Mantle cell lymphoma (MCL) is an incurable disease with a highly variable clinical course. The prognosis after relapse is generally poor, and no standard of care exists. We investigated the postrelapse outcomes of 149 patients who were initially treated in the Nordic Lymphoma Group trials, MCL2 or MCL3, both representing intensive cytarabine-containing frontline regimens including autologous stem cell transplant. Patients with progression of disease before 24 months (POD24, n = 51, 34%) displayed a median overall survival of 6.6 months compared with 46 months for patients with later POD (n = 98, 66%; P < 0.001). MCL international prognostic index, cell proliferation marker, blastoid morphology, and TP53 mutations showed independent prognostic value irrespective of POD24, and in a combined, exploratory risk score, patients with 0, 1, 2-3, or 4-5 high-risk markers, respectively, displayed a 5-year overall survival of 62%, 39%, 31%, and 0%. By a comparison of median progression-free survival of the different salvage therapies in the relapse setting, bendamustine-rituximab was superior to all other combination chemotherapy regimens; however, it was also associated with longer responses to last line of therapy. Collectively, we confirm the prognostic impact of POD24 and highlight the relevance of other biomarkers, and we emphasize the importance of novel therapies for patients with high-risk features at first POD.

BackgroundAutologous stem-cell transplantation (ASCT) is a common treatment for lymphoma but it has some mortality.MethodsAll 433 lymphoma patients who underwent ASCT for lymphoma at Karolinska Huddinge 1994–2016 were investigated, including CD34+ cell amounts, medications, infectious and other complications, intensive care, longitudinal laboratory values, and secondary myeloid neoplasia.ResultsThe 100-day non-relapse and overall mortalities were 5.6% and 7.2%. Stem-cell harvests < 5 million CD34+ cells/kg correlated with inferior 100-day and long-term survival. Prior to conditioning (93% BEAM), elevated (both 3–9 and ≥ 10 mg/L) C-reactive protein (CRP) and creatinine, and low albumin (but not higher age) predicted inferior higher 100-day survival. Intravenous antibiotics were given to 97% (22% positive blood cultures) and parenteral nutrition to 89%. After 1 year, 86% had normalized hemoglobin. The 5-year risk for secondary myeloid neoplasia was 4.1%, associated with smaller harvests.ConclusionsBefore starting conditioning, patients should have preferably harvested ≥ 5 million CD34+ cells/kg and normal CRP, albumin, and creatinine. It appears safe to transplant patients ≥ 66 years.Electronic supplementary materialThe online version of this article (10.1186/s40164-019-0131-3) contains supplementary material, which is available to authorized users.

Obesity is a known risk factor for venous and arterial thrombosis but the mechanisms are still unclear. In women, obesity is correlated with low-grade inflammation and recent data show that BMI is positively associated with thrombin generation. We explored the correlations between obesity, inflammation and thrombin generation in women with increased thrombotic risk by looking at a cohort of women with prior venous thrombosis. One hundred and fifty-six women age 18-65 years were enrolled at diagnosis of first venous thromboembolism (VTE). Plasma samples were obtained at least 3 weeks after cessation of anticoagulant treatment. Thrombin generation was determined with the calibrated automated thrombography (CAT) assay and the Innovance ETP assay. Thrombin generation started later but was more pronounced with higher endogenous thrombin generation potential (ETP) determined with CAT in patients with obesity. The Innovance ETP assay showed results consistent with CAT. Furthermore, patients with obesity had significantly higher levels of fibrinogen, C-reactive protein and plasminogen activator inhibitor-I (PAI-I) than patients without obesity. Increased levels of fibrinogen were the main determinant of the prolonged lag-time in patients with obesity whereas higher levels of prothrombin could account for the difference in the ETP between the groups. We found an association between BMI and ETP values using two different methods to measure thrombin generation. Obesity correlated with increased thrombin generation in women with VTE and the main determinants of this hypercoagulable state were increased levels of fibrinogen and prothrombin. This shows a possible link between obesity, low-grade inflammation and increased thrombin generation in women at increased risk for future thrombosis.