Heidi Mocikova

Central nervous system involvement in mantle cell lymphoma: clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network

BACKGROUND Central nervous system (CNS) involvement in mantle cell lymphoma (MCL) is uncommon, and the manifestations and natural history are not well described. PATIENTS AND METHODS We present the data on 57 patients with MCL who developed CNS involvement, from a database of 1396 consecutively treated patients at 14 institutions. RESULTS The crude incidence of CNS involvement was 4.1%, with 0.9% having CNS involvement at diagnosis. Blastoid histology, B-symptoms, elevated lactate dehydrogenase, Eastern Cooperative Group performance status ≥2 and a high Mantle Cell Lymphoma International Prognostic Index score were enriched in the cohort with CNS involvement, and the presence of ≥1 of these features defined a high-risk subset (an actuarial risk of CNS involvement 15% at 5 years) in a single-institution subset. The median time to CNS relapse was 15.2 months, and the median survival from time of CNS diagnosis was 3.7 months. The white blood cell count at diagnosis <10.9 × 10⁹/l, treatment of CNS involvement with high-dose anti-metabolites, consolidation with stem cell transplant and achievement of complete response were all associated with improved survival. CONCLUSIONS In MCL, CNS involvement is uncommon, although some features may predict risk. Once manifest outlook is poor; however, some patients who receive intensive therapy survive longer than 12 months.

Role of [18F]-fluoro-2-deoxy-D-glucose positron emission tomography in early and late therapy assessment of patients with advanced Hodgkin lymphoma treated with bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine and prednisone.

Abstract The prognostic value of positron emission tomography (PET) in early therapy response assessment, after completion of chemotherapy and 3 months after the end of treatment in advanced Hodgkin lymphoma (HL) remains to be defined. We report the results of 69 patients with first presentation of advanced HL. [18F]-fluoro-2-deoxy-d-glucose (FDG)-PET scan was performed after four cycles (PET-4), on completion of chemotherapy after 6/8 cycles (PET-6/8) and 3 months after the completion of chemotherapy (PET 3-months). Median follow-up was 55 months. The negative predictive value (NPV) for PET-4, PET-6/8 and PET 3-months was 98%, 95% and 97%, respectively. The 4-year progression-free survival (PFS) for PET-4 negative (n = 51) and PET-4 positive (n = 18) patients was 96% and 78%, respectively (p = 0.016). The 4-year PFS for PET-6/8 negative (n = 59) and PET-6/8 positive (n = 9) patients was 95% and 78%, respectively (p = 0.046). Patients with a large mediastinal mass constituted nearly all of the PET-4 positive (16/18) and PET-6/8 positive (8/9) patients. After radiotherapy of PET-6/8 positive patients, PET 3-months was negative in 64 (97%) and positive in two (3%) patients. PET 3-months after the end of chemotherapy was of limited value when the interim PET-4 was negative. Interim PET after four cycles of bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP) is a strong prognostic marker for PFS in advanced HL.

Platelet activity and aspirin efficacy after off-pump compared with on-pump coronary artery bypass surgery: Results from the prospective randomized trial PRAGUE 11-Coronary Artery Bypass and REactivity of Thrombocytes (CABARET)

OBJECTIVES Changes in hemostasis after off-pump coronary artery bypass grafting are still being discussed. There is a lack of information about platelet activity and aspirin efficacy after coronary artery bypass grafting. The aim of this study was to assess and compare platelet activity and aspirin efficacy early and late after off-pump and on-pump coronary artery bypass grafting. METHODS Eighty patients were enrolled in a prospective randomized study. Platelet activity was determined based on membrane expression of antigen CD62P (P-selectin) by means of flow cytometric analysis. Aspirin efficacy was assessed by using arachidonic acid-induced platelet aggregation. Blood samples were collected before the operation, immediately postoperatively, and on days 1, 2, 5, and 30. RESULTS In the off-pump group expression of P-selectin was markedly increased in comparison with preoperative values, with a maximum difference observed on day 2 (+53%, P = .02), and it was significantly higher compared with that seen in the on-pump group on days 2 and 5 (+53% vs +4%, P = .004, and +20% vs -16%, P = .005). On day 30, P-selectin expression was similar both between the groups and in comparison with the preoperative values. Arachidonic acid-induced platelet aggregation was gradually decreasing until day 30, but on day 2, there was an unexpected increase in aggregation that was more expressed in the off-pump group. CONCLUSIONS The platelet activity is higher in the early postoperative period in off-pump compared with on-pump coronary artery bypass grafting. The present aspirin strategy seems to be insufficient in the early postoperative period, irrespective of the surgical technique used.

Pre-transplant positron emission tomography in patients with relapsed Hodgkin lymphoma

This retrospective study evaluated the secondary clinical risk score at relapse, the prognostic significance of pre-transplant positron emission tomography (PET), and complete remission (CR) assessed by computed tomography (CT) after salvage chemotherapy before autologous stem cell transplant (ASCT) in 76 patients with relapsed/refractory Hodgkin lymphoma (HL). Median follow-up after ASCT was 23 months. Overall 11/20 PET-positive and 14/56 PET-negative patients relapsed after ASCT. In univariate analysis, only PET negativity before ASCT was significantly associated with better 2-year progression-free survival (PFS) (72.7 ± 6.3% vs. 36.1 ± 11.6%, p = 0.01) and 2-year overall survival (OS) (90.3 ± 4.1% vs. 61.4 ± 11.6%, p = 0.009). Other factors were not significant. In multivariate analysis, none of the evaluated factors were significant for PFS and OS. However, positive pre-transplant PET identified a population with worse PFS and OS at least in univariate analysis.

Radiotherapy with rituximab may be better than radiotherapy alone in first-line treatment of early-stage follicular lymphoma: is it time to change the standard strategy?

Early-stage follicular lymphoma (FL) has traditionally been treated with involved-field radiotherapy (RT). Rituximab (R) is a low-toxic, efficient systemic therapy for FL, but there are no data about its clinical impact in early FL. We retrospectively analyzed 93 patients with stage I–II indolent FL treated with RT (n = 65) or RT + R (n = 14) or R alone (n = 14). Median follow-up was 5.0 years for patients with RT, 2.8 years for the RT + R subgroup and 2.5 years for patients treated with R. The complete response rate was 92%, 100% and 86% (not significant) and the median PFS was 3.3 years, not reached and 4.9 years (p = 0.035) for the RT, RT + R and R arms, with no impact on overall survival. R combined with RT seems to give better results in terms of global FL control, but longer follow-up and prospective comparison are needed to verify these results.

Glycemia, triglycerides and disease severity are best associated with higher platelet activity in patients with stable coronary artery disease

BackgroundInconsistent findings are reported about the relation of platelet activity to disease severity in stable patients with chronic coronary artery disease (CAD). Nevertheless, most reports studied only very small groups of patients. The purpose aim of our study was to assess the relation of platelet activity to disease severity in sufficient number of patients with chronic CAD.MethodsOne hundred and sixty stable patients with chronic CAD were studied (25 with single-, 63 with double- and 72 with triple-vessel disease). 91% of them were on aspirin, 1.6% on clopidogrel medication. Platelet activity was determined as membrane expression of antigens CD62P (P-selectin, as % of positive cells) and CD41 (part of GpIIb/IIIa integrin, as mean fluorescence intensity) by flow cytometry. Platelet aggregability was measured by ADP-optical aggregometry. Data sets were compared by Kruskal-Wallis test, correlation by Spearman test. Data are shown as median with 25–75 percentiles.ResultsMembrane CD62P expression correlated with vessel severity (P < 0.001, Kruskal-Wallis test). Patients with triple-vessel disease had the highest CD62P expression (1.6; 1.1–2.0) followed by patients with double-vessel (1.2; 0.63–1.95) and single-vessel (0.7; 0.30–0.84) disease. Positive correlation was found between CD62P expression with triglycerides (r = 0.49, P < 0.05) and CD41 with fasting glucose (r = 0.48, P < 0.05). No differences in CD41 expression or ADP aggregability were found between groups.ConclusionHigher platelet activity is present in patients with more severe CAD. More aggressive anti-platelet treatment in these patients should be considered, especially when metabolic syndrome is simultaneously present.

Role of rituximab in treatment of patients with primary central nervous system lymphoma: a retrospective analysis of the Czech lymphoma study group registry

Abstract We have investigated whether the addition of rituximab to methotrexate, procarbazine, vincristine, radiotherapy and cytarabine was associated with improved outcome of primary central nervous system lymphomas (PCNSL). Of 164 patients, 49 received rituximab. Median age was 63 years, median Karnofsky performance score (KPS) was 60 and median follow-up of living patients was 59.5 months. 1- and 2-year PFS were 49.7 and 37.9%, 1- and 2-year OS were 57.0 and 45.3%. Median progression-free survival (PFS), but not overall survival (OS) was significantly better for patients treated with rituximab (22.9 vs. 10.9 months, p = 0.037). In multivariate analysis, age ≤70 years and KPS ≥90 were predictive for PFS and OS, rituximab was an independent prognostic factor for PFS only. In landmark analyses, rituximab was not found beneficial for long-term survivors and no group particularly benefited from rituximab. In conclusion, addition of rituximab was associated with improved PFS, but not OS in this unselected cohort of PCNSL patients.

Impact of rituximab maintenance and maintenance schedule on prognosis in first-line treatment of follicular lymphoma. Retrospective analysis from Czech Lymphoma Study Group (CLSG) database.

Abstract Rituximab maintenance (RM) improves time to progression (PFS) in advanced follicular lymphoma (FL), but the impact of various RM schedules remains unknown. This study performed a retrospective evaluation of RM given for up to 2 years vs observation in 319 untreated FL patients (stage II–IV; grade 1–3A) responding to RCHOP induction and a comparison of two different RM schedules (RM8 = eight doses given every 3 months and RM12 = 12 doses given every 2 months). A total of 183 patients received RM and 136 patients were observed; 5-year PFS was better in the RM arm, 74.1% vs 52.3% (p < 0.001), which was projected in 5-year OS 93.8% vs 87.5% (p = 0.005). However, 5-year PFS was similar in both the RM8 (n = 54) and RM12 (n = 56) arms. In the first line, RM significantly prolongs PFS and OS in FL, but different RM schedules bring a similar benefit.

The use of formalin‐fixed, paraffin‐embedded lymph node samples for the detection of minimal residual disease in mantle cell lymphoma

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Frontline intensive chemotherapy improves outcome in young, high-risk patients with follicular lymphoma: pair-matched analysis from the Czech Lymphoma Study Group Database

Abstract Optimal frontline treatment in younger high tumor-burden risk follicular lymphoma patients remains a challenge given the reduced efficacy of standard immunochemotherapy (R-CHOP) in widespread disease and unclear role of intensive induction. The retrospective non-randomized pair-matched (1:3) analysis compared 48 intermediate/high Follicular Lymphoma International Prognostic Index (FLIPI) patients receiving intensive rituximab sequential chemotherapy (R-SQ) with 144 random controls (R-CHOP) matched for age, FLIPI score, and maintenance delivery. Complete response rates were 91.7% and 74.1%, respectively (p = .038). After a median follow-up of 8.8 (R-SQ) and 6.5 years (R-CHOP), 5-year time to treatment failure, progression-free survival, and overall survival were 80.9%, 83.2%, and 100% and 57.5%, 60.3%, and 92.1% (p = .0044; p = .0047; p = .22), respectively. Intensive treatment was accompanied by higher acute hematologic toxicity and infections, comparable non-hematologic toxicity, and incidence of secondary malignancies. Intensive induction demonstrates superior long-term disease control compared to R-CHOP, with higher acute hematologic toxicity, but without acute treatment-related mortality. Further studies are needed to define ultra-high-risk FL patients benefiting most from treatment intensity.