No significant improvement in the outcome of patients with Waldenström's macroglobulinemia treated over the last 25 years.

The treatment of Waldenström's macroglobulinemia (WM) has changed over the last decades, mainly because of the introduction of nucleoside analogues and of rituximab while novel agents such as bortezomib have been recently introduced. We performed an analysis to investigate whether the outcome of patients with WM has improved over the last years, compared to that of patients who started treatment before new drugs became widely available, especially as part of the frontline treatment. We analyzed 345 symptomatic patients with WM: 130 who initiated treatment before and 215 who started treatment after January 1, 2000. Patients who started treatment in the latter group were older and had more often elevated beta2-microglobulin but the other characteristics were similar between the two groups. Most patients who started treatment before January 1, 2000 were treated upfront with alkylating agent-based regimens and most patients who started treatment after January 1, 2000 received rituximab-based regimens as initial treatment. Objective response (63 and 59%, respectively) and median overall survival, OS, (106.5 months for Group A and is estimated at 94 months for Group B, P = 0.327) were similar. There was also no difference regarding OS or cause specific survival (CSS) in each risk group according to IPSSWM. Our observation may be explained by the indolent course of WM in several patients and by the lack of profound cytoreduction in patients with high-risk disease. Possible differences in the 15- or 20-year survival rate between the two groups may be detected with further follow-up of these patients.

D-dimer, factor VIII and von Willebrand factor predict a non-dipping pattern of blood pressure in hypertensive patients.

AIM: The aim of this study is to assess whether the haemostatic markers D-dimer, factor VIII (FVIII) and von Willebrand factor (VWF) are predictive of non-dipping status in treated hypertensive patients; so, as easy available laboratory data can predict non-dipping pattern and help with the selection of the patients whom circadian blood pressure should be re-examined. PATIENTS AND METHODS: Forty treated hypertensive patients with essential hypertension were included in the study. Twenty-four-hour ambulatory blood pressure monitoring was performed in all patients. Daytime and nocturnal average systolic, diastolic and mean blood pressures were calculated. Patients were characterised as "non-dippers" on the basis of a less than 10 % decline in nocturnal blood pressure (BP); either systolic or diastolic or mean (MAP). D-dimer as marker of fibrinolytic function, FVIII activity and VWF antigen as marker of endothelial dysfunction were measured on plasma. The predictive efficiency was analysed by receiver operating characteristic (ROC) curves. Youden index was used for the estimation of the cut-off points and the associated values for sensitivity and 1-specificity. RESULTS: Plasma levels of D-dimer, FVIII and VWF were significantly higher in non-dippers as compared with dippers, irrespective of the classification used (BP index); all P < 0.05. The ROC curves indicated a good diagnostic efficiency for D-dimer (AUC(ROC) = 0.697, 0.715 and 0.774), FVIII (AUC(ROC) = 0.714, 0.692 and 0.755) and VWF (AUC(ROC) = 0.706, 0.740 and 0.708) in distinguishing non-dipping pattern (systolic, diastolic or mean) in the study population; all P < 0.05. Among the three haemostatic markers, D-dimer presents the most satisfactory sensitivity/1-specificity for the differentiation of non-dippers, with a cut-off point >168 ng/ml (sensitivity/1-specificity for systolic BP non-dippers of 0.789/0.381, for diastolic BP non-dippers 0.923/0.444 and for MAP non-dippers 0.875/0.375). CONCLUSION: In conclusion, D-dimer has a good predictive value for non-dipping pattern and the decision for the 24-h ambulatory blood pressure re-monitoring among dippers could rely on its values.

Synchronous BALT Lymphoma and Squamous Cell Carcinoma of the Lung: Coincidence or Linkage?

A 72-year-old man presented with weight loss, fever, and malaise. Chest radiograph and CT revealed two large ill-defined masses in middle and left lower lobes. CT-guided biopsy of left lower lobe mass disclosed bronchus-associated lymphoid tissue (BALT) lymphoma. Middle lobe mass was considered second deposit in contralateral lung. The patient received chemotherapy for BALT. Followup CT disclosed regression of left lower lobe mass and stability of middle-lobe mass and of right paratracheal lymph nodes. CT-guided biopsy of middle-lobe mass revealed squamous cell lung carcinoma. Surgical biopsy of right paratracheal lymph nodes revealed malignancy. Disease was staged T3, N2, and M0. Combined chemotherapy for lung cancer and BALT lymphoma was initiated.

Prognostication of the high-risk WM patient.

Waldenström's macroglobulinemia is characterized by a protracted course in most patients and the median survival may be long. However, a subset of patients may present with more aggressive disease that is associated with short survival. In order to better characterize these "poor-risk" patients, we identified patients who died within 2 years from the initiation of front-line treatment. These patients were older and had more often features of aggressive disease, such as elevated LDH and low serum albumin than the standard-risk population. Furthermore, only a minority of poor-risk patient had a response to initial therapy. However, conventional clinical factors or even the lack on response could not adequately identify poor-risk patients, indicating the need for novel molecular or other markers that would be able to effectively recognize patients at greatest need for aggressive therapies.

Atrial fibrillation and hypercoagulability: dependent on clinical factors or/and on genetic alterations?

UNLABELLED: It is well known that atrial fibrillation is associated with high incidence of thromboembolic events, propably due to a prothrombotic or hypercoagulable state. However, it is unclear whether or not there is any difference of this prothrombotic state in the clinical subgroups of atrial fibrillation patients, that is, in those with paroxysmal, persistent or permanent atrial fibrillation. From the other side the role of the arrhythmia duration on the changes of coagulative variables in atrial fibrillation patients is not clearly enough. The contribution of genetic and functional alterations in factors of the coagulation and fibrinolytic pathways (that is hemostatic risk factors) to the development of hypercoagulation state in atrial fibrillation requires clarification. We investigated therefore (1) if there are differences in the prothrombotic state between patients with different clinical status of the arrhythmia, (2) if the arrhythmia duration per se could be an independent determinant of the prothrombotic state in all atrial fibrillation patients and (3) if coexistent genetic alterations in haemostatic risk factors in patients with atrial fibrillation could contribute to the development of prothrombotic abnormalities. METHODS: Over a period of 23 months, we studied 55 patients with chronic non-valvular atrial fibrillation. We recruited 18 consecutive patients (13 men, mean age 59 +/- 10 years) with paroxysmal atrial fibrillation 17 patients (11 men, mean age 61 +/- 7 years) with persistent atrial fibrillation who underwent elective successful DC and remained in sinus rhythm at the 3 month visit and 20 patients (14 men mean age 64 +/- 9) with permanent atrial fibrillation. Blood results were compared to 17 age-sex- and race-matched controls. The prothrombotic state was quantified by measurement of plasma levels of fibrinogen, soluble P -selectin (an index of platelet activation) and von Willebrand factor (a marker of endothelial dysfunction). We assessed the frequencies of factor V Leiden and prothrombin variant G20210A to determine whether particular inherited haemostatic risk factors may have contribution to the development of prothrombotic state in atrial fibrillation patients. RESULTS: Permanent atrial fibrillation was associated with significant raised levels of von Willebrand factor, fibrinogen levels and soluble P -selectin compared to matched controls (all p < 0.001) and matched patients with paroxysmal and permanent AF (all p ranged between <0.003 and <0.002). Patients with persistent atrial fibrillation had significantly elevated von Willebrand factor levels (p = 0.0064) and fibrinogen levels (p = 0.002), but not Soluble P -selectin (p = 0.509). when compared to controls. Patients with paroxysmal atrial fibrillation had significantly elevated levels of P -selectin (p = 0.005) and fibrinogen (p = 0.003), but not von Willebrand factor (p =.0.61) compared to controls. Stepwise multiple regression analyses demonstrated that the arrhythmia duration (approximately 3 years) was an independent predictor of abnormal von Willebrand factor, fibrinogen and soluble P -selectin levels. Restoration of sinus rhythm in paroxysmal atrial fibrillation subgroup and successful electrical cardioversion of patients with permanent fibrillation atrial fibrillation did not significantly alter levels of the affected factors. The frequency of factor V Leiden was 8.9 in all studied patients with atrial fibrillation, versus 2.4% in the control group (odds ratio [OR] 4.6 [95% confidence (CI) 1.4-17.5], p = 0.02). The frequency of the prothrombin variant G20210A was 6.4.% compared with control group 1.6% (OR 4.9 [95% confidence interval (CI) 1.2-2.9], p = 0.04). There was a trend towards an increased frequency of factor V Leiden and/or prothrombin variant G20210A in patients age <55 years and in patients living at a particular area of Thrace mountains. CONCLUSIONS: Our results showed that there were significant differences in the prothrombotic state when patients with paroxysmal, and persistent atrial fibrillation were compared to matched that there were significant differences in the prothrombotic state when patients with paroxysmal, and persistent atrial fibrillation were compared to matched patients with permanent atrial fibrillation and controls in sinus rhythm. The duration of the arrhythmia (about 3 years) was an independent predictor of abnormal measured factors. We found for the first time that some genetic alterations in haemostatic risk factors could be coexist in atrial fibrillation patients and may be a contributor to the development of hypercoagulability in atrial fibrillation patients.