Gray zone lymphoma with features intermediate between classical Hodgkin lymphoma and diffuse large B-cell lymphoma: characteristics, outcomes, and prognostication among a large multicenter cohort.

Gray zone lymphoma (GZL) with features between classical Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) is a recently recognized entity reported to present primarily with mediastinal disease (MGZL). We examined detailed clinical features, outcomes, and prognostic factors among 112 GZL patients recently treated across 19 North American centers. Forty-three percent of patients presented with MGZL, whereas 57% had non-MGZL (NMGZL). NMGZL patients were older (50 versus 37 years, P = 0.0001); more often had bone marrow involvement (19% versus 0%, P = 0.001); >1 extranodal site (27% versus 8%, P = 0.014); and advanced stage disease (81% versus 13%, P = 0.0001); but they had less bulk (8% versus 44%, P = 0.0001), compared with MGZL patients. Common frontline treatments were cyclophosphamide-doxorubicin-vincristine-prednisone +/- rituximab (CHOP+/-R) 46%, doxorubicin-bleomycin-vinblastine-dacarbazine +/- rituximab (ABVD+/-R) 30%, and dose-adjusted etoposide-doxorubicin-cyclophosphamide-vincristine-prednisone-rituximab (DA-EPOCH-R) 10%. Overall and complete response rates for all patients were 71% and 59%, respectively; 33% had primary refractory disease. At 31-month median follow-up, 2-year progression-free survival (PFS) and overall survival rates were 40% and 88%, respectively. Interestingly, outcomes in MGZL patients seemed similar compared with that of NMGZL patients. On multivariable analyses, performance status and stage were highly prognostic for survival for all patients. Additionally, patients treated with ABVD+/-R had markedly inferior 2-year PFS (22% versus 52%, P = 0.03) compared with DLBCL-directed therapy (CHOP+/-R and DA-EPOCH-R), which persisted on Cox regression (hazard ratio, 1.88; 95% confidence interval, 1.03-3.83; P = 0.04). Furthermore, rituximab was associated with improved PFS on multivariable analyses (hazard ratio, 0.35; 95% confidence interval, 0.18-0.69; P = 0.002). Collectively, GZL is a heterogeneous and likely more common entity and often with nonmediastinal presentation, whereas outcomes seem superior when treated with a rituximab-based, DLBCL-specific regimen.

Venous thromboembolism in patients with prior stroke.

Patients with prior stroke are susceptible to venous thromboembolism (VTE). We studied patients with stroke in the Worcester VTE study of 2488 consecutive patients hospitalized with VTE. In all, 288 (11.6%) had a clinical history of stroke and 2200 (88.4%) did not. Patients with stroke were more likely to die inhospital (9.2% vs 4%) and within 30 days of VTE diagnosis (16.7% vs 6.9%) compared with patients without stroke (all P < .001). Recent immobilization (adjusted odds ratio [OR] 2.15; 95% confidence interval [CI] 1.15-4.09) and inferior vena cava (IVC) filter insertion (adjusted OR 2.1; 95% CI 1.15-3.83) were associated with a doubling of inhospital death. Recent immobilization (adjusted OR 1.84; 95% CI 1.19-2.83) and IVC filter insertion (adjusted OR 1.94; 95% CI 1.2-3.14) were associated with an increased risk of death within 30 days of VTE. In conclusion, patients with VTE and prior stroke were more than twice as likely to die while hospitalized and within 30 days of VTE diagnosis.

Venous thromboembolism in patients with chronic obstructive pulmonary disease.

OBJECTIVE: Our aim was to compare the clinical characteristics, prophylaxis, treatment, and outcomes of venous thromboembolism in patients with and without previously diagnosed chronic obstructive pulmonary disease. METHODS: We analyzed the population-based Worcester Venous Thromboembolism Study of 2488 consecutive patients with validated venous thromboembolism to compare clinical characteristics, prophylaxis, treatment, and outcomes in patients with and without chronic obstructive pulmonary disease. RESULTS: Of 2488 patients with venous thromboembolism, 484 (19.5%) had a history of clinical chronic obstructive pulmonary disease and 2004 (80.5%) did not. Patients with chronic obstructive pulmonary disease were older (mean age 68 vs 63 years) and had a higher frequency of heart failure (35.5% vs 12.9%) and immobility (53.5% vs 43.3%) than patients without chronic obstructive pulmonary disease (all P<.0001). Patients with chronic obstructive pulmonary disease were more likely to die in hospital (6.8% vs 4%, P=.01) and within 30 days of venous thromboembolism diagnosis (12.6% vs 6.5%, P<.0001). Patients with chronic obstructive pulmonary disease demonstrated increased mortality despite a higher frequency of venous thromboembolism prophylaxis. Immobility doubled the risk of in-hospital death (adjusted odds ratio, 2.21; 95% confidence interval, 1.35-3.62) and death within 30 days of venous thromboembolism diagnosis (adjusted odds ratio, 2.04; 95% confidence interval, 1.43-2.91). CONCLUSION: Patients with chronic obstructive pulmonary disease have an increased risk of dying during hospitalization and within 30 days of venous thromboembolism diagnosis. Immobility in patients with chronic obstructive pulmonary disease is an ominous risk factor for adverse outcomes.

Venous thromboembolism in patients with diabetes mellitus.

PURPOSE: The majority of epidemiological studies demonstrate an increased risk of venous thromboembolism among diabetic patients. Our aim was to compare clinical characteristics, prophylaxis, treatment, and outcomes of venous thromboembolism in patients with and without previously diagnosed diabetes. METHODS: We studied diabetic patients in the population-based Worcester Venous Thromboembolism Study of 2488 consecutive patients with validated venous thromboembolism. RESULTS: Of 2488 venous thromboembolism patients, 476 (19.1%) had a clinical history of diabetes. Thromboprophylaxis was omitted in more than one third of diabetic patients who had been hospitalized for non-venous-thromboembolism-related illness or had undergone major surgery within 3 months before diagnosis. Patients with diabetes were more likely than nondiabetic patients to have a complicated course after venous thromboembolism. Patients with diabetes were more likely than patients without diabetes to suffer recurrent deep vein thrombosis (14.9% vs 10.7%) and long-term major bleeding complications (16.4% vs 11.7%) (all P=.01). Diabetes was associated with a significant increase in the risk of recurrent deep vein thrombosis (adjusted odds ratio [AOR] 1.74; 95% confidence interval [CI], 1.21-2.51). Aspirin therapy at discharge (AOR 1.59; 95% CI, 1.1-2.3) and chronic kidney disease (AOR 2.19; 95% CI, 1.44-3.35) were independent predictors of long-term major bleeding. CONCLUSION: Patients with diabetes who developed venous thromboembolism were more likely to suffer a complicated clinical course. Diabetes was an independent predictor of recurrent deep vein thrombosis. We observed a low rate of thromboprophylaxis in diabetic patients. Further studies should focus on venous thromboembolism prevention in this vulnerable population.

Isolated calf deep vein thrombosis in the community setting: the Worcester Venous Thromboembolism study.

The prevalence of isolated calf deep vein thrombosis (DVT) in the community setting is relatively unexplored. Confusion remains with regards to its management and contemporary natural history. The purpose of this investigation was to describe the number of cases of calf DVT in the community, use of early management strategies, and rates of venous thromboembolism (VTE) recurrence and major bleeding. The medical records of residents of the Worcester (MA) metropolitan area with ICD-9 codes consistent with potential VTE during 4 study years (1999/2001/2003/2005) were validated by trained nurses. Patient demographic/clinical characteristics, treatment practices, and outcomes were evaluated. Isolated calf DVT was diagnosed in 166 (11.1%) of 1,495 patients with lower extremity DVT. Patients with calf DVT were less likely to be discharged on anticoagulants or with an IVC filter than patients with proximal DVT (84.1 vs. 92.3%). The rates of VTE recurrence and pulmonary embolism did not differ significantly between patients with calf DVT and proximal DVT at 6 months (11.0 vs. 8.7%, 2.6 vs. 1.8%, respectively). Patients with calf DVT had higher adjusted risk of early (14-day) VTE recurrence/extension (OR 2.34, 95% CI 1.01-5.44). Patients with calf DVT had lower rates of major bleeding at 6 months compared to patients with proximal DVT (5.2 vs. 9.3%, P = 0.04). Rates of recurrent VTE and major bleeding following calf DVT in the community are much higher than in randomized clinical trials of patients with proximal or calf DVT. Further study of management strategies for isolated calf DVT is needed.