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Find video protocols related to scientific articles indexed in Pubmed.
Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
J. Natl. Cancer Inst. Monographs
PUBLISHED: 09-01-2014
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Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes.
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Medical history, lifestyle, family history, and occupational risk factors for diffuse large B-cell lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
J. Natl. Cancer Inst. Monographs
PUBLISHED: 09-01-2014
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Although risk factors for diffuse large B-cell lymphoma (DLBCL) have been suggested, their independent effects, modification by sex, and association with anatomical sites are largely unknown.
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Lenalidomide Combined With R-CHOP Overcomes Negative Prognostic Impact of Non-Germinal Center B-Cell Phenotype in Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Phase II Study.
J. Clin. Oncol.
PUBLISHED: 08-18-2014
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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.
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Frontline therapy of AML: should the older patient be treated differently?
Curr Hematol Malig Rep
PUBLISHED: 05-20-2014
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Optimal treatment of acute myeloid leukemia (AML) in older adults (age ?60 years) remains largely undefined, in part because of the inadequate response to available therapies, the poor prognosis relative to younger adults, the heterogeneity of the population, and the difficulty in determining who is fit for intensive therapy. In contrast to younger patients, there remains uncertainty about disease biology and molecular prognostic factors in elderly AML. While almost all patients may benefit from treatment, with the exception of reduced intensity allogeneic transplantation, there is little evidence that further intensifying therapy will improve outcomes. In fact, recent studies suggest that de-intensified treatment may in fact be superior and allow access to therapy for more patients. Both the disease and the patient must be approached holistically in order to make the best frontline treatment choice together. It is critical that we support well-designed clinical trials to develop more effective frontline therapies, develop more informative biomarkers, and to better understand who is a candidate for curative treatment.
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Socioeconomic disparities in mortality after diffuse large B-cell lymphoma in the modern treatment era.
Blood
PUBLISHED: 04-04-2014
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Despite advances in treatment, including the introduction of rituximab, survival after diffuse large B-cell lymphoma (DLBCL) remains heterogeneous. However, no studies have considered the association between neighborhood socioeconomic status (SES) and race/ethnicity on DLBCL mortality before (1988-2000) and after (2001-2009) the introduction of rituximab. We studied all 33,032 DLBCL patients diagnosed between 1988-2009 in California for vital status through December 31, 2010. Patients diagnosed from 2001 to 2009 vs 1988 to 2000 had significantly decreased overall and DLBCL-specific mortality. However, those living in lower SES neighborhoods had 34% (95% confidence interval [CI], 27%-40%) and 24% (95% CI, 16%-32%) higher mortality rate from all causes and lymphoma, respectively, than patients in higher SES neighborhoods. The magnitude of mortality disparities by neighborhood SES was more marked in younger (<65 years) than in older patients (?65 years), in married than nonmarried patients, and after 2000. We concluded that patients living in low SES neighborhoods had substantially worse survival after DLBCL, and this disparity was striking in younger (ie, not eligible for Medicare-aged) patients, married patients, and after the introduction of rituximab. These disparities suggest there are barriers, including inadequate insurance coverage with additional financial burden, to effective treatment among socioeconomically disadvantaged patients.
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The investigational agent MLN2238 induces apoptosis and is cytotoxic to CLL cells in vitro, as a single agent and in combination with other drugs.
Br. J. Haematol.
PUBLISHED: 01-27-2014
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Chronic lymphocytic leukaemia (CLL) is the most common haematological malignancy in the U.S. The course of the disease has been shown to be negatively impacted by increased levels of BCL2. Strategies to downregulate BCL2 and shift the balance towards cellular demise are actively being explored. Therefore, we examined whether the investigational agent MLN2238 could inhibit the proteasomal machinery and induce CLL cell death while also downregulating BCL2. MLN2238-induced cell death was studied in peripheral blood mononuclear cells from 28 CLL patients. MLN2238 produced a dose-dependent reduction in BCL2 and CLL cell viability with maximum cell death observed at a 50 nmol/l concentration by 48 h. Annexin-V staining, PARP1 and caspase-3 cleavage along with an increase in mitochondrial membrane permeability were noted after cells were treated with MLN2238; however, apoptosis was only partially blocked by the pan-caspase inhibitor z-VAD.fmk. Furthermore, we observed enhanced anti-CLL effects in tumour cells treated with either a combination of MLN2238 and the BH3 mimetic AT-101 or MLN2238 and fludarabine. Together, our data suggest the potential for proteasome inhibitor based therapy in CLL and the rationale design of drug combination strategies based on CLL biology.
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A Phase I and Pharmacodynamic Study of AT9283, a Small-Molecule Inhibitor of Aurora Kinases in Patients With Relapsed/Refractory Leukemia or Myelofibrosis.
Clin Lymphoma Myeloma Leuk
PUBLISHED: 09-03-2013
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This study sought to identify the maximum tolerated dose (MTD) of AT9283, an inhibitor of Aurora kinases A and B, in patients with relapsed or refractory leukemias. Other endpoints included pharmacokinetics, safety and tolerability, pharmacodynamics, and preliminary evidence of efficacy.
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Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status.
J. Clin. Oncol.
PUBLISHED: 09-03-2013
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FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) are associated with early relapse and poor survival. Quizartinib potently and selectively inhibits FLT3 kinase activity in preclinical AML models.
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AT-101 downregulates BCL2 and MCL1 and potentiates the cytotoxic effects of lenalidomide and dexamethasone in preclinical models of multiple myeloma and Waldenström macroglobulinaemia.
Br. J. Haematol.
PUBLISHED: 07-17-2013
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Multiple myeloma, the second most common haematological malignancy in the U.S., is currently incurable. Disruption of the intrinsic apoptotic pathway by BCL2 and MCL1 upregulation is observed in >80% of myeloma cases and is associated with an aggressive clinical course. Remarkably, there is no approved drug with the ability to target BCL2 or MCL1. Thus, we investigated the anti-tumour effects of a pan-BCL2 inhibitor, AT-101, which has high binding specificity for BCL2 and MCL1 in preclinical models of plasma cell cancers (Multiple myeloma and Waldenström macroglobulinaemia). Gene expression and immunoblot analysis of six plasma cell cancer models showed upregulation of BCL2 family members. AT-101 was able to downregulate BCL2 and MCL1 in all plasma cell cancer models and induced apoptotic cell death in a caspase-dependent manner by altering mitochondrial membrane permeability. This cytotoxic effect and BCL2 downregulation were further potentiated when AT-101 was combined with lenalidomide/dexamethasone (LDA). NanoString nCounter mRNA quantification and Ingenuity Pathways Analysis revealed differential changes in the CCNA2, FRZB, FYN, IRF1, PTPN11 genes in LDA-treated cells. In summary, we describe for the first time the cellular and molecular events associated with the use of AT-101 in combination with lenalidomide/dexamethasone in preclinical models of plasma cell malignancy.
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Examining racial differences in diffuse large B-cell lymphoma presentation and survival.
Leuk. Lymphoma
PUBLISHED: 06-19-2013
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We performed a retrospective cohort analysis of 701 (533 white and 144 black) patients with diffuse large B-cell lymphoma (DLBCL) treated at two referral centers in southern United States between 1981 and 2010. Median age of diagnosis for blacks was 50 years vs. 57 years for whites (p < 0.001). A greater percentage of blacks presented with elevated lactate dehydrogenase levels, B-symptoms and performance status ? 2. More whites (8%) than blacks (3%) had a positive family history of lymphoma (p = 0.048). There were no racial differences in the use of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; 52% black vs. 47% white, p = 0.73). While black race predicted worse survival among patients treated with CHOP (hazard ratio [HR] 1.8, p < 0.001), treatment with R-CHOP was associated with improved survival irrespective of race (HR 0.61, p = 0.01). Future studies should examine biological differences that may underlie the observed racial differences in presentation and outcome.
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Unrelated donor allogeneic transplantation after failure of autologous transplantation for acute myelogenous leukemia: a study from the center for international blood and marrow transplantation research.
Biol. Blood Marrow Transplant.
PUBLISHED: 04-21-2013
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The survival of patients with relapsed acute myelogenous leukemia (AML) after autologous hematopoietic stem cell transplantation (auto-HCT) is very poor. We studied the outcomes of 302 patients who underwent secondary allogeneic hematopoietic cell transplantation (allo-HCT) from an unrelated donor (URD) using either myeloablative (n = 242) or reduced-intensity conditioning (RIC; n = 60) regimens reported to the Center for International Blood and Marrow Transplantation Research. After a median follow-up of 58 months (range, 2 to 160 months), the probability of treatment-related mortality was 44% (95% confidence interval [CI], 38%-50%) at 1-year. The 5-year incidence of relapse was 32% (95% CI, 27%-38%), and that of overall survival was 22% (95% CI, 18%-27%). Multivariate analysis revealed a significantly better overal survival with RIC regimens (hazard ratio [HR], 0.51; 95% CI, 0.35-0.75; P <.001), with Karnofsky Performance Status score ?90% (HR, 0.62; 95% CI, 0.47-0.82: P = .001) and in cytomegalovirus-negative recipients (HR, 0.64; 95% CI, 0.44-0.94; P = .022). A longer interval (>18 months) from auto-HCT to URD allo-HCT was associated with significantly lower riak of relapse (HR, 0.19; 95% CI, 0.09-0.38; P <.001) and improved leukemia-free survival (HR, 0.53; 95% CI, 0.34-0.84; P = .006). URD allo-HCT after auto-HCT relapse resulted in 20% long-term leukemia-free survival, with the best results seen in patients with a longer interval to secondary URD transplantation, with a Karnofsky Performance Status score ?90%, in complete remission, and using an RIC regimen. Further efforts to reduce treatment-related mortaility and relapse are still needed.
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Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab.
J. Clin. Oncol.
PUBLISHED: 01-07-2013
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Inotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20(+)/CD22(+) B-cell non-Hodgkin lymphoma (NHL).
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An examination of educational gaps in the diagnosis and treatment of myelodysplastic syndromes.
Cancer Control
PUBLISHED: 01-29-2011
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Myelodysplastic syndromes (MDS) comprise a heterogeneous group of hematologic malignancies, with an incidence rate of 3.4 cases per 100,000 in the United States. MDS affects patients predominantly over 60 years of age. As these syndromes are not well understood by many medical practitioner, patients with MDS may be underrecognized or underdiagnosed. The availability of new MDS treatment options further establishes the need to more closely assess gaps in clinical practice and underscores the necessity to develop educational activities to address those gaps.
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NCCN Clinical Practice Guidelines in Oncology: myelodysplastic syndromes.
J Natl Compr Canc Netw
PUBLISHED: 01-15-2011
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These suggested practice guidelines are based on extensive evaluation of the reviewed risk-based data and indicate useful current approaches for managing patients with MDS. Four drugs have recently been approved by the FDA for treating specific subtypes of MDS: lenalidomide for MDS patients with del(5q) cytogenetic abnormalities; azacytidine and decitabine for treating patients with higher-risk or nonresponsive MDS; and deferasirox for iron chelation of iron overloaded patients with MDS. However, because a substantial proportion of patient subsets with MDS lack effective treatment for their cytopenias or for altering disease natural history, clinical trials with these and other novel therapeutic agents along with supportive care remain the hallmark of management for this disease. The role of thrombopoietic cytokines for management of thrombocytopenia in MDS needs further evaluation. In addition, further determination of the effects of these therapeutic interventions on the patients quality of life is important.(116,119,120,128,129) Progress toward improving management of MDS has occurred over the past few years, and more advances are anticipated using these guidelines as a framework for coordination of comparative clinical trials.
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New prognostic markers in acute myeloid leukemia: perspective from the clinic.
Hematology Am Soc Hematol Educ Program
PUBLISHED: 07-09-2010
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Acute myeloid leukemia (AML) is a disease with marked heterogeneity in both response to therapy and survival. Cytogenetics, age, and performance status have long determined prognosis and therapy. The advent of molecular diagnostics has heralded an explosion in new prognostic factors, including gene mutations in KIT, FLT3 (Fms-like tyrosine kinase 3), NPM1 (nucleophosmin 1), and CEBPA (CCAAT enhancer-binding protein-?). Microarray technology can now identify unique gene expression signatures associated with prognosis. Similarly microRNA expression, single nucleotide polymorphism arrays, and DNA methylation signatures have recently described important new prognostic subgroups of AML, and are contributing to our understanding of AML disease biology. Combined with proteomic profiling, these technologies have helped identify new targets and signaling pathways, and may soon help to identify individual patients likely to benefit from specific therapies, including allogeneic hematopoietic cell transplantation. In summary, new clinical and molecular prognostic markers have begun to significantly improve our understanding of AML biology. We are now close to a time when we will be able to use these prognostic factors and technologies to identify new targets for therapy and to determine who may benefit from that therapy, and ultimately change how we treat individual patients with AML.
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NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: report from the Committee on the Epidemiology and Natural History of Relapse following Allogeneic Cell Transpla
Biol. Blood Marrow Transplant.
PUBLISHED: 04-06-2010
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Allogeneic hematopoietic stem cell transplantation (alloHSCT) is increasingly being used for treatment of hematologic malignancies, and the immunologic graft-versus-tumor effect (GVT) provides its therapeutic effectiveness. Disease relapse remains a cause of treatment failure in a significant proportion of patients undergoing alloHSCT without improvements over the last 2-3 decades. We summarize here current data and outline future research regarding the epidemiology, risk factors, and outcomes of relapse after alloHSCT. Although some factors (eg, disease status at alloHSCT or graft-versus-host disease [GVHD] effects) are common, other disease-specific factors may be unique. The impact of reduced-intensity regimens on relapse and survival still need to be assessed using contemporary supportive care and comparable patient populations. The outcome of patients relapsing after an alloHSCT generally remains poor even though interventions including donor leukocyte infusions can benefit some patients. Trials examining targeted therapies along with improved safety of alloHSCT may result in improved outcomes, yet selection bias necessitates prospective assessment to gauge the real contribution of any new therapies. Ongoing chronic GVHD (cGVHD) or other residual post-alloHSCT morbidities may limit the applicability of new therapies. Developing strategies to promptly identify patients as alloHSCT candidates, while malignancy is in a more treatable stage, could decrease relapses rates after alloHSCT. Better understanding and monitoring of minimal residual disease posttransplant could lead to novel preemptive treatments of relapse. Analyses of larger cohorts through multicenter collaborations or registries remain essential to probe questions not amenable to single center or prospective studies. Studies need to provide data with detail on disease status, prior treatments, biologic markers, and posttransplant events. Stringent statistical methods to study relapse remain an important area of research. The opportunities for improvement in prevention and management of post-alloHSCT relapse are apparent, but clinical discipline in their careful study remains important.
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Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkins lymphoma: results of a phase I study.
J. Clin. Oncol.
PUBLISHED: 03-22-2010
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PURPOSE Inotuzumab ozogamicin (CMC-544) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. This was a phase I study to determine the maximum-tolerated dose (MTD), safety, and preliminary efficacy of inotuzumab ozogamicin in an expanded MTD cohort of patients with relapsed or refractory CD22(+) B-cell non-Hodgkins lymphoma (NHL). PATIENTS AND METHODS Inotuzumab ozogamicin was administered intravenously as a single agent once every 3 or 4 weeks at doses ranging from 0.4 to 2.4 mg/m(2). Outcomes included MTD, safety, pharmacokinetics, response, progression-free survival (PFS), and overall survival. Results Seventy-nine patients were enrolled. The MTD was determined to be 1.8 mg/m(2). Common adverse events at the MTD were thrombocytopenia (90%), asthenia (67%), and nausea and neutropenia (51% each). The objective response rate at the end of treatment was 39% for the 79 enrolled patients, 68% for all patients with follicular NHL treated at the MTD, and 15% for all patients with diffuse large B-cell lymphoma treated at the MTD. Median PFS was 317 days (approximately 10.4 months) and 49 days for patients with follicular NHL and diffuse large B-cell lymphoma, respectively. CONCLUSION Inotuzumab ozogamicin has demonstrated efficacy against CD22(+) B-cell NHL, with reversible thrombocytopenia as the main toxicity.
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Improvements in survival after follicular lymphoma by race/ethnicity and socioeconomic status: a population-based study.
J. Clin. Oncol.
PUBLISHED: 05-18-2009
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A recent report suggested improvements in survival after follicular lymphoma (FL), but not for all racial/ethnic groups. To better understand the reasons for these FL survival differences, we examined the joint influences of diagnostic period, race/ethnicity, and neighborhood socioeconomic status (SES) on survival in a large population-based case series.
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Rituximab use and survival after diffuse large B-cell or follicular lymphoma: a population-based study.
Leuk. Lymphoma
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To determine whether reported socioeconomic disparities in survival might be related to treatment, we examined patient and tumor characteristics associated with receipt of rituximab and survival in the National Cancer Institutes Patterns of Care Studies (2003 and 2008) for patients with diffuse large B-cell (DLBCL) and follicular (FL) lymphoma. Patients with DLBCL (n = 1192) were less likely to receive rituximab if they were older, black or Asian, lacked private medical insurance, had impaired performance status, had no lactate dehydrogenase measurements or were diagnosed with stage I disease. Patients with FL (n = 476) were less likely to receive rituximab if they were unmarried or non-Hispanic white. Receipt of rituximab did not differ by neighborhood median income. Treatment with rituximab was associated with better survival for patients with DLBCL, but not patients with FL. Lower rituximab use in patients with DLBCL without private insurance suggests that previously identified socioeconomic disparities in survival may, in part, be explained by receipt of rituximab.
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Clinical presentation, diagnosis, and prognosis of myelodysplastic syndromes.
Am. J. Med.
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Myelodysplastic syndromes (MDS) comprise a group of underrecognized hematologic clonal malignancies with variable propensity for leukemic transformation that can present a diagnostic challenge because they lack hallmark symptoms. MDS can present with varying degrees of anemia, neutropenia, and thrombocytopenia, and at presentation can range from indolent to life threatening. The clinician should have a heightened level of suspicion when treating elderly patients and those with prior exposure to chemotherapy, radiation, and environmental toxins in the presence of unexplained cytopenias. Chronic anemia should not be considered a natural consequence of aging. Approximately 1 in 6 patients with unexplained anemia may have findings compatible with MDS, suggesting that MDS should be considered higher in the differential diagnosis. Primary care physicians are encouraged to conduct comprehensive evaluations to exclude non-MDS-related causes for persistent cytopenias. Patients with pancytopenia, bicytopenia, or any persistent and unexplained isolated cytopenia (and particularly unexplained macrocytic anemia) should be referred to a specialist to establish a diagnosis.
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Targeted therapy of acute myeloid leukemia in 2012: towards individualized therapy.
Hematology
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Advances in molecular diagnostics in acute myeloid leukemia (AML) have translated into significant advances in our understanding of disease prognosis and biology, and the identification of new targets for therapy. The best described of these are mutations in Fms-like tyrosine kinase 3, nucleophosmin 1, and CCAAT enhancer-binding protein-alpha in those with cytogenetically AML, which allow more accurate risk stratification and help better target patients who may benefit from allogeneic transplantation (specifically those with activating FLT3 mutation). Among the new targets identified for clinical trials are FLT3 mutation (a target for tyrosine kinase inhibitors), CD33 expression (a target of monoclonal antibodies and immunotoxins), aberrant methylation (target of hypomethylating agents), and overexpression of the chemokine receptor CXCR4 (a target for inhibition by small molecule or monoclonal antibody). We are advancing towards an era of personalized medicine in AML, and can now better identify specific patients who may benefit from specific therapies with less toxicity.
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Primary central nervous system B cell lymphoma with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma.
Int J Clin Exp Pathol
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B cell lymphoma with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma (DLBCL/BL) is a new lymphoma entity which is recognized in the current World Health Organization (WHO) classification (2008). We report a case of a primary central nervous system lymphoma (PCNSL) with findings consistent with DLBCL/BL. It is characterized by a very aggressive clinical course, and a widespread multifocal involvement of the CNS. Our case shows that a DLBCL/BL can manifest in the CNS alone without any systemic involvement.
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What is Visualize?

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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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

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.