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Find video protocols related to scientific articles indexed in Pubmed.
ACR Appropriateness Criteria Follow-up of Hodgkin Lymphoma.
J Am Coll Radiol
PUBLISHED: 07-28-2014
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The main objectives of follow-up studies after completion of treatment for Hodgkin lymphoma are detection of recurrence for salvage therapy and monitoring for sequelae of treatment. The focus of the follow-up shifts, with time after treatment, from detection of recurrence to long-term sequelae. A majority of recurrence is detected by history and physical examination. The yield for routine imaging studies and blood tests is low. Although routine surveillance CT scan can detect recurrence not detected by history and physical examination, its benefit in ultimate survival and cost-effectiveness is not well defined. Although PET scan is a useful tool in assessing response to treatment, its routine use for follow-up is not recommended. Long-term sequelae of treatment include secondary malignancy, cardiovascular disease, pneumonitis, reproductive dysfunction, and hypothyroidism. Follow-up strategies for these sequelae need to be individualized, as their risks in general depend on the dose and volume of radiation to these organs, chemotherapy, age at treatment, and predisposing factors for each sequela. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is either lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
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Phosphoinositide 3-kinase inhibitors in lymphoma.
Curr Opin Oncol
PUBLISHED: 07-16-2014
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The phosphoinositide 3-kinase (PI3K) pathway, with downstream targets including Akt and mammalian target of rapamycin, has been implicated in numerous human cancers, including hematologic malignancies and lymphomas. The development and refinement of PI3K inhibitors directed toward this pathway show promising clinical efficacy. This review will discuss the emerging body of clinical data in lymphoid malignancies and present future directions for research utilizing these inhibitors.
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Early Failure of Frontline Rituximab-Containing Chemo-immunotherapy in Diffuse Large B Cell Lymphoma Does Not Predict Futility of Autologous Hematopoietic Cell Transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-27-2014
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The poor prognosis for patients with diffuse large B cell lymphoma (DLBCL) who relapse within 1 year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1 year of initial diagnosis. The ERF cohort was compared with those relapsing >1 year after initial diagnosis (late rituximab failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS) of ERF versus LRF cohorts at 3 years were 9% (95% confidence interval [CI], 6% to 13%) versus 9% (95% CI, 5% to 13%), 47% (95% CI, 41% to 52%) versus 39% (95% CI, 33% to 46%), 44% (95% CI, 38% to 50%) versus 52% (95% CI, 45% to 59%), and 50% (95% CI, 44% to 56%) versus 67% (95% CI, 60% to 74%), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk [RR], 1.31; P = .34). The ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR, 2.08; P < .001) and overall mortality (RR, 3.75; P <.001) within the first 9 months after autologous HCT. Beyond this period, PFS and OS were not significantly different between the ERF and LRF cohorts. Autologous HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS, 44%) and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.
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MYC-associated and double-hit lymphomas: A review of pathobiology, prognosis, and therapeutic approaches.
Cancer
PUBLISHED: 03-25-2014
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Aberrant expression of the v-myc avian myelocytomatosis viral oncogene homolog (MYC) proto-oncogene has known transformative potential in healthy human cells. Chromosomal MYC rearrangements and consequent MYC overexpression is the defining lesion in Burkitt lymphoma (BL), conferring a highly proliferative state. However, abnormalities of MYC are increasingly appreciated in non-BL histologies, including diffuse large B-cell lymphoma (DLBCL) and B-cell lymphomas intermediate between BL and DLBCL, with a particularly aggressive clinical phenotype. Although there are conflicting data regarding prognostic implications of isolated MYC aberrancy in these non-BLs, the co-occurrence of MYC rearrangements and either the antiapoptotic gene B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL2) or the transcriptional repressor BCL6 leads to an entity termed double-hit B-cell lymphoma (DHL) (or triple-hit if all 3 abnormalities are observed) with a particularly poor prognosis and no established treatment paradigms. Notably, a distinct pattern of gene expression profiling has been noted when MYC is overexpressed in BL compared with other lymphomas, supporting the notion that, although MYC promotes target gene transcription, the target genes vary by disease subtype. The frequency of MYC activity depends on the method of detection and ranges from 5% to 10% using fluorescence in situ hybridization but up to 30% of DLBCL using immunohistochemistry. Standard therapies developed for DLBCL are less effective when the disease is driven by MYC, leading to lower response rates and response durations. An important clinical challenge is to pre-emptively identify MYC-associated lymphomas and to subsequently develop trials specifically for this group of patients. However, the design of such studies is complicated by variable definitions of MYC-associated lymphoid malignancies and the lack of effective therapies to date. The objective if the current review was to evaluate the implications of MYC aberrancy with respect to the B-cell lymphoma double-hit and triple-hit phenotypes and to consider the available data for clinical and practical management. Cancer 2014. © 2014 American Cancer Society.
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The impact of race, ethnicity, age and sex on clinical outcome in chronic lymphocytic leukemia: a comprehensive Surveillance, Epidemiology, and End Results analysis in the modern era.
Leuk. Lymphoma
PUBLISHED: 03-05-2014
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To analyze racial, ethnic, sex and age disparities in chronic lymphocytic leukemia (CLL), we examined population-based overall survival (OS) data from Surveillance, Epidemiology, and End Results (SEER)-13 (1992-2009) across various races/ethnicities over two consecutive 9-year periods: era 1 (1992-2000) and era 2 (2001-2009). We analyzed 28 590 patients (whites: 24 438, blacks: 1954, Hispanics: 1389 and Asians/Pacific Islanders [A/PI]: 809). A higher proportion of whites were aged > 80 years (22% vs. 17% [Hispanics], 16% [blacks], 16% [A/PI]; p < 0.001). Higher socioeconomic status (SES) was also identified for A/PI and whites compared with blacks and Hispanics (p < 0.001). OS for all patients improved at 5 years (66% vs. 60%, p < 0.0001) and was significant in all races/ethnicities except A/PI. Patients of higher SES had better outcomes than others independent of era, but both SES classes experienced relative improvement in their OS across eras. The OS of patients with CLL has improved in the modern era but racial/ethnic, gender and SES differences persist, warranting further investigation.
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The impact of race, age, and sex in follicular lymphoma: A comprehensive SEER analysis across consecutive treatment eras.
Am. J. Hematol.
PUBLISHED: 01-07-2014
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The impact of race/ethnicity and the additional factors of age, sex, and socioeconomic status (SES) on follicular lymphoma (FL) outcomes have not been comprehensively studied and are not well defined. We examined population-based FL data from >18,000 patients in SEER-13 (1992-2009) investigating race/ethnicity and the impact of relevant factors including sex, age, and SES. Further, we compared data over two consecutive periods: Era-1 (1992-2000, n = 8,355) and Era-2 (2001-2009, n = 10,475). We identified 18,830 FL patients (White: n = 15,116; Hispanic: n = 1,627; Asian/Pacific Islander (A/PI): n = 1,002; and Black: n = 846). Median ages (years) differed significantly by race/ethnicity: White: 62.1, Hispanic: 57.3, A/PI: 60.7, and Black: 56.8 (P < 0.01 each race versus White). Overall survival (OS) was superior in Era-2 versus Era-1 for all patients (5-year: 76.7% versus 67.4%, respectively, P < 0.001). Further, survival was significantly improved for all age groups <80 years, for males (P = 0.0019), and females (P < 0.001) across eras. Females had superior OS compared with males in Era-1 (P = 0.004), but not in Era-2. Additionally, all races, except A/PI, had improved 5-year OS rates from Era-1 to Era-2. Finally, OS improved across eras for lower and higher SES populations; however those with higher SES were superior to lower SES patients in both eras. In conclusion, and in the largest comprehensive evaluation of US-based FL patients to date, we show that despite improvements in OS for FL over time, critical disparities across races/ethnicities, sex, and age groups remain in the modern era and warrant further studies.
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Autologous or Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Chemotherapy-Sensitive Mantle-Cell Lymphoma: Analysis of Transplantation Timing and Modality.
J. Clin. Oncol.
PUBLISHED: 12-16-2013
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To examine the outcomes of patients with chemotherapy-sensitive mantle-cell lymphoma (MCL) following a first hematopoietic stem-cell transplantation (HCT), comparing outcomes with autologous (auto) versus reduced-intensity conditioning allogeneic (RIC allo) HCT and with transplantation applied at different times in the disease course.
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Dissecting follicular lymphoma: high versus low risk.
Hematology Am Soc Hematol Educ Program
PUBLISHED: 12-10-2013
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Progress in the management of follicular lymphoma (FL) has translated to improved outcomes, with most patients surviving a decade or more from the time of diagnosis. However, the disease remains quite heterogeneous and a substantial number of patients have more aggressive disease with short responses to therapy and/or transformation to higher-grade lymphomas. Given the lack of a single standard approach, it is important to understand sources of heterogeneity among patients that influence initial management, surveillance strategies, and overall prognosis. Most of the validated tools, such as the Follicular Lymphoma International Prognostic Index (FLIPI) and FLIPI-2, apply to the frontline setting, and there is an unmet need for prognostic tools in relapsed and refractory disease states. In particular, the number of prior treatment regimens may be less important than the duration of response to the most recent regimen and the type of prior therapy received. Furthermore, despite awareness of progressive genetic and epigenetic derangements and a growing appreciation of the microenvironments role in FL outcomes, there is no validated means of incorporating biologic data into clinical prognostic indices. This review highlights the current state of knowledge regarding risk stratification in FL.
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A systematic review of comparative schedule-related toxicities with maintenance rituximab in follicular and mantle cell lymphomas.
Leuk. Lymphoma
PUBLISHED: 11-01-2013
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We conducted a systematic review of grade 3/4 adverse events (AEs) reported in prospective trials enrolling patients with follicular lymphoma (FL) and mantle cell lymphoma (MCL) receiving maintenance rituximab (MR). Random-effects models were used to calculate summary estimates and 95% confidence intervals for the proportion of AEs occurring during MR. Differences by induction program, histology, setting and MR schedule were examined by stratified analyses and univariate random-effects meta-regression. Eleven trials met the search criteria, with nine sufficiently reporting AEs during the MR phase. Of 1009 patients receiving MR, the proportion experiencing cumulative grade 3/4 toxicity was 24% (95% confidence interval [CI]: 14-36%). Patients receiving MR every 6 months as four weekly infusions for 2 years had significantly less toxicity compared with those receiving MR every 2 months (10% vs. 28%; p = 0.035). Patients treated with rituximab alone during induction had fewer toxicities compared to those treated with rituximab plus chemotherapy induction (12% vs. 35%; p = 0.031). Myelosuppression and infections were the most common toxicities. Our literature analysis suggests that MR given every 6 months and rituximab alone as induction may be associated with fewer grade 3/4 AEs for patients with FL and MCL; however, assessing the true independent impact of induction regimens and schedule on toxicity will require prospective trials.
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Pre-diagnosis cigarette smoking and overall survival in non-Hodgkin lymphoma.
Br. J. Haematol.
PUBLISHED: 05-15-2013
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We examined whether smoking prior to non-Hodgkin lymphoma (NHL) diagnosis was associated with overall survival (OS) and conducted a meta-analysis to assess the evidence relating pre-diagnosis cigarette smoking with OS. Among 523 NHL patients, worse OS was suggested for greater pre-diagnostic smoking habits when compared to never smokers. In the meta-analysis (n = 5 patient populations), inferior OS was observed for greater number of cigarettes smoked per day, years of cigarette smoking, and pack-years of cigarette smoking. The inferior survival was more pronounced for follicular than for diffuse large B cell lymphoma. Pre-diagnosis cigarette smoking may adversely impact the survival of NHL patients.
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A phase I/II trial of bortezomib combined concurrently with gemcitabine for relapsed or refractory DLBCL and peripheral T-cell lymphomas.
Br. J. Haematol.
PUBLISHED: 05-14-2013
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There remains an unmet therapeutic need for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL). We conducted a phase I/II trial with bortezomib (dose-escalated to 1·6 mg/m(2) ) given concurrently with gemcitabine (800 mg/m(2) ) days 1 + 8 q21 d. Of 32 patients, 16 each had relapsed/refractory PTCL and DLBCL. Median prior therapies were 3 and 35% had failed transplant. Among the first 18 patients, 67% experienced grade 3/4 neutropenia and/or grade 3/4 thrombocytopenia resulting in repeated treatment delays (relative dose intensity: 46%). Thus, the study was amended to give bortezomib and gemcitabine days 1 + 15 q28 d, which resulted in markedly improved tolerability. Among all patients, the overall response rate (ORR) was 24% with 19% complete remission (CR; intent-to-treat (ITT) ORR 16%, CR 13%), which met criteria for futility. The ORR for DLBCL was 10% (CR 10%) vs. 36% for PTCL (CR 27%). Among 6 PTCL patients treated on the modified schedule, ORR by ITT was 50% (CR 30%). Altogether, concurrent bortezomib/gemcitabine given days 1 + 8 q21 d was not tolerable, while modification to a bi-monthly schedule allowed consistent treatment delivery. Whereas efficacy of this combination was low in heavily pre-treated DLBCL, there was a signal of activity in relapsed/refractory PTCL utilizing the modified schedule.
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Dietary patterns and the risk of non-Hodgkin lymphoma.
Public Health Nutr
PUBLISHED: 05-09-2013
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OBJECTIVE: Previous studies examining the role of single foods or nutrients in the aetiology of non-Hodgkin lymphoma (NHL) have produced inconsistent findings. Few studies have examined associations for dietary patterns, which may more accurately reflect patterns of consumption and the complexity of dietary intake. The objective of the present study was to examine whether dietary patterns identified by factor analysis were associated with NHL risk. DESIGN: Case-control. SETTING: Population-based sample residing in Nebraska from 1999 to 2002. SUBJECTS: A total of 336 cases and 460 controls. RESULTS: Factor analysis identified two major dietary patterns: (i) a Meat, Fat and Sweets dietary pattern characterized by high intakes of French fries, red meat, processed meat, pizza, salty snacks, sweets and desserts, and sweetened beverages; and (ii) a Fruit, Vegetables and Starch dietary pattern characterized by high intakes of vegetables, fruit, fish, and cereals and starches. In multivariable logistic regression models, the Meat, Fat and Sweets dietary pattern was associated with an increased risk of overall NHL (ORQ4 v. Q1 = 3·6, 95 % CI 1·9, 6·8; P trend = 0·0004), follicular lymphoma (ORQ4 v. Q1 = 3·1, 95 % CI 1·2, 8·0; P trend = 0·01), diffuse large B-cell lymphoma (ORQ4 v. Q1 = 3·2, 95 % CI 1·1, 9·0; P trend = 0·09) and marginal zone lymphoma (ORQ4 v. Q1 = 8·2, 95 % CI 1·3, 51·2; P trend = 0·05). No association with overall or subtype-specific risk was detected for the Fruit, Vegetables and Starch dietary pattern. No evidence of heterogeneity was detected across strata of age, sex, BMI, smoking status or alcohol consumption. CONCLUSIONS: Our results suggest that a dietary pattern high in meats, fats and sweets may be associated with an increased risk of NHL.
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Dietary intake of fruits and vegetables and overall survival in non-Hodgkin lymphoma.
Leuk. Lymphoma
PUBLISHED: 04-30-2013
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In a cohort of 301 patients with non-Hodgkin lymphoma (NHL), we examined whether the pre-diagnostic consumption of fruits and vegetables, or of nutrients concentrated in fruits and vegetables, was associated with overall survival (OS). Proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. A total of 91 deaths occurred in the patient cohort over a median follow-up period of 8.2 years. No association with OS was detected for a dietary pattern characterized by high intakes of fruits, vegetables and starch; fruit intake; vegetable intake; or nutrient intake in patients diagnosed with overall NHL, follicular lymphoma or diffuse large B-cell lymphoma. Higher intakes of carotene-rich vegetables (HR = 0.4 [0.2-1.0]; p trend = 0.05) and ?-carotene (HRT3 vs. T1 = 0.4 [0.2-0.9]; p trend = 0.03) were associated with better OS among ever smokers. Overall, our data suggest that the intake of fruits and vegetables prior to diagnosis is not associated with OS in patients with NHL.
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An upward trend in the age-specific incidence patterns for mantle cell lymphoma in the USA.
Leuk. Lymphoma
PUBLISHED: 02-07-2013
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Although an increased incidence of mantle cell lymphoma (MCL) has been reported, age-specific incidence patterns have not been described. Further analyses could inform investigation into the etiology of this disease. We conducted an epidemiologic study using the 13 Surveillance, Epidemiology, and End Results (SEER) registries to evaluate MCL incidence from 1992 through 2009. We calculated the proportional changes in the incidence of MCL for subpopulations defined by age, race/ethnicity and gender over time and the racial/ethnic and gender disparities. We observed a 130.9% increase in MCL incidence from 1992-1994 to 2005-2009. The increase was strongest for males (199.0%) and for whites (153.0%). The incidence increased 161%, 200%, 398% and 429% from 1992-1994 to 2005-2009 in white men ages 50-59, 60-69, 70-79 and 80+, respectively, whereas the increase in white females was 86%, 82%, 50% and 193% in the corresponding age groups. We observed a male-to-female incidence rate ratio (IRR) of 2.65 and a white-to-black IRR of 2.21. Our analysis confirmed significant increases in MCL, and illustrated that the incidence is increasing more rapidly in elderly persons, particularly in white males. We also identified novel age-specific temporal trends by race/ethnicity and sex. In addition, we found that the gender and white-to-black disparities have grown over time. Our findings may impact MCL etiologic investigation and treatment research.
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A phase 2 study of epothilone B analog BMS-247550 (NSC 710428) in patients with relapsed aggressive non-Hodgkin lymphomas.
Cancer
PUBLISHED: 01-10-2013
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The management of relapsed aggressive lymphomas remains problematic. Ixabepilone (BMS-247550, epothilone B analog), a potent inhibitor of tubulin disassembly, has promising preclinical and early-phase clinical activity in drug-resistant malignancies.
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The anti-CD80 primatized monoclonal antibody, galiximab, is well-tolerated but has limited activity in relapsed Hodgkin lymphoma: Cancer and Leukemia Group B 50602 (Alliance).
Leuk. Lymphoma
PUBLISHED: 01-04-2013
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Relapsed Hodgkin lymphoma remains a clinical challenge, with few non-cytotoxic treatment options. CD80 is a surface antigen that normally functions as a co-stimulatory molecule but is aberrantly and uniformly expressed on Reed-Sternberg cells. Galiximab is a primatized monoclonal antibody against CD80, with a favorable toxicity profile demonstrated in other lymphomas. Cancer and Leukemia Group B (CALGB) 50602 (Alliance) tested single-agent galiximab in a highly refractory group of patients with Hodgkin lymphoma (median 3 prior regimens, 83% failing after prior stem cell transplant) to determine the efficacy. The overall response rate was 10.3% and the median progression-free survival was 1.6 months. Galiximab was well-tolerated, with minimal grade 3 or 4 toxicities. Despite this preclinical rationale, single-agent galiximab had limited activity in heavily pretreated Hodgkin lymphoma.
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A retrospective multicenter analysis of elderly Hodgkin lymphoma: outcomes and prognostic factors in the modern era.
Blood
PUBLISHED: 11-23-2011
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We investigated a recent (January 1999 to December 2009) cohort of 95 elderly Hodgkin lymphoma subjects. At diagnosis, median age was 67 years (range, 60-89 years), whereas 61% had significant comorbidity, 26% were unfit, 17% had a geriatric syndrome, and 13% had loss of activities of daily living. Overall response rate to therapy was 85%, whereas incidence of bleomycin lung toxicity was 32% (with associated mortality rate, 25%). With 66-month median follow-up, 2-year and 5-year overall survival were 73% and 58%, respectively (advanced-stage, 63% and 46%, respectively). Most International Prognostic Score factors were not prognostic on univariate analyses, whereas Cox multivariate regression identified 2 risk factors associated with inferior overall survival: (1) age more than 70 years (2.24; 95% CI, 1.16-4.33, P = .02) and (2) loss of activities of daily living (2.71; 95% CI, 1.07-6.84, P = .04). Furthermore, a novel survival model based on number of these risk factors (0, 1, or 2) showed differential 2-year OS of 83%, 70%, and 13%, respectively (P < .0001) and 5-year OS of 73%, 51%, and 0%, respectively (P < .0001).
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Analysis of very elderly (?80 years) non-hodgkin lymphoma: impact of functional status and co-morbidities on outcome.
Br. J. Haematol.
PUBLISHED: 11-16-2011
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Data on outcome, prognostic factors, and treatment for very elderly non-Hodgkin lymphomas (NHL) is sparse. We conducted a multicentre retrospective analysis of NHL patients ?80?years (at diagnosis) treated between 1999 and 2009. Detailed characteristics were obtained including geriatric syndromes, activities of daily living (ADLs), and co-morbidities using the Cumulative Illness Rating Scale-Geriatrics (CIRS-G). We identified 303 patients: 170 aggressive NHL (84% B cell/16% T cell) and 133 indolent NHL (82% B cell/18% T cell). Median age was 84?years (80-95). A geriatric syndrome was present in 26% of patients, 18% had ?1 grade 4 CIRS-G, and 14% had loss of ADLs. At 49-month median follow-up, 4-year progression-free (PFS) and overall survival (OS) for aggressive NHLs were 31% and 44% respectively (stage I/II: PFS 53% and OS 66%; stage III/IV: PFS 20% and OS 32%; P?
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Maintenance rituximab in follicular non-Hodgkin lymphoma: facts and controversies.
Leuk. Lymphoma
PUBLISHED: 10-24-2011
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The advent of rituximab, a chimeric monoclonal antibody against CD20, has arguably improved and changed the natural history of non-Hodgkin lymphoma and has become an essential component of front-line and relapsed disease treatment strategies. Given its tolerability and long half-life, rituximab has been investigated in the maintenance setting in follicular lymphoma. Several landmark studies have demonstrated improvement in progression-free survival in patients receiving maintenance rituximab compared to those observed. These favorable results were witnessed in front-line and in the relapsed setting using a variety of induction programs such as rituximab monotherapy or chemoimmunotherapy. Importantly, toxicities were predictable and manageable. Despite these encouraging results, many vital and practical questions remain unanswered. In this review, we critically analyze the data that led to the widespread use of maintenance rituximab in follicular lymphoma and attempt to answer the most important questions facing practicing oncologists when deciding on using this approach in their patients.
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Outcome of lower-intensity allogeneic transplantation in non-Hodgkin lymphoma after autologous transplantation failure.
Biol. Blood Marrow Transplant.
PUBLISHED: 09-30-2011
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We studied the outcome of allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning regimens (reduced-intensity conditioning and nonmyeloablative) in patients with non-Hodgkin lymphoma who relapsed after autologous hematopoietic stem cell transplantation. Nonrelapse mortality, lymphoma progression/relapse, progression-free survival (PFS), and overall survival were analyzed in 263 patients with non-Hodgkin lymphoma. All 263 patients had relapsed after a previous autologous hematopoietic stem cell transplantation and then had undergone allogeneic hematopoietic stem cell transplantation from a related (n = 26) or unrelated (n = 237) donor after reduced-intensity conditioning (n = 128) or nonmyeloablative (n = 135) and were reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2006. The median follow-up of survivors was 68 months (range, 3-111 months). Three-year nonrelapse mortality was 44% (95% confidence interval [CI], 37%-50%). Lymphoma progression/relapse at 3 years was 35% (95% CI, 29%-41%). Three-year probabilities of PFS and overall survival were 21% (95% CI, 16%-27%) and 32% (95% CI, 27%-38%), respectively. Superior Karnofsky Performance Score, longer interval between transplantations, total body irradiation-based conditioning regimen, and lymphoma remission at transplantation were correlated with improved PFS. Allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning is associated with significant nonrelapse mortality but can result in long-term PFS. We describe a quantitative risk model based on pretransplantation risk factors to identify those patients likely to benefit from this approach.
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Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study.
J. Clin. Oncol.
PUBLISHED: 08-01-2011
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The aims of this multicenter study were to evaluate the response rate, progression-free survival, and toxicity of the combination of bortezomib, bendamustine, and rituximab in patients with follicular lymphoma whose disease was relapsed or refractory to prior treatment.
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Dietary intake of fruit and vegetables and risk of non-Hodgkin lymphoma.
Cancer Causes Control
PUBLISHED: 06-09-2011
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Few studies have evaluated the potential association between consumption of fruit and vegetables and non-Hodgkin lymphoma (NHL) by histologic subtype, and the results of these studies have been inconsistent.
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Personalized treatment of lymphoma: promise and reality.
Semin. Oncol.
PUBLISHED: 03-23-2011
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Lymphoma comprises two groups of diseases: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Within both subsets are numerous variations with distinct biologic, molecular, and cytogenetic characteristics. The World Health Organization (WHO) classification of NHL, for example, now identifies several dozen broad entities and nearly 60 unique clinicopathologic subtypes. In addition to pathologic heterogeneity, there is clinical diversity within lymphomas, with some patients achieving cure, others having prolonged disease stabilization, and still others experiencing a rapidly fulminant decline and death. It is increasingly appreciated that both clinical and biological features strongly influence outcome. Practical implementation of a personalized approach to treatment is urgently needed, but efforts thus far have focused primarily on prognostication, with much less emphasis on determining therapeutic options. Nevertheless, better prognostic tools will facilitate the design of "risk-stratified" trials that will ultimately benefit patients. Thus far, the development of personalized treatment in lymphomas clusters into several broad approaches: refinement of clinical prognostic models for better risk stratification, use of high-throughput technology to identify biologic subtypes within pathologically similar diseases, "response-adapted" changes in therapy via imaging with [(18)F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and anti-idiotype vaccines. An important unmet need is the implementation of these tools into treatment choices for individual patients, and this is the focus of intense ongoing research.
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Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma.
Blood
PUBLISHED: 02-25-2011
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Romidepsin (depsipeptide or FK228) is a histone deacetylase inhibitor, one of a new class of agents active in T-cell lymphoma. A phase 2 trial was conducted in cutaneous (CTCL) and peripheral (PTCL) T-cell lymphoma. Major and durable responses in CTCL supported the approval of romidepsin for CTCL. Forty-seven patients with PTCL of various subtypes including PTCL NOS, angioimmunoblastic, ALK-negative anaplastic large cell lymphoma, and enteropathy-associated T-cell lymphoma were enrolled. All patients had received prior therapy with a median of 3 previous treatments (range 1-11); 18 (38%) had undergone stem-cell transplant. All patients were evaluated for toxicity; 2 patients discovered to be ineligible were excluded from response assessment. Common toxicities were nausea, fatigue, and transient thrombocytopenia and granulocytopenia. Complete responses were observed in 8 and partial responses in 9 of 45 patients, for an overall response rate of 38% (95% confidence interval 24%-53%). The median duration of overall response was 8.9 months (range 2-74). Responses were observed in various subtypes, with 6 responses among the 18 patients with prior stem-cell transplant. The histone deacetylase inhibitor romidepsin has single agent clinical activity associated with durable responses in patients with relapsed PTCL.
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T-cell-depleted allogeneic transplant without donor leukocyte infusions results in excellent long-term survival in patients with multiply relapsed Lymphoma. Predictors for survival after transplant relapse.
Leuk. Lymphoma
PUBLISHED: 12-10-2010
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We analyzed 67 patients with lymphoma who received alemtuzumab-based conditioning regimens for allogeneic stem cell transplant and no post-transplant DLI. The median age was 54 (24-70), 43% had unrelated donors, 34% had chemotherapy refractory disease, and 25% had an elevated LDH. With a median follow-up for survivors of 35 months, the estimated 3-year progression-free survival (PFS) and overall survival (OS) were 30% and 47%, respectively. Chemosensitivity by CT and pre-transplant LDH were independent prognostic factors for both overall survival and progression-free survival. Patient age, performance status, donor type, lymphoma subtype, disease sensitivity by PET, and conditioning regimen did not correlate with PFS and OS. Patients who relapsed greater than 6 months after allogeneic transplant were frequently able to re-enter a subsequent durable remission. Our experience confirms the curative potential of alemtuzumab-containing RIC regimens for allogeneic HCT in patients with relapsed lymphoma without prophylactic DLI. An elevated pre-transplant LDH and chemorefractory disease prior to transplant confer a worse prognosis, while PET scan findings do not have this same implication. Patients who relapse greater than 6 months after their transplant are likely to achieve a subsequent remission with any of a variety of interventions, suggesting that GVL effects can be operative even after recurrence. Our outcomes challenge the utility of the common practice of prophylactic DLI after T-depleted transplant for lymphoma.
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Temsirolimus has activity in non-mantle cell non-Hodgkins lymphoma subtypes: The University of Chicago phase II consortium.
J. Clin. Oncol.
PUBLISHED: 09-13-2010
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Despite high initial remission rates, most lymphomas relapse and require further therapy. The mammalian target of rapamycin (mTOR) pathway is a validated target in mantle cell lymphoma, but has not been extensively evaluated in other lymphomas.
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The impact of MYC expression in lymphoma biology: beyond Burkitt lymphoma.
Blood Cells Mol. Dis.
PUBLISHED: 07-23-2010
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Although classically described as the driving oncogene in Burkitt lymphoma (BL), abnormalities of MYC have been recognized in other non-Hodgkin lymphomas as well. For example, MYC is overexpressed in approximately 10% of diffuse large B-cell lymphomas (DLBCL), conferring an adverse prognosis with chemoresistance and shortened survival; only approximately 30% of patients achieve long-term survival despite modern therapies. In contrast to BL, MYC aberrations in DLBCL are usually associated with multiple cytogenetic abnormalities and other genetic lesions, such as concurrent BCL2 translocations. Patients with so-called "double-hit" lymphomas have a worse outcome with few survivors beyond 6 months. It is unclear why MYC translocations are diagnostic in BL but prognostic in other lymphomas; different mechanisms underlying MYC abnormalities and a unique target set of genes may explain some of the variance. Furthermore, MYC possesses nontranscriptional functions other than transcriptional controls on genes regulating cell growth and may also influence the lymphoma microenvironment. Here we summarize current knowledge regarding MYC in lymphomas other than Burkitt lymphoma, with an emphasis on transcriptional, epigenetic, clinical, and microenvironmental consequences.
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Phase II study of immunomodulation with granulocyte-macrophage colony-stimulating factor, interleukin-2, and rituximab following autologous stem cell transplant in patients with relapsed or refractory lymphomas.
Leuk. Lymphoma
PUBLISHED: 05-26-2010
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High-dose chemotherapy followed by autologous stem cell transplant (ASCT) leads to durable remissions in approximately half of patients with chemosensitive relapsed or refractory aggressive lymphomas; however, many will relapse despite ASCT secondary to persistent minimal residual disease (MRD) or malignant graft contamination. Post-transplant rituximab may eradicate MRD. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) might enhance the efficacy of rituximab by augmenting antibody-dependent cellular cytotoxicity (ADCC). We hypothesized that given together, rituximab, GM-CSF, and IL-2 might eradicate MRD and improve event-free survival following ASCT. Forty-six patients with relapsed non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) were enrolled. Stem cells were mobilized with G-CSF and GM-CSF following chemotherapy. Following BEAM conditioning, patients received GM-CSF until neutrophil engraftment. Between days + 30 and + 120, patients received one dose of rituximab 375 mg/m(2) (cycle 1), followed by three cycles of GM-CSF 250 microg/m(2)/day SQ days 1-5, IL-2 1.5 x 10(6) IU/m(2)/day SQ days 6-12, and rituximab 375 mg/m(2) IV day 9, repeated every 21 days. Thirty-eight patients were eligible for post-ASCT immunotherapy. Nine patients completed 1-2 cycles and 21 completed 3-4 cycles; eight patients did not receive post-ASCT immunotherapy. Grade 3-4 neutropenia and grade 3 thrombocytopenia were observed. With a median follow-up of 30 months, the estimated 5-year OS and EFS for all patients eligible for immunotherapy are 65% and 45%, respectively. Post-ASCT immunomodulation with rituximab, IL-2, and GM-CSF was feasible and safe, but not all patients were able to continue on to post-ASCT immunotherapy.
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Multicenter analysis of 80 solid organ transplantation recipients with post-transplantation lymphoproliferative disease: outcomes and prognostic factors in the modern era.
J. Clin. Oncol.
PUBLISHED: 01-19-2010
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PURPOSE Adult post-transplantation lymphoproliferative disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. METHODS We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) -related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). Results Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21% (P < .0001) and 33% (P = .0001), respectively, without rituximab. Notably, of all relapses, only 9% (4 of 34 patients) occurred beyond 12 months from PTLD diagnosis. On multivariate regression analysis, three factors were associated with progression and survival: CNS involvement (PFS, 4.70; P = .01; OS, 3.61; P = .04), bone marrow involvement (PFS, 2.95; P = .03; OS, 3.14; P = .03), and hypoalbuminemia (PFS, 2.96; P = .05; OS, 3.64; P = .04). Furthermore, a survival model by multivariate CART analysis that was based on number of adverse factors present (ie, 0, 1, > or = 2) was formed: 3-year PFS rates were 84%, 66%, 7%, respectively, and 3-year OS rates were 93%, 68%, 11%, respectively (P < .0001). CONCLUSION This large, multicenter, retrospective analysis suggests significantly improved PFS and OS associated with early rituximab-based treatment in PTLD. In addition, clinical factors at diagnosis identified patients with markedly divergent outcomes.
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Temsirolimus in mantle cell lymphoma and other non-Hodgkin lymphoma subtypes.
Semin. Oncol.
PUBLISHED: 12-08-2009
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Temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR), has anti-tumor activity in patients with relapsed or refractory mantle cell lymphoma (MCL) and other mature lymphoid neoplasms. mTOR is an intracellular kinase that controls the mRNA translation of many proteins (eg, cyclin D1) that can act as oncogenes and contribute to lymphomagenesis. Characterized by overexpression of cyclin D1, MCL was identified as a disease that might be susceptible to mTOR inhibition. When single-agent temsirolimus was explored in two phase II studies for treatment of patients with relapsed or refractory MCL, it demonstrated anti-tumor activity, with overall response rates of 38% and 41%. Subsequently, a three-arm, randomized phase III trial was conducted to compare two dosing regimens of temsirolimus with investigators choice of therapy for heavily pretreated patients with relapsed or refractory MCL (N = 162; randomized 1:1:1). Once-weekly intravenous temsirolimus 175 mg for 3 weeks followed by 75 mg once weekly (175/75) significantly improved progression-free survival (hazard ratio = 0.44; P = .0009) versus investigators choice therapy. Median progression-free survival durations were 4.8 and 1.9 months, respectively. The objective response rates were 22% in the 175/75 group and 2% in the investigators choice group (P = .0019). For patients receiving temsirolimus, the most frequent grade 3 or 4 adverse events were thrombocytopenia, anemia, neutropenia, and asthenia. The results of this trial established a recommended clinical dose for temsirolimus monotherapy in patients with relapsed or refractory MCL and validated the importance of mTOR in the pathogenesis of advanced MCL. Objective responses also have been reported for other mature B-cell neoplasms (eg, diffuse large B-cell lymphoma or follicular lymphoma) in the phase II setting. Temsirolimus as monotherapy or in combination with other active agents warrants further investigation for treatment of MCL and other non-Hodgkin lymphomas.
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Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies.
J. Clin. Oncol.
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Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. We evaluated ibrutinib (PCI-32765), a small-molecule irreversible inhibitor of BTK, in patients with B-cell malignancies.
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Phytanic acid and the risk of non-Hodgkin lymphoma.
Carcinogenesis
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Greater consumption of red meat, processed meat and dairy products has been associated with an increased risk of non-Hodgkin lymphoma (NHL) in several previous reports. Phytanic acid, a saturated fatty acid obtained primarily through the consumption of ruminant meat and dairy products, may offer a potential underlying mechanism for these associations. In a population-based case-control study of 336 cases and 460 controls conducted in Nebraska during 1999-2002, we examined whether phytanic acid-containing foods or total phytanic acid intake, estimated from a food frequency questionnaire and the published phytanic acid values of 151 food items, were associated with increased NHL risk. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals for overall NHL and the common NHL histologic subtypes. In multivariable models, higher intakes of density-adjusted beef [OR(T3 vs. T1) = 1.5 (1.1-2.2); P(trend) = 0.02], total dairy products [OR = 1.5 (1.1-2.2); P(trend) = 0.02) and milk [OR = 1.6 (1.1-2.3); P(trend) = 0.01] were associated with an increased risk of NHL. Intake of total phytanic acid was positively associated with NHL risk [OR = 1.5 (1.0-2.1); P(trend) = 0.04]. In analyses stratified by NHL subtype, greater consumption of beef was associated with an increased risk of diffuse large B-cell lymphoma, and greater consumption of milk was associated with an increased risk of follicular lymphoma (FL). Total phytanic acid intake was associated with an increased risk of FL and small lymphocytic lymphoma/chronic lymphocytic leukemia. Our results provide support that total phytanic acid and phytanic acid-containing foods may increase NHL risk.
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Dietary nitrate and nitrite intake and risk of non-Hodgkin lymphoma.
Leuk. Lymphoma
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Although established risk factors such as immunodeficiency and viral infections may be responsible for a portion of cases of non-Hodgkin lymphoma (NHL), the vast majority of cases of NHL remain unexplained. The role of dietary nitrate and nitrite in NHL risk is of interest since they are precursors of N-nitroso compounds, and nitrosoureas have been shown to induce B- and T-cell lymphomas in animal studies. However, few studies have evaluated the potential association between consumption of nitrate and nitrite and NHL by subtype or chromosomal translocation status, and the results of these studies have been inconsistent. We estimated the dietary intake of nitrate and nitrite using a food frequency questionnaire in a population-based, case-control study of 348 cases and 470 controls conducted in Nebraska in 1999-2002. A non-significant excess risk of NHL was found among women who reported an intake of nitrite in the highest quartile compared to the lowest quartile (odds ratio [OR] = 1.6; 95% confidence interval [CI]: 0.8-2.9), particularly nitrite from animal sources (OR = 1.9; 95% CI: 1.0-3.4). No significant associations were observed for nitrate or nitrite by NHL subtype. Although there were some increases in risk that support the N-nitroso hypothesis, they were not significant and do not confer strong evidence of an association.
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Conditioning regimens for allotransplants for diffuse large B-cell lymphoma: myeloablative or reduced intensity?
Blood
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The best conditioning regimen before allogeneic transplantation for high-risk diffuse large B-cell lymphoma (DLBCL) remains to be clarified. We analyzed data from 396 recipients of allotransplants for DLBCL receiving myeloablative (MAC; n = 165), reduced intensity (RIC; n = 143), or nonmyeloablative conditioning (NMAC; n = 88) regimens. Acute and chronic GVHD rates were similar across the groups. Five-year nonrelapse mortality (NRM) was higher in MAC than RIC and NMAC (56% vs 47% vs 36%; P = .007). Five-year relapse/progression was lower in MAC than in RIC/NMAC (26% vs 38% vs 40%; P = .031). Five-year progression-free survival (15%-25%) and overall survival (18%-26%) did not differ significantly between the cohorts. In multivariate analysis, NMAC and more recent transplant year were associated with lower NRM, whereas a lower Karnofsky performance score (< 90), prior relapse resistant to therapy, and use of unrelated donors were associated with higher NRM. NMAC transplants, no prior use of rituximab, and prior relapse resistant to therapy were associated with a greater risk of relapse/progression. In conclusion, allotransplantation with RIC or NMAC induces long-term progression-free survival in selected DLBCL patients with a lower risk of NRM but with higher risk of lymphoma progression or relapse.
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Marginal zone lymphoma of the thoracic dura causing spinal cord compression.
J Clin Neurosci
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Primary extra-nodal marginal zone B cell lymphoma (Ex-MZBCL) or mucosa-associated lymphoid tissue (MALT) lymphoma of the cranial dura is a rare but well-known entity. We describe a 58-year-old woman with primary MALT lymphoma of the spinal dura causing extreme thickening of the dura and spinal cord compression who initially presented with acute spinal cord compression from a chronic epidural lesion. She was treated with surgery and radiotherapy and diagnosed with a mature B-cell lymphoma based on gene rearrangement studies. Two years following the completion of radiotherapy, she presented with an increase in the size of the residual mass that was suggestive of an epidural lesion. On re-exploration, no epidural lesion was found; however, the dura was extremely thickened causing spinal cord compression. Clinical course, histological evaluation, immunostaining and gene rearrangement studies resulted in a final diagnosis of primary Ex-MZBCL of the spinal dura. To our knowledge, this is the first report of Ex-MZBCL in the spinal dura. This diagnosis should be considered when evaluating spinal cord lesions in patients with primary central nervous system (CNS) lymphoma, especially recurrent lesions, since this group of tumors carries a favorable outcome compared to other primary CNS lymphomas.
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Targeting ALK: a promising strategy for the treatment of non-small cell lung cancer, non-Hodgkins lymphoma, and neuroblastoma.
Target Oncol
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Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that affects a number of biological and biochemical functions through normal ligand-dependent signaling. It has oncogenic functions in a number of tumors including non-small cell lung cancer (NSCLC), anaplastic large cell lymphoma, and neuroblastoma when altered by translocation or amplification or mutation. On August 2011, a small molecule inhibitor against ALK, crizotinib, was approved for therapy against NSCLC with ALK translocations. As we determine the molecular heterogeneity of tumors, the potential of ALK as a relevant therapeutic target in a number of malignancies has become apparent. This review will discuss some of the tumor types with oncogenic ALK alterations. The activity and unique toxicities of crizotinib are described, along with potential mechanisms of resistance and new therapies beyond crizotinib.
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Meat intake and risk of non-Hodgkin lymphoma.
Cancer Causes Control
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We conducted a population-based, case-control study to test the hypothesis that consumption of meat and meat-related mutagens increases the risk of non-Hodgkin lymphoma (NHL), and whether the associations are modified by N-acetyltransferase (NAT) 1 and 2. Participants (336 cases and 460 controls) completed a 117-item food frequency questionnaire. The risk of NHL was associated with a higher intake of red meat (OR = 1.5; CI, 1.1-2.2), total fat (OR = 1.4; CI, 1.0-2.1), and oleic acid (OR = 1.5; CI, 1.0-2.2). NHL risk was also associated with a higher intake of very well-done pork (OR = 2.5; 95 % CI, 1.4-4.3) and the meat-related mutagen MeIQx (OR = 1.6; 95 % CI, 1.1-2.3). Analyses of the major NHL histologic subtypes showed a positive association between diffuse large B cell lymphoma (DLBCL) and higher intake of red meat (OR = 2.1; 95 % CI, 1.1-3.9) and the association was largely due to meat-related mutagens as a positive association was observed for higher intakes of both MeIQx (OR = 2.4; 95 % CI, 1.2-4.6) and DiMeIQx (OR = 1.9; 95 % CI, 1.0-3.5). Although the OR for follicular lymphoma (FL) was also increased with a higher red meat intake (OR = 1.9; 95 % CI, 1.1-3.3), the association appeared to be due to increased oleic acid (OR = 1.7; 95 % CI: 0.9-3.1). We found no evidence that polymorphisms in NAT1 or NAT2 modify the association between NHL and meat-related mutagens. Our results provide further evidence that red meat consumption is associated with an increase in NHL risk, and new evidence that the specific components of meat, namely fat and meat-related mutagens, may be impacting NHL subtype risk differently.
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Targeting mTOR in mantle cell lymphoma: current and future directions.
Best Pract Res Clin Haematol
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The PI3K/Akt/mTOR pathway is an important therapeutic target in mantle cell lymphoma. Ample preclinical data suggests this axis contributes not only to pathogenesis, but remains tonically activated and can be targeted with available agents. Classic mTOR inhibitors, which allosterically bind to mTORC1 and include temsirolimus and everolimus, show efficacy in heavily pretreated and elderly patients. However, only a portion of patients respond and durability is limited. Numerous resistance mechanisms have been identified, including paradoxical Akt activation. Currently, several ongoing trials are combining mTOR inhibitors with other agents that either block upstream components of the PI3K/Akt/mTOR axis or that inhibit complementary signaling pathways, with hopes of improving outcomes. Dual inhibition of mTORC1 and mTORC2 using small molecule catalytic site inhibitors against the mTOR kinase may also prove to be superior to first generation agents, but clinical data remains nascent. Several dozen ongoing clinical trials should help refine the optimal use of mTOR inhibitors for MCL patients.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.