Treatment of multiple myeloma: an emphasis on new developments. |
Thu, Jul 22,2010 |
Not all patients who fulfill the minimal criteria for diagnosis of multiple myeloma should be treated. If doubt exists about beginning therapy, one should wait and re-evaluate the patient in 2 or 3 months. There is no evidence that early treatment of multiple myeloma is advantageous. All patients should be considered possible candidates for an autologous stem cell transplantation. If they are deemed to be eligible, they should be treated for 3 to 4 months with therapy that does not damage the hematopoietic stem cells. Currently, most physicians use thalidomide plus dexamethasone or dexamethasone alone for induction. Vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) have been used in the past. Autologous stem cell transplantation prolongs disease-free survival and overall survival. The treatment-related mortality rate is 1% to 2%. Melphalan, 200 mg/m2, is the most widely used preparative regimen. Although allogeneic transplantation is attractive, the mortality rate (about 20%) is too high to recommend conventional allogeneic transplantation. Non-myeloablative transplantation is currently under investigation. If the patient is not a candidate for autologous stem cell transplantation, therapy with melphalan and prednisone is a good choice. Patients with relapsed or refractory disease may be treated with dexamethasone, thalidomide and dexamethasone, bortezomib (Velcade, PS-341), or lenalidomide (Revlimid, not yet approved by the Food and Drug Administration).
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The complex nature of the interaction between disease activity and therapy on the lipid profile in patients with pediatric systemic lupus erythematosus. |
Thu, Jul 22,2010 |
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OBJECTIVE: To determine the prevalence of lipid abnormalities at different times and to determine the influence of both the disease and corticosteroid therapy on lipid abnormalities in pediatric patients with systemic lupus erythematosus (SLE). METHODS: Lipid measurements were obtained in an inception cohort of 139 pediatric patients with SLE (114 females). Fasting levels of total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol in the SLE patients were compared with those in age- and sex-matched control subjects. Disease activity levels and medication dosages were obtained at the time of lipid measurements. RESULTS: At the time of diagnosis, the mean levels of total cholesterol, LDL cholesterol, and triglycerides were highest, whereas the mean levels of HDL cholesterol were lowest. The percentage of patients with abnormal triglyceride values was highest at diagnosis, decreased at year 1, and then remained relatively constant thereafter. The mean total cholesterol and LDL cholesterol levels decreased at year 1 as compared with the time of diagnosis and then remained relatively constant. The lowest mean HDL cholesterol levels were found at the time of diagnosis, and these values rose with time. Comparison of lipid levels at different prednisone dosages and disease activity levels revealed that changes in triglyceride levels were mainly associated with changes in disease activity, changes in both total cholesterol and LDL cholesterol levels were associated with changes in the prednisone dosage and not disease activity, and low levels of HDL cholesterol were associated with active SLE, whereas the prednisone dosage was associated with increased levels of HDL cholesterol. CONCLUSION: Factors intrinsic to SLE appear to alter lipid levels. Control of SLE may be the most important factor in improving abnormal lipid profiles, and paradoxically, prednisone therapy may improve abnormal lipid levels.
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Cardiac function and cardiopulmonary performance in patients after treatment for non-Hodgkin's lymphoma. |
Thu, Jul 22,2010 |
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Authors conducted a one-year prospective study to determine whether CHOP regimen (cyclophosphamide, doxorubicin, vincristin, and prednisone), used in the treatment of aggressive non-Hodgkin s lymphoma, is associated with the presence of an early impairment of cardiac function. Forty seven patients were prospectively examined (27 male and 20 female) aged 49+/-14 years who were treated with CHOP regimen. Rest echocardiography was performed at baseline and one-year control. Cardiopulmonary exercise test was carried out at one-year control examination. The ejection fraction (EF), parameters of diastolic function, myocardial performance index (MPI), and pVO2 were used as parameters of cardiopulmonary performance. The cumulative dose (CD) of doxorubicin was 277+/-56 (300 mg/m(2)) was given. The baseline EF 64+/-5% (64%) decreased to 58+/-7% (57%) at the one-year control (p<0.0001). 23% of patients exhibited a drop in EF >10% during the follow-up. 43% revealed a pathologically increased value of MPI >0.55, and 47% impaired diastolic function compared to the baseline values, respectively. 21% of patients exhibited a decrease of pVO(2) < 20 ml/kg/min, and 17% pVO(2) < 80% of the reference value, respectively. None of the patients developed signs of heart failure. The Doppler parameters of both diastolic and global LV function were the most affected measures and significantly influenced the cardiopulmonary performance. Multivariate analysis showed that CD > or =300 mg/m(2) (OR=8.08; p<0.05) and the presence of risk factors (OR=9.48; p<0.008) are the best predictors of cardiotoxicity. The results show that subclinical cardiac impairment was frequent in patients receiving the CHOP regimen with safe cumulative doses of doxorubicin. The value of described changes for the development of heart failure has to be assessed during the prospective follow-up.
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Cell death, proliferation and repair in human myocarditis responding to immunosuppressive therapy. |
Thu, Jul 22,2010 |
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In this study, we evaluate cell death, proliferation and repair in left ventricular endomyocardial biopsies from 20 patients with active lymphocytic myocarditis worsening or recovering from cardiac dysfunction after 6-months immunosuppression. Apoptosis and necrosis were assessed by in situ ligation of hairpin probes, proliferation by Ki67 and MCM5 labelling of myocytes, repair by electron microscopy, morphometric study of percent myofibrillar area and real-time polymerase chain reaction of alpha-and beta-Myosin Heavy Chain (MHC). Apoptosis and necrosis decreased in post- vs pretreatment biopsies by 85 and 62%, respectively in responders, while increased by 42 and 46% in nonresponders. Ki67 and MCM5-positive myocytes were higher vs controls at baseline and increased by 43 and 38% at follow-up in responders and by 75 and 63% in nonresponders. Myofibrillar area reduced in pretreatment samples, increased by 33% at follow-up in responders, correlated with percent enhancement of ejection fraction and was associated with increased alpha-MHC expression and alpha/beta-MHC ratio. In follow-up biopsies of nonresponders, myofibrillar area diminished by 36% and correlated with percent decrease of ejection fraction. Our results suggest that recovery of cardiac function in myocarditis responding to immunosuppression is associated with inhibition of cell death, activation of cell proliferation and with newly synthesized contractile material.
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Phase III intergroup study of fludarabine phosphate compared with cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed patients with stage III and IV low-grade malignant Non-Hodgkin's lymphoma. |
Thu, Jul 22,2010 |
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PURPOSE: To compare the efficacy and safety of fludarabine phosphate with cyclophosphamide, vincristine, and prednisone (CVP) in 381 previously untreated, advanced-stage, low-grade (lg) non-Hodgkin's lymphoma (NHL) patients in a phase III, multicenter study. PATIENTS AND METHODS: Between 1993 and 1997, patients were randomly assigned to treatment with either fludarabine (25 mg/m2 intravenously [IV] daily for 5 days every 4 weeks) or CVP (cyclophosphamide 750 mg/m2 IV on day 1; vincristine, 1.4 mg/m2 IV on day 1; and prednisone, 40 mg/m2 orally on days 1 through 5 every 4 weeks). Results Overall response (OR) rates were significantly improved in the fludarabine arm versus the CVP arm, both for the intent-to-treat (ITT) population and assessable patients (P < .001). Complete response (CR) rates in the ITT population were also higher after fludarabine treatment. The CR rate was 38.6% for fludarabine compared with 15.0% for CVP. There were no statistically significant differences in time to progression (TTP), time to treatment failure (TTF), and overall survival (OS) between treatment groups. WHO grades 3 and 4 hematologic adverse events were more common in the fludarabine arm. However, concerning the higher incidence of granulocytopenia, this did not translate to more infections in fludarabine-treated patients. CONCLUSION: Newly diagnosed lgNHL patients who received fludarabine achieved higher OR and CR rates compared with CVP-treated patients. No differences in TTP, TTF, and OS were noted. Fludarabine is a highly active single agent in lgNHL. Combination therapies incorporating fludarabine are now being further evaluated as first-line therapy in follicular NHL.
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Uveitis in autoimmune hepatitis: a case report. |
Thu, Jul 22,2010 |
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In this case report we describe for the first time an association between autoimmune hepatitis (AIH) and uveitis, without any doubts about other possible etiologies, such as HCV, since all the old reports describe the association of AIH with iridocyclitis before tests for HCV-related hepatitis could be available. A 38-year-old businessman with abnormal liver function tests and hyperemia of the bulbar conjunctiva was admitted to the hospital. Six years before admission, the patient presented with persistent fever, arthralgias, conjunctival hyperemia, leukocytosis and increased ESR, referred to acute rheumatic fever. The presence of systemic diseases, most commonly associated with uveitis, was investigated without results and the patient was then treated with topical corticosteroids. His symptoms resolved. A test for anti-nuclear antibodies was positive, at a titre of 1:320, with a speckled and nucleolar staining pattern. Liver ultrasound showed mild hepatomegaly with an increased echostructure of the liver. Percutaneous liver biopsy was performed under ultrasound assistance. Histological examination showed necroinflammation over the portal, periportal and lobular areas, fibrotic portal tracts, with periportal fibrosis and occasional portal-to-portal bridgings, but intact hepatic architecture. Some hepatocytes showed barely discernible granules of hemosiderin in the lobular area. Bile ductules had not any significant morphological alterations. METAVIR score was A2-F3, according to the modified HAI grading/fibrosis staging. The patient was diagnosed to have AIH with mild activity and fibrosis and was discharged on 25 mg prednisone, entering clinical and biochemical remission, further confirming diagnosis. After discharge the patient continued to have treatment with corticosteroids as an outpatient at a dose of 5 mg. On January 2002 the patient was readmitted to the hospital. A test for anti-nuclear antibodies was positive, at a titre of 1:320, with a speckled and nucleolar staining pattern. Anti-smooth muscle antibody test was also positive (1:160), while anti-LKM antibodies were negative. Ophthalmologic examination revealed inflammatory cells and proteinaceous flare in the anterior chamber of the left eye, and a stromal lesion in the cornea. He was maintained on immunosuppressive therapy (5 mg prednisone plus topical antibiotic therapy for two weeks) and then discharged. A complete remission of the symptoms was registered on follow-up. At present (July 2005), the patient is on prednisone (5 mg) and has no symptoms. Liver function tests are also within the normal range.
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Hairy cell leukemia in pregnancy |
Thu, Jul 22,2010 |
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Pregnancy complicated by HCL is an extremlely rare event: only 5 report of HCL in pregnancy have been previously described. A 36-year-old women was diagnosed of HCL presented in 14 week of her 5th pregnancy. Therapy was initiated in 18 wk of gestation with IFN-alpha at dose 6 x 106 U subcutaneous 3 times per week and prednisone 20 mg/d. IFN-alpha administration was well tolerated. After IFN-alpha therapy partial remission was achieved. The course of the pregnancy was normal. At week 39 of gestation a cesarean cection was performed and the patient delivered a healthy male infant weighing 3460 g with Apgar score of 10. The placenta was of normal size, no infiltration of hairy cell was founded. Post-partum course was uncomplicated. The patient elected to not breast feed her infant. 3 weeks after delivery patient had a 5-days course of 2CDA
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Effect of a copper gradient on plant community structure. |
Thu, Jul 22,2010 |
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Vegetation data including plant cover, biomass, species richness, and vegetation height was sampled on a copper-contaminated field with total copper contents varying from 50 to almost 3,000 mg/kg soil. The field was covered by early succession grassland dominated by Agrostis stolonifera. Plant cover, biomass, species richness, and vegetation height generally decreased with increasing copper content, although the highest biomass was reached at intermediate copper concentrations. Multivariate statistical analyses showed that plant community composition was significantly correlated with soil copper concentration and that community composition at soil copper concentrations above 200 mg/kg differed significantly from community composition at lower copper levels. Comparison of single-species (Black Bindweed, Fallopia convolvulus) performance at the field site and in laboratory tests involving field soil and spiked soil indicates that the laboratory tests conventionally applied for risk assessment purposes do not overestimate copper effects. Interaction between copper and other stressors operating only in the field probably balance the higher bioavailability in spiked soil.
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Complete response in multiple myeloma: clinical trial E9486, an Eastern Cooperative Oncology Group study not involving stem cell transplantation. |
Thu, Jul 22,2010 |
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BACKGROUND: The importance of obtaining a complete response (CR) in multiple myeloma (MM) treated with chemotherapy is unclear. METHODS: The Eastern Cooperative Oncology Group evaluated 653 previously untreated patients with active MM randomized to vincristine, carmustine (BCNU), melphalan, cyclophosphamide, and prednisone (VBMCP), to VBMCP and recombinant interferon alfa-2 (INFalpha-2), or to VBMCP and high-dose cyclophosphamide. RESULTS: Objective response was achieved in 420 (67%) of the 628 eligible patients, and 85 (14%) achieved a CR. Patients receiving VBMCP and recombinant INFalpha-2 had a significantly higher CR (18%) than those receiving VBMCP alone (10%) (P = .02). The CR rate for VBMCP and high-dose cyclophosphamide was 12%. Median duration of survival was 3.5 years for all eligible patients, and the estimated 5-year survival rate was 31%. The median duration of survival from the date of objective response was 5.1 years for those who achieved a CR and 3.3 years for those with a partial response (P < .0001). The median postresponse survival was 6.6 years in the 21 patients in CR with nonclonal disease and 4.4 years in the 11 patients in CR who had persistent clonal disease. All patients with negative immunofixation results and nonclonal plasma cells in whom polymerase chain reaction was performed had a positive result (presence of tumor DNA). CONCLUSION: Patients in whom a CR was achieved had a longer survival than those who had a partial response.
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Inflammatory pseudotumor of the cavernous sinus and skull base. |
Thu, Jul 22,2010 |
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Inflammatory pseudotumor is a non-neoplastic process of unknown etiology characterized by a proliferation of connective tissue with an inflammatory infiltrate. Intracranial inflammatory pseudotumors classically involve the cavernous sinus but can also occur in the supratentorial or infratentorial compartments and spinal canal. Symptoms are dependent on location, and, when present in the cavernous sinus, typically include cranial nerve palsies of those nerves in the cavernous sinus. These lesions are rapidly responsive to steroid therapy. Surgery is typically indicated for biopsy only, but complete resection may be justified for lesions outside the cavernous sinus.
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