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)

Although hepatic veno-occlusive disease (HVOD) is a common complication of allogenic bone marrow transplantation (BMT), pulmonary veno-occlusive disease (PVOD) is very rare. Only three cases have been described in the literature. We report the case of a 19-year-old woman who developed PVOD accompanied by microangiopathic hemolytic anemia (MAHA) and hemolytic uremic syndrome (HUS) 1 year after a second BMT for relapsed acute lymphoblastic leukemia (ALL). Autopsy examination revealed obstruction of the small pulmonary veins with edematous thickening of the intima. These findings are compatible with PVOD. Pulmonary GVHD and pulmonary aspergillosis were also observed. Various etiologic factors have been implicated in PVOD after BMT. We postulate that pulmonary GVHD and pulmonary infection including aspergillosis played an important role in the occurrence of both PVOD and HUS in our patient. Microangiopathic cytokines released in response to the GVHD and infection may damage the intima of microvessels that were previously injured by the two BMT. Despite appropriate therapy, the microangiopathic process was irreversible and the patient died. Thus, measures must be taken to prevent and treat PVOD after BMT.
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PMID:Pulmonary veno-occlusive disease accompanied by microangiopathic hemolytic anemia 1 year after a second bone marrow transplantation for acute lymphoblastic leukemia. 885 72

We investigated the nature of hemostatic alterations occurring after bone marrow transplantation. In 45 patients, we evaluated the coagulation parameters, naturally occurring anticoagulants and thrombomodulin at days +15 and +22 after conditioning therapy. It was observed that endothelial cell damage is a central pathogenetic mechanism in some BMT complications. The increased plasma level of thrombomodulin after conditioning therapy is therefore discussed as a marker of endothelial cell injury. At day +15 a significant increase of fibrinogen from 276.1 mg/dI to 389.1 mg/dI was observed, while the natural anticoagulants all decreased significantly. Eleven patients with clinical complications related to endothelial damage had a significant thrombomodulin increase which, in uncomplicated patients, remained unchanged or resulted in lower than baseline values. Analysis of the data shows a strong correlation between clinical findings, reflecting endothelial cell injury and thrombomodulin increase when the increment is > or = 30%. We found a significant elevation in thrombomodulin in 70% of clinical complications related to endothelial cell damage namely: septicemia, GVHD, VOD. There were four cases (or 9%) of false positive data, and only two (or 4.5%) of false negative results. We therefore propose thrombomodulin assessment as a valid parameter to monitor chemotherapy toxicity-related complications.
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PMID:Increased plasma level of vascular endothelial glycoprotein thrombomodulin as an early indicator of endothelial damage in bone marrow transplantation. 886 50

The safety and potential efficacy of FK506 in combination with a short course of methotrexate (MTX) for the prevention of acute graft-versus-host disease (GVHD) after marrow transplantation from HLA-matched unrelated donors was evaluated in a single-arm Phase II study conducted at two centers. Forty-three patients, 15 to 54 (median 41) years of age, were transplanted for hematologic malignancies. Thirty-seven of 43 evaluable patients had evidence of sustained marrow engraftment. Five patients died before day 17 after transplantation. The median time to an absolute neutrophil count of > 0.5 x 10(5)/L was 21 (range, 14 to 30) days. Nephrotoxicity (serum creatinine concentration > 2 mg/dL or doubling of baseline) occurred in 32 patients (74% cumulative incidence during the first 100 days after transplant). Other adverse effects included hypertension (n = 27), hyperglycemia (n = 27), neurotoxicity (n = 9) and thrombotic thrombocytopenic purpura (n = 2). Severe veno-occlusive disease of the liver occurred in 9 (21%) of the 43 patients. Eighteen patients (42%) developed grades II to IV acute GVHD and five (12%) developed grades III to IV acute GVHD. Twelve of 25 evaluable patients developed extensive chronic GVHD within 1 year of marrow transplantation resulting in an estimate of the probability of developing this complication of 48%. The cumulative incidence of transplant-related mortality during the first 100 days was 37%. Kaplan-Meier estimates of disease-free survival at 2 years for good-risk, poor-risk, and all patients were 65%, 4%, and 32%, respectively. FK506 in combination with a short course of MTX appears active in preventing acute GVHD after marrow transplantation from unrelated donors. Further studies comparing the combination of FK506 and MTX with cyclosporine and MTX for the prevention of acute GVHD are warranted.
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PMID:FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors. 889 34

Thrombopoietin (TPO) is a growth and differentiation factor for megakaryocytes and platelets. An ELISA was developed for measuring TPO concentrations in human sera. The mean +/- S.D. of TPO level obtained in 29 control subjects was 0.87 +/- 0.35 fmol/ml. We measured the TPO level in 36 patients after allogeneic bone marrow transplantation (BMT) and determined the relationship between blood levels of TPO and changes in the circulating platelet mass. In general, a reciprocal relationship was observed between TPO and platelet count (r = -0.609, P < 0.0001; n = 165). With the decrease in the platelet mass after myeloablative therapy, the TPO level increased proportionally and peaked during the platelet nadir. The peak concentration of TPO ranged from 20-50 fmol/ml. The TPO level decreased with the normalization of the platelet mass. In contrast, the TPO level decreased during acute graft-versus-host disease (GVHD) in several patients. Furthermore, the TPO level was significantly lower in the patients with hepatic veno-occlusive disease (VOD) than in the patients after BMT without GVHD and VOD in the samples of less than 50000/microliters platelets (P < 0.005). These findings suggest that in the patients given allogeneic BMT, TPO has an important role in the physiologic regulation of platelet production and that liver damage due to acute GVHD and VOD may decrease the TPO level.
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PMID:Serum thrombopoietin level after allogeneic bone marrow transplantation: possible correlations with platelet recovery, acute graft-versus-host disease and hepatic veno-occlusive disease. Nagoya Bone Marrow Transplantation Group. 892 86

Successful allogeneic peripheral blood progenitor cell (PBPC) transplantation has recently been reported by several transplant centers. This is a first report describing allogeneic PBPC transplantation in five patients using related pediatric donors between the ages of 4 and 13 years. Donors underwent 3 or 4 days of rhG-CSF treatment (6 micrograms/kg q 12 h) for stem cell peripheralization prior to PBPC collection, which was performed by continuous-flow apheresis on day 4 or 5. Venous access was exclusively by ante-cubital veins. A median of 2.2 times (range 1.4-3.6) the donor's total blood volume (TBV) was processed per procedure. In cases where the donor's TBV was < 2 liters, the blood cell separator was primed with human serum albumin (HSA-5%), and anticoagulation was performed using a combination of heparin (pre-apheresis bolus + continuous infusion (CI)) and/or ACD-A (CI at a reduced rate). The median number of CD34+ cells collected per kg of donor body weight (b.w.) and per liter of donor blood processed during each procedure was 128 x 10(4) (range 58 x 10(4)-314 x 10(4)). Between one and two aphereses were sufficient to collect a safe CD34+ cell engraftment dose of 3 or 4 x 10(6)/kg of recipient b.w. Two PBPC recipients were parents, and three were siblings. After freezing and thawing, the median number of CD34+ cells per kg of recipient b.w. thawed and transfused was 8.5 x 10(6) (range 3.2 x 10(6)-9.7 x 10(6)). The time to PMN > 1000/microliters was between 10 and 16 days (four out of five evaluable patients), and platelets > 20000/microliters were reached between day 13 and 14 post-transplantation (three out of five evaluable patients). Two out of three evaluable patients developed grades one and three acute GVHD, and one out of three developed chronic GVHD. Two patients died of sepsis and VOD at day 10 and 19, respectively. Two adult patients are alive and in cytogenetic and molecular remission of CML at +339 and +227 days post-allotransplantation. One 3-year-old girl with hemophagocytic lymphohistiocytosis is in remission at +304 days post-transplantation. Using pediatric donors for allogeneic PBPC transplantation appears to be safe, yields a sufficient amount of progenitors for prompt engraftment, and results in clinical outcome similar to adult PBPC allotransplantation.
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PMID:Allogeneic peripheral blood stem cell transplantation using normal patient-related pediatric donors. 893 41

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

A patient with CML in accelerated phase received G-CSF-mobilized PBPC from an unrelated HLA genotypically matched donor. The blood groups of the patient and donor were bidirectionally incompatible. Hematologic recovery was rapid with > 500 PMN/microliter on day +9. Starting on day +5 bilirubin levels increased from 1.3 mg/dl up to a maximum of 18 mg/dl on day +14. Clinical signs and laboratory tests supported major hemolysis. Blood typing on day +16 revealed early blood-group change, consistent with donor-derived antibodies produced by passenger-lymphocytes which may have mediated severe hemolysis. The early onset and strong intensity of the hyperbilirubinemia could be a specific feature of ABO-incompatible allogeneic PBPC transplantation which would be difficult to differentiate from GVHD or VOD.
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PMID:Rapid engraftment after allogeneic ABO-incompatible peripheral blood progenitor cell transplantation complicated by severe hemolysis. 902 62

Hepatic veno-occlusive disease (VOD) is a frequent and severe complication after bone marrow transplantation (BMT). We previously have described plasminogen activator inhibitor-1 (PAI-1) as a possible marker of VOD. To confirm the significance of this finding, we now determined PAI-1 levels in 31 of 186 consecutive patients undergoing BMT who developed hyperbilirubinemia greater than 3 mg/dL for various reasons. Diagnoses were made by clinical criteria and confirmed by biopsy in 23 of 31 patients. They included VOD (n = 7), acute graft-versus-host disease (GVHD) of the liver (n = 7), and other hepatic injury (n = 17). PAI-1 (mean +/- SD) was significantly (P < .001) elevated in patients with VOD (321.6 +/- 161.2 ng/mL) as compared with patients with GVHD (22.8 +/- 8.4 ng/mL) or other hepatic damage (32.8 +/- 30.8 ng/mL) at the timepoint of bilirubin increase. At the peak bilirubin concentration, the corresponding PAI-1 levels were 426.1 +/- 230.0 ng/mL in patients with VOD, 41.0 +/- 20.6 ng/ mL in patients with GVHD, and 44.6 +/- 32.9 ng/mL in patients with other hepatic injury (P < .001 VOD v GVHD/other hepatic injury). Our results underline the relevance of PAI-1 in the differential diagnosis of hyperbilirubinemia after BMT and its significance as a sensitive and specific marker of severe VOD.
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PMID:Plasminogen activator inhibitor-1 confirms the diagnosis of hepatic veno-occlusive disease in patients with hyperbilirubinemia after bone marrow transplantation. 905 43

Suspected deep or systemic mycosis in patients undergoing high-dose therapy and autologous or allogeneic bone marrow transplantation (BMT) requires an immediate systemic antimycotic therapy. Intravenous therapy with the standard drug conventional amphotericin-B is associated with severe adverse effects like nephrotoxicity and chills. Furthermore, BMT patients often receive other potential nephrotoxic drugs such as CsA or virustatics. In this study, we report 74 BMT-patients treated with liposomal amphotericin-B for culture-documented aspergillosis (n = 5) or candidiasis (n = 6), or for serologically (n = 35) or clinically suspected mycosis or as prophylaxis (n = 2). Therapy was initiated with a median dose of 2.8 (0.64-5.09) mg/kg body-weight and continued for 13 (1-55) days. The drug was excellently tolerated and only in one was therapy stopped due to severe chills and fever. Severe organ impairment was not observed under therapy with liposomal amphotericin-B. Creatinine decreased in five patients after an increase under preceding therapy with the conventional formulation. Influence of liposomal amphotericin-B on bilirubin and transaminases was difficult to evaluate due to therapy-related toxicity, veno-occlusive disease (VOD), and graft-versus-host disease (GvHD). 10/11 culture-positive patients died from aspergillosis (5/5) or candidiasis (5/6), but in 9/11 of these subjects the immunity was additionally compromised by GvHD, steroid therapy, and VOD. Liposomal amphotericin-B was effective in preventing relapse of systemic mycosis in 10/12 patients with a history of aspergillosis (n = 11) or candidiasis (n = 1). We conclude, that favourable toxicity of liposomal amphotericin-B should encourage dose escalation studies of liposomal amphotericin-B randomised against the conventional formulation and that the comparison of patients undergoing BMT with patients under standard chemotherapy might be difficult because of additional risk factors of the BMT-patients.
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PMID:Antimycotic therapy with liposomal amphotericin-B for patients undergoing bone marrow or peripheral blood stem cell transplantation. 908 39

Ten children with myelodysplastic syndrome underwent an allogeneic bone marrow transplantation (BMT) with an intensified conditioning regimen. The median age of the patients was 8 years (range 2-10), and included 6 males and 4 females. The subtype of the disease was refractory anemia (RA) in 4, RA with excess blasts (RAEB) in 4, RAEB in transformation (RAEB-T) in 1, and juvenile chronic myelogenous leukemia (JCML) in 1. All patients were conditioned with high-dose cytosine arabinoside (12000 mg/m2), cyclophosphamide (120 mg/kg) and either total body irradiation (10-13.2 Gy) or busulfan (16 mg/kg or 560 mg/m2). Cyclosporine A and/or methotrexate were used for the prophylaxis of graft-versus-host disease (GVHD). Engraftment was prompt in all but one patient. Severe acute GVHD (grade 3) (n = 1), interstitial pneumonitis (n = 1) and veno-occlusive disease of the liver (n = 1) occurred. The disease relapsed in one patient with RAEB-T. Seven of the 10 patients were alive and disease free 2-74 months after BMT. The disease-free survival rate at 4 years was 69 +/- 15%. All surviving patients were in the full performance status. The examined children with MDS tolerated this intensified conditioning regimen well.
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PMID:Therapeutic trial of intensified conditioning regimen with high-dose cytosine arabinoside, cyclophosphamide and either total body irradiation or busulfan followed by allogeneic bone marrow transplantation for myelodysplastic syndrome in children. 911 98


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