Laurie H Sehn

BC Cancer Agency, Vancouver, British Columbia, Canada

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Publications (74)640.7 Total impact

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    ABSTRACT: Gray zone lymphoma (GZL) with features between classical Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) is a recently recognized entity reported to present primarily with mediastinal disease. We examined detailed clinical features, outcomes, and prognostic factors among 112 GZL patients treated across 19 North American centers. Forty-three percent of patients presented with mediastinal disease (MGZL), while 57% did not (NMGZL). NMGZL patients were older ((50 versus 37 years,) (P) (=0.0001); more often had) bone marrow involvement (19% versus 0%, P=0.001); >1 extranodal site (27% versus 8%, P=0.014); and advanced stage disease (81% versus 13%, respectively, P=0.0001); but less bulk (8% versus 44%, respectively, P=0.0001). Common frontline treatments were cyclophosphamide-doxorubicin-vincristine-prednisone +/- rituximab (CHOP+/-R) 46%, doxorubicin-bleomycin-vinblastine-dacarbazine +/- rituximab (ABVD+/-R) 30%, and dose-adjusted etoposide-doxorubicin-cyclophosphamide-vincristine-prednisone-rituximab (DA-EPOCH-R) 10%. Overall and complete response rates for all patients were 71% and 59%, respectively; 33% had primary refractory disease. At 31-month median follow-up, 2-year progression-free survival (PFS) and overall survival rates were 40% and 88%, respectively. Interestingly, MGZL outcomes appeared similar compared with NMGZL patients. On multivariable analyses, performance status and stage were highly prognostic for survival. Additionally, patients treated with ABVD+/-R had markedly inferior 2-year PFS (22% versus 52%, P=0.03) compared with DLBCL-directed therapy (CHOP+/-R and DA-EPOCH-R), which persisted on Cox regression (HR 1.88, 95%CI 1.03-3.83, P=0.04). Furthermore, rituximab was associated with improved PFS on multivariable analyses (HR 0.35, 95%CI 0.18-0.69, P=0.002). Collectively, GZL is a heterogeneous and likely more common entity that includes non-mediastinal presentation, while outcomes appear superior when treated with a rituximab-based, DLBCL-specific regimen. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    American Journal of Hematology 06/2015; DOI:10.1002/ajh.24082 · 3.48 Impact Factor
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    ABSTRACT: Although it is generally regarded appropriate to start chemotherapy promptly after a diagnosis of diffuse large B-cell lymphoma (DLBCL), the optimal time from diagnosis to treatment (TDT) is unknown. A total of 689 patients diagnosed with DLBCL and treated with ≥1 cycle of CHOP-R with curative intent during 2003 - 2008 in British Columbia were identified: 347 (50%) TDT ≤4 weeks, 277 (40%) TDT 5-8 weeks, 65 (10%) TDT >8 weeks. For the respective TDT groups, 5-year OS estimates were 61%, 74%, 63% (p=0.006); 5-year PFS 57%, 70%, 61% (p=0.006); and 5-year DSS 64%, 80%, 77% (p<0.001). In multivariate analysis, TDT >8 weeks was associated with worse OS (HR 1.20 (95% CI 1.03, 1.41), p=0.020), PFS (HR 1.33 (95% CI 1.15, 1.54), p<0.001), and DSS (HR 1.40 (95% CI 1.10, 1.78), p=0.006). Clinicians should endeavor to initiate curative chemotherapy as soon as possible after a diagnosis of DLBCL is established.
    Leukemia & lymphoma 05/2015; DOI:10.3109/10428194.2015.1055480 · 2.61 Impact Factor
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    ABSTRACT: Patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) have an unfavourable prognosis with few treatment options. Polatuzumab vedotin is an antibody-drug conjugate containing an anti-CD79B monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. We aimed to assess the safety and clinical activity of polatuzumab vedotin in relapsed or refractory B-cell NHL and chronic lymphocytic leukaemia (CLL). In this phase 1, multicentre, open-label study, we enrolled patients with documented NHL or CLL expected to express CD79B (confirmation of CD79B expression was not required) and for whom no suitable therapy of curative intent or higher priority existed from 13 centres. The primary endpoints of the study were to assess safety and tolerability, determine the maximum tolerated dose, and identify the recommended phase 2 dose of polatuzumab vedotin as a single agent and in combination with rituximab. A 3 + 3 dose-escalation design was used in which we treated patients with polatuzumab vedotin (0·1-2·4 mg/kg every 21 days) in separate dose-escalation cohorts for NHL and CLL. After determination of the recommended phase 2 dose, we enrolled patients with relapsed or refractory diffuse large B-cell lymphoma and relapsed or refractory indolent NHL into indication-specific cohorts. We also enrolled patients with relapsed or refractory NHL into an additional cohort to assess the feasibility of the combination of polatuzumab vedotin and rituximab 375 mg/m(2). Patients who received any dose of polatuzumab vedotin were available for safety analyses. This study is registered with ClinicalTrials.gov, number NCT01290549. Between March 21, 2011, and Nov 30, 2012, we enrolled 95 patients (34 to the NHL dose-escalation cohort, 18 to the CLL dose-escalation cohort, 34 with NHL to the expansion cohort at the recommended phase 2 dose, and nine with NHL to the rituximab combination cohort; no expansion cohort of CLL was started due to lack of activity in the dose-escalation cohort). The recommended phase 2 dose in NHL was 2·4 mg/kg as a single agent and in combination with rituximab; the maximum tolerated dose in CLL was 1·0 mg/kg as a result of dose-limiting toxic effects reported in two of five patients given 1·8 mg/kg. Grade 3-4 adverse events were reported in 26 (58%) of 45 patients with NHL treated at the single-agent recommended phase 2 dose, and the most common grade 3-4 adverse events were neutropenia (18 [40%] of 45), anaemia (five [11%]), and peripheral sensory neuropathy (four [9%]). Serious adverse events were reported in 17 (38%) of 45 patients, and included diarrhoea (two patients), lung infection (two patients), disease progression (two patients), and lung disorder (two patients). Seven (77%) of nine patients in the rituximab combination cohort had a grade 3-4 adverse event, with neutropenia (five [56%]), anaemia (two [22%]), and febrile neutropenia (two [22%]) reported in more than one patient. 11 (12%) of 95 patients died during the study: eight with relapsed or refractory diffuse large B-cell lymphoma (due to progressive disease in four patients, infections in three patients [two treatment related], and treatment-related worsening ascites in one patient) and three with relapsed or refractory CLL (due to progressive disease, pulmonary infection, and pneumonia; none thought to be treatment-related). At the recommended phase 2 dose, objective responses were noted in 23 of 42 activity-evaluable patients with NHL given single-agent polatuzumab vedotin (14 of 25 with diffuse large B-cell lymphoma, seven of 15 with indolent NHL, and two with mantle-cell lymphoma) and seven of nine patients treated with polatuzumab vedotin combined with rituximab. No objective responses were observed in patients with CLL. Polatuzumab vedotin has an acceptable safety and tolerability profile in patients with NHL but not in those with CLL. Its clinical activity should be further assessed in NHL. Genentech. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 04/2015; 16(6). DOI:10.1016/S1470-2045(15)70128-2 · 24.73 Impact Factor
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    ABSTRACT: We aimed to assess the prognostic significance of follicular lymphoma (FL)-associated macrophages in the era of rituximab treatment and maintenance. We applied IHC for CD68 and CD163 to two large tissue microarrays (TMAs). The first TMA included samples from 186 patients from the BC Cancer Agency (BCCA) who had been treated with first line systemic treatment including rituximab, cyclophosphamide, vincristine and prednisone. The second contained 395 samples from PRIMA trial patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, and randomized to rituximab maintenance or observation. Macrophage infiltration was assessed using Aperio image analysis. Each of the two cohorts was randomly split into training/validation sets. An increased CD163 positive pixel count was predictive of adverse outcome in the BCCA dataset (5-year progression-free survival (PFS) 38% v 72%, respectively, P=0.004 in the training cohort and 5-year PFS 29% v 61%, respectively, P=0.004 in the validation cohort). In the PRIMA trial, an increased CD163 pixel count was associated with favourable outcome (5-year PFS 60% v 44%, respectively, P=0.011 in the training cohort and 5-year PFS 55% v 37%, respectively, P=0.030 in the validation cohort). CD163-positive macrophages predict outcome in FL but their prognostic impact is highly dependent on treatment received. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 04/2015; DOI:10.1158/1078-0432.CCR-14-3253 · 8.19 Impact Factor
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    ABSTRACT: Splenic marginal zone lymphoma (SMZL) accounts for less than 2% of all non-Hodgkin lymphomas. We identified 107 cases diagnosed with SMZL between 1985 and 2012 from the British Columbia Cancer Agency Centre for Lymphoid Cancer and Lymphoma Pathology Databases. Patient characteristics were: median age 67 years (range 30-88), male 40%, stage IV 98%, splenomegaly 93%, bone marrow involvement 96%, peripheral blood involvement 87%. As initial treatment, 52 underwent splenectomy (10 with chemotherapy), 38 chemotherapy alone (21 chemoimmunotherapy containing rituximab, 1 rituximab alone), two antivirals for hepatitis C, and 15 were only observed. The 10-year overall survival for first-line splenectomy versus chemotherapy was 61% and 42%, respectively [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·26-0·88, P = 0·017]. The 10-year failure-free survival (FFS) after first-line splenectomy vs chemotherapy was 39% and 14%, respectively (HR 0·48, 95% CI 0·28-0·80, P = 0·004). Among the 38 patients who received first-line chemotherapy, FFS was similar between those receiving rituximab (n = 22) and those who did not (n = 16) (HR 0·64, 95% CI 0·31-1·34, P = 0·238). Fifteen patients transformed to aggressive lymphoma with median time to transformation of 3·5 years (range 6 months to 12 years) and the 10-year transformation rate was 18%. In conclusion, splenectomy remains a reasonable treatment for patients with SMZL. © 2015 John Wiley & Sons Ltd.
    British Journal of Haematology 04/2015; 169(4). DOI:10.1111/bjh.13320 · 4.96 Impact Factor
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    ABSTRACT: Double-hit lymphoma is characterized by the presence of concurrent MYC (myelocytomatosis oncogene) and BCL2 (B-cell lymphoma 2) gene rearrangements. Prognosis is poor with standard chemoimmunotherapy. Since 2003, the British Columbia Cancer Agency has used CODOX-M/IVAC+R (cyclophosphamide, vincristine, doxorubicin, methotrexate, cytarabine, ifosfamide, and etoposide, combined with rituximab) followed by consolidative hematopoietic cell transplantation as definitive treatment for double-hit lymphoma. A retrospective review of the survival outcomes of patients with double-hit lymphoma treated at our institution was conducted. Thirty-two patients diagnosed with non-Hodgkin lymphoma with concurrent MYC and BCL2 translocations from 2003 to 2013 were identified. Cases with MYC or BCL2 amplification and those with overexpression in immunohistochemistry analysis were excluded. Median age at diagnosis was 53.0 years (range, 35.5-70.9 years), 23 (72%) were male, and 30 (94%) had stage III to IV disease. CODOX-M/IVAC+R was administered in 25 (78%) patients and 20 (80%) achieved a partial remission or better, of which 9 (36%) had a complete remission. Nineteen of the 32 (59%) patients underwent upfront hematopoietic cell transplantation. At a median follow-up of living patients of 26.4 months, 14 (44%) were alive in remission, 15 (47%) died, and 3 (9%) were alive in relapse. The 2-year progression-free survival (PFS) and overall survival (OS) of all patients were 41% and 53%, respectively. The sixteen patients treated with CODOX-M/IVAC+R followed by hematopoietic cell transplantation had a 2-year PFS of 60% and 2-year OS of 82%. Patients with double-hit lymphoma treated with CODOX-M/IVAC+R followed by hematopoietic cell transplantation can achieve durable remissions, although disease progression before transplantation remains a significant problem. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinical Lymphoma, Myeloma and Leukemia 01/2015; 15(6). DOI:10.1016/j.clml.2014.12.015 · 2.02 Impact Factor
  • Laurie H. Sehn
    Blood 12/2014; 125(1). DOI:10.1182/blood-2014-09-594580 · 10.43 Impact Factor
  • Laurie H Sehn, Randy D Gascoyne
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    ABSTRACT: While the majority of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone), patients who fail R-CHOP have a dismal outcome. Thus, optimization of front-line therapy, as well as the development of more effective salvage strategies remains an important objective. Advances in molecular genetics have vastly improved our understanding of the biological diversity of DLBCL and have lead to the discovery of key oncogenic pathways. In addition to the major molecular designations of germinal center B-cell (GCB) and activated B-cell (ABC) subtypes, next generation sequencing technologies have unveiled the remarkable complexity of DLBCL and identified unique molecular targets that may be differentially exploited for therapeutic benefit. These findings have translated into a growing list of promising novel agents. Moving forward, it is of paramount importance to recognize the heterogeneity of DLBCL and to investigate these targeted agents within patient populations who are most likely to benefit. It will be necessary to prioritize drugs that affect key driver pathways and to combine them rationally to optimize their benefit. Improved prognostication and the availability of predictive biomarkers will be crucial to allow for the possibility of individualized risk-adapted therapy. Copyright © 2014 American Society of Hematology.
    Blood 12/2014; 125(1). DOI:10.1182/blood-2014-05-577189 · 10.43 Impact Factor
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    ABSTRACT: Effective treatment of diffuse large B cell lymphoma (DLBCL) is plagued by heterogeneous responses to standard therapy, and molecular mechanisms underlying unfavorable outcomes in lymphoma patients remain elusive. Here, we profiled 148 genomes with 91 matching transcriptomes in an R-CHOP-treated DLBCL cohort to uncover molecular subgroups linked to treatment failure. Systematic integration of high-resolution genotyping arrays and RNA-seq data revealed novel deletions in RCOR1 to be associated with unfavorable progression free survival (P = 0.001). Integration of expression data from the clinical samples with data from RCOR1 knockdowns in the lymphoma cell lines KM-H2 and Raji yielded an RCOR1 loss-associated gene signature comprising of 233 genes. This signature identified a subgroup of patients with unfavorable overall survival (OS) (P = 0.023). The prognostic significance of the 233-gene signature for OS was reproduced in an independent cohort comprising 195 R-CHOP treated patients (P = 0.039). Additionally, we discovered that within the IPI low risk group, the gene signature provides additional prognostic value that was independent of the cell-of-origin phenotype. Taken together, we present a novel and reproducible molecular subgroup of DLBCL, impacting risk-stratification of R-CHOP treated DLBCL patients and revealing a possible new avenue for therapeutic intervention strategies.
    Blood 11/2014; 125(6). DOI:10.1182/blood-2013-06-507152 · 10.43 Impact Factor
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    ABSTRACT: High-dose therapy and autologous stem cell transplant (HDT/ASCT) is the preferred treatment for chemosensitive relapsed/refractory Hodgkin lymphoma (HL). The role for HDT/ASCT in chemoresistant HL is less well defined. We evaluated long-term outcomes of relapsed/refractory HL patients whose disease was refractory to secondary chemotherapy preceding HDT/ASCT.
    Annals of Oncology 08/2014; 25(11). DOI:10.1093/annonc/mdu387 · 6.58 Impact Factor
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    ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable therapeutic responses and alternative therapies are needed for patients with unfavourable treatment outcomes after standard treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). One promising candidate is brentuximab vedotin, an antibody-drug conjugate targeting CD30-expressing cells. However, CD30 (TNFRSF8) expression patterns in DLBCL are not well described thus far. Here, we examined CD30 expression in a population-based cohort of immunocompetent patients from British Columbia with de novo DLBCL using immunohistochemistry. 385 cases of formalin-fixed paraffin-embedded DLBCL in tissue microarrays were evaluated. 95 cases (25%) harboured CD30+ tumour cells. Using a > 0% cut-off, CD30 expression was predictive of superior 5-year progression-free survival within R-CHOP treated germinal centre B-cell-like (GCB) DLBCL (86% vs. 64%, P = 0·020), which was independent of the International Prognostic Index. Epstein-Barr virus (EBV) was identified in 11 (3%) cases, all of which were non-GCB (P = 0·001) and almost exclusively positive for CD30 expression (10/11) (P < 0·001). We conclude CD30 is expressed in a substantial proportion of DLBCL and CD30 immunohistochemistry may be a useful prognostic marker in R-CHOP treated GCB-DLBCL. The significant association of CD30 with EBV-positive non-GCB DLBCL suggests a distinct pathobiology for these cases.
    British Journal of Haematology 08/2014; DOI:10.1111/bjh.13085 · 4.96 Impact Factor
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    ABSTRACT: Vascular endothelial growth factor is involved in lymphoma growth, suggesting a potential role for anti vascular endothelial growth factor therapies in hematological malignancies. In this phase III study, patients with CD20-positive diffuse large B-cell lymphoma were randomized to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone plus either placebo (R-CHOP) or bevacizumab (RA-CHOP). Treatment was administered every 21 (8 cycles) or 14 days (6 cycles plus 2 rituximab cycles) per institutional practice. An early analysis of risk/benefit by the Data and Safety Monitoring Board showed that RA-CHOP increased cardiotoxicity without prolonging progression-free survival compared with R-CHOP, and the trial was stopped early. The study protocol was amended to allow for 12 additional months of follow-up to evaluate safety. With 787 patients enrolled, median follow up was 23.7 and 23.6 months for R-CHOP and RA-CHOP, respectively. Median progression-free survival for R-CHOP and RA CHOP was 42.9 and 40.2 months, respectively (hazard ratio=1.09; P=0.49). The proportion of deaths was identical for R-CHOP (21%, 83/387) and RA-CHOP (21%, 82/390). Relative to R-CHOP, RA-CHOP had a higher rate of left ventricular ejection fraction perturbation (18% versus 8%; odds ratio=2.51; 95% confidence interval: 1.60-3.93) and congestive heart failure (16% versus 7%; odds ratio=2.79; 95% confidence interval: 1.72-4.54). Bevacizumab added to R-CHOP increased cardiac events, without increasing efficacy, arguing against further evaluation of RA-CHOP in patients with diffuse large B-cell lymphoma. The MAIN study is registered at clinicaltrials.gov, NCT00486759.
    Haematologica 06/2014; DOI:10.3324/haematol.2013.100818 · 5.87 Impact Factor
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    ABSTRACT: Due to disease rarity, there is limited information regarding the optimal therapy and outcome of patients with advanced stage nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). 42 patients with NLPHL by the REAL/WHO classification with advanced stage disease were identified and paired 1:2 with a matched control with classical Hodgkin lymphoma (CHL) with matching by age, gender, stage, decade of diagnosis, and treatment received. The median follow-up was 11.3 years (range 1.9-35.5) for NLPHL patients and 10.7 years (1.6-26.3) for CHL patients. The majority received ABVD-like chemotherapy. Although the 10 year overall survival (OS) (P=0.579) and Hodgkin lymphoma-freedom from treatment failure (HL-FFTF) were similar between NLPHL and CHL (75% vs 73%, P=0.610), the time to progression (TTP), which also includes the development of secondary aggressive lymphoma, was inferior in NLPHL (10 y 63% vs 73%, P=0.040). Splenic involvement was associated with an inferior 10 y TTP in patients treated with ABVD (48 vs 71%, P=0.049) and an increased cumulative incidence of transformed aggressive lymphoma (P=0.014) providing a rationale for further evaluation of CHOP +/- rituximab in NLPHL.
    Blood 04/2014; 123(23). DOI:10.1182/blood-2013-12-541078 · 10.43 Impact Factor
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    ABSTRACT: We examined the relationship between location of residence at the time of diagnosis of diffuse large B-cell lymphoma (DLBCL) and health outcomes in a geographically large Canadian province with publicly funded, universally available medical care.Patients and Methods.The British Columbia Cancer Registry was used to identify all patients 18-80 years of age diagnosed with DLBCL between January 2003 and December 2008. Home and treatment center postal codes were used to determine urban versus rural status and driving distance to access treatment.Results.We identified 1,357 patients. The median age was 64 years (range: 18-80 years), 59% were male, 50% were stage III/IV, 84% received chemotherapy with curative intent, and 32% received radiotherapy. There were 186 (14%) who resided in rural areas, 141 (10%) in small urban areas, 183 (14%) in medium urban areas, and 847 (62%) in large urban areas. Patient and treatment characteristics were similar regardless of location. Five-year overall survival (OS) was 62% for patients in rural areas, 44% in small urban areas, 53% in medium urban areas, and 60% in large urban areas (p = .018). In multivariate analysis, there was no difference in OS between rural and large urban area patients (hazard ratio [HR]: 1.0; 95% confidence interval [CI]: 0.7-1.4), although patients in small urban areas (HR: 1.4; 95% CI: 1.0-2.0) and medium urban areas (HR: 1.4; 95% CI: 1.0-1.9) had worse OS than those in large urban areas.Conclusion.Place of residence at diagnosis is associated with survival of patients with DLBCL in British Columbia, Canada. Rural patients have similar survival to those in large urban areas, whereas patients living in small and medium urban areas experience worse outcomes.
    The Oncologist 02/2014; 19(3). DOI:10.1634/theoncologist.2013-0343 · 4.54 Impact Factor
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    ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and "double-hit" DLBCL, with both MYC and BCL2 translocations has a poor prognosis. In this study, we investigated whether MYC and BCL2 protein expression in tissue would predict survival in DLBCL. The study included 106 cases of de novo DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or CHOP-like regimens. The results were validated on an independent cohort of 205 DLBCL patients. Patients with low expression of BCL2 (≤30%) and MYC (≤50%) had the best prognosis, whereas those with high BCL2 (>30%) and MYC (>50%) had the worst outcome. In multivariate analysis, the combination of the BCL2 and MYC was an independent predictor of overall survival (OS) and event-free survival (EFS) (P = 0·015 and P = 0·005, respectively). The risk of death was nine times greater for patients with high BCL2 and MYC compared to those with low expression. High BCL2 and MYC was a strong predictor of poor OS (P < 0·001) and EFS (P = 0·0017) in patients with the germinal centre B-cell (GCB) type, but not in the non-GCB type. In DLBCL, high co-expression of MYC and BCL2 was an independent predictor of poor survival, and could be used to stratify patients for risk-adapted therapies.
    British Journal of Haematology 02/2014; DOI:10.1111/bjh.12763 · 4.96 Impact Factor
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    ABSTRACT: The cellular microenvironment in follicular lymphoma is of biological and clinical importance. Studies on the clinical significance of non-malignant cell populations have generated conflicting results, which may partly be influenced by poor reproducibility in immunohistochemical marker quantification. In this study, the reproducibility of manual scoring and automated microscopy based on a tissue microarray of 25 follicular lymphomas as compared to flow cytometry is evaluated. The agreement between manual scoring and flow cytometry was moderate for CD3, low for CD4 and moderate to high for CD8 with some labs scoring closer to the flow cytometry results. Agreement in manual quantification across the 7 laboratories was low to moderate for CD3, CD4, CD8 and FOXP3 frequencies, moderate for CD21, low for MIB1 and CD68 and high for CD10. Manual scoring of the architectural distribution resulted in moderate agreement for CD3, CD4 and CD8 and low agreement for FOXP3 and CD68. Comparing manual scoring to automated microscopy demonstrated that manual scoring increased the variability in the low and high frequency interval with some labs showing a better agreement with automated scores. Manual scoring reliably identified rare architectural patterns of T-cell infiltrates. Automated microscopy analyses for T-cell markers by two different instruments were highly reproducible and provided acceptable agreement with flow cytometry. These validation results provide explanations for the heterogeneous results on the prognostic value of the microenvironment in follicular lymphoma. We recommend a more objective measurement such as computer-assisted scoring in future studies of the prognostic impact of microenvironment in follicular lymphoma patients.
    Haematologica 02/2014; DOI:10.3324/haematol.2013.095257 · 5.87 Impact Factor
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    ABSTRACT: The International Prognostic Index (IPI) has been the basis for determining prognosis in patients with aggressive non-Hodgkin lymphoma (NHL) for the past 20 years. Using raw clinical data from the National Comprehensive Cancer Network (NCCN) database collected during the rituximab era, we built an enhanced IPI with the goal of improving risk stratification. Adults (n=1,650) with de novo diffuse large B-cell lymphoma (DLBCL) diagnosed over a 10-year period at 7 NCCN cancer centers were included. Clinical features were assessed for their prognostic significance, with statistical efforts to further refine the categorization of age and normalized LDH. This new NCCN-IPI identified 5 predictors (age, LDH, sites of involvement, Ann Arbor stage, ECOG performance status) and assigned a maximum of 8 points. Four risk groups were formed: low (0-1), low-intermediate (2-3), high-intermediate (4-5) and high (6-8). Compared to the IPI, the NCCN-IPI better discriminated low and high risk subgroups (5-year overall survival [OS]: 96% vs 33%) than the IPI (5 year OS: 90% vs 54%), respectively. When validated using an independent cohort from the British Columbia Cancer Agency (n=1,138), it also demonstrated enhanced discrimination for both low and high risk patients. The NCCN-IPI is easy to apply and more powerful than the IPI for predicting survival in the rituximab era.
    Blood 11/2013; 123(6). DOI:10.1182/blood-2013-09-524108 · 10.43 Impact Factor
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    ABSTRACT: PURPOSEMantle-cell lymphoma (MCL) has a variable natural history but is incurable with current therapies. MicroRNAs (miRs) are useful in prognostic assessment of cancer. We determined an miR signature defining aggressiveness in B-cell non-Hodgkin lymphomas (NHL) and assessed whether this signature aids in MCL prognosis. METHODS We assessed miR expression in a training set of 43 NHL cases. The miR signature was validated in 44 additional cases and examined on a training set of 119 MCL cases from four institutions in Canada. miRs significantly associated with overall survival were examined in an independent cohort of 114 MCL cases to determine association with patient outcome. miR expression was combined with current clinical prognostic factors to develop an enhanced prognostic model in patients with MCL.ResultsFourteen miRs were differentially expressed between aggressive and indolent NHL; 11 of 14 were validated in an independent set of NHL (excluding MCL). miR-127-3p and miR-615-3p were significantly associated with overall survival in the MCL training set. Their expression was validated in an independent MCL patient set. In comparison with Ki-67, expression of these miRs was more significantly associated with overall survival among patients with MCL. miR-127-3p was combined with Ki-67 to create a new prognostic model for MCL. A similar model was created with miR-615-3p and Mantle Cell Lymphoma International Prognostic Index scores. CONCLUSION Eleven miRs are differentially expressed between aggressive and indolent NHL. Two novel miRs were associated with overall survival in MCL and were combined with clinical prognostic models to generate novel prognostic data for patients with MCL.
    Journal of Clinical Oncology 07/2013; 31(23). DOI:10.1200/JCO.2012.45.3050 · 17.88 Impact Factor
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    ABSTRACT: IntroductionA number of novel therapies are under investigation in relapsed or refractory peripheral T-cell lymphoma (PTCL); however, their relative impact on outcome is unknown. We examined the survival of patients with PTCL after relapse or progression in the absence of hematopoietic stem-cell transplantation and explored factors influencing survival. The three most common subtypes encountered in North America were evaluated: PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large-cell lymphoma (ALCL; anaplastic lymphoma kinase [ALK] positive and ALK negative. PATIENTS AND METHODS After exclusions, 153 patients were analyzed (PTCL-NOS, n = 79 [52%]; AITL, n = 38 [25%]; ALK-positive ALCL, n = 11 [7%]; ALK-negative ALCL, n = 27 [16%; including ALK status unknown, n = 1]). RESULTS: hazard ratio [HR], 2.09; P = .002; second PFS: HR, 1.66; P = .030). CONCLUSION Most patients with relapsed or refractory PTCL have poor outcomes with short survival. Select patients with good PS have more favorable outcomes with standard chemotherapy.
    Journal of Clinical Oncology 04/2013; 31(16). DOI:10.1200/JCO.2012.44.7524 · 17.88 Impact Factor
  • Laurie H Sehn
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    ABSTRACT: Outcome in diffuse large B-cell lymphoma (DLBCL) has improved over the last decade and will likely improve further with the introduction of novel agents. At the present time, clinical prognostic factors are limited in their ability to identify patients with sufficiently poor outcome to justify deviation of therapy away from R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) outside of a clinical trial. Similarly, with the exception of the concurrent translocation of MYC and BCL2, there are no validated biologic markers that can be used to guide initial therapy in routine practice. Recognition of the molecular heterogeneity of DLBCL is of paramount importance and must be taken into consideration when investigating new therapies. It will be vital for novel targeted agents to be evaluated in patient populations enriched for those who are most likely to benefit. The identification of prognostic and predictive biomarkers should be initiated during the early phase of drug development so that these tests can be validated within phase 3 trials. Although currently available techniques such as immunohistochemistry may still be used, gene-expression profiling and whole genomic analytic techniques will likely play a major role in the evaluation of patients in the future to determine optimal personalized treatment for DLBCL.
    Hematology 12/2012; 2012:402-9. DOI:10.1182/asheducation-2012.1.402 · 2.86 Impact Factor

Publication Stats

3k Citations
640.70 Total Impact Points

Institutions

  • 2006–2015
    • BC Cancer Agency
      • • Centre for Lymphoid Cancer
      • • Radiation Therapy Program
      Vancouver, British Columbia, Canada
  • 2004–2014
    • University of British Columbia - Vancouver
      • Division of Medical Oncology
      Vancouver, British Columbia, Canada
  • 2012
    • BC Cancer Research Centre
      Vancouver, British Columbia, Canada
  • 2008
    • Stanford University
      • Department of Medicine
      Palo Alto, California, United States
    • Vancouver Prostate Centre
      Vancouver, British Columbia, Canada