Cemp, a mitoxantrone containing combination, in the treatment of intermediate and high grade non-hodgkin's lymphoma: an effective and non toxic therapeutic alternative for adult and elderly patients.

Here we report the results of a randomised multicenter phase III clinical trial which assesses the therapeutic efficacy and tolerability of a chemotherapy protocol CEMP (cyclophosphamide, etoposide, mitoxantrone and prednisone) in adult and elderly patients with advanced intermediate and high-grade NHL. Between October 1991 and October 1995, 139 patients, aged 55 to 79 years, with diffuse intermediate and high-grade lymphoma, were enrolled. A considerable percentage of patients had clinically aggressive disease: 32.4% had systemic symptoms, 79% had stage III or IV disease, 33.8% had bone marrow involvement, 46% had splenic involvement and 42.5% had increased values of serum lactate dehydrogenate. Complete remission was achieved in 70 of the 139 patients (51.9%) and PR in 12 (16.6%) with an overall response of 68.5%. The overall response survival rate at 6 years was 39%, whereas DFS rate was 48.7% and PFS rate was 28.5%. At four years 49% of the patients were still in CR. Dividing the patients in two groups, under and over 65 years of age, we obtained the same results as far as overall response is concerned. No toxic deaths occurred, neither cardiac, renal nor liver complications happened. CEMP regimen is an effective and safe protocol with good results in elderly people, well comparable to those achieved in younger ones.

Upper-extremity deep vein thrombosis. Risk factors, diagnosis, and complications.

BACKGROUND: Little is known about the clinical, diagnostic, and prognostic aspects of upper-extremity deep vein thrombosis (UEDVT). OBJECTIVES: To identify the clinical and laboratory parameters associated with this disease, to assess the diagnostic accuracy of ultrasonographic methods for its detection, and to establish the frequency of both early and late complications. PATIENTS AND METHODS: After a careful history was taken, 58 consecutive patients with signs and symptoms that were clinically suggestive of UEDVT underwent the determination of antithrombin III and protein C and S levels and resistance to activated protein C and lupuslike anticoagulants. Compression ultrasonography, color flow Doppler imaging, and Doppler ultrasonography were performed prior to venography. Patients with confirmed UEDVT underwent objective tests to detect a pulmonary embolism and were followed up prospectively to record recurrent thromboembolic events and postthrombotic sequelae. RESULTS: Findings from venography confirmed UEDVT in 27 patients (47%). Central venous catheters, thrombophilic states, and a previous leg vein thrombosis were statistically significantly associated with UEDVT. Sensitivity and specificity of compression ultrasonography (96% and 93.5%, respectively) and color flow Doppler imaging (100% and 93%, respectively) were comparable and better than those of Doppler ultrasonography (81% and 77%, respectively). Objective findings suggestive of a pulmonary embolism were recorded in 36% of the patients with UEDVT. After a mean follow-up of 2 years, 2 patients with UEDVT experienced recurrent thromboembolic events, and 4 had postthrombotic sequelae. CONCLUSIONS: Symptomatic UEDVT is associated with central venous catheters, thrombophilic states, and a previous leg vein thrombosis. Both compression ultrasonography and color flow Doppler imaging are accurate methods for its detection. A pulmonary embolism is a common complication of the disease. Finally, this disorder may recur and may be followed by postthrombotic sequelae.

The long-term clinical course of acute deep venous thrombosis.

BACKGROUND: In patients who have symptomatic deep venous thrombosis, the long-term risk for recurrent venous thromboembolism and the incidence and severity of post-thrombotic sequelae have not been well documented. OBJECTIVE: To determine the clinical course of patients during the 8 years after their first episode of symptomatic deep venous thrombosis. DESIGN: Prospective cohort study. SETTING: University outpatient thrombosis clinic. PATIENTS: 355 consecutive patients with a first episode of symptomatic deep venous thrombosis. MEASUREMENTS: Recurrent venous thromboembolism, the post-thrombotic syndrome, and death. Potential risk factors for these outcomes were also evaluated. RESULTS: The cumulative incidence of recurrent venous thromboembolism was 17.5% after 2 years of follow-up (95% CI, 13.6% to 22.2%), 24.6% after 5 years (CI, 19.6% to 29.7%), and 30.3% after 8 years (CI, 23.6% to 37.0%). The presence of cancer and of impaired coagulation inhibition increased the risk for recurrent venous thromboembolism (hazard ratios, 1.72 [CI, 1.31 to 2.25] and 1.44 [CI, 1.02 to 2.01], respectively). In contrast, surgery and recent trauma or fracture were associated with a decreased risk for recurrent venous thromboembolism (hazard ratios, 0.36 [CI, 0.21 to 0.62] and 0.51 [CI, 0.32 to 0.87], respectively). The cumulative incidence of the post-thrombotic syndrome was 22.8% after 2 years (CI, 18.0% to 27.5%), 28.0% after 5 years (CI, 22.7% to 33.3%), and 29.1% after 8 years (CI, 23.4% to 34.7%). The development of ipsilateral recurrent deep venous thrombosis was strongly associated with the risk for the post-thrombotic syndrome (hazard ratio, 6.4; CI, 3.1 to 13.3). Survival after 8 years was 70.2% (CI, 64.7% to 75.6%). The presence of cancer increased the risk for death (hazard ratio, 8.1; CI, 3.6 to 18.1). CONCLUSION: Patients with symptomatic deep venous thrombosis, especially those without transient risk factors for deep venous thrombosis, have a high risk for recurrent venous thromboembolism that persists for many years. The post-thrombotic syndrome occurs in almost one third of these patients and is strongly related to ipsilateral recurrent deep venous thrombosis. These findings challenge the widely adopted use of short-course anticoagulation therapy in patients with symptomatic deep venous thrombosis.

Changing features of proximal vein thrombosis over time.

Recently, the sensitivity of impedance plethysmography (IPG) for the diagnosis of acute deep-vein thrombosis (DVT) in symptomatic outpatients has been questioned. In order to verify whether a change in the venographic pattern of DVT has occurred over years, accounting for the decreased sensitivity of IPG, the authors compared two series of consecutive venograms demonstrating proximal DVT, performed between 1984-1988 (166 patients) and 1990-1992 (140 patients). They evaluated both the extension and the occlusiveness of deep-vein thrombi in the two series. Moreover, changes in the referral characteristics of patients were investigated. In the second series of venograms a significant decrease in thrombi extension, expressed by a lower prevalence of iliac vein thrombosis (29% versus 43%; P = 0.0074) was observed; moreover, a significant increase in the prevalence of nonocclusive thrombi (22% versus 8%; P = 0.0004) was also recorded in the second series when compared with the first. During the study period, among the referral characteristics of patients, the authors observed both a significant decrease in the prevalence of proximal DVT (from 31% to 24%; P < 0.01) and a slight and not statistically significant decrease in the median time elapsed between onset of symptoms and referral for objective testing (from eight and a half to seven days). In conclusion, proximal deep-vein thrombi are currently less extensive and occlusive than observed in the past. These results might depend on earlier referral of less symptomatic patients and might explain the recently reported decrease in IPG sensitivity for proximal DVT.

A simple ultrasound approach for detection of recurrent proximal-vein thrombosis.

BACKGROUND: The objective of this study was to develop a simple ultrasound method for measuring thrombus regression in patients with proximal deep-vein thrombosis (DVT) and to test its utility for the detection of DVT recurrence. METHODS AND RESULTS: The study comprised a cross-sectional survey and a prospective investigation (149 and 145 patients, respectively). In both phases, the normalization rate of a previously abnormal ultrasound test, applying the criterion of full compressibility of the common femoral and popliteal veins (C-US method), was assessed. In the prospective study, the vein diameter under maximum compression (thrombus thickness) was measured in the abnormal venous segments at scheduled times (1, 3, 6, and 12 months). In patients presenting with suspected DVT recurrence, the procedure was repeated and results were compared with those available from the previous examination. Noncompressibility of a previously normal(ized) venous segment and enlargement of thrombus thickness (> or = 2 mm) were considered diagnostic of proximal DVT recurrence. The diagnostic accuracy of the C-US method alone, as well as of the combined ultrasound methods (C-US + thrombus thickness), was assessed against contrast phlebography. C-US test normalization occurred in only 30% of patients within 1 year. A significant reduction of the thrombus mass (P < .0001) was recorded throughout the entire study period. However, a major decrease in thrombus mass (> 50%) was recorded within the first 3 months. Of 29 patients who developed a suspected recurrent DVT, phlebography confirmed diagnosis in 11. The C-US method alone showed an excellent accuracy (100%) but was applicable in only 6 patients (21%). Both the sensitivity and the specificity for proximal DVT recurrence of the combined ultrasound methods were 100% (95% confidence interval, 69% to 100% and 81% to 100%, respectively) and were applicable in all patients. CONCLUSIONS: The serial ultrasound measurement of thrombus mass after an acute episode of DVT may allow the correct identification of patients who develop a recurrent proximal-vein thrombosis.

Dermatan sulphate: a safe approach to prevention of postoperative deep vein thrombosis.

To assess the efficacy and safety of dermatan sulphate (MF 701) in preventing postoperative deep vein thrombosis (DVT), 324 patients aged 40 years or over undergoing elective major general surgical operations were included in a randomized trial comparing MF 701 (100 mg intramuscularly once a day) with unfractionated calcium heparin (UFH, 5000 units subcutaneously three times daily). Both treatments were initiated before operation and continued until discharge. In all, 316 patients were included in the analysis (MF 701, 157; UFH, 159). Serial impedance plethysmography was performed in all patients; a 125I-radiolabelled fibrinogen uptake test was added to impedance plethysmography in a randomized subsample of 62 patients (MF 701, 28; UFH, 34). Positivity in either test was confirmed where possible by venography. DVT was diagnosed by venography or, when this could not be performed, by positivity of either impedance plethysmography or fibrinogen uptake test. The incidence of DVT was 3.1 per cent (patients receiving MF 701) and 1.6 per cent (those receiving UFH) in patients undergoing impedance plethysmography alone, and 7.1 and 11.8 per cent, respectively, in those undergoing both impedance plethysmography and fibrinogen uptake test; in neither case was the difference between treatments statistically significant. There were five in-hospital deaths, two in patients receiving MF 701 and three in patients on UFH. The incidence of clinically overt haemorrhage was 5.7 per cent in patients on MF 701 and 17.6 per cent in those on UFH (P less than 0.01). Postoperative transfusions and reoperations due to bleeding were significantly less frequent in patients receiving MF 701. Mortality rates at 3 months were similar for the two treatment groups. Compared with standard prophylaxis using UFH, MF 701 showed a similar efficacy with a significantly greater safety.