Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A retrospective analysis was performed on 263 consecutive patients aged over 60 with de novo acute myeloid leukemia (AML) diagnosed in a single institution between 1979 and 1998. Eighty-nine patients (33%) received only palliative treatment, while 174 patients (67%) were treated with different intensive chemotherapy regimens. The 5- and 10-year overall survival (OS) for the whole series was 7.7+/-1.2 and 4.3+/-1.6%, respectively. For patients receiving chemotherapy, OS was 10.5+/-2.5 and 7+/-2.6%, while for those patients receiving supportive treatment it was 1.1+/-1.1 and 0%, respectively (P=0.002). Within the group of patients receiving chemotherapy, the complete remission (CR) rate was 46%; treatment failure rate was 54% (36% due to treatment-related mortality and 18% due to resistant disease). Variables influencing CR rate were FAB subtype, CD7 positivity, chemotherapy regimen, creatinine level, hepatomegaly, and period of diagnosis. Median disease-free survival (DFS) duration was 8.4 months with a probability of being disease-free at 10 years of 10+/-5%. There were no significant differences in DFS according to age. According to the period of diagnosis (1979-1986 vs. 1987-1998), improvements in the CR rate (27 vs. 56%, P=0.0002), and OS (10.9 vs. 15.7 months, P=0.0007) were observed. This large single-center study of unselected de novo AML elderly patients substantiates the progressive improvement achieved in the management of elderly patients with AML, probably due to an improvement in supportive care and the administration of conventional induction chemotherapy.
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PMID:Recent improvements in outcome for elderly patients with de novo acute myeloblastic leukemia. 1139 74

Farnesyl protein transferase inhibitors (FTIs) represent a new class of anticancer agents specifically targeting aberrant biologic processes involved with cellular transformation and malignancy. Originally developed to inhibit tumors by preventing activation of oncogenic ras genes via suppression of their posttranslational farnesylation, their anticancer activity appears to stem from their ability to inhibit farnesylation of various proteins that mediate signal transduction, growth, apoptosis, and angiogenesis. The safety, biologic activity, clinical response, and pharmacokinetics of R115777, a potent, orally active FTI, were recently investigated in a phase I dose-ranging study in patients with acute leukemias. Patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myelogenous leukemia (CML) in blast crisis received R115777 100 mg, 300 mg, 600 mg, 900 mg, or 1,200 mg twice daily for 21 days. Cycles were repeated every 28 to 31 days for up to four cycles. An overall response rate of 29% (10/34 evaluable patients) was observed across all R115777 doses. R115777 was well tolerated; common adverse events included fatigue, increased creatinine, nausea, and neutropenia. Dose-limiting toxicity occurred at 1,200 mg twice daily. Farnesylation of lamin A and HDJ-2, examined as biologic end points, was inhibited by R115777 doses > or = 600 mg twice daily. Pharmacokinetic evaluation suggests that R115777 is concentrated in bone marrow at steady state. The biologic and antitumor activity and favorable tolerability of R115777 support further clinical evaluation alone and in combination therapy in hematologic malignancies.
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PMID:Farnesyl protein transferase inhibitors as targeted therapies for hematologic malignancies. 1152 24

Analysis of data from 806 patients with newly diagnosed adult acute myelocytic leukemia (AML) (not including acute promyelocytic leukemia [APL] patients) treated at M.D. Anderson Cancer Center from 1995 through 1999 indicated that among patients entering a particular week of induction therapy, mortality rates were 6%, 8%, 6%, 9%, and 6% during weeks 1 to 2, 3 to 4, 5 to 6, 7 to 8, and 9 to 10, respectively. Because the mortality rate was not higher in the period immediately after treatment began, a definition of the period covered by the term "immediate" is somewhat arbitrary rather than "biologic," as might be the case if the early weeks were distinguished by a particularly high mortality rate. M.D. Anderson researchers have focused on the treatment complications and deaths occurring in the first 4 weeks after the beginning of induction therapy. In the first week, infection contributed to 71% of the deaths and pulmonary hemorrhage associated with diffuse alveolar damage contributed to 44%; the incidence of infection rose while the incidence of hemorrhage decreased during weeks 2 to 4. The associations between 4-week mortality rates with age, performance status, and white blood cell (WBC) count are well known. Study data suggest that elevated pretreatment levels of uric acid and tumor necrosis factor-alpha (TNF-alpha) levels are similarly associated with 4-week mortality. The prognostic significance of hyperuricemia appears independent of WBC, creatinine, and TNF-alpha. M.D. Anderson investigators have studied the roles of pheresis, TNF-alpha receptor-blocking agents, continuous venovenous dialysis, and newer antifungal agents in reducing early mortality. In particular, data from a retrospective M.D. Anderson analysis of pheresis (146 patients with WBC > 50,000 +/- microL) suggest that the value of this procedure is questionable. Preliminary data also point to the potential value of the TNF-alpha alpha receptor blocker etanercept (Enbrel, Immunex Corp, Seattle, WA) in patients at high risk of early death. Data from a randomized M.D. Anderson trial suggest that oral fluconazole plus itraconazole capsules are equivalent to liposomal amphotericin in antifungal prophylaxis. Because neither alternative appears satisfactory, researchers at M.D. Anderson are examining the role of intravenous itraconazole, which produces higher concentrations than itraconazole capsules in prophylaxis, and the role of FK 463 in treatment of fungal infections.
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PMID:Reducing mortality associated with immediate treatment complications of adult leukemias. 1169 50

A 54-year-old woman developed polymyositis 6 months after allogeneic bone marrow transplantation (BMT) for acute myelogenous leukemia transformed from myelodysplasia. At the onset of myositis, the patient had oral dryness, and the histology of oral mucosa was compatible with chronic graft-versus-host disease (GVHD). Muscle biopsy revealed focal muscle necrosis with massive lymphocytic infiltration. She was diagnosed with polymyositis, and the dose of cyclosporine was increased. Three months later, a complete resolution of myositis had been obtained, and the cyclosporine was tapered off. However, 51 months after the first episode of myositis, she again noted severe myalgia and was diagnosed with a recurrence of polymyositis based on high serum creatinine kinase (CK) and the findings of magnetic resonance imaging (MRI). At that time, chronic GVHD in other organs was not present. She achieved a second remission of polymyositis with cyclosporine, and has remained in remission for 4 years. The pathogenesis of myositis can be attributed to the immunologic imbalance characteristic of the post-allogeneic BMT setting.
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PMID:Recurrent acute myositis after allogeneic bone marrow transplantation for myelodysplasia. 1218 1

The aim of this study was to evaluate in 65 patients, who had previously undergone allogenic bone marrow transplantation (ABMT), the bone mineral density (BMD), the skeletal turnover and the prevalence of vertebral fractures. At the moment of recruiting, 10 of 65 transplanted subjects (15.3%) presented with signs of rejection of the transplanted tissue, thus they were excluded. The remaining 55 patients (21 males, 34 females, mean age 30.8 +/- 6.4 years), with a follow-up of 60 +/- 9 months after the transplant and without any treatment inducing osteopenia, underwent ABMT respectively for: chronic myeloid leukemia (n = 24); acute myeloid leukemia (n = 18); acute lymphatic leukemia (n = 13). One hundred and ten healthy control subjects (42 males and 68 females, mean age 31.0 +/- 3.7 years) matching with the patients for age, weight and height, were successively enrolled. All the participants were submitted to a densitometric evaluation (DEXA) of lumbar spine (L1-L4), of femoral neck and total femur; besides some skeletal metabolism parameters were dosed, such as: total alkaline phosphatase, bone alkaline phosphatase and urinary excretion of C-terminal telopeptide fragments normalized to creatinine. On the contrary, the morphometric evaluation, performed through a lateral dorsolumbar radiography, was actually carried out only in patients who had already undergone ABMT. The L1-L4 BMD study showed: 10/55 osteoporotic (18.1%), 19/55 osteopenic (34.5%) and 26/55 normal patients (47.4%). In transplanted patients BMD values, obtained at the three considered sites, resulted significantly reduced (p < 0.01) in comparison to controls. Moreover, in patients who underwent ABMT, a statistically significant increase was observed, in comparison to healthy subjects, in total alkaline phosphatase (p < 0.01), in bone alkaline phosphatase (p < 0.01) and in urinary excretion of C-terminal telopeptide fragments normalized to creatinine levels (p < 0.001). Seven of the 55 transplanted patients (12.7%) presented at the moment of Rx morphometric evaluation at least one vertebral fracture: 6 of whom were affected by osteoporosis and 1 by osteopenia. In conclusion, the subjects who had previously undergone ABMT maintain, even at a certain time after the transplant and without any rejection, an increased skeletal turnover and BMD values meanly lower than normal, leading to an increased risk for vertebral fracture.
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PMID:[Bone mass, bone metabolism, and prevalence of spinal fractures in recipients of allogenic bone marrow transplantation for leukemia]. 1552 45

The prognosis of Fabry disease has changed since enzyme-replacement treatment was introduced. Therefore, early diagnosis is instrumental. We describe a family presenting with chronic renal failure and proteinuria in which classic skin and neurological features were absent and the diagnosis of Fabry disease was difficult and not established until a second family member developed renal abnormalities. A 35-year-old man was admitted because he was overweight and had hypertension, with a serum creatinine level of 1.3 mg/dL (115 micromol/L) and protein excretion of 870 mg/d. Because 1 brother, who died years ago at the age of 32 years of acute myeloid leukemia, also had chronic renal failure and proteinuria, the diagnosis of Fabry disease was entertained. In the index patient, acroparesthesia, hypohidrosis, pain, angiokeratomas of the skin, and cornea verticillata suggesting Fabry disease were absent. Conversely, renal biopsy showed typical globotriaosylceramide deposits, and leukocyte alpha-galactosidase (alpha-GLA) A activity was decreased. Analysis of the alpha-GLA gene showed the mutation E66K. The mutation also was found in another asymptomatic 30-year-old brother who also had chronic renal failure and proteinuria, but normal extrarenal findings. In the brother who died, Fabry disease, missed at autopsy because of cancer-related findings, could be confirmed after repeated review of histological slides. Mutation carriers also included the mother, a sister (both without abnormalities), and a nephew (with episodic pains in his feet). We conclude that familial chronic renal failure combined with proteinuria is suggestive of Fabry disease, and such specific mutations as E66K predominantly may affect the kidneys.
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PMID:Chronic renal failure and proteinuria in adulthood: Fabry disease predominantly affecting the kidneys. 1586 41

Benzene has been used in various industries as glues or solvents in Korea. Since 1981, a preparation containing more than 1% benzene is not allowed to be manufactured, used or dealt with in the workplace, except in laboratories and in those situations benzene must be used in a completely sealed process as specified in Industrial Safety and Health Act (ISHA). Claims for compensation of hematopoietic diseases related to benzene have been rising even though the work environment has been improved. This study was conducted to assess the status of benzene exposure in different industries in Korea. We reviewed the claimed cases investigated by the Korea Occupational Safety and Health Agency (KOSHA) between 1992 and 2000. The Survey of National Work Environment Status in 1998 was analyzed to assume the number of workers and factories exposed to benzene. In 2000, six factories were investigated to evaluate benzene exposure. Personal air monitoring was performed in 61 workers and urine samples were collected from 57 workers to measure trans,trans-muconic acid (t,t-MA). Hematologic examination has performed. Thirty-four cases of hematopoietic diseases were investigated by KOSHA including eight cases of myelodysplastic syndrome and eight cases of acute myelocytic leukemia. Eight cases were accepted as related to benzene exposure. The number of workers possibly exposed to benzene can be estimated to be 196,182 workers from 6219 factories based on the database. The geometric mean of benzene in air was 0.094 (0.005-5.311) ppm. Seven samples were higher than 1 ppm but they did not go over the 10 ppm occupational exposure limit (OEL) value in Korea. The geometric mean of trans,trans-muconic acid in urine was 0.966 (0.24-2.74) mg/g creatinine. The benzene exposure level was low except in a factory where benzene was used to polymerize other chemicals. The ambient benzene from 0.1 to 1 ppm was significantly correlated with urine t,t-MA concentration (r=0.733, p<0.01). Hematologic parameters did not show significant difference among groups divided into the level of exposure. Korean workers were not highly exposed to benzene and the level of exposure was mostly less than 1 ppm. However, there might be an excessive risk of hematopoietic disorders due to relatively high past exposure. The OEL value of benzene was amended to 1 ppm from 10 ppm in 2002 and was effective since July 2003.
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PMID:Occupational exposure to benzene in South Korea. 1593 1

Nesiritide is a recombinant formulation of B-type natriuretic peptide used most commonly in the treatment of adults with decompensated congestive heart failure. The physiologic effects of BNP include natriuresis, diuresis, and smooth muscle relaxation. These physiologic effects result in its beneficial therapeutic effects, including a decrease in afterload, resulting in increased cardiac output with improved peripheral perfusion. The authors report on a 17-year-old with acute myelogenous leukemia who was admitted to the Pediatric ICU for treatment of septic shock, respiratory failure, myocardial dysfunction, and renal insufficiency. After the initial stabilization of his hemodynamic status, nesiritide was started and resulted in a stable balance of fluid intake versus output without the use of diuretics, improvement in myocardial function, and recovery of renal function manifested by a decrease of blood urea nitrogen and creatinine back to baseline values. The end-organ effects of nesiritide, previous reports regarding its use in the pediatric population, and its potential applications in the ICU setting are discussed.
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PMID:Nesiritide in a pediatric oncology patient with renal insufficiency and myocardial dysfunction following septic shock. 1602 Jan 20

The purpose of this study is to compare the long-term effects of an angiotensin II receptor blocker (ARB) and a long-acting calcium channel blocker (CCB) on left ventricular geometry, hypertensive renal injury and a circulating marker of collagen synthesis in hypertensive patients. Patients with essential hypertension (24 men and 19 women; age, 37-79 years) were treated with a long-acting CCB, amlodipine (AML; 2.5-7.5 mg once daily) for 6 months. Then, AML was switched to an ARB, candesartan (CS; 4-12 mg once daily), in 22 patients (CS group), while AML was continued in the remaining 21 patients for another 6 months (AML group). At the end of each treatment period, ambulatory blood pressure monitoring (ABPM), echocardiography and sampling of blood and urine were performed. The average office blood pressure during the latter period was comparably controlled in the AML and the CS groups (AML: 130 +/- 8/87 +/- 7 mmHg; CS: 133 +/- 11/ 88 +/- 7 mmHg), while the average systolic blood pressure of 24-h ABPM was significantly lower in the AML than in the CS group (127 +/- 9 vs. 133 +/- 14 mmHg, p<0.05). Consequently, the left ventricular mass index was significantly decreased in the AML group (102 +/- 18 to 92 +/- 12 g/m2, p<0.05), while the change was insignificant in the CS group (103 +/- 25 to 98 +/- 21 g/m2). On the other hand, plasma procollagen I C-terminal peptide (PICP), a marker of collagen synthesis, was lowered by CS (86 +/- 21 to 70 +/- 21 ng/ml, p<0.01), but was not significantly affected by AML (80 +/- 127 to 74 +/- 91 ng/ml). CS reduced urinary albumin excretion (57 +/- 123 to 26 +/- 33 mg/g creatinine, p<0.05), but AML did not bring about significant changes (85 +/- 27 to 73 +/- 19 mg/g creatinine). The results suggested that long-acting CCBs are effective in improving left ventricular hypertrophy by controlling 24-h blood pressure, while ARBs possess protective effects against cardiovascular fibrosis and renal injury beyond their antihypertensive effects.
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PMID:Protective effects of an angiotensin II receptor blocker and a long-acting calcium channel blocker against cardiovascular organ injuries in hypertensive patients. 1613 66

This study determines vancomycin (VAN) population pharmacokinetics (PK) in adult patients with hematological malignancies. VAN serum concentration data (n = 1,004) from therapeutic drug monitoring were collected retrospectively from 215 patients. A one-compartment PK model was selected. VAN pharmacokinetics population parameters were generated using the NONMEM program. A graphic approach and stepwise generalized additive modeling were used to elucidate the preliminary relationships between PK parameters and clinical covariates analyzed. Covariate selection revealed that total body weight (TBW) affected V, whereas renal function, estimated by creatinine clearance, and a diagnosis of acute myeloblastic leukemia (AML) influenced VAN clearance. We propose one general and two AML-specific models. The former was defined by CL (liters/h) = 1.08 x CL(CR(Cockcroft and Gault)) (liters/h); CV(CL) = 28.16% and V (liters) = 0.98 x TBW; CV(V) =37.15%. AML models confirmed this structure but with a higher clearance coefficient (1.17). The a priori performance of the models was evaluated in another 59 patients, and clinical suitability was confirmed. The models were fairly accurate, with more than 33% of the measured concentrations being within +/-20% of the predicted value. This therapeutic precision is twofold higher than that of a non-customized population model (16.1%). The corresponding standardized prediction errors included zero and a standard deviation close to unity. The models could be used to estimate appropriate VAN dosage guidelines, which are not clearly defined for this high-risk population. Their simple structure should allow easy implementation in clinical software and application in dosage individualization using the Bayesian approach.
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PMID:Population pharmacokinetic analysis of vancomycin in patients with hematological malignancies. 1630 55


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