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)

Patients with graft-versus-host disease (GVHD) develop multiple organ failure (MOF), so systematic management is needed. First, patients should be kept in a clean room. Antibiotics, anti-fungal drugs and gamma-globulins are essential for the prevention and treatment of infections. If patients are hypoxic for the nasal cannula or the mask, continuous positive airway pressure (CPAP) or artificial ventilation must be used. In the treatment of hepatic dysfunction, lactulose, branched chain amino acid, glucagon-insulin, and Prostaglandin E1 (PGE1) are given. If plasma exchanges are ineffective, a bilirubin absorption therapy may remain partially effective. In the treatment of renal failure, diuretics, PGE1 and dopamine are given. Hemofiltration and hemodialysis will be effective. But the effective treatment for post-transfusion GVHD is unavailable, so systematic management of GVHD is no more than allopathic treatment.
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PMID:Systematic management of graft-versus-host disease (GVHD). 792 35

Carboplatin is a second-generation platinum complex developed to be less ototoxic and nephrotoxic than cisplatin. The major toxicity was found to be myelosuppression; thus, it was tried in acute leukemia. When given by daily bolus injection for 5 days, carboplatin exhibited some activity but was associated with additional nonhematologic toxicity as well. When administered by continuous infusion, responses were higher and toxicity less. The Eastern Cooperative Oncology Group (ECOG) conducted a phase II study of carboplatin 315 mg/m2 daily given by continuous infusion for 5 days to adults with refractory and relapsed acute leukemia. A second course was given if the bone marrow on day 14 revealed persistent leukemia. Those achieving a complete remission (CR) were given an additional course as consolidation. The median age was 49 years among acute myelogenous leukemia (AML) patients and 46 years in acute lymphoblastic leukemia (ALL) patients. Of 46 eligible patients enrolled in the study (36 AML and 10 ALL), 8 (17%) achieved a CR (6 AML and 2 ALL). Remissions were observed in 2 of 10 primary refractory patients (1 AML and 1 ALL). When treated in first relapse, 5 of 14 patients (36%) achieved a CR. In 38 instances marrow specimens were examined after treatment; 10 (26%) showed no change, 16 (42%) were hypoplastic, and 12 (32%) were hypoplastic with residual leukemic cells. Of the 18 deaths that occurred on study, 14 were due to infection, 2 due to infection and bleeding, 1 due to uncontrolled gastrointestinal bleeding and 1 due to graft-versus-host disease in a patient who had relapsed after bone marrow transplantation. Marrow suppression was usually prolonged. Nonhematologic toxicity was mild. Gastrointestinal toxicity consisted of easily controlled nausea and vomiting. Three patients had grade 3 diarrhea. Grade 3 or more renal toxicity was observed in 8 patients, all of whom had received nephrotoxic antibiotics for treatment of bacterial or fungal infections. One patient died of renal failure that developed near the end of a second induction course. Ototoxicity was observed in 11 patients (24%) and was grade 2 or less in all but 3. These results indicate that carboplatin is an active agent in leukemia. Further studies are under way in combination with other agents such as etoposide, mitoxantrone, 5-azacytidine, and daunorubicin in treatment of acute leukemia and in combination with ifosfamide and etoposide in refractory lymphomas.
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PMID:High-dose carboplatin in the treatment of hematologic malignancies. 823 1

Patients who are heavily immunosuppressed, such as those undergoing intensive anti-cancer chemotherapy, are at risk for development of accidental engraftment and graft-versus-host disease when they undergo transfusion with cellular blood components, a condition known as transfusion-associated graft-versus-host disease (TA-GVHD). To prevent this complication, it is routine to irradiate such blood components prior to their transfusion, although the minimum irradiation dose required is uncertain. The development of probable TA-GVHD is reported in a 10-year-old child following transfusions of platelets and packed red cells that had been irradiated at a nominal dose of 15 Gy. The transfusions were given during treatment for relapse of acute myeloid leukemia. Although the child developed complications including exfoliative dermatitis, delayed bone marrow regeneration, renal failure requiring dialysis, and respiratory failure requiring assisted respiration, she recovered from the episode of TA-GVHD after treatment with high-dose methylprednisolone and antithymocyte globulin. However, her leukemia relapsed, and she died. This experience suggests that the irradiation of cellular blood components at a nominal dose of 15 Gy prior to their transfusion to heavily immunosuppressed patients may be insufficient to prevent TA-GVHD.
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PMID:Transfusion-associated graft-versus-host disease: report of an occurrence following the administration of irradiated blood. 851 87

To determine if partial T cell depletion and intensive post-transplant immunosuppression is effective for the prevention of graft-versus-host disease (GVHD) in pediatric recipients of HLA-non-identical marrow transplants, 10 children with leukemia received high-dose thiotepa, cyclophosphamide and total body irradiation followed by transplantation of CD3-depleted marrow from matched unrelated or one-antigen mismatched related adult donors. To maximize the number of stem cells infused, a large volume (1-1.51) of marrow was harvested from the donors. After immunopurging, the marrow infused contained a median of 3.7 x 10(6) CD34+ cells/kg, 1.4 x 10(6) CD3+ cells/kg, and 1.6 x 10(6) CD5+ cells/kg as assessed by flow cytometry. Cyclosporine, methylprednisolone and anti-CD4 ricin A chain immunotoxin (XZ-CD5) were used for prevention of GVHD post-transplant. All patients achieved an ANC > 0.5 x 10(9)/l. No patient developed capillary leak syndrome or renal failure from XZ-CD5. Five developed grade 2-4 acute GVHD, and all responded to treatment with steroids. Five of nine evaluable patients developed chronic GVHD. Two patients relapsed, but the most common cause of death was infection with or without chronic GVHD. Four patients survive 10+ to 27+ months post-transplant. XZ-CD5 is well-tolerated in T cell-depleted marrow transplant recipients. However, partial T cell depletion and intensive post-transplant immunosuppression did not prevent moderate acute GVHD or chronic GVHD. This may have been due to the high number of T cells infused with the marrow.
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PMID:Prevention of graft-versus-host disease with anti-CD5 ricin A chain immunotoxin after CD3-depleted HLA-nonidentical marrow transplantation in pediatric leukemia patients. 875 Feb 62

This trial was designed to test the use of CD34+ selected haemopoietic stem cells (HSC) in HLA-mismatched donor-recipient pairs, following intensive conditioning with thiotepa, antilymphocyte globulin (ALG), cyclophosphamide and single-dose total-body irradiation (sTBI). 10 patients aged 16-50 with advanced malignancies and a two- or three-antigen mismatched family donor entered this study. Donor marrow and G-CSF primed peripheral blood cells were processed separately on CD34 columns (Ceprate). The median number of infused CD34+ cells were 5.66 x 10(6)/ kg, with 0.55 x 10(6)/kg CD3+ cells. Nine patients received cyclosporin for graft-versus-host disease (GvHD) prophylaxis. Median neutrophil counts on day 21 were 2 x 10(9)/l with a median platelet count of 60 x 10(9)/l, but CD4 counts remained extremely depressed throughout the study. Acute GvHD was scored as grade 0-I in two patients, as grade II in seven, and grade III in one. Eight patients died at a median interval of 72 d from HSCT (range 20-144) due to cytomegalovirus (CMV) associated interstitial pneumonitis (IP) (n = 5), renal failure (n = 1). GvHD (n = 1) and Aspergillus meningitis (n = 1). Two patients are alive 365-495 d post transplant, one in remission and one in relapse. This study suggests that large numbers of positively selected mismatched HSC can rapidly engraft after intensive conditioning regimen: however, profound post-transplant immunodeficiency leads to a high risk of lethal infectious complications.
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PMID:Transplantation of HLA-mismatched CD34+ selected cells in patients with advanced malignancies: severe immunodeficiency and related complications. 933 36

TNF-alpha (Tumor necrosis factor-alpha) is involved in many immunological and inflammatory processes, and might be expected to play an important role in the development of BMT-related complications. Triple therapy (pentoxifylline, ciprofloxacin and prednisone) with known anti-TNF activity was tested in 37 patients undergoing a hematopoietic progenitor transplant (HPT). A control group of 16 patients with similar characteristics was selected among consecutive patients receiving a HTP in a neighboring center who did not receive anti-TNF prophylaxis. Major transplant-related complications were registered (VOD, acute GVHD, infectious episodes, renal failure and mucositis) and survival status. TNF plasma concentrations were determined by ELISA, and pentoxifylline plasma concentrations were determined by HPLC. Among patients treated with pentoxifylline (PTX), ciprofloxacin and steroids, no difference in the mean survival time was observed compared with the control group. The incidence of procedure-related death up to day +35 was 11% in the study group and 6% in the control group. In spite of a tendency to a lower incidence of mucositis there was a higher incidence of infections (positive blood cultures) in the study group (49%) than in the control group (16.7%) (P = 0.16). This difference achieved statistical significance in patients receiving an allogeneic HPT (P = 0.05). It is likely that the use of steroids in the early period after transplant increases infectious episodes and makes control of GVHD difficult. The combined administration of steroids with pentoxifylline and ciprofloxacin has not proved beneficial in preventing mucositis, renal failure, VOD or GVHD, or in improving patient survival.
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PMID:Pentoxifylline, ciprofloxacin and prednisone failed to prevent transplant-related toxicities in bone marrow transplant recipients and were associated with an increased incidence of infectious complications. 946 81

Fifty leukemia patients were given bone marrow transplants (BMTs) from unrelated donors at Meitetsu Hospital. We studied the outcomes of their transplants from two perspectives: leukemia disease stage and acute graft versus host disease (GVHD). The probability of disease-free survival for standard-risk, high-risk, and super-high risk patients was 65%, 29%, and 8%, respectively. The main causes of death were septicemia, cardiac and renal failure, and relapse of leukemia in the high- and super-high risk patients, and grade III-IV acute GVHD in the standard-risk patients. The incidence of grade II-IV and grade III-IV acute GVHD was 32% and 17%, respectively. All 7 patients in whom grade III-IV severe acute GVHD developed died. We conclude that better control of acute GVHD and treatment of early stage complications are clearly important to improving the outcome of BMTs from unrelated donors, especially for high and super-high risk patients.
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PMID:[Outcomes of 50 leukemia patients who received bone marrow transplants from unrelated donors]. 975 Apr 53

The aim of this study was to investigate the effect of a bone marrow transplantation (BMT) on renal function in children. In a 5-year period, 142 children received a BMT at the Department of Pediatrics of the University Hospital Leiden. The study was performed retrospectively using the estimated glomerular filtration rate before and 1 year after BMT, and weekly measurements of serum creatinine during the first 3 months after BMT for assessment of renal function. Patient characteristics (sex, age, diagnosis), conditioning regimen, type of BMT, major complications (sepsis, veno-occlusive disease and graft-versus-host disease (GVHD)) and the use of nephrotoxic medication were listed. In the first 3 months after BMT 17 (12%) patients died, 13 from transplant-related complications other than renal failure and four from relapse of the disease. Forty-eight children (34%) had a period with acute renal insufficiency. A high pre-BMT serum creatinine, transplantation with either a non-HLA-identical related or a matched unrelated donor were risk factors for acute renal insufficiency after BMT. Sepsis and the use of intravenous vancomycin were risk factors for acute renal insufficiency only for patients with a high pre-BMT serum creatinine. GVHD seemed to have a beneficial effect on renal function of BMT recipients. One year after BMT a total of 35 (25%) patients had died, 16 from transplant-related complications and 19 from relapse of the disease; another 17 patients could not be evaluated. Twenty-five of 90 evaluable children (28%) had chronic renal insufficiency. Chronic renal insufficiency 1 year after BMT was correlated with a high serum creatinine in the first 3 months after BMT. None of the children of this retrospective study on renal function after BMT needed dialysis.
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PMID:Bone marrow transplantation in children: consequences for renal function shortly after and 1 year post-BMT. 975 43

We present a 41 woman who underwent an allogeneic bone marrow transplantation as a treatment for a multiple myeloma. After presenting graft-versus-host disease, hyperbilirubinemia, cyclosporine toxic levels, renal failure and peripheral schistocytosis, she developed complex partial seizures and bilateral hypodensity lesions in occipital lobes. Fulminant microangiopathy was diagnosed; though promptly treated with immunoglobulins and fenitoin, she died in few days. Necropsy showed diffuse thrombotic disease and a haematoma in left occipital lobe. We review the types of thrombotic microangiopathy described up to now, and the different pathogenic theories related to them. According to our reviewing of the literature, this is the first case of fulminant thrombotic microangiopathy ever described in Spanish language.
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PMID:[Fulminant angiopathy caused by allogenic transplantation of bone marrow with cerebral involvement: clinico-pathologic correlation]. 984 32

The aim of our study was to assess the efficacy of extracorporeal photopheresis (ECP) in chronic graft-versus-host disease (GVHD). Eleven patients with chronic cutaneous GVHD were studied. Four had mucosal involvement and five had pulmonary involvement. All had failed to improve on first- and second-line therapy. Three patients received ECP alone; the remainder continued to receive steroids and/or immunosuppressive therapy. Patients received ECP twice monthly for 4 months and then once monthly for 3 months. They were evaluated by serial skin scores, mucosal and skin photography, pulmonary function tests, biochemical and haematological parameters. Nine patients showed objective evidence of cutaneous improvement with a mean reduction in skin score of 48% overall. In the 10th patient, skin scores and oral involvement improved on twice monthly ECP but deteriorated when reduced to once monthly. The final patient died from renal failure secondary to cyclosporin toxicity. Two out of five patients with lung involvement showed a mild improvement in pulmonary function tests. Liver function tests were abnormal in five patients; they improved in one and deteriorated in three. All patients receiving concomitant immunosuppressive/steroid therapy were able to reduce drug dosages by trial completion. Our results indicate that ECP can benefit patients with cutaneous and mucosal chronic GVHD who have failed on first- and second-line therapies. The effect on the systemic manifestations of GVHD is less consistent.
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PMID:Extracorporeal photopheresis (ECP) in the treatment of chronic graft-versus-host disease (GVHD) 1071 39


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