William R Macon

Mayo Clinic - Rochester, Rochester, Minnesota, United States

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Publications (93)541.41 Total impact

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    ABSTRACT: Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 08/2014;
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    ABSTRACT: Background: Mantle cell lymphoma (MCL) is a unique type of lymphoma with a prognosis intermediate between indolent and aggressive types. The purpose of this study was to study blood cytokine levels in newly diagnosed and relapsed MCL patients with respect to patterns of abnormalities and relationship to the MCL International Prognostic Index (MIPI) score.Patients and Methods: We analyzed blood levels of 30 cytokines using a multiplex ELISA in 88 patients with newly diagnosed MCL (pre-treatment levels) and 20 with relapsed MCL and compared them with controls without known lymphoma. Elevated cytokine levels were compared with clinical outcome and the MIPI score.Results: In the 88 newly diagnosed MCL patients we found significantly elevated levels compared to controls of IL-12, IP-10, sIL-2Rα, MIG, IL-1RA, IL-8, MIP-1α and MIP-1β (all p<0.05). Of these elevated cytokines, sIL-2Rα, IL-8, MIG, MIP-1α and MIP-1β were predictive of inferior event-free survival, and sIL-2Rα (HR=1.94; p=0.038), IL-8 (HR=2.17; p=0.015), and MIP-1β (HR=2.10; p=0.016) were independent of MIPI score; only sIL-2Rα (HR=2.35; p=0.041) was associated with overall survival after adjustment for MIPI. In the relapsed MCL patient group, the only significantly elevated plasma cytokines that predicted EFS were sILȐ2Rα (HR=2.90; p=0.04) and IL-8 (HR=3.75; p=0.02).Conclusion: Elevated blood levels of sIL-2Rα and the pro-inflammatory cytokines IL-8 and MIP-1β are poor prognostic factors in MCL patients and independent of MIPI score. These factors, if validated, will provide important additions to the MIPI and guide the development of new therapies for patients with elevated levels of these cytokines.
    American Journal of Hematology 08/2014; · 4.00 Impact Factor
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    ABSTRACT: ALK-negative anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALK-positive ALCL but lacks chromosomal rearrangements of the ALK gene. The genetic and clinical heterogeneity of ALK-negative ALCL has not been delineated. We performed immunohistochemistry and fluorescence in situ hybridization on 73 ALK-negative ALCLs and 32 ALK-positive ALCLs and evaluated the associations among pathology, genetics, and clinical outcome. Chromosomal rearrangements of DUSP22 and TP63 were identified in 30% and 8% of ALK-negative ALCLs, respectively. These rearrangements were mutually exclusive and were absent in ALK-positive ALCLs. Five-year overall survival rates were 85% for ALK-positive ALCLs, 90% for DUSP22-rearranged ALCLs, 17% for TP63-rearranged ALCLs, and 42% for cases lacking all three genetic markers (p<0.0001). Hazard ratios for death in these 4 groups after adjusting for International Prognostic Index and age were 1.0 (reference group), 0.58, 8.63, and 4.16, respectively (p=7.10 x 10(-5)). These results were similar when restricted to patients receiving anthracycline-based chemotherapy as well as to patients not receiving stem-cell transplantation. Thus, ALK-negative ALCL is a genetically heterogeneous disease with widely disparate outcomes following standard therapy. DUSP22 and TP63 rearrangements may serve as predictive biomarkers to help guide patient management.
    Blood 06/2014; · 9.78 Impact Factor
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    ABSTRACT: aPatients with diffuse large B-cell lymphoma (DLBCL) and pre-treatment bone marrow (BM) involvement require a restaging BM biopsy to document complete remission (CR). We investigated whether BM assessment by restaging PET-CT could obviate the need for a repeat BM biopsy. Patients with DLBCL and a positive BM biopsy at diagnosis were identified from the Mayo Clinic Lymphoma Data Base. The concordance of BM status on restaging histopathology and PET-CT reports and the positive (PPV) and negative predictive value (NPV) of PET-CT were determined. 1080 patients with DLBCL were evaluated and 69 patients (6%) had DLBCL involving the BM at diagnosis. Of 46 patients who completed frontline chemoimmunotherapy, 34 had a restaging PET-CT and BM biopsy and were included in the analysis. Thirty-three patients had a negative BM by both PET-CT and BM biopsy; one patient had persistent BM involvement by biopsy and PET-CT. Thus, restaging PET-CT had 100% PPV and 100% NPV for assessing residual BM disease. The findings were validated in a prospective cohort of 68 DLBCL patients treated on a phase II clinical trial where four patients (6%) had DLBCL involving the BM at diagnosis. All had a negative BM by both restaging BMB and PET-CT. Compared with the gold standard of BM biopsy, PET-CT had a 100% NPV to exclude residual BM disease after frontline therapy. If further validated, DLBCL practice guidelines and response criteria could be modified so that BM biopsy is no longer required to document CR if the restaging PET-CT is negative.
    American Journal of Hematology 05/2014; · 4.00 Impact Factor
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    ABSTRACT: Abstract There are few studies examining complementary and alternative medicine (CAM) use and beliefs among non-Hodgkin lymphoma (NHL) survivors. 719 NHL patients from the University of Iowa/Mayo Clinic Molecular Epidemiology Resource who completed the 3-year post-diagnosis questionnaire were included in this study. 636 (89%) reported ever using CAM, with 78% utilizing vitamins, 54% alternative therapies and 45% herbals. Female gender was associated with increased overall CAM use (P<.0001) as well as use of vitamins (P<.0001), herbals (P=.006) and alternative therapy (P=.0002) for cancer. Older age (>60) was associated with increased vitamin use (P=.005) and decreased herbal use (P=.008). Among users, 143 (20%) believe CAM assists healing, 123 (17%) believe CAM relieves symptoms, 122 (17%) believe CAM gives a feeling of control, 110 (15%) believe CAM assists other treatments, 108 (15%) believe CAM boosts immunity, 26 (4%) believe CAM cures cancer, and 36 (5%) believe CAM prevents the spread of cancer.
    Leukemia & lymphoma 04/2014; · 2.61 Impact Factor
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    ABSTRACT: The diagnosis of peripheral T-cell and NK-cell lymphomas (PTNKCL) is difficult with few standards for required ancillary studies. We evaluated a series of PTNKCLs using a tiered approach to immunohistochemistry and molecular genetic characterization to document diagnostic accuracy and clinical relevance. Seven hematopathologists reviewed 374 cases that included PTNKCL and non-PTNKCL cases to mimic diagnostic practice. Cases received tier 0, 1, and 2 diagnoses by 3 independent pathologists, on the basis of hematoxylin and eosin stains and progressive immunohistochemistry panels. A tier 2b diagnosis was rendered when gene rearrangement data were available, and a final consensus diagnosis was rendered after discussion of each case. Across all 374 cases, consensus agreement was 92.5%. For PTNKCLs, World Health Organization subclassification was possible in 16.5%, 37.1%, 82.8%, and 85.9% of individual reviewer diagnoses at tier 0, 1, 2, and 2b, respectively. Gene rearrangement contributed to a change in diagnosis in 51 of 647 (8%) individual reviews. Following this algorithm may provide prognostic information on the basis of individual marker expression in common PTNKCL types (CD4 in peripheral T-cell lymphoma, not otherwise specified and PD-1 in angioimmunoblastic T-cell lymphoma). This evidence-based approach to the diagnosis of PTNKCL informs practicing pathologists, clinical trial designers, and policy-makers regarding required ancillary studies.
    The American journal of surgical pathology 03/2014; · 4.06 Impact Factor
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    ABSTRACT: Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data. Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France. In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL. Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.
    Journal of Clinical Oncology 02/2014; · 18.04 Impact Factor
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    ABSTRACT: Peripheral T-cell lymphomas (PTCLs) are a heterogenous group of aggressive non-Hodgkin's lymphomas that are incurable in the majority of patients with current therapies. Outcomes associated with anthracycline-based therapies are suboptimal, but remain the standard of care for most patients, even though the benefits of this approach remain uncertain. This study retrospectively examined outcomes in a cohort of North American PTCL patients treated with both anthracycline- and nonanthracycline-containing regimens. The incorporation of anthracycline-containing regimens was associated with improved progression-free survival (PFS) and overall survival (OS). Patients treated with nonanthracycline-containing regimens were more likely to have high-risk features and were less likely to undergo high-dose therapy and stem cell transplantation. However, anthracycline use remained an independent predictor of improved PFS and OS when adjusting for these confounding variables. Anthracycline-based regimens and consolidation with high-dose therapy and autologous stem cell transplantation in appropriately selected patients remains a viable option for patients unable to participate in a clinical trial. Long-term disease-free survival is not optimal, highlighting the need for an improved understanding of disease pathogenesis, and the development of novel therapeutic strategies.
    Blood Cancer Journal 01/2014; 4:e214. · 1.40 Impact Factor
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    ABSTRACT: The detection of serum free light (FLC) is useful in the diagnosis of several hematological diseases. The role and biological relevance of monoclonal or polyclonal FLC elevations in predicting long-term outcome in diffuse large B-cell lymphoma (DLBCL) is unknown. We determined the relationship of the type of FLC elevations to outcome, tumor genotype, and pattern of serum cytokine elevations in 276 patients with untreated DLBCL. Elevated FLC was an adverse prognostic factor through 6 years of follow-up (monoclonal, EFS HR = 3.56, 95% CI: 1.88-6.76, p<0.0001; polyclonal, EFS HR = 2.56, 95% CI: 1.50-4.38, p=0.0006). 73% of DLBCL tumors with monoclonal FLC elevations were activated B-cell type (ABC) vs. 33% from patients with normal FLC. Only ABC-DLBCL lines secreted kappa FLC in vitro and this secretion could be inhibited by the NF-κB inhibitor bortezomib. Patients with monoclonal FLC had significantly (all p<0.001) elevated serum levels of IL-12, sIL-2Rα, IL-1R, and IP-10. Patients with polyclonal elevations of FLC had higher levels of IL-6 (p=0.033), IL-8 (p=0.025), sIL2Rα (p=0.011), and IL-1R1 (p=0.041). The combination of elevated FLC and a CXC superfamily chemokine IP-10 predicted a particularly inferior outcome characterized by late relapse. These elevated abnormal FLC and cytokines are potentially useful biomarkers for prognosis and selecting agents for untreated DLBCL.
    American Journal of Hematology 12/2013; · 4.00 Impact Factor
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    ABSTRACT: Cytokines are important immune mediators of classical Hodgkin lymphoma (CHL) pathogenesis, and circulating levels at diagnosis may help predict prognosis. Germline single nucleotide polymorphisms (SNPs) in immune genes have been correlated with cytokine production and function. We investigated whether selected germline SNPs in IL10 (rs1800890, rs1800896, rs1800871, rs1800872), TNFA (rs1800629), IL6 (rs1800795), ILRN (rs419598), INFG (rs2430561) and CCL17 (rs223828) were associated with circulating levels of related cytokines at diagnosis and progression-free survival (PFS) in CHL. Patients were from France (GELA, N=464; median age=32years) and the United States (Iowa/Mayo Specialized Program Of Research Excellence [SPORE], N=239; median age=38years); 22% of 346 CHL cases with EBV tumor status were positive. There was no association with any of the SNPs with cytokine levels. Overall, there was no association of any of the SNPs with PFS. In exploratory analyses by EBV status, TNFA rs1800629 (HRAA/AG=2.41; 95%CI, 1.17-4.94) was associated with PFS in EBV-negative GELA patients, with similar trends in the SPORE patients (HRAA/AG=1.63; 95%CI, 0.61-4.40). In a meta-analysis of the two studies, TNFA (HRAA/AG=2.11; 95%CI, 1.18-3.77; P=0.01) was statistically significant, and further adjustment for the international prognostic system did not alter this result. This study showed that germline variation in TNFA was associated with CHL prognosis for EBV-negative patients, which will require confirmation. These results support broader studies on the differential impact of genetic variation in immune genes on EBV-positive vs. EBV-negative CHL pathogenesis.
    Cytokine 09/2013; · 2.52 Impact Factor
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    ABSTRACT: PURPOSEThis study sought to characterize transformation incidence and outcome for patients with follicular lymphoma (FL) in a prospective observational series begun after diffusion of rituximab use. PATIENTS AND METHODS Patients with newly diagnosed FL were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource from 2002 to 2009. Patients were actively followed for re-treatment, clinical or pathologic transformation, and death. Risk of transformation was analyzed via time to transformation by using death as a competing risk.ResultsIn all, there were 631 patients with newly diagnosed grade 1 to 3a FL who had a median age at enrollment of 60 years. At a median follow-up of 60 months (range, 11 to 110 months), 79 patients had died, and 60 patients developed transformed lymphoma, of which 51 were biopsy proven. The overall transformation rate at 5 years was 10.7%, with an estimated rate of 2% per year. Increased lactate dehydrogenase was associated with increased risk of transformation. Transformation rate at 5 years was highest in patients who were initially observed and lowest in patients who initially received rituximab monotherapy (14.4% v 3.2%; P = .021). Median overall survival following transformation was 50 months and was superior in patients with transformation greater than 18 months after FL diagnosis compared with patients with earlier transformation (5-year overall survival, 66% v 22%; P < .001). CONCLUSION Follicular transformation rates in the immunochemotherapy era are similar to risk of death without transformation and may be lower than reported in older series. Post-transformation prognosis is substantially better than described in older series. Initial management strategies may influence the risk of transformation.
    Journal of Clinical Oncology 07/2013; · 18.04 Impact Factor
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    ABSTRACT: Nearly all information about patients with chronic lymphocytic leukaemia (CLL) who develop diffuse large B-cell lymphoma [Richter syndrome (RS)] is derived from retrospective case series or patients treated on clinical trials. We used the Mayo Clinic CLL Database to identify patients with newly diagnosed CLL between January 2000 and July 2011. Individuals who developed biopsy-proven RS during follow-up were identified. After a median follow-up of 4 years, 37/1641 (2·3%) CLL patients developed RS. The rate of RS was approximately 0·5%/year. Risk of RS was associated with advanced Rai stage at diagnosis (P < 0·001), high-risk genetic abnormalitites on fluorescence in situ hybridization (P < 0·0001), unmutated IGHV (P = 0·003), and expression of ZAP70 (P = 0·02) and CD38 (P = 0·001). The rate of RS doubled in patients after treatment for CLL (1%/year). Stereotyped B-cell receptors (odds-ratio = 4·2; P = 0·01) but not IGHV4-39 family usage was associated with increased risk of RS. Treatment with combination of purine analogues and alkylating agents increased the risk of RS three-fold (odds-ratio = 3·26, P = 0·0003). Median survival after RS diagnosis was 2·1 years. The RS prognosis score stratified patients into three risk groups with median survivals of 0·5 years, 2·1 years and not reached. Both underlying characteristics of the CLL clone and subsequent CLL therapy influence the risk of RS. Survival after RS remains poor and new therapies are needed.
    British Journal of Haematology 07/2013; · 4.94 Impact Factor
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    ABSTRACT: BACKGROUND: Perforation is a serious life-threatening complication of lymphomas involving the gastrointestinal (GI) tract. Although some perforations occur as the initial presentation of GI lymphoma, others occur after initiation of chemotherapy. To define the location and timing of perforation, a single-center study was carried out of all patients with GI lymphoma. PATIENTS AND METHODS: Between 1975 and 2012, 1062 patients were identified with biopsy-proven GI involvement with lymphoma. A retrospective chart review was undertaken to identify patients with gut perforation and to determine their clinicopathologic features. RESULTS: Nine percent (92 of 1062) of patients developed a perforation, of which 55% (51 of 92) occurred after chemotherapy. The median day of perforation after initiation of chemotherapy was 46 days (mean, 83 days; range, 2-298) and 44% of perforations occurred within the first 4 weeks of treatment. Diffuse large B-cell lymphoma (DLBCL) was the most common lymphoma associated with perforation (59%, 55 of 92). Compared with indolent B-cell lymphomas, the risk of perforation was higher with aggressive B-cell lymphomas (hazard ratio, HR = 6.31, P < 0.0001) or T-cell/other types (HR = 12.40, P < 0.0001). The small intestine was the most common site of perforation (59%). CONCLUSION: Perforation remains a significant complication of GI lymphomas and is more frequently associated with aggressive than indolent lymphomas. Supported in part by University of Iowa/Mayo Clinic SPORE CA97274 and the Predolin Foundation.
    Annals of Oncology 05/2013; · 7.38 Impact Factor
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    ABSTRACT: We evaluated the association of dietary fat and protein intake with risk of non-Hodgkin lymphoma (NHL) in a clinic-based study in 603 cases (including 218 chronic lymphocytic leukemia/small lymphocytic lymphoma, 146 follicular lymphoma, and 105 diffuse large B-cell lymphoma) and 1007 frequency-matched controls. Usual diet was assessed with a 128-item food-frequency questionnaire. Unconditional logistic regression was used to estimate ORs and 95% CIs, and polytomous logistic regression was used to assess subtype-specific risks. trans Fatty acid (TFA) intake was positively associated with NHL risk [OR = 1.60 for highest vs. lowest quartile (95% CI = 1.18, 2.15); P-trend = 0.0014], n3 (ω3) fatty acid intake was inversely associated with risk [OR = 0.48 (95% CI = 0.35, 0.65); P-trend < 0.0001], and there was no association with total, animal, plant-based, or saturated fat intake. When examining intake of specific foods, processed meat [OR = 1.37 (95% CI = 1.02, 1.83); P-trend = 0.03], milk containing any fat [OR = 1.47 (95% CI = 1.16, 1.88); P-trend = 0.0025], and high-fat ice cream [OR = 4.03 (95% CI = 2.80, 5.80); P-trend < 0.0001], intakes were positively associated with risk, whereas intakes of fresh fish and total seafood [OR = 0.61 (95% CI = 0.46, 0.80); P-trend = 0.0025] were inversely associated with risk. Overall, there was little evidence for NHL subtype-specific heterogeneity. In conclusion, diets high in TFAs, processed meats, and higher fat dairy products were positively associated with NHL risk, whereas diets high in n3 fatty acids and total seafood were inversely associated with risk.
    Journal of Nutrition 03/2013; · 4.20 Impact Factor
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    ABSTRACT: The peripheral blood absolute lymphocyte/monocyte count ratio at diagnosis (ALC/AMC-DX) predicts survival in classical Hodgkin lymphoma (cHL). However, a limitation of the ALC/AMC-DX is the inability to assess sequentially the host/tumor interaction during treatment. Therefore, we retrospectively examined the ALC/AMC ratio, as a surrogate marker of host immunity (ALC) and tumor microenvironment (AMC), at each adriamycin, bleomycin, vinblastine and dacarbazine treatment cycle as a predictor for clinical outcomes. From 1990 until 2008, 190 cHL patients were diagnosed, treated and followed at Mayo Clinic Rochester and qualified for the study. The ALC/AMC ratio at each treatment cycle was a predictor for overall survival (OS) and progression-free survival (PFS). An ALC/AMC ratio 1.1 versus ALC/AMC <1.1 during treatment cycles was an independent predictor for OS (hazard ratio (HR)=0.14; 95% confidence interval (CI): 0.04-0.40; P<0.0002) and for PFS (HR=0.19; 95% CI: 0.05-0.82; P<0.03). The ALC/AMC ratio during treatment cycles is a predictor for survival and provides a platform to develop therapeutic modalities to manipulate the ALC/AMC ratio during chemotherapy to improve clinical outcomes in cHL.
    Blood Cancer Journal 01/2013; 3:e110. · 1.40 Impact Factor
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    ABSTRACT: PURPOSE: To evaluate the association of body mass index (BMI) and physical activity (PA) during adulthood and at the age of 18 years with risk of non-Hodgkin lymphoma (NHL). METHODS: We enrolled 950 newly diagnosed NHL patients and 1146 frequency-matched clinic-based controls. Height, weight, and PA (recent adult and at the age of 18 years) were self-reported. Odds ratios (ORs), 95% confidence intervals, and tests for trend were estimated using unconditional logistic regression adjusted for age, gender, and residence. RESULTS: BMI at the age of 18 years was associated with an increased NHL risk (OR, 1.38 for highest vs. lowest quartile; p-trend = .0012), which on stratified analysis was specific to females (OR, 1.90; p-trend = .00025). There was no association of adult BMI with NHL risk. Higher PA in adulthood (OR, 1.03; p-trend = .85) or at the age of 18 years (OR, 0.88; 95% confidence interval, 0.72-1.07) was not associated with risk, but there was an inverse association for adult PA that was specific to females (OR, 0.71; p-trend = .039). Only BMI at the age of 18 years remained significantly associated with NHL risk when modeled together with PA in adulthood or at the age of 18 years. There was little evidence for heterogeneity in these results for the common NHL subtypes. CONCLUSIONS: Early adult BMI may be of greatest relevance to NHL risk, particularly in females.
    Annals of epidemiology 11/2012; · 2.95 Impact Factor
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    ABSTRACT: BACKGROUND: Abnormal immune function is a key factor in predisposition to non-Hodgkin lymphoma (NHL). We evaluated the association of 30 cytokines individually and as a profile with diffuse large B-cell (DLBCL) and follicular (FL) lymphomas. METHODS: We used a multiplexed assay to measure 30 cytokine concentrations in pre-treatment serum in a case-control study of 234 FL, 188 DLBCL, and 400 control participants. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age and sex, and polytomous regression was used to evaluate heterogeneity between FL and DLBCL. Principal components analysis (PCA) was used to assess cytokine profiles associated with FL and DLBCL. RESULTS: In single cytokine modeling, we found that 12 of the 30 circulating serum cytokines were significantly (P<0.05) associated with FL and/or DLBCL after accounting for multiple testing (q<0.05). Soluble IL-2R (sIL-2R) had the strongest association with both FL (OR=6.0 for highest versus lowest tertile, 95% CI 3.8-9.5; p-trend=1.8×10(-21)) and DLBCL (OR=7.6, 95% CI 4.5-13.1; p-trend=7.2×10(-20)). IL1RA and IL-12p40 also showed similar associations for DLBCL and FL. In contrast, HGF, MIG, and MIP-1α had a stronger association with DLBCL compared to FL, and IL-6, IL-8, IL-10, IFN-γ, IP-10, and VEGF were only statistically significantly associated with DLBCL after accounting for multiple testing. However, in PCA modeling, a cytokine profile based on sIL-2R, IL-1RA, MIG, IP-10, IL-8, and IL-12p40 explained most of the variability between controls and both FL and DLBCL. CONCLUSIONS: We identified some cytokines unique to DLBCL, but overall cytokine associations were more similar than distinct for DLBCL and FL. While these data are limited by concerns of reverse causality, they do suggest cytokines and cytokine profiles that can be prioritized in future studies.
    Cytokine 09/2012; · 2.52 Impact Factor
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    ABSTRACT: CD3 expression by immunohistochemistry was historically considered restricted to T-lineage or NK-lineage neoplasms but recently has been reported in rare cases of mature B-cell neoplasms, frequently in association with Epstein-Barr virus. Here, we describe the pathologic features of 21 B-cell lineage neoplasms that express CD3 protein by immunohistochemistry: 12 diffuse large B-cell lymphomas (DLBCLs); 2 plasmablastic lymphomas (PBLs); 4 plasma cell neoplasms; 2 Burkitt lymphomas; and 1 nodal follicular lymphoma, grade 3A. CD20 expression was negative or only partially positive in 13/21 cases. Epstein-Barr virus was positive in 3/20 tested cases (2 PBLs and 1 DLBCL). All tested neoplasms (14/14) had clonal immunoglobulin gene rearrangements, and no clonal T-cell gene rearrangements were detected (0/14). The 12 DLBCLs segregated into 2 main groups: 7 demonstrated features of plasmacytic differentiation but did not meet criteria for PBL, and 5 had anaplastic features. In addition to morphology, other features shared among the DLBCLs with plasmacytic differentiation, the plasma cell neoplasms, and the PBLs included extranodal presentation, cytoplasmic localization of CD3, and lack of expression of other T-cell antigens in most cases. In contrast, DLBCLs with anaplastic features and the single follicular lymphoma coexpressed multiple T-cell antigens in a predominantly membranous pattern and presented with nodal disease in a relatively younger patient population. Our data expand the spectrum of morphologic, phenotypic, and clinical features of B-cell neoplasms aberrantly expressing CD3. As these neoplasms often lack typical expression of B-cell antigens, knowledge of these features will help avoid misclassification.
    The American journal of surgical pathology 09/2012; 36(9):1364-70. · 4.06 Impact Factor
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    ABSTRACT: Although standard clinical prognostic factors predict outcome in diffuse large B-cell lymphoma (DLBCL), predicting the outcome of patients might be further refined using biological factors. We tested whether serum cytokines could provide prognostic information in DLBCL patients. Thirty cytokines were measured in pretreatment samples from newly diagnosed DLBCL patients using a multiplex ELISA. Sixty-nine patients treated with R-CHOP plus epratuzumab were used in an initial cohort and 185 patients treated with standard R-CHOP served as a subsequent validation cohort. In the initial cohort, elevated serum interleukin-10 [IL-10; hazard ratio (HR) = 6.6, P = 0.022], granulocyte macrophage colony-stimulating factor (HR = 10.8, P= 0.027) and IP-10 (interferon-inducible protein-10, CXCL10; HR = 3.32, P = 0.015) were associated with event-free survival (EFS). An identical analysis of the subsequent validation cohort confirmed that elevated serum levels of IP-10 were strongly associated with a poor EFS (HR = 2.42, P = 0.0007); and also identified interleukin-8 (IL-8; HR = 3.40, P = 0.00002) and interleukin-2 receptor (IL-2R, CD25; HR = 2.59, P = 0.0012) as significantly associated with prognosis. The prognostic significance of elevated IP-10 remained significant after adjustment for the International Prognostic Index (EFS - HR 1.99, P = 0.009, overall survival-HR 1.93, P = 0.021). Elevated pretreatment serum IP-10 levels are therefore associated with an increased likelihood of disease relapse and an inferior survival in patients with DLBCL.
    American Journal of Hematology 05/2012; 87(9):865-9. · 4.00 Impact Factor
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    ABSTRACT: Abstract 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.
    Leukemia & lymphoma 05/2012; 53(11):2159-65. · 2.61 Impact Factor

Publication Stats

2k Citations
541.41 Total Impact Points

Institutions

  • 2002–2014
    • Mayo Clinic - Rochester
      • • Department of Hematology
      • • Department of Laboratory Medicine & Pathology
      Rochester, Minnesota, United States
  • 2012
    • University of Rochester
      • School of Medicine and Dentistry
      Rochester, NY, United States
  • 2006–2012
    • Mayo Foundation for Medical Education and Research
      • Division of Hematology
      Scottsdale, AZ, United States
  • 1990–2001
    • Vanderbilt University
      • • Department of Medicine
      • • Division of Hematology and Oncology
      Nashville, MI, United States
  • 1997
    • Hospital of the University of Pennsylvania
      • Department of Pathology and Laboratory Medicine
      Philadelphia, PA, United States