Svetomir N Markovic

..In this review we will discuss the advantages and limitations of the two new approved agents, current clinical trials designed to overcome these limitations, and future clinical trials that we feel hold the most promise...

..This knowledge might also open the way for improved timing of treatment(s) for improved clinical efficacy...

..We conducted a phase II trial evaluating the clinical efficacy of ABT-510 and its effects on biomarkers of angiogenesis and immunity in patients with metastatic melanoma (MM)...

..Herein we review the state-of-the-art in metastatic melanoma diagnostics and therapeutics with particular emphasis on multi-disciplinary clinical management...

..In this report, the authors present the results from a clinical trial that evaluated the safety and immunologic efficacy of the MPS160 vaccine in patients with metastatic melanoma...

..Bortezomib is a proteasome inhibitor with manageable clinical toxicity and laboratory evidence of anti-melanoma activity. Therefore, it was considered for clinical testing in patients with metastatic melanoma...

..The simplicity and reliability of the assay provide for high-throughput applications and automation. The utility and application of this method are discussed...

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..To improve the clinical and immunologic efficacy of therapy without compromising patient safety, we performed a further dose escalation trial in patients with metastatic melanoma...

..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...

..These results provide evidence that vaccination with antigen-pulsed DC with CpG ODN as adjuvant can lead to effective tumor regression and long-term survival in a murine model of colon carcinoma...

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

..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...

..Increasing evidence shows chemotherapy in combination with vascular endothelial growth factor (VEGF) inhibition is a clinically active therapy for patients with metastatic melanoma (MM)...

..This study suggests that baseline N/L ratio at diagnosis is a simple, inexpensive,standardized prognostic factor to assess clinical outcomes in DLBCL patients treated with R-CHOP...

..AMD3100, a CXCR4 antagonist, mobilizes CD34+ stem cells in patients with NHL undergoing ASCT. We sought to study the impact of AMD3100 on A-ALC collection in patients with NHL undergoing ASCT...

..The present findings have practical implications for the propagation of antigen-specific T-cell lines in vitro and could be useful for expansion of therapeutic T cells for adoptive transfer...

..These findings bear clinical significance for the design of peptide-based therapeutic vaccines for human cancer patients...

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

..These results further support the central role of non-neoplastic myeloid-lineage cells in follicular lymphoma biology...

..This study was performed to evaluate the addition of temozolomide (TMZ) to whole brain radiotherapy (WBRT) for brain metastases from melanoma...

..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...

..7, P < .0001) NK-15. Multivariate analysis showed only NK-15 as a prognostic factor for survival, suggesting that the survival benefit observed by IL-15 is most likely mediated by enhanced NK cell recovery post-APHSCT...

..A phase 1 trial of this 3-drug combination reported that 6 of 28 patients treated with bortezomib followed by paclitaxel and carboplatin achieved a partial response (including 2 of 5 patients with metastatic melanoma)...

..Therefore, in patients with metastatic melanoma, the combination of chemotherapy with an agent that specifically targets VEGF might be able to control tumor growth and progression more effectively than chemotherapy alone...

..Although much work remains to be done to improve the survival of patients with melanoma, clinically meaningful results seem within reach...

..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...

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..These findings have implications for the design of T cell-based cancer immunotherapy...

..IL-2 and IFN-alpha up-regulated NK cell activity at 14 days post ASCT. They may be useful as immunomodulators as early as 14 days post ASCT to eradicate or control minimal residual disease...

..We, therefore, studied whether the peripheral blood absolute lymphocyte count/absolute monocyte count ratio at diagnosis affects survival in classical Hodgkin's lymphoma...

..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...

..ABI-007 is an albumin-bound formulation of paclitaxel that has demonstrated single-agent activity against metastatic melanoma...

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

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

..These unconventional roles for Th lymphocytes, which require direct cell-to-cell communication with CTLs, are clear examples of how versatile these immunoregulatory cells are...

..These results suggest the potential use of this vaccination strategy for future clinical applications...

..Also because STEAP-292.2L is a more immunogenic peptide able to induce CTL recognition of these STEAP-containing tumors and may have potential as an antitumor peptide vaccine...

..These findings suggest a novel role of Th cells as pAPC for the development of memory immune responses...

..0 x 10(9)/L (N=122) (P < .0001). This study suggests that new-onset lymphopenia measured by ALC can be used as marker to assess risk of DLBCL relapse during routine follow-up for after APHSCT...

..These immunologic changes may explain the successful metastasis of melanoma in the midst of the immune environment of the sentinel lymph node, and lend insights into the mechanisms of lymphatic metastases in other solid malignancies...

..These characteristics can be modified and continued evaluation of immunomodulatory drugs, vaccination strategies and cellular therapies to delay/prevent disease progression are warranted...

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

..CONCLUSIONS: Human HTLs are capable of effectively recognizing epitopes derived from PSMA. The information presented here should facilitate the design of improved vaccination strategies for prostate cancer...

..Multivariate analysis demonstrated A-ALC as an independent prognostic indicator for OS and TTP. These results indicate that an infused dose of autograft lymphocytes significantly impacts clinical outcome post-APHSCT in MM...

..Herein we present our institutional treatment algorithm, which allows for individualization based on the patient's presentation...

..The increase in T regulatory cells associated with interleukin-2 treatment suggests that interleukin-2 may be immunosuppressive in this setting...

..This study showed that, in newly diagnosed MM, ALC is an independent prognostic factor for OS, suggesting a significant role of host immune status in the survival of MM...

..These results support potential clinical trials of the low-dose cytokine combination as adjuvant therapy for melanoma...

..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...

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

..Individualized conventional chemotherapy delivery by synchronizing treatment with pre-existing patient-specific biorhythms may improve clinical outcomes in metastatic melanoma...

..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...

..This article will review the use of peptide-based vaccines for the treatment of cancer by inducing antitumor T-lymphocyte responses...

..In conclusion, ALC > or = 500 cells/microl on day 15 post-ASCT was associated with significantly better survival in patients with metastatic breast cancer, suggesting the importance of early immune recovery post-ASCT in these patients...

..Multivariate analysis demonstrated ALC > or = 500 cells/microl at all time points to be an independent prognostic factor for survival. Our data suggest a critical role of lymphocyte (immune) recovery on survival after IC in AML...

..These data suggest that apheresis instrument settings should be optimized to collect CD34(+) cells as well as an A-ALC target, with direct impact on survival post-APHSCT...

..Further, we discuss possible mechanisms responsible for the suboptimal central nervous system response observed in these patients and alternative therapies for patients with melanoma metastatic to the brain...

..A subset of melanoma patients appear to lack an organized immune response to the tumor, which portends a poor prognosis...

..81, P = .015)). These findings suggest the possibility of exploring anti-TGF-β therapy to restore NK function in melanoma...

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

..The knowledge gained from analyzing similarities and differences between the physiologic state of pregnancy and the pathologic state of cancer could lead to identification of new potential targets for cancer therapeutic agents...

..The focus of this review is to summarize the emerging therapies and investigational agents in the treatment of melanoma over the last 5 years...

..Patients with metastatic melanoma (MM) have very few therapy options. Based on reports of responses to paclitaxel and carboplatin (PC), 31 patients with MM were treated with PC...

..By stimulating DCs with two distinct activation signals, a previously unrecognized phenotype exhibiting augmented antigen-presenting functions was obtained...

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..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...

..Herein we provide a succinct summary of the current progress in this field in order to guide future investigations...

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

..Part 2 (which will appear in the April 2007 issue) will review melanoma staging, prognosis, and treatment...

..e., epitope spreading). These results suggest that similar strategies should be followed for conducting clinical studies in patients...

..These results underline the importance of demonstrating antitumor reactivity of peptide-induced CTLs for the selection of epitopes destined to become immunotherapeutic for prostate cancer...

..Such alterations induced by androgen deprivation may have implications for enhancing immune responses to immunotherapy and for accelerating the recovery of the immune system following chemotherapy...

..Our study was directed at identifying antigenic T-lymphocyte epitopes at the PAX3/FKHR translocation point area...

..This prognostic score was independent of the IPI and added to its ability to identify high-risk patients...

..Based on preclinical data showing synergy with taxane and platinum compounds, a phase II combination trial in metastatic melanoma patients is ongoing...

..The AMC/ALC score was able to further stratify DLBCL clinical outcomes by COO. The AMC/ALC score was independent of COO and added to its ability to identify patients with high-risk disease...

..In summary, the lack of significant antitumor activity of KW-2189 and its associated toxicity suggest that further testing of this regimen in patients with stage IV melanoma is not warranted...

..Herein, we review some of the recent advances in novel therapeutic developments for the treatment of metastatic melanoma...

..These results are relevant for the design of a simple, inexpensive and widely applicable peptide-based vaccine to prevent PTLD in solid organ transplant patients...

..These results suggest that T cells are able to interact with other T cells to regulate immune responses by presenting MHC peptide complexes that have been snatched away from nearby APC...

..Aerosol delivery of GM-CSF is feasible, safe, and possibly effective. Aerosol cytokine delivery may achieve effective immunological activation against cancer in the lung and is worthy of further study...

..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...

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..To understand this discrepancy, we attempted to define immune homeostasis of 209 patients with melanoma across stages of disease relative to normal controls...

..Autologous HPC collection focus has been CD34+ cell yield but product content of other cells is important for patient survival, complications, and resource utilization...

..A second population of cells was strongly immunoreactive for keratin (wide-spectrum polyclonal antibody) and BerEp4. To our knowledge, this is the first description of a malignant basomelanocytic tumor complicated by metastatic melanoma...

..Chemotherapy may be gaining a role with newer agents that penetrate the blood-brain barrier. Combined modality therapy appears to be the future direction of treatment of multiple metastases...

..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...

..Newer treatments, including anti-CD30 monoclonal antibodies, show promise. However, further study is needed to develop optimal therapeutic strategies...

..This is due, at least in part, to effects of VEGF on antigen presenting cell (APC) function. We therefore compared immune polarity changes in mouse models of cancer with those seen in human patients...

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..In this study, we examine the type of help that CD4 T cells may provide and propose a model of Th cell-CTL interaction that reduces CTL death. Our results show a novel role for Th cells in the maintenance of CTL responses...

..Together, these results indicate that CpG therapy could be promising as a single agent for the treatment of some tumors such as cervical carcinoma...

..It produced clinical improvement and decreased the number of circulating Sézary cells in a previously ECP-refractory patient...

..In one patient, we have evidence of upregulation of melanoma-specific cytotoxic T-cells. Further study is warranted to understand the impact of this therapy on the natural history of metastatic cancer...

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..These findings underline the importance of antigen-specific helper T lymphocytes for the regulation and maintenance of CTL immunity, and have implications for the design of therapeutic vaccines for cancer...

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..Future issues in design of aerosol cancer treatment include identifying effective combinations of agents, schedules, and use of aerosol therapy at home as adjuvant therapy...

..If successful, this "proof-of-principle" clinical trial will justify further development of B7-DC XAb as a cancer therapeutic with potential universal application for all malignant disorders. ..