indicate that allogeneic BMT is the major therapeutic strategy for patients whose survival could not be expected by conventional chemotherapy and that drug intensification for conditioning regimen is also important.
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PMID:Allogeneic bone marrow transplantation as a therapeutic modality for hematological disorders: a report based on 39 cases. 786 58

Gastrointestinal (GI) disease is frequent in all types of immunocompromised patients but occurs with greatest frequency in patients with acquired immunodeficiency syndrome (AIDS). Thus, much of this review deals with human immunodeficiency virus (HIV)-related GI diseases. Gastrointestinal diseases in other immunocompromised patients are compared with those in patients with AIDS. Conditions unique to transplant recipients, such as graft-versus-host disease (GVHD) and posttransplant lymphoproliferative disorders (PTLDs), are discussed separately. We have divided these GI diseases into four main categories: (1) HIV-related inflammatory conditions other than opportunistic infections (HIV-related enteropathy, proctocolitis, and CD8 lymphocytosis); (2) inflammatory conditions unrelated to HIV or opportunistic infections (neutropenic enterocolitis, regional enteritislike enteropathy, and GVHD); (3) opportunistic infections (illnesses caused by herpesvirus, cytomegalovirus, and miscellaneous other viruses; Mycobacterium, Candida, Histoplasma, Cryptococcus, Cryptosporidium, Microsporida, Isospora, Leishmania, Toxoplasma and Strongyloides organisms as well as Pneumocystitis carinii; and (4) neoplasias (Kaposi's sarcoma [KS], AIDS-related non-Hodgkin's lymphoma [NHL], HIV-related Hodgkin's disease [HD], PTLDs, and miscellaneous neoplasms). The prevalence, pathogenesis, clinical manifestations, gross pathological findings, and microscopic features of each disease entity are discussed.
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PMID:Gastrointestinal disease in the immunocompromised patient. 795 57

Twenty-one patients with non-Hodgkin's lymphoma (NHL) felt to be incurable with conventional chemotherapy underwent high-dose chemo +/- radiotherapy and allogeneic sibling donor transplant. The median patient age was 27 years (range 6-47 years); 13 were male and 8 female. By the working formulation, 6 patients at diagnosis had low-grade NHL, 8 intermediate-grade, and 7 high-grade disease. Three patients were in first remission at transplant, 3 in an advanced remission, 5 had failed to respond to initial therapy while 4 had a partial response to initial therapy, and 6 were in relapse (first or beyond). Sixteen patients were conditioned with cyclophosphamide, etoposide and total body irradiation (TBI), 4 with cyclophosphamide and TBI, and one with a combination of busulfan, melphalan and cyclophosphamide. GVHD prophylaxis was variable. At last follow-up, 8 of 21 patients remain alive and progression-free at a median of 37.5 months (range 6-58 months); actuarial event-free survival is 38% (95% confidence interval 17-58%). Thirteen patients died at a median of 2 (range 0.5-8) months post-BMT, 5 from regimen-related toxicity, 3 from acute GVHD, 2 from infections related to chronic GVHD and 3 from disease progression. Factors which were adverse predictors of progression-free survival included low-grade disease, presence of B symptoms at BMT, Karnofsky performance status at BMT and female sex. We concur with previous workers in concluding that allogeneic BMT may offer effective therapy for selected patients with incurable NHL. Major issues to be considered include timing of BMT and disease status at BMT.
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PMID:Allogeneic bone marrow transplantation for poor-prognosis non-Hodgkin's lymphoma. 813 43

87 patients underwent bone marrow transplantation (BMT) in Innsbruck between 1983 and 1992. 81 patients were suffering from hematologic malignancies and severe aplastic anemia and six patients had advanced solid tumours/sarcoma. 56% of the patients undergoing HLA-identical sibling BMT were in an advanced or refractory stage of disease at the time of BMT. 19 patients underwent autologous BMT and 5 patients received a graft from an HLA-matched unrelated donor. Patients were treated with standard conditioning regimens according to the underlying disease. Cyclosporine A (CsA) was given prophylactically against graft-versus-host disease (GVHD) either alone or in combination with methotrexate. Probability of survival for patients transplanted in the first chronic phase of chronic myelogenous leukemia (CML) was 85%, whereas the disease free survival (DFS) for patients transplanted in accelerated phase or blast crisis was only 40%. DFS for acute myelogenous leukemia (AML) in first complete remission and acute lymphoblastic leukemia (ALL) standard-risk (i.e., first or second complete remission) was 71% and 60%, respectively. All patients transplanted for non-Hodgkin's lymphoma (NHL) or Hodgkin's disease had refractory or advanced disease. Probability of survival for lymphoma patients was 60%. Acute GVHD > grade II developed in 35% of patients undergoing HLA-identical sibling BMT (46% in the high-risk group vs. 21% in the standard-risk group). Main causes of death in the high-risk group were relapse (31%), severe bacterial or fungal infections (17%), interstitial pneumonia (11%) and acute GVHD (6%).
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PMID:[Innsbruck results of bone marrow transplantation in treatment of hematologic neoplasms and solid tumors]. 819 54

Paraneoplastic pemphigus is a recently described autoimmune disease characterized by painful mucosal ulceration and polymorphous skin lesions in association with an underlying neoplasm. Distinct autoantibodies bind desmoplakin I, desmoplakin II, bullous pemphigoid antigen and an uncharacterized 190 kDa antigen. A case is presented of paraneoplastic pemphigus that developed after radiotherapy for non-Hodgkin's lymphoma in a 53 year old man. Multiple skin biopsies showed a lichenoid reaction without acantholysis. Immunofluorescence and mucosal biopsies were required to establish the correct diagnosis. Corneal opacities resembling lichenoid graft-versus-host disease and retinal haemorrhages, which developed in the patient, have not been previously documented. Despite high doses of immunosuppressive agents and plasmaphoresis, the patient eventually died from respiratory failure.
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PMID:Paraneoplastic pemphigus triggered by radiotherapy. 859 11

We undertook an analysis of 2,150 recipients of bone marrow transplant (BMT) at the University of Minnesota to determine the incidence of post-BMT malignant neoplasms (MNs). Fifty-one patients developed 53 MNs, compared with 4.3 expected from general population rates (standardized incidence ratio [SIR], 11.6, 95% confidence interval [CI], 8.2-14.5). These included 22 occurrences of B-cell lymphoproliferative disorder (BLPD), 17 solid nonhematopoietic tumors, 10 myelodysplastic syndromes (MDS), 1 acute myelogenous leukemia (AML), 2 non-Hodgkin's lymphoma (NHL), and 1 Hodgkin's disease (HD). The estimated actuarial incidence of any post-BMT malignancy was 9.9% +/- 2.3% at 13 years posttransplant. The cumulative probability of BLPD plateaued at 1.6% +/- 0.3% by 4 years from transplant and factors independently associated with increased risk included in vitro T-cell depletion of marrow (relative risk (RR) = 11.9, P < .001), HLA mismatch (RR = 8.9, P < .001), use of antithymocyte globulin (ATG) for graft versus host disease (GVHD) prophylaxis (RR = 5.9, P < .001) or in the preparative regimen (RR = 3.1, P = .03) and primary immunodeficiency (RR = 2.5, P = .06). The cumulative probability of developing solid malignancy was 5.6% +/- 2.2% at 13 years from BMT. Malignant melanomas were the most common (SIR, 10.3, 95% CI 1.9 to 25.4). The actuarial incidence of MDS/AML plateaued at 2.1% +/- 0.8% at 9 years and was seen most often in older patients receiving autologous peripheral blood stem cells for HD or NHL. These data document that BMT recipients are at an increased risk of later malignancy, which may add significant morbidity and mortality to the transplant process. Methods for screening and identification of individuals at increased risk need to be addressed in future studies.
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PMID:Malignant neoplasms following bone marrow transplantation. 861 87

Eight consecutive patients with relapsed/refractory non-Hodgkin's lymphoma or Hodgkin's disease received conditioning therapy with BCNU, etoposide, cytosine arabinoside and melphalan (BEAM) followed by autologous blood stem cell transplantation (ABSCT). Cyclosporine was administered from day +1 until day +28 post-ABSCT to induce autologous graft-versus-host disease (GVHD) for a possible antitumor effect. Three patients developed histologically documented grade II GVHD between 22-40 days post-transplant. GVHD resolved with local hydrocortisone 1% application in one patient and after a short course of steroid in the remaining two patients. Further studies are required to document any beneficial antitumor effect of such therapy following ABSCT.
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PMID:Cyclosporine-induced autologous graft-versus-host disease following autologous blood stem cell transplantation for lymphoma. 880 18

Between October 1991 and May 1994, 42 patients were treated with cyclophosphamide, thiotepa, and total body irradiation followed by an allogeneic transplantation of marrow depleted of T cells with soybean agglutinin and E-rosetting. Patients included in this study had acute myelogenous leukemia (13), chronic myelogenous leukemia (12), acute lymphocytic leukemia (nine), Hodgkin's disease or non-Hodgkin's lymphoma (four), multiple myeloma (three), or myelodysplastic syndrome (one). The mean age was 34 (range 8 to 51 years). Nineteen patients had a matched sibling donor and 18 received marrow from 6/6 matched unrelated donors while five received transplants from unrelated donors disparate at one DR locus (5/6 match). Time to granulocyte engraftment (AGC > or = 500/mm3) occurred at a mean of 16.5 days for related and 11.4 days for unrelated transplant recipients, and was related to the increased use of G-CSF in the unrelated population. There was no correlation with number of mononuclear cells, T cells, or CD34-positive cells infused, the rate of engraftment or the incidence of transplant complications. Multivariate analysis determined that G-CSF administration and a diagnosis other than ALL were the only factors associated with a faster rate of engraftment. Patients receiving unrelated donor transplants, those with ALL, or those who had a low T cell number infused (< or = 8.0 x 10(3) cells/kg) experienced delayed hospital discharge. The regimen resulted in excellent rates of engraftment (95.2%) with only one failure to engraft and one graft rejection. The incidence of grade III-IV acute graft-versus-host disease was 0% with sibling and 26.1% with unrelated donors. There were no cases of veno-occlusive disease. Fifty percent of patients are alive with a mean follow-up of 26.4 months. We conclude that this regimen is well tolerated and results in excellent engraftment with a low incidence of severe graft-versus-host disease and few therapy-related toxicities.
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PMID:Minimizing graft rejection in allogeneic T cell-depleted bone marrow transplantation. 893 45

Recently various cytokines have been introduced into the clinic and have played important therapeutic roles in the treatment of hematological malignancies. Among these cytokines, I have focused on interferon (IFN) and granulocyte (G) or granulocyte-macrophage (GM) colony stimulating factor (CSF), which are currently the most useful cytokines, in this review. IFN-alpha has been approved for chronic myelogenous leukemia (CML), multiple myeloma and hairy cell leukemia. In addition, IFN-alpha has therapeutic potentials for low grade non-Hodgkin's lymphoma, cutaneous T cell lymphoma and adult T cell leukemia/lymphoma. Thus, IFN-alpha is one of the most useful and wide-ranging antitumor agents in hematological malignancies. Most striking effects have been studied in chronic phase CML. Cytogenetic responses are seen in 30-40% of the treated patients and a complete cytogenetic response can be seen in about 10%. Long-term survival can be expected in these patients. Considering the risk of graft-versus-host disease-associated mortality in allogeneic bone marrow transplantation, the category of treatment is difficult to choose in IFN-responsive patients. Elucidation of the antitumor mechanism of IFN, as a prototype for other biological response modifiers, may revolutionize cancer treatment. G- and GM-CSF (CSFs) have reduced the duration of neutropenia, incidence of infectious episodes and days of hospitalization following cancer chemotherapy or stem cell transplantation. CSFs have also been used to mobilize peripheral blood stem cells and to increase dose intensity of chemotherapeutic agents. Leukemic cells from many patients with acute myelogenous leukemia (AML) have surface receptors for CSFs and may proliferate in response to CSFs. However, several randomized studies showed that CSFs can be used safely and effectively in augmenting neutrophil recovery in patients with AML when given after induction chemotherapy. Various trials have been made to prime leukemic cells by CSFs to make them more susceptible to chemotherapy, but no convincing evidence has been obtained.
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PMID:Cytokine therapy for hematological malignancies. 899 Jun 22

In an effort to decrease the relapse rate following autologous bone marrow transplantation for non-Hodgkin's lymphoma, patients were given cyclosporine and interferon following autologous marrow transplantation. Forty patients with intermediate grade non-Hodgkin's lymphoma that was relapsed or refractory to standard chemotherapy underwent autologous marrow transplantation. The preparative regimen consisted of cyclophosphamide 6.8 g/m2, etoposide 1600 mg/m2, and carmustine 400 mg/m2 over 4 days followed by reinfusion of bone marrow. Intravenous cyclosporine was started on day -1 as a 16 mg/kg loading dose followed by 3.6 mg/kg/day for 28 days after transplant. Patients were begun on alpha-interferon (starting dose, 0.5 million units s.c. every other day) following platelet engraftment (median day 24 post-transplant) and continued on 1.5 million units s.c. daily for 2 years. Regimen-related toxicities resulted in four (10%) deaths. Twenty-one (53%) patients developed marked erythema of the palms, soles, and arms. Biopsies of the erythema were consistent with grade I GVHD. Patients who did not develop rashes were not biopsied. The erythema persisted for a median of 10 days and resolved in all cases without treatment. Visceral GVHD was not apparent. All patients have been followed for a median of 24 months (range 12-54 months). To date, only five patients (13%) have relapsed after bone marrow transplant. Multivariant analysis could not identify risk factors for relapse post-transplant. Disease-free survival of all patients is 77% (95% confidence interval, 67-93%). The results of this pilot study suggest that the administration of cyclosporine and interferon may decrease the relapse rate of relapsed/refractory non-Hodgkin's lymphoma following autologous bone marrow transplantation.
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PMID:The treatment of relapsed or refractory intermediate grade non-Hodgkin's lymphoma with autologous bone marrow transplantation followed by cyclosporine and interferon. 902 49


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