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1.  The use of FDG-PET in diffuse large B cell lymphoma (DLBCL): predicting outcome following first line therapy 
Cancer Imaging  2014;14(1):34.
Positron emission tomography (PET) using 18fluoro-2-deoxyglucose (FDG) has become a standard clinical tool for staging and response assessment in aggressive lymphomas. The use of PET scans in clinical trials is still under exploration, however. In this review, we examine current data regarding PET in DLBCL, and its potential applicability to development of a surrogate endpoint to expedite clinical trial conduct. Interim PET scanning in DLBCL shows mixed results, with qualitative assessment variably associated with outcome. Addition of quantitative assessment might improve predictive power of interim scans. Data from multiple retrospective studies support that PET-defined response at end of treatment correlates with outcome in DLBCL. Optimal technical criteria for standardization of acquisition and criteria for interpretation of scans require further study. Prospective studies to define the correlation of PET-defined response and time-dependent outcomes such as progression free survival (PFS) and overall survival (OS), critical for development of PET as a surrogate endpoint for clinical trials, are ongoing. In conclusion, evolving data regarding utility of PET in predictcing outcome of patients with DLBCL show promise to support the use of PET as a surrogate endpoint in clinical trials of DLBCL in the future.
doi:10.1186/s40644-014-0034-9
PMCID: PMC4264252  PMID: 25608713
Lymphoma; Surrogate endpoint; Positron emission tomography
2.  Mechanism-Based Epigenetic Chemosensitization Therapy of Diffuse Large B Cell Lymphoma 
Cancer discovery  2013;3(9):1002-1019.
Although aberrant DNA methylation patterning is a hallmark of cancer, the relevance of targeting DNA methyltransferases (DNMT) remains unclear for most tumors. In diffuse large B-cell lymphoma (DLBCL) we observed that chemo-resistance is associated with aberrant DNA methylation programming. Prolonged exposure to low-dose DNMT inhibitors (DNMTIs) reprogrammed chemo-resistant cells to become doxorubicin sensitive without major toxicity in vivo. Nine genes were recurrently hypermethylated in chemo-resistant DLBCL. Of these, SMAD1 was a critical contributor, and reactivation was required for chemosensitization. A phase I clinical study was performed evaluating azacitidine priming followed by standard chemoimmunotherapy in high-risk newly diagnosed DLBCL patients. The combination was well tolerated and yielded a high rate of complete remission. Pre and post azacitidine treatment biopsies confirmed SMAD1 demethylation and chemosensitization, delineating a personalized strategy for the clinical use of DNMTIs.
doi:10.1158/2159-8290.CD-13-0117
PMCID: PMC3770813  PMID: 23955273
Non-Hodgkin lymphoma; epigenetic; DNA methylation; DNMT inhibitor; chemoresistance
3.  NK/T cell non-Hodgkin lymphoma in a HIV-positive patient 
Journal of Hematopathology  2010;3(1):35-40.
NK/T lymphomas have rarely been reported in HIV/AIDS patients. Here we report a case of a 37-year-old woman, with AIDS and a recent diagnosis of Kaposi sarcoma in a mesenteric lymph node, who presented with extra-ocular nerve palsies and gastrointestinal bleeding. A small intestine resection specimen revealed an extra-nodal NK/T cell lymphoma, nasal type. The unique presentation of this rare and aggressive lymphoma in the setting of AIDS and Kaposi sarcoma underscores the importance of maintaining a broad differential diagnosis when evaluating a malignant neoplasm from a HIV-positive patient.
doi:10.1007/s12308-010-0057-5
PMCID: PMC2883910  PMID: 21373175
Natural killer/T cell lymphoma; AIDS; HIV; Kaposi sarcoma
4.  Durable Responses with the Metronomic Regimen RT-PEPC in Elderly Patients with Recurrent Mantle Cell Lymphoma 
Cancer  2010;116(11):2655-2664.
BACKGROUND
Targeting the tumor microenvironment and angiogenesis is a novel lymphoma therapeutic strategy. We report safety, activity and angiogenic profiling with the RT-PEPC regimen (rituximab with thalidomide, and prednisone, etoposide, procarbazine and cyclophosphamide) in recurrent mantle cell lymphoma (MCL).
METHODS
RT-PEPC includes induction (months 1–3) of weekly rituximab × 4, daily thalidomide (50 mg) and PEPC, then maintenance thalidomide (100 mg), oral PEPC titrated to neutrophil count, and rituximab every 4 months. Endpoints included safety, efficacy, quality of life (QoL), and translational studies including tumor angiogenic phenotyping, plasma VEGF and circulating endothelial cells.
RESULTS
Twenty-five pts were enrolled (22 evaluable) with median age 68 yrs (range 52–81), 24 (96%) stage III/IV, 18 (72%) IPI 3–5, 20 (80%) high risk MIPI, median 2 prior therapies (range 1–7), and 15 (60%) bortezomib progressors. At a median follow-up of 38 months, ORR was 73% (32% CR/CRu, 41% PR, n=22) and median PFS 10 months. Four CRs are ongoing (6+, 31+, 48+ and 50+ months). Toxicities included grade 1–2 fatigue, rash, neuropathy and cytopenias including grade 1–2 thrombocytopenia (64%) and grade 3–4 neutropenia (64%). Two thromboses and 5 grade 3–4 infections occurred. QoL was maintained or improved. Correlative studies demonstrated tumor autocrine angiogenic loop (expression of VEGFA and VEGFR1) and heightened angiogenesis and lymphangiogenesis in stroma. Plasma VEGF and circulating endothelial cells trended down with treatment.
CONCLUSIONS
RT-PEPC has significant and durable activity in MCL, with manageable toxicity and maintained QoL. Novel low-intensity approaches warrant further evaluation, potentially as initial therapy in elderly patients.
doi:10.1002/cncr.25055
PMCID: PMC3004744  PMID: 20235190

Results 1-4 (4)