Stephen Ansell

..For patients who fail HDCT with ASCT, brentuximab vedotin, palliative chemotherapy, non-myeloablative allogeneic transplant or participation in a clinical trial should be considered...

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..To determine the safety, maximum-tolerated dose (MTD), and efficacy of MDX-060 in patients with relapsed or refractory CD30+ lymphomas, sequential phase I and II studies were performed...

..However, a randomized controlled trial will be required to determine whether the addition of IL-12 adds to the efficacy of rituximab in B-cell NHL...

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..Patients with these histologies who subsequently progress after salvage chemotherapy and autologous stem cell transplantation (ASCT) have very limited treatment options and are in need of novel effective therapies...

..We conclude that inhibition of survivin expression is an attractive therapeutic strategy in aggressive non-Hodgkin's lymphomas, and that combining survivin ASO with rituximab may enhance the efficacy of this approach...

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

..A significant increase was seen in the serum levels of BLyS (P = 0.0001) after rituximab therapy. The increase was independent of genetic variability in the BLyS gene...

..Blocking anti-CTLA-4 monoclonal antibodies improves host resistance to immunogenic tumors, and the anti-CTLA-4 antibody ipilimumab (MDX-010) has clinical activity against melanoma, prostate, and ovarian cancers...

..Future studies will therefore be needed to explore the efficacy of combinations of these agents and to develop a rational strategy for their use...

..Patients with chemoresistant disease or whose disease relapses subsequently should be treated with novel experimental therapies...

..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)...

..We therefore tested its efficacy and toxicity in combination with rituximab (an antiCD20 antibody) in patients with relapsed or refractory mantle cell lymphoma...

..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...

..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...

..For patients who fail HDCT with ASCT, palliative chemotherapy, nonmyeloablative allogeneic transplant, or participation in a clinical trial should be considered...

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

..These data suggest that IL-12 and rituximab is an active combination and further studies of this combination in B-cell non-Hodgkin lymphoma are warranted...

..New therapies are clearly needed for these patients...

..Most patients could be salvaged with immunomodulatory drugs or radiation. The 5-year survival is 94%. Herein, we describe a system of monitoring response and progression among patients with POEMS after ASCT...

..The subset of patients without lytic lesions or t(11;14) but with immunophenotypic features suggestive of MM need further study...

..The outcome may not be different from that of younger patients in terms of TRM and EFS...

..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...

..Methods are needed to reduce treatment-related toxicity so that more patients can receive full-dose conditioning chemotherapy...

..04). Topotecan can safely be dose escalated to 4.5 mg/m(2)/d in combination with CY, carboplatin and AHSCT. This trial is registered at ClinicalTrials.gov as NCT00652691...

..In conclusion, ALC is correlated with clinical outcome and requires further study. (Blood. 2001;98:579-585)..

..Nevertheless, consistent with reported experience of others, overall outcomes remain less than optimal and unpredictable...

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

..0001, respectively). Multivariate analysis demonstrated A-ALC to be an independent prognostic indicator for OS and PFS. These data support our hypothesis that ALC-15 and survival are dependent upon the dose of infused A-ALC in NHL...

..Our data also show that IFN-lambda1 induces phosphorylation of STAT1, STAT3 and Erk. Taken together, our results suggest that IFN-lambda1 may regulate myeloma cell biology and could prove to be therapeutically important...

..01). Patients with early, high IPI-R relapse after first-line therapy have a dismal outcome with SCT and should receive experimental therapies...

..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...

..In addition, the low number of in vitro or in vivo models significantly challenges extensive analysis. In this manuscript, we review the molecular basis of this disease...

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..This finding provides a strong rationale for the investigation of cellular immunotherapy in B-cell NHL...

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..The objective of this study was to test cladribine (2-CDA) alone and in combination with rituximab in patients with mantle cell lymphoma (MCL)...

..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...

..To review the characteristics and outcomes of amyloidosis patients treated with high-dose chemotherapy and stem cell reconstitution...

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

..The overall 100-day survival rate was 98.9%. Our experience shows that outpatient transplant is feasible for all patients with multiple myeloma and results in shorter hospital stays and low treatment-related mortality rates...

..All surviving patients displayed excellent performance status without ongoing chronic graft versus host disease. We conclude that ASCT is an effective salvage therapy for fludarabine-refractory CLL but late relapses can occur...

..These data support a role for germ line variation in immune genes, particularly genes associated with a proinflammatory state, as predictors of late survival in DLBCL...

..Taken together, these studies reveal a novel role for NHL B cells in the development of intratumoral regulatory T cells...

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..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)...

..Unraveling the mechanisms of the syndrome both in the context of ASCT and in general are challenges for the future...

..This is the first study confirming the ALC-15 survival role prospectively and identifying NK cells as the key ALC-15 lymphocyte subset affecting survival after APHSCT...

..Common variation in host immune genes warrants further evaluation as a promising class of prognostic factors in follicular lymphoma...

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..In conclusion, tIPI at the time of histological transformation is an important predictor of OS. A time to transformation > 4 years from diagnosis is associated with better OS...

..004) and rituximab therapy (P = 0.03) were significant. Low IPI and rituximab therapy led to an improved overall survival in patients with CD20-positive PTLD...

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

..In conclusion, further studies of this schedule of TOPA in this patient population are not recommended due to the lack of tumor response and significant hematologic toxicity...

..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...

..To our knowledge, this is the first published report that shows the strong association of Rai stage with CXCR4 and CCR7 expression levels in B-CLL cells...

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

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

..To assess the activity of von Willebrand factor-cleaving protease (vWF-CP) in patients with thrombotic thrombocytopenic purpura (TTP) complicating bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT)...

..5 x 10(9) cells/l ("not yet reached" versus 42 months, P < 0.0001; 57 versus 15 months, P < 0.002 respectively). Thus, ALC recovery on day 15 post ASCT in HD is associated with better survival and requires further study...

..In vitro, imatinib mesylate caused variable degrees of growth suppression of myeloid and erythroid progenitors that unfortunately did not translate into clinical benefit...

..A lower dose of the drug might be more tolerable without compromising therapeutic value. Patients with PTMM and/or markedly increased circulating CD34+ cell counts might be susceptible to thalidomide-induced thrombocytosis...

..This study describes a novel technique that identifies proteins dysregulated in MCL...

..The relationship of ALC-15 with clinical outcomes in primary systemic amyloidosis is unknown...

..Here we focus on APRIL, exploring its normal and pathological functions, and comparing the therapeutic molecules currently under development that target BLyS/BAFF alone, or APRIL and BLyS/BAFF together...

..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...

..Achievement of FLC response was a better predictor of survival than achievement of complete hematologic response or normalization of the FLC ratio. FLC measurements both before and after PBSCT are important predictors of patient outcome...

..0025, respectively). Multivariate analysis demonstrated TILC to be an independent prognostic indicator for OS and PFS. These findings suggest that the immune status of the host at the time of aphaeresis may predict survival after ASCT...

..677, P < 0.0001). These data suggest a critical role of FL patients' immune status at diagnosis on survival...

..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...

..0001). Multivariate analysis demonstrated K-ALC recovery post-ASCT to be an independent prognostic indicator for OS and PFS. These data support our hypothesis that the K-ALC post-ASCT is associated with clinical outcome in NHL...

..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...

..Taken together, these data indicate that human lymphoma B cells are sensitive to autologous CTL-mediated cell death but are protected by the inhibitory function of intratumoral T(reg) cells...

..The current review should serve as an introduction to the subject for clinician investigators, physicians and medical scientists in training, practicing clinicians, and other students of medicine...

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..Taken together, our results suggest that T(reg) cells are highly represented in the area of B-cell NHL and that malignant B cells are involved in the recruitment of these cells into the area of lymphoma...

..This is the first identification of ligands that selectively activate TACI without simultaneously triggering BCMA or BAFF-R. This finding may help explain the alternative outcomes of signaling from this family of receptors in B cells...

..CONCLUSION: A prognostic model has been developed for PTLD patients using one center's 30 years of experience. We propose additional confirmation and validation of these prognostic factors in larger prospective studies...

..To assess the efficacy of radiotherapy (RT) in the treatment of primary non-Hodgkin lymphoma (NHL) of the parotid gland...

..The purpose of this study was to assess the value of FDG PET/CT in this aggressive type of non-Hodgkin lymphoma...

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..This treatment combination will lead to a novel therapeutic approach to modulating Treg cells that will result in clinical benefit for patients with B-cell NHL. ..