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)

Cyclophosphamide (CY) was activated in vitro with washed rat liver microsomes and cofactors. Pretreatment of mouse spleen cells in vitro with the activated drug abolished their capacity to give a primary antibody response to SRBC and levan on transfer to irradiated syngeneic recipients. However, responsiveness returned if challenge was delayed for 7 or more days after transfer. Part of this was shown to be of donor origin by an allotype marker. The treatment of normal spleen cells with activated CY in vitro also prevented B cells from regenerating their immunoglobulin receptors after capping with anti-immunoglobulin serum. The induction of suppression required contact between lymphocytes and activated CY for at least 30 min at 37 degrees and did not appear following incubation for 1 h at 0 degrees. Since the antibody response of drug-treated spleen cells to SRBC could not be restored with purified normal B or T cells, it is probable that B and T lymphocytes are both susceptible to suppression by activated CY in vitro. Similar pretreatment abrogated the graft-versus-host (GVH) reactivity of spleen cells as measured by survival and in a popliteal lymph node assay. B cell chimerism in F1 recipients of drug-treated parental spleen cells was demonstrated by the presence of congenic allotype markers. This suggests a possible approach for the attenuation of GVH disease which is associated with bone marrow transplantation in man.
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PMID:The capacity of microsomally-activated cyclophosphamide to induce immunosuppression in vitro. 3 18

A 26-year-old man with severe aplastic anemia was treated with high-dose Cyclophosphamide followed by the infusion of bone marrow cells from his HLA-identical sister. After initial intake of the graft, rejection ensued by day 46 which was followed by a permanent complete aplasia. After 4 months, bone marrow retransplantation with the same donor was attempted after a more intensive conditioning regimen. This led to permanent engraftment with rapid normalization of the blood counts lasting now for over 12 months. The patient has since remained in excellent clinical condition without signs of graft-versus-host disease.
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PMID:Successful allogeneic bone marrow retransplantation with the same donor after graft rejection: application of a modified conditioning regimen. 38 Jun 89

Graded doses of Cyclophosphamide (Cy) or 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) were given to CD2F1 or C57Bl/6 mice. One, 45 or 60 days later the animals were tested for allograft responses, competence of producing cytotoxic lymphocytes in vitro and lethal graft-versus-host disease (GVHD) in vivo, delayed-type hypersensitivity (DTH) and humoral antibody responses against sheep red blood cells (SRBC). Both agents produced strong inhibitory effects, except for DTH, when given 1 day before the antigenic stimulus. However immunodepression lasted for at least 60 days after DTIC, whereas relatively rapid recovery of immune responsiveness was detected in mice treated with Cy. When Cy or DTIC were given to allogeneic donor mice 1 day before spleen cell transfer, immunodepressed recipients did not undergo GVHD. However when drugs were administered to recipient mice inoculated with allogeneic spleen cells, lethal GVHD occurred when Cy but not DTIC was given to the hosts. DTH responses were potentiated by Cy when the drug was given 1 day before sensitization. In contrast hypersensitivity reactions were not affected by DTIC treatment. It was concluded that DTIC is a potent and long-lasting immunodepressive agent, capable of affecting various T-cell subpopulations and possibly B lymphocytes in mice. Since the drug inhibits immune response when given before the antigenic stimulation, it was suggested that DTIC acts through a mechanism similar to that of alkylating non phase-specific agents.
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PMID:Drug induced modulation of immune responses in mice: effects of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) and cyclophosphamide (Cy). 40 14

From October 1987 to December 1990, 101 patients with acute myeloid leukemia (AML) were randomized to be transplanted in first complete remission (CR1). Preparative regimen including Cytoxan (120 mg/kg) with total body irradiation (CYTBI) (N = 50) or busulfan (16 mg/kg) (BUSCY) (N = 51) was followed by allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling. Mean time between diagnosis and BMT was 119 days. The outcome for CYTBI at 2 years is better for probability of disease-free survival (DFS) (72% v 47%) (P less than .01), survival (75% v 51%) (P less than .02), relapse (14% v 34%) (P less than .04), and transplant mortality (8% v 27%) (P less than .06). In multivariable analysis, higher relapse and decreased survival and DFS were associated with BUSCY regimen, while chronic graft-versus-host disease also influenced independently the probability of relapse. This demonstrates the present limitation of busulfan use in this setting, possibly due to probable individual variations in biodisponibility. Furthermore, besides the anti-leukemic effect of preparative regimens, this trial points out the progress accomplished in BMT management (transplant mortality = 8% in CYTBI) over the last 20 years as well as the effectiveness of transplant in early first CR after CYTBI (DFS = 72% at 2 years).
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PMID:Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: a randomized trial of a busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: a report from the Group d'Etudes de la Greffe de Moelle Osseuse. 1139 26

Since 1980, 107 consecutive patients (pts) underwent bone marrow transplantation (BMT) for nonconstitutional severe aplastic anemia (SAA) at our institution. All received conditioning with Cytoxan (150 mg/kg) and thoraco-abdominal irradiation (6 Gy) from an HLA-identical sibling donor. Mean age was 19 years (5 to 46 years). Forty-nine pts had less than 0.2 x 10(9)/L PMN and 53 failed to respond to previous immunosuppressive therapy before BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate (22 pts), cyclosporine (52 pts), or both (33 pts). With a median follow-up of 45 months (12 to 120 months), overall actuarial survival was 68% (confidence interval 95%:9.7). Of 16 factors tested, five were shown to adversely influence survival by multivariate analysis: grade greater than or equal to 2 acute GVHD (relative risk [RR]: 5.5), prior immunosuppressive therapy (RR: 3.5), female as donor (RR: 2.4), nonidiopathic SAA (RR: 2), and more than 0.2 x 10(9)/L PMN AA (RR: 2). Because acute GVHD was the most potent factor for survival, we analysed risk factors for acute GVHD. By multivariate analysis, 2 of 14 factors tested were independent: male as recipient (RR: 3) and previous alloimmunization of the donor (RR: 4.3). On long-term follow-up, chronic GVHD was observed in 49 pts of 89 surviving more than 100 days (55%). Multivariate analysis showed that infection before transplant (RR: 1.3) and previous history of acute GVHD (RR: 1.8) were associated with an increased risk of chronic GVHD.
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PMID:Bone marrow transplantation in 107 patients with severe aplastic anemia using cyclophosphamide and thoraco-abdominal irradiation for conditioning: long-term follow-up. 193 58

4 patients (3 female, 1 male) bone marrow transplanted for severe aplastic anemia (3 allogeneic, 1 syngeneic) became pregnant or parented children 19, 37, 81, and 34, 52 months, respectively, after BMT. Conditioning regimen consisted of 200 mg/kg Cyclophosphamide. Donor buffy coat cells were used for rejection prophylaxis, and methotrexate was used as GVHD prophylaxis. 1 female patient developed a mild chronic graft versus host disease with vaginal sclerosis which made a cesarean section necessary. 3 out of 5 pregnancies were uneventful. 1 patient had mumps in the 14th week, another patient had a late abortion in the 25th week of unknown cause. A high incidence of offspring complications was noticed including 1) persistence of fetal circulation syndrome, 2) erythroblastosis fetalis, and 3) prolonged newborn-icterus. These observations confirm previous reports on resumed fertility after BMT for SAA. A relation between the unexpected high incidence of pre-, peri-, and postpartal complications and the BMT procedure can neither be proved nor excluded.
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PMID:[Pregnancy and fetal complications after bone marrow transplantation]. 194 50

We have performed bone marrow transplants on four children with severe aplastic anemia who lacked an human leukocyte antigen (HLA)-identical sibling donor. Patients were prepared with cyclophosphamide and 600 cGy fractionated total body irradiation, and then received marrow from a parent donor mismatched for one (two patients), two (one patient), or three (one patient) HLA antigens. All four patients engrafted. One died early of acute graft-versus-host disease. The three others showed sustained complete hematopoietic reconstitution. Two are alive and hematologically normal 43-87 months after transplant. Both have had acute and chronic graft-versus-host disease (CGVHD), and one of the two remains on immunosuppressive drugs. The fourth died at 48 months after transplant of CGVHD. The previous experience with HLA-incompatible marrow transplants is reviewed, and the rationale for this preparative regimen is discussed. Cyclophosphamide and 600 cGy fractionated total body irradiation is an effective preparative regimen for children with severe aplastic anemia receiving transplants from HLA-nonidentical parental donors, allowing engraftment and full hematologic reconstitution.
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PMID:Successful treatment of severe aplastic anemia by bone marrow transplantation from HLA nonidentical family members: preliminary results utilizing cyclophosphamide and 600 cGY fractionated total body irradiation. 202 71

Three patients, a 28 years old female (case 1), and two males aged 32 and 18 (cases 2 and 3) received allogeneic bone marrow transplants for acute non lymphatic leukemia (cases 1 and 2) and severe aplastic anemia (case 3) from HLA identical siblings. All patients were conditioned with Busulfan and Cyclophosphamide, and received GVHD prophylaxis with cyclosporin and steroids. Disease free survival is greater than 232, greater than 50 and greater than 201 days. Hematological reconstitution was detected 12, 13 and 10 days post transplant. All patients presented fever during the first month and received broad spectrum antibiotics including amphotericin in case 3. Acute GVHD presented in case 3 and chronic GVDH in case 1. Both patients responded to higher doses of cyclosporine and steroids. Allogeneic bone marrow transplant is a complex and expensive therapy, but can benefit a selected group of patients who fare poorly with conventional therapy. This report communicates the first three successful allogeneic bone marrow transplants performed in Chile.
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PMID:[Allogenic bone marrow transplantation: report of 3 cases in Chile]. 248 57

The SAA Registry of the EBMT now contains data on 171 children younger than 15 years of age with acquired SAA and undergoing BMT between 1970 and 1988. The overall actuarial survival is 63% at 10 years. In a multivariate Cox analysis, the year of transplant was the most important prognostic factor with a significant advantage for children grafted in 1984-88 (81%) vs 1981-83 (67%) and 1970-80 (41%) (p = 0.02). Cyclosporine A given for GVHD prophylaxis, no treatment before transplant and an interval less than 90 days from diagnosis to BMT were all favourable variables in univariate analysis. As regard to transplant procedures, the better results were obtained using Cyclophosphamide and Cyclosporine A (78%) followed by Cyclophosphamide plus irradiation plus Cyclosporine A (77%). Sex, etiology and the severity of the aplasia had no impact on survival in both uni and multivariate analysis.
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PMID:Allogeneic bone marrow transplantation (BMT) for acquired severe aplastic anaemia (SAA) in children. 269 23

A 2-year-old girl being prepared for a bone marrow transplant for treatment of stage IV neuroblastoma suffered a fatal graft v host (GVH) reaction following a transfusion on nonirradiated packed RBC. GVH disease is a recognized complication of transfusion in patients with leukemia and lymphoma and is a frequent complication following bone marrow transplantation. GVH disease has also been reported in pediatric patients with solid tumors who have received sufficient chemotherapy to render them immunocompromised. GVH disease can be prevented by irradiating all blood products with at least 1,500 rad for patients having total lymphocyte counts less than 1,000/microL or for those who have received greater than 30 mg/kg/d of Cytoxan.
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PMID:Fatal graft v host disease in a child with neuroblastoma following a blood transfusion. 379 74


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