Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CSA toxicity includes renal impairment, microangiopathic hemolytic anemia (MAHA), thrombocytopenia (T), and consumptive coagulopathy (CC). We report five BMT patients who developed CSA-associated hematological toxicity. All were conditioned with Ara-C, Cyclophosphamide, Methylprednisolone, TBI, and in two cases busulfan. IV CSA was started the day after marrow infusion and, when practicable, changed to the enteral route. Five patients developed MAHA and T resulting in significantly increased transfusion requirements. All patients had renal impairment and red cell fragmentation. In all patients fragmentation was noted before renal impairment. All developed disproportionate increases in BUN relative to serum creatinine consistent with decreased renal perfusion. Hypertension followed renal impairment in four cases and occurred at the same time as the renal impairment in one case. Two developed CC, prolongation in APTT, and marked decreases in plasma fibrinogen. All patients improved on reduction of the CSA dose. BMT recipients receiving CSA at variable doses may develop evidence of a TTP-like syndrome and/or CC.
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PMID:Coagulation defects in cyclosporine A treated allogeneic bone marrow transplant patients. 304 63

Endothelial damage is thought to be a contributing factor in the pathogenesis of Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndromes (TTP/HUS). The present studies measured two markers of endothelial cell stimulation and/or activation [von Willebrand Factor (vWF:Ag) and thrombomodulin (TM)] in patients with TTP/HUS disorders and compared them to controls. The patient groups consisted of adults with TTP/HUS, with (n = 13) and without (n = 14) peak Cr levels >2.0 mg/dl. Additionally, 52 patients with Bone Marrow Transplant-associated Thrombotic Microangiopathy (BMT-TM) following allogeneic BMT were evaluated. Both vWF:Ag and TM were elevated in all patient groups compared to controls. TTP/HUS patients with peak Cr >2.0 mg/dl had higher TM levels (P < 0.001) than did those with peak Cr levels below 2 mg/dl. However, thrombomodulin/ creatinine (TM/Cr) ratios did not differ in these two groups nor did they differ from controls. BMT-TM pts had higher vWF:Ag levels and higher TM/Cr ratios than controls and TTP/ HUS, P < 0.001. The median TM/Cr ratio in BMT-TM was 91 (range = 34-229) compared to 38 (range = 29-50) in controls, P < 0.001 and 38 (range = 6 to 156) in TTP/HUS, P < 0.001. Additionally both TM (P < 0.001) and TM/Cr (P < 0.02) were higher in patients with Grades 3 and 4 BMT-TM compared to those with Grade 2 BMT-TM. These results suggest that endothelial cell activation occurs in TTP/HUS and BMT-TM. Since TM/Cr ratios were higher in BMT-TM compared to TTP/HUS, these findings suggest that the mechanism of elevated TM in BMT-TM cannot be explained solely by altered renal excretion. Taken together, these findings strongly indicate a role of endothelial cell damage in BMT-TM.
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PMID:Plasma von Willebrand Factor Antigen (vWF:AG) and thrombomodulin (TM) levels in Adult Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndromes (TTP/HUS) and bone marrow transplant-associated thrombotic microangiopathy (BMT-TM). 894 57

Growth factor administration to donors prior to bone marrow (BM) harvesting results in an enrichment of the graft for myeloid precursors. In animals, growth factor-primed BM has a higher repopulating ability than untreated BM. Ten patients received an HLA-identical sibling, allogeneic transplant using granulocyte colony-stimulating factor (G-CSF)-stimulated BM. Stimulation consisted of G-CSF at 10 microg/kg/day for 2 days prior to harvest. Patients were transplanted for various benign and malignant hematological conditions. The GVHD prophylaxis consisted of cyclosporine, methotrexate and/or prednisone. Compared to untreated historical control BM, stimulated BM infusions contained similar number of nucleated cells (mean +/- s.d.: 3.5 +/- 1.5 vs 4.0 +/- 0.9 x 10(8)/kg), CD34+ cells (mean +/- s.d.: 7.5 +/- 3.0 vs 9.4 +/- 6.7 x 10(6)/kg), and CD3+ cells (mean +/- s.d.: 129 +/- 30 vs 190 +/- 59 x 10(6)/kg) but higher numbers of granulocyte-macrophage colony-forming units (mean +/- s.d.: 20 +/- 12 vs 96 +/- 34 x 10(4)/kg). Patients receiving stimulated BM had prompt and stable engraftment of white cells and platelets. On average they attained an ANC of > or = 1 x 10(9)/l 9 days earlier and a platelet count of > or = 20 x 10(9)/l 6 days earlier than historical controls receiving unstimulated HLA-identical sibling BM. Hospitalization was shortened by a mean of 10 days and transfusion requirements were modest. None of the patients developed severe GVHD or disease relapse. Two patients died of severe VOD post-BMT and thus were unevaluable for platelet engraftment. A third patient died of TTP on day 76 post-BMT. Seven patients are alive and well 49-585 days post-BMT. Stimulated BM may provide a valuable alternative to allogeneic BM and PBSC transplants. Ideal stimulation regimens need to be investigated.
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PMID:A pilot study of allogeneic bone marrow transplantation using related donors stimulated with G-CSF. 946 75

We reviewed 24 episodes of thrombotic microangiopathy (TMA) representing 22 patients from July 1989 to July 1998. Nine cases presented with a community acquired (CA group) thrombotic thrombocytopenic purpura or hemolytic uremic syndrome (TTP/HUS), 3 cases were related to pregnancy (P group), 10 cases were compatible with TMA after bone marrow transplantation or chemotherapy (BMT/C group), and 2 cases had a background of scleroderma (SC group). Twenty episodes were treated exclusively with therapeutic plasma exchange (TPE) using fresh frozen plasma (FFP) replacement. In the BMT/C group, 4 patients underwent immunoadsorption with the Prosorba protein A column in addition to TPE. The CA, P, and SC groups had favorable outcomes with 78% (7 of 9), 100% (3 of 3), and 100% (2 of 2) survival, respectively. Despite intensive therapy, there was only 1 survivor in the BMT/C group (1 of 10). Successful outcome required up to 57 TPE treatments. We could not document any benefit to immunoadsorption with the Prosorba protein A column.
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PMID:Extracorporeal treatment of thrombotic microangiopathy: a ten year experience. 1060 20

Candidemia is a serious complication in patients following allogeneic blood, marrow, and organ transplantation. Fourteen patients developed nosocomial fungemia among 204 allogeneic marrow transplants performed during 1997-1999. Incidence of hematogenous candidiasis was 6.8 per 100 allogeneic BMT. All 14 had an indwelling central venous catheter (CVC) and fluconazole (100-200 mg daily) was given prophylactically. In 11 (78.5%) neutropenic patients, duration between agranulocytosis and diagnosis of fungemia was (median, +/- s.d.) 10 +/- 8 days. Candida glabrata (53.3%) was the most common yeast species, followed by C. krusei (33.3%), and C. parapsilosis (13.3%). Candida albicans was conspicuously absent. Ten patients (71.4%) had primary transplant-related complication (>2 days) including hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) (n = 5), severe hemorrhagic cystitis (n = 3), and bacteremia (n = 2). Seven (50.0%) patients expired and in three (21.4%) deaths were attributed to fungemia. The impact of a primary transplant-related complication on short-term survival in this setting was not significant (P = 0.07) (HUS/TTP (P > 0.5); neutropenia (P > 0.5); GVHD (P = 0.35)). Removal of CVC did not alter outcome in our group (P > or = 0.5) although in patients with persistent fungemia (>72 h), and those with preceding bacteremia, mortality was significantly higher (P = 0.002). Conventional prognosticators of poor outcome did not adversely effect short-term survival in our transplant recipients with hematogenous candidiasis. The predominance of C. glabrata and C. krusei breakthrough infections was similar to what is seen with high-dose fluconazole (400 mg) prophylaxis, and no adverse effects of low-dose fluconazole in terms of increased incidence of non-susceptible Candida species was seen.
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PMID:Candida glabrata and Candida krusei fungemia after high-risk allogeneic marrow transplantation: no adverse effect of low-dose fluconazole prophylaxis on incidence and outcome. 1178 48