Thomas E Witzig

..6-fold increase in activity (P = .004). CONCLUSION: Our data suggest serum BLyS levels are elevated in patients with familial B-CLL and that elevated BLyS levels correlate with the presence of a T at -871 in the BLyS promoter...

..3 months (95% CI: 5.3-14.0), the median event-free survival (EFS) was 5.3 months (95% CI: 3.9-11.0), and the median overall survival was 30.5 months (95% CI: 17.8-60.6). We conclude that rituximab can be safely added to standard DHAP...

..This review will discuss the rationale for and summarize the reported findings of initial and ongoing investigations of mTOR inhibitors and other small molecule targeted therapies in the treatment of lymphoma...

..Everolimus has single-agent activity in relapsed/refractory aggressive NHL and provides proof-of-concept that targeting the mTOR pathway is clinically relevant...

..To report the results of treating patients with orbital pseudolymphomas with the anti-CD20 monoclonal antibody rituximab...

..Therefore 90Y-ibritumomab tiuxetan radioimmunotherapy is a useful new treatment modality for patients with B cell NHL. Future trials are needed to define the optimal time in the disease course when this modality should be used...

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..This study presents the safety data from 349 patients in five studies of outpatient treatment with (90)Y ibritumomab tiuxetan...

..Given its efficacy in a wide range of hematologic malignancies, we conducted a phase II trial (NHL-001) of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL)...

..Current trials are testing RIT as initial therapy with rituximab maintenance, as adjuvant therapy after chemotherapy, or in high-dose protocols with stem-cell support...

..Based on results obtained to date, it appears that inhibitors of the PI3-K/mTOR pathway hold promise as single agents and in combination for hematologic malignancies...

..To examine the feasibility for identifying and enumerating cytokeratin positive (CK+) cells in the peripheral blood of breast cancer patients...

..Future trials will build on these results and determine at what point in the disease course this modality can best be utilized to maximize the benefits to the patient...

..Patients with MGUS with NHL should be administered chemotherapy. Screening the serum and urine of patients with lymphoplasmacytoid NHL would likely identify more patients with gamma- or mu-HCD...

..Ibritumomab tiuxetan radioimmunotherapy targets the same antigen as rituximab and has demonstrated efficacy in rituximab-naïve NHL. This study evaluated ibritumomab tiuxetan in the treatment of rituximab-refractory follicular NHL...

..Studies integrating these novel agents earlier in the disease course or in combination with each other will hopefully produce more durable responses with less toxicity...

..The goals of this study were to assess the overall response rate (ORR) to rituximab in this patient population and to determine the time-to-progression (TTP) and time-to-subsequent-chemotherapy (TTSC)...

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..The goal is to provide the hematologist/oncologist background information on these new agents and understand their current and potential role in the management of patients...

..This higher dose ProMACECytaBOM regimen can be given to older adult patients in an outpatient setting. Phase III studies would be required to determine if it produces a superior overall survival compared to other regimens...

..In addition, syndecan-1 is present on the less mature (CD45+) PC, and there is heterogeneity of expression within and between patients. The relevance of the bFGF bound to myeloma cells via syndecan-1 remains to be elucidated...

..This study tested whether temsirolimus (previously known as CCI-779), an inhibitor of the mammalian target of rapamycin kinase that regulates cyclin D1 translation, could produce tumor responses in patients with MCL...

..Future research is needed to delineate the signaling pathways used by the plasma cell after the adhesion receptor binds to its ligands. This information should help in designing more effective therapy for this fatal disease...

..The prognostic implications of a positive FC screen but a negative IM will require long-term patient follow-up...

..This study investigated the prognostic significance of TUNEL, bcl-2, p53, proliferation marker Ki-67 and DNA mismatch repair (MMR) status in patients with Dukes' stage B2 and C colorectal adenocarcinomas...

..To determine whether weekly epoetin alfa could improve hemoglobin (HgB) levels, reduce RBC transfusions, and improve quality of life (QOL) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy...

..In view of its excellent toxicity profile and novel mechanism of action, further studies in combination with other agents appear warranted. This trial is registered at www.clinicaltrials.gov as #NCT00082888...

..INTERPRETATION AND CONCLUSIONS: The median time to disease progression in patients with multiple myeloma who receive initial therapy with Thal/Dex and who do not undergo ASCT is 18 months...

..Thus, together these results define a novel signaling network in the WM tumor microenvironment controlling IgM secretion and suggest CCL5 as a potential target for the treatment of this disease...

..To determine the long-term effects of a combined regimen of lenalidomide and dexamethasone (Rev-Dex) on time to progression, progression-free survival, and overall survival (OS) in patients with multiple myeloma...

..3% vs 9.2%, P = .058) and peripheral neuropathy (10.4% vs 0.9%, P < .001). Len/dex appears well-tolerated and more effective than thal/dex. Randomized trials are needed to confirm these results...

..We conclude that the number of circulating PCs measured by flow cytometry in patients with newly diagnosed MM is an independent predictor of survival...

..4, and 6.5 months, respectively. CMCs at the time of ASCT is an independent prognostic factor and in combination with cytogenetics provides a powerful scoring system that stratifies patients and guides management...

..These results need confirmation in larger, prospectively designed studies...

..This assay has prognostic value in plasma cell proliferative disorders. There are limited data on serum FLC in B-cell malignancies...

..99, P = 0.009, overall survival-HR 1.93, P = 0.021). Elevated pretreatment serum IP-10 levels are therefore associated with an increased likelihood of disease relapse and an inferior survival in patients with DLBCL...

..To conduct in vitro studies as well as a phase 2 clinical trial in patients with smoldering or indolent multiple myeloma to determine if interleukin 1 (IL-1) inhibitors can delay or prevent active myeloma...

..CONCLUSIONS: Thalidomide is useful in the treatment of patients with relapsed multiple myeloma and produced durable response in approximately one third of patients, with median response duration of nearly 1 year...

..These correlations were not consistent across the total patient population, and therefore, could not be exploited to predict hematologic toxicity...

..Patients ended treatment due to progressive disease (18 patients), death (3) and other (2). The data suggest that imatinib is not an active agent in patients with relapsed or refractory multiple myeloma...

..Grade 3-4 nonhematologic adverse events were noted in 55% of patients. Randomized trials are needed to determine the role of early therapy in SMM...

..In AL patients, we saw limited activity of single-agent lenalidomide, but significant activity of the combination with dexamethasone, which warrants further investigation...

..CRd is an effective and well-tolerated regimen for upfront therapy of MM with high response rates and excellent 2-year OS, and is suitable for long-term therapy...

..The use of modern testing is imperative to characterize a patient's risk for progression. PET/CT plays an important role in the diagnostic work-up...

..ALC/AMC-DX is a low cost, already standarized, biomarker to predict clinical outcomes in NLPHL...

..These results provide a mechanistic rationale for a clinical trial of a combination of HDI and mTOR inhibitors for DLBCL...

..The goal of this analysis was to evaluate the therapy given to patients who relapsed after 90Y ibritumomab tiuxetan...

..015; OR = 0.68; 95% 0.56-0.84) remained noteworthy. Associations were similar for the common NHL subtypes. In summary, we provide evidence for a role of genetic variation in complement genes, particularly C5 and C9, and NHL risk...

..Outside a randomized clinical trial, these results present the strongest data supporting the role of PBSCT in selected patients with AL...

..Collectively, the data presented demonstrate a previously undescribed role for monocytes in T-cell lymphoproliferative disorders...

..Autologous stem cell transplant should be considered in all eligible patients with relapsed disease...

..To determine the clinical and laboratory features of newly diagnosed multiple myeloma...

..05), G-CSF (P = .03), and TNF-α (P = .04). pSTAT3 IHC in DLBCL tumors has the potential to identify patients for STAT3 pathway-directed therapy; Myc IHC is a potential marker for inferior EFS in GCB patients...

..Patients with progressive disease on DHAP should be considered for alternative salvage regimens or experimental therapy...

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..Radioimmunotherapy with radiolabeled monoclonal antibodies to CD20 produces a high response rate in patients with recurring non-Hodgkin lymphoma (NHL), but the durability of those remissions is not well defined...

..89 x 10(9)/l (5/39, 13%) (P < 0.0001). Multivariate analysis showed ALC to be an independent predictor for TTP. This study supports our hypothesis that a higher ALC predicts longer TTP following rituximab therapy...

..These targeted approaches to the treatment of malignancy, and lymphoma in particular, hold great promise...

..Given that high-frequency MSI (MSI-H) and diploidy are correlated, we determined whether they are independent prognostic variables...

..The incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 33%, 13%, and 3%, respectively. Reduced-dose ibritumomab tiuxetan is safe and well tolerated and has significant clinical activity in this patient population...

..02). Angiogenesis is increased in solitary plasmacytoma and is a significant predictor of progression to myeloma and provides further evidence of its importance in the pathogenesis of myeloma...

..We conclude that pomalidomide appears to be a valuable drug covering an unmet clinical need in patients with previously treated AL. The trial is registered at www.clinicaltrials.gov as NCT00558896...

..We conclude that the degree of bone marrow angiogenesis is a prognostic marker in patients with multiple myeloma and does not decrease significantly after therapy...

..Furthermore, BLyS was found to increase the viability and proliferation of malignant B cells from WM patients. Due to the role of BLyS in WM, strategies to inhibit BLyS may potentially have therapeutic efficacy in these patients...

..This phase II study was done to determine the efficacy and toxicity of IL-12 in combination with rituximab in patients with B-cell non-Hodgkin's lymphoma (NHL)...

..Four patients experienced a Grade 3 or higher pulmonary toxicity. Everolimus has single-agent activity in relapsed/refractory HL and provides proof-of-concept that targeting the mTOR pathway in HL is clinically relevant...

..5% vs. 4.2%, P = 0.129) were higher with Rd. Results of this case-matched analysis suggest that there is significant additive value when clarithromycin is added to Rd. Randomized phase III trials are needed to confirm these results...

..This set of recommendations represents such an effort-the development of a set of consensus guidelines by a group of experts to manage patients with newly diagnosed disease based on an interpretation of the best available evidence...

..These studies are the first to characterize APRIL-TACI-specific signaling and suggest a role for this ligand-receptor pair in FL B-cell growth...

..Others have reported that N-terminal pro-brain natriuretic peptide (NT-proBNP) is a valuable prognostic marker. We sought to develop a staging system for patients with AL...

..Recent data also suggest that vitamin D insufficiency is related to inferior prognosis in some cancers, although there are no data for NHL...

..Age > or = 40 years seems to add substantially to the risk. In patients who do not die from acute pulmonary toxicity, both OS and PFS seem equal, despite the omission of bleomycin...

..07). The expression of CD138, CD56 and CD54 were higher among the CD45- PCs. This study demonstrates important biological correlates of CD45 expression on myeloma cells...

..Additional studies are needed to further define the role of bevacizumab in the management of this group of patients...

..01; IL-6, 24% versus 70% at 2 years, P = 0.01). None of the other parameters predicted response or PFS, and no significant changes in cytokine levels occurred with therapy...

..The use of (90)Y ibritumomab tiuxetan does not preclude subsequent therapy with other conventional treatment options...

..Clinical trials are warranted in these diseases to learn the therapeutic benefit of anti-CD52 immunotherapy...

..The outcome of these studies will be helpful in deciding how best to integrate this new modality into the treatment paradigm of NHL...

..CDDO-Im also inhibited survival pathways that have been shown to be important in WM. Overall, our data suggest that ST are likely to provide therapeutic efficacy for WM patients...

..96 x 10(9)/l (N=46) (P<0.0001). This study suggests that lymphopenia measured by ALC can be used as a marker to assess risk of DLBCL relapse during routine follow-up after standard chemotherapy...

..We conclude that stromal cell IL-8 production parallels MM disease activity, is IL-1beta induced, and correlates with bone marrow angiogenesis...

..Substantial clinical improvement and long-term survival are possible...

..The objective of this study was to test a low dose of (25 mg weekly) of the mammalian target of rapamycin kinase inhibitor temsirolimus for patients with relapsed mantle cell lymphoma (MCL)...

..CONCLUSIONS: 2ME2 has significant activity against myeloma cell lines and primary myeloma cells both in vitro and in an animal model. Clinical trials are required to evaluate its activity in patients with MM...

..In summary, we found that BLyS and its receptors represent a potentially important therapeutic target in B-cell lymphoma...

..007. BM MVD at the time of initial diagnosis is an important prognostic factor for OS and PFS in patients undergoing autologous transplantation as frontline therapy for myeloma...

..65). The lack of response to initial induction therapy does not appear to preclude a good response to SCT. We recommend that patients with primary refractory MM be offered early SCT...

..Atacicept (TACI-Ig), a recombinant fusion protein that inhibits both B-lymphocyte stimulator and a proliferation-inducing ligand, may be a novel treatment for B-cell malignancies...

..Maximizing RIT benefit requires healthcare providers to utilize algorithms assisting with treatment decisions...

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..The aim of this study was to learn if inhibition of the mammalian target of rapamycin (mTOR) would produce tumor responses...

..For diffuse NHL, 64% of the cases were nodal, and there was no association of HRT with either nodal or extra-nodal sites. These data suggest that HRT is a risk factor for follicular NHL but not for diffuse or small lymphocyte NHL or CLL...

..ALC-R was an independent prognostic factor for OS [RR = 0.4, P < 0.01] and PFS [RR = 0.5, P < 0.005]. ALC-R predicts survival suggesting that host immunity is an important variable predicting survival in first relapsed DLBCL...

..This retrospective analysis was conducted to determine the number of patients achieving long-term durable responses with (90)Y ibritumomab tiuxetan treatment...

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..The kidney is affected by immunoglobulin light chain amyloidosis (AL) in more than 50% of patients who present with the disease, but long-term predictors for and outcomes after renal replacement therapy are not well described...

..Using this system, 49%, 38%, and 13% of patients were in stage I, stage II, and stage III, respectively. Determining levels of circulating biomarkers may be the most powerful tool for staging patients with AL undergoing PBSCT...

..The actuarial risk of myelodysplasia development at ten years was 18%. As the survival of patients with plasma cell disorders improves, myelodysplasia may be a more common cause of morbidity and mortality for this group...

..Older age, however, is associated with proximal tumor site independent of MSI status...

..We investigated whether treatment with multiple alkylating agents improved the response rate or survival time, compared with melphalan and prednisone therapy...

..Overall response rate was 94% including seven very good partial responses and five complete responses. Addition of 153Sm EDTMP to melphalan conditioning appears to be safe, well-tolerated and worthy of further study...