Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many approaches have been taken to reducing the rate of graft failure and the incidence of graft-versus-host disease (GVHD) in bone marrow transplantation (BMT) of patients with severe aplastic anemia (SAA). The combination of cyclophosphamide with irradiation has had unequivocal success in reconstituting a sustained engraftment, but this procedure has severe associated risks such as second malignancies. Recently, cyclophosphamide (CYC) plus antithymocyte globulin (ATG) has been shown to be an effective alternative to irradiation-based programs in retransplants. Based on these experiences, the current clinical trial was started to prepare patients suffering from SAA for marrow transplantation from HLA-identical siblings with ATG plus CYC. Nine patients have been enrolled into the study so far. They received a total dose of 200 mg/kg CYC and concomitantly 120 mg/kg or 90 mg/kg ATG, followed by cyclosporine plus methotrexate as post-transplantation GVHD prophylaxis. Eight of nine patients survived without any transplant-associated complications; i.e., they had a documented stable engraftment without rejection and without acute or chronic GVHD. One patient died due to an Aspergillus sepsis prior to a definite engraftment. Although our data are preliminary because of the small number of patients enrolled and a follow-up of only 30 months, CYC plus ATG appears to be an effective preparative regimen for BMT in patients with SAA, resulting in a favorable outcome.
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PMID:Cyclophosphamide/antithymocyte globulin conditioning of patients with severe aplastic anemia for marrow transplantation from HLA-matched siblings: preliminary results. 765 56

Totally 436 Chinese patients having received multiple transfusions of red cells and platelets on more than three occasions were screened for red cell antibodies. Twenty-six (6%) of them were positive. Anti-E, -Mia, and -c were the common alloantibodies. Nine patients were immunized during the period of regular transfusions, with a newly immunized rate of 2% (9/436). Among 436 patients, 387 were screened for HLA antibodies by lymphocytotoxicity test (LCT). The overall positive rate was 35%. Most of the antibodies identified were against the high-frequency HLA antigens in the Chinese population. About 10% of the LCT-positive cases reverted to negative state during the follow-up period. After chloroquine stripping of the target platelets, mixed passive hemagglutination assay was used to detect platelet antibodies other than HLA antibody. Fifty-eight of 161 cases (36%) were positive for platelet antibodies, but half of them disappeared within 1 month. Nineteen of the 58 patients had sepsis and 2 had jaundice. These findings suggested that HLA and platelet antibodies are common among Chinese, though their clinical significance and the role in platelet damage are doubtful.
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PMID:Red cells, HLA and platelet antibody formation in patients with multiple transfusions. 781 4

It is a matter of concern that the elderly donor may have increased risks in the peri-operative period due to age-related changes in various organ. Nephrosclerosis, atherosclerosis and low GFR of an elderly kidney may portend a poor graft outcome. A retrospective analysis of our live related renal transplant program (from June 1989 to December 1993) revealed that 27 of the donors were above 60 years of age. 21 of the recipients have been followed up for more than 1 year. These patients were compared with a cohort of 25 patients (donor age < 45 years) with similar HLA match, immunosuppressive protocol, and follow-up period more than 1 year. Graft survival at 1 year was 86% and 88% in the recipients from elderly and younger donors respectively; 1 patient in the control group died of fulminant sepsis. Mean follow-up was 21.6 months in the study group and 22.8 months in the control group. Allograft function was evaluated by serum creatinine and differential GFR by Tc DTPA scan. Serum creatinine (mg%) was 1.3 +/- 0.2 and 1.4 +/- 0.2 in the study group and 1.3 +/- 0.3, 1.2 +/- 0.3 in the control group at 3 and 12 months respectively. Glomerular filtration rate (ml/min) was 36.5 +/- 11.6 and 43.7 +/- 12.4 in the recipients from elderly donors whereas those from the younger donors had GFR (ml/min) of 40.6 +/- 9.6 and 49.6 +/- 14.2 at 3 and 12 months respectively, GFR continued to improve in both groups with follow-up. There was no difference in incidence or severity of ATN In the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Should elderly donors be accepted in a live related renal transplant program? 786 13

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

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 163 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor-recipient combinations were at least one-haplotype disparate, and 21 were two-haplotype disparate. Transient sensitization occurred in 2% and permanent sensitization in 7%. Over a 10-year period, the DST+Aza allograft survival rate is similar to the HLA-identical sibling transplants. The CMV sepsis rate was only 2%, and there were no lymphoproliferative neoplasms. The low rate of sensitization (7%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of early rejection (3%) argues for a modification of the immunologic response.
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PMID:Beneficial effects of donor-specific transfusions on long-term renal allograft function. 787 58

Fifteen patients (nine male, six female) with severe aplastic anemia (SAA) undergoing HLA-identical allogeneic bone marrow transplantation (BMT) received preparative regimens consisting of cyclophosphamide and total lymphoid irradiation. Patients were aged from eight to 26 years (median 15 years). Prophylaxis of graft versus host disease (GVHD) including cyclosporine and short course methotrexate was administered. One early death occurred at day 8 post BMT. Among the other 14 patients, one died of sepsis at day 53 with no evidence of engraftment, 13 were engrafted despite the number of donors exposed in transfusions of previous blood components. Eleven patients have survived from six to 100 months (median, 54 months), post BMT. The remaining two patients died of acute GVHD-related infections on days 44 and 63. Acute GVHD occurred among eight of 13 engrafted patients, five of whom were grades II-IV clinically. Chronic GVHD developed among five patients, three of whom were clinically progressive and extensive. Two of three patients with extensive chronic GVHD had received transfusion of donor's buffy coat after BMT. Our data indicate an engraftment rate of 87% (13/15). The projected probability of disease-free survival was 73% (11/15) at 9.3 years after BMT according to the Kaplan-Meier model. Further efforts must be made to eliminate GVHD and to control fatal infections.
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PMID:Bone marrow transplantation for severe aplastic anemia. 791 56

In liver transplantation (LTx), numerous studies have failed to demonstrate an adverse effect of HLA-A,B,DR incompatibility or of donor-specific positive cross-match on survival of the recipients. In this study, we examined the effect of antidonor cytotoxic antibody and HLA compatibility in 800 LTx recipients with CsA-based immunosuppression. Thirty-four of 482 (7%) recipients were transplanted across a positive donor-specific T cell cross-match. Four-year patient and graft survival was 71% and 67%, respectively, in negative cross-match recipients and 53% and 50%, respectively, in positive cross-match recipients (P = 0.0051 and P = 0.023). Neither B cell-positive cross-match nor the presence of panel reactive antibody (PRA) had an adverse impact on the liver allograft outcome. Interestingly, 21/58 (36.2%) patients with PRA > or = 10% had a positive T cell cross-match, whereas only 7/382 (1.8%) patients with PRA < 10% did (P < 0.0001). This indicates the predictive value of PRA cross-match results. B lymphocyte cross-match results also were strongly correlated with the presence of PRA, as 26/57 (45.6%) of the patients with PRA > or = 10% had a positive cross-match, whereas only 22/394 (5.6%) with PRA < 10% did (P < 0.0001). Analysis of HLA compatibility demonstrated a significant impact on patient's survival, comparing only 0-2 vs. 6 HLA-A+B+DR mismatches and 0 vs. 1 vs. 2 HLA-DR mismatches. Four-year patient survival rate for 0 to 2 antigen mismatches was 86%, whereas for 6 antigen mismatches it was 62% (P = 0.025). Overall actuarial 4-year patient survival rate in HLA-DR-mismatched groups (0 vs. 1 vs. 2) was 84%, 73%, and 64%, respectively (P = 0.033). In no mismatched category was graft survival rate significantly different. Sepsis or rejection was the cause of graft loss in 1/10 (10%), 21/75 (28%), and 34/85 (40%) patients with 0, 1, and 2 HLA-DR mismatches, respectively. The difference between patient and graft survival was accounted for by survival after retransplantation, which was lower in patients with more HLA-DR mismatches in primary transplants. The latter group received intensive immunosuppressive therapy during the first month after primary transplantation, as compared with those with fewer HLA-DR mismatches (P = 0.04). The above data suggest that prospective cross-match should be performed in patients with > or = 10% PRA if it is logistically feasible.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA compatibility and liver transplant outcome. Improved patient survival by HLA and cross-matching. 767 11

One hundred forty-seven patients with hematologic diseases and treated by allogeneic marrow transplants received graft-versus-host disease (GVHD) prevention with methotrexate and cyclosporine. In addition, 73 of the 147 patients were randomized to receive methylprednisolone during the first 35 days after transplant to improve GVHD prevention, whereas 74 patients were randomized not to receive methylprednisolone. The randomized trial enabled us to examine whether methylprednisolone increased the risk of infection after marrow grafting. Charts of study patients were analyzed retrospectively for infection events including bacteremia, septicemia, and fungemia. The randomization was stratified by diagnosis, patient age, genotypic HLA identity, and assignment to laminar airflow room isolation. All patients were given a short course of methotrexate (no longer than 11 days) and cyclosporine for no longer than 180 days after marrow transplantation. Methylprednisolone was begun on the day of marrow grafting at a dose of 1 mg/kg body weight intravenously in divided AM and PM doses through day 22. Methylprednisolone was administered at a dose of 0.5 mg/kg in divided doses from days 22 through 35, and then discontinued. Infections were analyzed for the time interval ending on day 65 after transplantation, which included the period of methylprednisolone administration and 1 month thereafter. Seventy-one episodes of first infection events were observed in patients receiving methylprednisolone compared with 47 episodes in patients not receiving the drug. Predominant infections were bacteremias, followed in descending order by fungemias and septicemias. The most prevalent organisms cultured were gram-positive bacteria, especially coagulase-negative Staphylococcus and Streptococcus species. Pseudomonas species were the most common gram negative bacteria, and the most prevalent fungus was Candida albicans. Multivariable Cox regression analysis showed that patients receiving methylprednisolone had a 1.5 times higher risk of infection (P = .03), with acute GVHD being another independent risk factor for infections (P = .005). Methylprednisolone, when added to GVHD prevention by methotrexate and cyclosporine, increases the risk of infection during the early posttransplantation period.
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PMID:Increased risk of infection in marrow transplant patients receiving methylprednisolone for graft-versus-host disease prevention. 804 48

We report a case of sepsis due to Trichosporon cutaneum in a 20-year-old patient with acute promyelocytic leukemia. Neutropenia with a hypocellular marrow persisted for 90 days after two courses of induction chemotherapy with mitoxantrone and ara-C. Amphotericin B, fluconazole, and granulocyte-macrophage colony-stimulating factors were administered. Neutropenia (ANC < 1,000/microL) resolved 14 days after HLA-identical bone marrow transplantation. The patient is in remission, with a performance status of 100%, more than 1 year after transplantation.
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PMID:Long-term survival after allogeneic bone marrow transplantation complicated by trichosporosis. 811 5

Between October 1988 and December 1992, 167 patients with leukemia receiving marrow transplants from HLA-identical donors and conditioned with cyclophosphamide (120 mg/kg) were randomized to additional treatment with either busulfan (16 mg/kg, n = 88) or total body irradiation (TBI; n = 79). The busulfan-treated patients had an increased cumulative incidence of veno-occlusive disease of the liver, ie, 12% compared with 1% in the TBI group (P = .009). Furthermore, hemorrhagic cystitis occurred in 24% of the busulfan patients versus 8% in the TBI patients (P = .003). In patients with advanced disease beyond first remission or first chronic phase, transplantation-related mortality was 62% among the busulfan-treated patients compared with 12% among the TBI recipients (P = .002). These differences between the two groups were statistically significant in multivariate analysis. Seizures were seen in 6% of the busulfan-treated patients and were absent in the TBI group (P = .03). Grade II-IV of acute graft-versus-host disease (GVHD) was similar in the two groups, but grade III-IV and chronic disease was more common in the busulfan-treated group (P = .04). Death associated with GVHD occurred in 17% of the busulfan-treated group and 2% of the TBI group (P = .003). Patients treated with busulfan had a 3-year actuarial survival of 62%, which was worse than the 76% among those treated with TBI (P < .03). In multivariate analysis, poor survival was associated with advanced disease (P < .0001), no posttransplant septicemia (P = .0006), grade II-IV GVHD (P = .006), and busulfan treatment (P < .02). The incidence of relapse did not differ between the two groups. Relapse-free survival was also similar in the two treatment groups on analysis of data from all patients, children, patients with early disease, and those with acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia. However, in adults (P = .05) and patients with advanced disease (P = .005), leukemia-free survival was significantly better in those treated with TBI. We conclude that patients treated with busulfan have more early toxicity and an increased transplant-related mortality in patients with advanced disease. TBI is therefore the treatment of choice, especially in adults and patients with advanced disease. However, busulfan is an acceptable alternative for patients with early disease and for those in whom TBI is not feasible.
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PMID:A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group. 816 51


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