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Öğe Absolute monocyte/lymphocyte count prognostic score is independent of immunohistochemically determined cell of origin in predicting survival in diffuse large B-cell lymphoma(Informa Healthcare, 2012) Porrata, Luis F.; Ristow, Kay; Habermann, Thomas M.; Ozsan, Nazan; Dogan, Ahmet; Macon, William; Colgan, Joseph P.; Witzig, Thomas E.; Inwards, David J.; Ansell, Stephen M.; Micallef, Ivana N.; Johnston, Patrick B.; Nowakowski, Grzegorz S.; Thompson, Carrie; Markovic, Svetomir N.The absolute monocyte/lymphocyte count prognostic score (AMC/ALC score) has not been directly compared with the cell of origin (COO) to predict overall survival (OS) and progression-free survival (PFS) in diffuse large B-cell lymphoma (DLBCL). Thus, we retrospectively examined a new cohort of 99 patients with DLBCL treated from 2008 to 2010, (1) to validate whether AMC/ALC score affects survival, (2) to investigate whether AMC/ALC score is independent of COO to predict survival and (3) to assess whether AMC/ALC score can further stratify clinical outcomes by COO. By univariate analysis, the AMC/ALC score was a predictor for OS and PFS. On multivariate analysis performed including the COO and the International Prognostic Index, AMC/ALC score remained an independent predictor for OS and PFS. The AMC/ALC score was able to further stratify DLBCL clinical outcomes by COO. The AMC/ALC score was independent of COO and added to its ability to identify patients with high-risk disease.Öğe CXCR5 polymorphisms in non-Hodgkin lymphoma risk and prognosis(Springer, 2013) Charbonneau, Bridget; Wang, Alice H.; Maurer, Matthew J.; Asmann, Yan W.; Zent, Clive S.; Link, Brian K.; Ansell, Stephen M.; Weiner, George J.; Ozsan, Nazan; Feldman, Andrew L.; Witzig, Thomas E.; Cunningham, Julie M.; Dogan, Ahmet; Habermann, Thomas M.; Slager, Susan L.; Novak, Anne J.; Cerhan, James R.CXCR5 [chemokine (C-X-C motif) receptor 5; also known as Burkitt lymphoma receptor 1 (BCR1)] is expressed on mature B-cells, subsets of CD4(+) and CD8(+) T-cells, and skin-derived migratory dendritic cells. Together with its ligand, CXCL13, CXCR5 is involved in guiding B-cells into the B-cell zones of secondary lymphoid organs as well as T-cell migration. This study evaluated the role of common germline genetic variation in CXCR5 in the risk and prognosis of non-Hodgkin lymphoma (NHL) using a clinic-based study of 1,521 controls and 2,694 NHL cases including 710 chronic lymphocytic leukemia/small lymphocytic lymphoma, 586 diffuse large B-cell lymphoma (DLBCL), 588 follicular lymphoma (FL), 137 mantle cell lymphoma (MCL), 230 marginal zone lymphoma (MZL), and 158 peripheral T-cell lymphoma (PTCL). Of the ten CXCR5 tag SNPs in our study, five were associated with risk of NHL, with rs1790192 having the strongest association (OR 1.19, 95 % CI 1.08-1.30; p = 0.0003). This SNP was most strongly associated with the risk of FL (OR 1.44, 95 % CI 1.25-1.66; p = 3.1 x 10(-7)), with a lower degree of association with DLBCL (OR 1.16, 95 % CI 1.01-1.33; p = 0.04) and PTCL (OR 1.29, 95 % CI 1.02-1.64; p = 0.04) but no association with the risk of MCL or MZL. For FL patients that were observed as initial disease management, the number of minor alleles of rs1790192 was associated with better event-free survival (HR 0.64; 95 % CI 0.47-0.87; p = 0.004). These results provide additional evidence for a role of host genetic variation in CXCR5 in lymphomagenesis, particularly for FL.Öğe Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP(Amer Soc Hematology, 2012) Gupta, Mamta; Maurer, Matthew J.; Wellik, Linda E.; Law, Mark E.; Han, Jing Jing; Ozsan, Nazan; Micallef, Ivana N.; Dogan, Ahmet; Witzig, Thomas E.STAT3 regulates cell growth by upregulating downstream targets, such as Myc. The frequency of phosphorylated STAT3 (pSTAT3) and Myc expression and their prognostic relevance is unknown within diffuse large B-cell lymphoma (DLBCL) germinal center B-cell (GCB) and non-GCB subtypes. pSTAT3 and Myc were studied by immunohistochemistry (IHC) on tumors from 40 DLBCL patients uniformly treated on a clinical trial of epratuzumab/rituximab-CHOP. A total of 35% of cases were pSTAT3-positive, and pSTAT3 positivity was more frequent in the non-GCB (P = .06) type but did not correlate with event-free survival (EFS). Myc expression was observed in 50% of cases and was more frequent in non-GCB type (P = .07). Myc-positive cases had inferior EFS in all patients, including the GCB and pSTAT3-positive cases, were more likely to express Myc (P = .06). Myc translocations involving the major breakpoint regions were found in 10% (3 of 29) of cases, and all 3 cases were GCB and had an inferior EFS (P = .09). pSTAT3, but not Myc expression, was correlated with elevated pretreatment serum cytokines, such as IL-10 (P = .05), G-CSF (P = .03), and TNF-alpha (P = .04). pSTAT3 IHC in DLBCL tumors has the potential to identify patients for STAT3 pathway-directed therapy; Myc IHC is a potential marker for inferior EFS in GCB patients. (Blood. 2012;120(22):4400-4406)