ALBERT

Description: ABSTRACT This paper presents an analysis of winter climate variability based on daily mean temperature and precipitation data since 1970 in the Chic-Chocs Mountain range (located in the Gaspé Peninsula, Eastern Quebec, Canada). Mountain environments are particularly sensitive to rapid climate change and are therefore good indicators of recent global warming. The main goal of this study is to demonstrate how joint probability temperature/precipitation distributions can be used to estimate winter condition changes (trends) for six meteorological stations in the study area (the altitudinal range for the stations is from 5 to 574 m). The presence and persistence of snow cover was also estimated. Previous studies have shown a lack of evidence of significant trends in snow-cover characteristics (density, depth and snow water equivalent (SWE)) from the early 1980s to the present, despite an increase in temperature over the same period. A reanalysis of these data sets in addition to the use of a combination of temperature and precipitation data categorized into four modes (warm/wet, warm/dry, cold/wet and cold/dry) was also performed. Despite this new analysis, no clear evidence of climate change could be found in the study area over the last four decades. The results revealed that patterns and trends are quite different from one station to another, but when the environment is taken into account (valley or plateau, coastal versus inland) some apparent patterns emerge.

Description: Introduction Chronic lymphocytic leukemia (CLL) diagnosis relies on a characteristic immunophenotype of B-cell lymphocytes. The modified Matutes scoring system is based on five key membrane markers: CD5, CD23, CD79b, FMC7 and surface membrane immunoglobulin (smIg) (Matutes et al., Leukemia 1994; modified by Moreau et al., Am J Clin Pathol 1997). CLL typically demonstrates dim staining for smIg, low or absent expression of CD22, CD79b and FMC7 and strong expression of CD5 and CD23. However, up to 7% of B-cell clonal lymphoproliferative disorder (CLPD) cannot be classified as CLL, nor as any other well described CLPD, namely: mantle cell lymphoma, marginal zone lymphoma, follicular lymphoma, hairy cell leukemia, diffuse large B-cell lymphoma, B-cell prolymphocytic leukemia or Waldenstrom's macroglobulinemia and are classified as atypical CLL (A-CLL) (Boucher et al., ASH 2013). Furthermore, leukemic phase of mantle cell lymphoma may mimic CLL (Nelson et al., Mod Pathol 2002), leading to suboptimal management. The expression of CD200 emerged as a powerful marker to distinguish MCL from CLL and therefore better recognize A-CLL (Spacek et al., ASH 2014). Clinical outcomes of patients with A-CLL with CD200 expression have not been compared to patients with classical CLL. Methods Patients diagnosed with CLL or A-CLL expressing CD200 on flow cytometry analysis performed at Maisonneuve-Rosemont Hospital (Montreal, Canada) between July 2014 and July 2015 were reviewed. Multiparameter flow cytometric immunophenotyping (8 colors) was performed on 1 x 106cells using the Euroflow panel of CLPD (van Dongen et al., Leukemia 2012). Data were acquired using FACS CantoII flow cytometer and FACSDiva software program (Becton Dickinson Bioscience, San Jose, CA) and were analysed with Infinicyt software (Cytognos SL, Salamanca, Spain). Diagnostic criteria for A-CLL were negative or ≤ intermediate expression of CD23, ≤ intermediate expression of CD5 or strong expression of CD20. We retrospectively collected data on clinical presentation, flow cytometry and cytogenetics analysis, therapies and outcomes. Treatment response was evaluated according to Hallek (Blood 2008). Comparison between outcomes were evaluated through time to first line therapy (TT1T), time to second line therapy (TT2T) and overall survival (OS) with Kaplan-Meier curves and log-rank tests and response to first line therapy (R1T) was compared with Fisher's test. Treatment was according to physician choice. Our study was approved by local research and ethic committees. Results We retrieved 25 CLL and 10 A-CLL patients with a median age of 67 (46-93) and 67 (51-81) respectively at diagnosis. All these 35 CLL expressed CD200 as per inclusion criteria. Among the 10 A-CLL: 4 did not express CD23 (2 were negative for t(11;14) by FISH analysis and 2 had negative immunohistochemistry staining for cyclin D1 on bone marrow biopsy), 4 had intermediate expression of CD23, 1 had intermediate expression of CD5 and CD23 and 1 had intermediate expression of CD5. One of the A-CLL not expressing CD23 had strong expression of CD20. At diagnosis, 3/25 (12%) CLL presented with Rai 3-4 stage compared to 1/9 (11%) of A-CLL. Deletion 17p was detected in none of the 7 CLL and 8 A-CLL patients tested and deletion 11q was detected in 2/9 (22%) CLL and 1/8 (13%) A-CLL patients tested. At time of analysis, 7 patients with CLL and 4 patients with A-CLL received treatment. Chlorambucil was administered to 4 CLL and 2 A-CLL patients, fludarabine, cyclophosphamide and rituximab to 2 CLL and 2 A-CLL patients and rituximab only to 1 CLL patient for refractory immune thrombocytopenia. After a median follow up of 18 months, no significant difference in outcomes was observed. Median TT1T was 26 months (m) for CLL and not reached (NR) for A-CLL (p=0.53). Complete remission was achieved for 2 CLL and 2 A-CLL and partial remission for 5 CLL and 2 A-CLL patients respectively (p=0.58). During follow up, 3 CLL and 3 A-CLL patients required second-line therapy. Median TT2T was 111 m for CLL and NR for A-CLL. No Richter transformation was observed and no difference in OS could be detected (only one death in the entire cohort). Conclusion Outcomes of atypical CLL expressing CD200 appear similar to CLL using CLL management strategies in this cohort. A longer follow-up of a larger cohort may allow us to confirm the value of this marker in guiding A-CLL management. Disclosures Fleury: Lundbeck: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau.

Description: Introduction Primary bone lymphoma (PBL) is an uncommon form of lymphoma. Diffuse large B-cell lymphoma (DLBCL) represents the main histology associated with PBL. Clinicopathological understanding and management of PBL rely only on retrospective series. Methods Cases of DLBCL diagnosed by bone biopsy treated in one referring center between 1993 and 2014 were retrospectively reviewed (Montreal, Canada). Bone biopsies done as part of the bone marrow analysis were excluded. Patients files were analyzed to determine if patient had primary bone lymphoma or systemic lymphoma with bony involvement. We excluded patient with distant lymph node or other extranodal involvement. Data on clinical presentation, staging procedures and treatment management including use of radiotherapy was collected. Staging was performed according to WHO classification of soft tissue tumors (2002). Survival time and time to recurrence were calculated from the date of the first documented treatment until recurrence or death with the Kaplan-Meier method. Prognostic factors of recurrence or death were explored with log-rank tests and Cox proportional hazards models. Competing risks analysis was attempted to isolate deaths from lymphoma and death from other causes. Our study was approved by local research and ethic committees. Results We retrieved 42 cases of PBL with a median age of 63 years (23-83) treated between October 1995 and April 2014. We identified 3/14 (21%) GCB and 11/14 (79%) non-GCB subtypes based on the modified Hans algorithm (Meyer et al., JCO 2011). The most common presenting symptom was pain (88%). 12/42 (33%) patients had an IPI score ≥ 3. We identified 18 (43%) stage I, 11 (26%) stage II and 13 (31%) stage IV. 20/42 (48%) had bulky disease (≥ 10cm). Among the 37 patients treated with curative intent, 36 (97%) received CHOP-based regimen and 23 (62%) received rituximab. 30 of these 37 (81%) patients received additional radiotherapy of which 67% received a dose of radiotherapy between 36-50 Gy. Overall response rate for patients treated with curative intent was 86%. With a median follow up of 64.8 months for the whole cohort, the 5- and 10-year overall survival was 73% and 54%, respectively. The 5- and 10-year progression-free survival was 70% and 49% respectively. Age, LDH, stage (I-II vs IV), ECOG (0-1 vs 2-4), IPI (0-2 vs 3-5), use of radiotherapy or addition of rituximab were associated with differences in survival and progression rates that did not reach statistical significance given the limited number of patients in our cohort and the fact that half of the deaths were attributed to other causes. A larger cohort would be required to demonstrate a benefit with rituximab. Response was based on positron emission tomography-computed tomography (TEP-CT) imaging in 12 patients. There was an insufficient number of patients to evaluate the role of adding radiotherapy in patient complete remission defined by PET-CT. Conclusion Our survival rates reproduce published data from series of PBL (Ramadan et al., Ann Oncol 2007; Bruno Ventre et al., Oncologist 2014), although the benefit of adding rituximab did not reach statistical significance in our cohort. The role of radiotherapy in the era of response defined by PET-CT remains to be defined. Disclosures Fleury: Gilead: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Lundbeck: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau.

Description: We survey the recent, fast-growing literature on peer effects in networks. An important recurring theme is that the causal identification of peer effects depends on the structure of the network itself. In the absence of correlated effects, the reflection problem is generally solved by network interactions even in nonlinear, heterogeneous models. By contrast, microfoundations are generally not identified. We discuss and assess the various approaches developed by economists to account for correlated effects and network endogeneity in particular. We classify these approaches in four broad categories: random peers, random shocks, structural endogeneity, and panel data. We review an emerging literature relaxing the assumption that the network is perfectly known. Throughout, we provide a critical reading of the existing literature and identify important gaps and directions for future research.