Deborah A Thomas

..Arsenic trioxide (ATO) is an effective agent for the salvage of patients with recurrent APL, and gemtuzumab ozogamicin (GO) has shown activity in patients with APL...

..A summary of the preliminary results of ongoing clinical trials is presented, and the future directions of thalidomide research in the oncology are discussed...

..Incorporation of monoclonal antibodies directed against CD20 into frontline chemotherapy regimens warrants investigation...

..Appropriate pharmacologic investigation, use of antigen modulation, and assessments of soluble antigen levels should be considered with future clinical trial s of MoAb's in HCL to optimize therapeutic strategies...

..Thalidomide is a putative antiangiogenesis agent with activity in several hematologic malignancies...

..In animal models, the encapsulation of vincristine into sphingomyelin liposomes or "sphingosomes" for injection (SV) has improved efficacy compared with conventional vincristine...

..Other modifications of the program could include incorporation of monoclonal antibodies and/or nucleoside analogs, particularly for slow responders or those with residual mediastinal disease...

..An increasing number of unique active new chemotherapeutic and biological agents are available for study. This chapter reviews new agents with the potential to be incorporated into therapeutic strategies for the treatment of ALL...

..Thalidomide analogues with more potent immunomodulatory activities and more favourable toxicity profiles may offer more promise as anti-AML therapy...

..Molecular CRs were achieved in both groups (SCT or no SCT). Outcome with hyper-CVAD and imatinib mesylate appears better than with prior regimens; continued accrual and longer follow-up of the current cohort is needed...

..Rituximab has significant activity and minimal toxicity in HCL and warrants further study. Rituximab should be explored further in HCL with regard to eradication of minimal residual disease and in combination with nucleoside analogs...

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..Vincristine (VCR) sulfate liposomes injection (VSLI) is a sphingomyelin/cholesterol nanoparticle encapsulated VCR formulation that improves the pharmacokinetic profile of VCR without augmenting neurotoxicity...

..quot; This review presents a comprehensive overview of the previously designated provisional entity of atypical BL/BLL in conjunction with a detailed comparison with BL and DLBCL...

..The role of angiogenesis in hematological malignancies, the rationale for the use of angiosuppressive therapy for these entities, and the status of novel antiangiogenic agents in clinical trials are discussed...

..Optimal use of these novel agents in the treatment schema of Ph-positive ALL will be paramount in ensuring continued success in the eradication of this disease...

..Improved outcome with the newer intensive chemotherapy regimens and the role of modalities such as autologous intensification, allogeneic bone marrow transplant, and radiotherapy are discussed...

..Preliminary data regarding the use of rituximab in frontline therapy for CD20- positive precursor B-cell ALL suggest its use may also be beneficial, particularly for the younger subsets...

..Herein, the available data regarding the prevalence and clinical relevance of MRD after therapy for HCL is reviewed...

..5 g/m2 IV on Days 1 and 2) to the standard hyper-CVAD regimen (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high dose methotrexate and cytarabine) would improve outcome...

..CONCLUSIONS: The addition of rituximab to hyper-CVAD may improve outcome in adult BL or B-ALL, particularly in elderly patients...

..A prospective, randomized study was conducted in patients aged 50 years or older with untreated, adverse karyotype, acute myeloid leukemia (AML) to assess troxacitabine-based regimes as induction therapy...

..The authors conducted a phase 1/2 study of tipifarnib in combination with idarubicin and cytarabine (IA) in 95 patients with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome...

..The combination of rituximab and alemtuzumab is feasible, has an acceptable safety profile, and has clinical activity with a short course in a group of patients with poor prognoses...

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..Grade 3/4 toxicities, including sepsis, neutropenic fever, and nausea/vomiting, were equivalent with MFAC and IA. CONCLUSIONS: Post-remission therapy with MFAC is feasible and well tolerated in patients with AML...

..Disease characteristics may potentially be used to identify patients that are more likely to benefit from such additional therapy...

..CONCLUSIONS: The study regimen had activity and significant toxicity in patients with RS or fludarabine-refractory CLL. It was not clearly better compared with hyper-CVXD alone in this patient population...

..04), and lower 4-week induction mortality (4% versus 15%, P =.07). Imatinib mesylate is currently being tested in combination with other drugs to improve the prognosis for blast-phase CML...

..4 months vs 5.8 months; P = .1). Clofarabine plus low-dose cytarabine has a higher response rate than clofarabine alone with comparable toxicity. This trial is registered at www.clinicaltrials.gov as no. NCT00088218...

..Pilot studies showed that alemtuzumab is active in lymphoproliferative disorders. The authors conducted a Phase II trial to evaluate the efficacy and safety of alemtuzumab in advanced or refractory chronic lymphoproliferative disorders...

..The objective of this study was to investigate the efficacy and safety of alemtuzumab, the humanized anti-CD52 monoclonal antibody, in patients with B-cell chronic lymphocytic leukemia and residual disease after chemotherapy...

..The 3-month cytogenetic response to imatinib mesylate refined the prognostic relevance of such studies in patients on imatinib mesylate therapy...

..5% per year for the third year onward. In a multivariate analysis of patients receiving fludarabine-based therapy at our center, FCR therapy emerged as the strongest independent determinant of survival...

..We conclude that imatinib mesylate effectively controlled CML that recurred after allogeneic SCT, but it was associated with side effects including myelosuppression and recurrence of severe GVHD...

..We aimed to define an accelerated phase (AP) in MF by characterizing disease features that can identify patients with median overall survival of <or= 12 months at any time in the disease course...

..Thus, there is little evidence to suggest that GO with or without IL-11 should be used instead of IA in older patients with newly diagnosed AML or myelodysplastic syndrome...

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..We identified pretreatment and treatment-associated factors that were associated with higher major cytogenetic response rates and with improved survival...

..Liposomal cytarabine given via intrathecal route concomitantly with systemic chemotherapy that crosses the blood-brain barrier such as high-dose MTX and cytarabine can result in significant neurotoxicity...

..Troxacitabine has significant single-agent activity. This study was conducted to define the dose-limiting toxicities (DLTs) of its combination with cytarabine (ara-C), idarubicin, or topotecan...

..Imatinib mesylate, a specific Bcr-Abl tyrosine kinase inhibitor, has shown encouraging activity in chronic myelogenous leukemia (CML)...

..Data regarding the prognostic impact of CXCR4 in patients with B-acute lymphoblastic leukemia (B-ALL) are sparse and limited to the pediatric population...

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..OSI-211 is a low-clearance, unilamellar liposomal formulation of a water-soluble camptothecin analogue, lurtotecan. OSI-211 has significant activity in severe combined immunodeficient mouse models of human leukemia...

..Understanding the causes of failure in older patients with acute lymphocytic leukemia (ALL) may help improve treatment strategies for patients in this particular age group...

..This unique 9-gene signature may better enable stratification of patients to proper therapeutic regimens and provides new insights into mechanisms of Ph+ ALL response to therapy...

..Dynamic prognostic significance of cytogenetic abnormalities in PMF should be further prospectively evaluated...

..The objective of this study was to investigate the role of mediastinal radiation therapy in patients who achieve a complete response (CR) to chemotherapy...

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..Precursor B-acute lymphoblastic leukemia occurring in patients with a history of malignancies is uncommon, and this condition is not well understood...

..Thus, the incidence of IA among CLL patients treated with FCR was comparable with historical rates. The diagnosis of AIHA can be considered even if the DAT is negative. Pre-existing AIHA need not preclude front-line FCR therapy...

..Based on these clinical, pharmacokinetic, and pharmacodynamic data, Triapine warrants further study in patients with hematologic malignancies...

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..005). We conclude that the TNF-alpha level serves as a prognostic factor in patients with CLL and that inhibition of TNF-alpha in these patients could have therapeutic importance...

..These data reflect the complexity by which angiogenic factors may affect the clinical behavior of patients with ALL, and this complexity should be considered in any therapeutic strategy incorporating antiangiogenic agents...

..In conclusion, CEP-701 resulted in modest efficacy and mild but frequent gastrointestinal toxicity in MF patients. The study was registered at http://clinicaltrials.gov as NCT00494585...

..In this Phase I, dose-seeking study, we investigated the dose-limiting toxicities (DLTs) and maximal tolerated dose (MTD) of oral topotecan in patients with hematological malignancies...

..Attainment of a second or later CR should be followed by allogeneic BMT when feasible owing to the paucity of long-term survivors with salvage chemotherapy alone...

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..The prognostic significance of these parameters was assessed in the context of intensive tyrosine kinase inhibitor (TKI)-based chemotherapy...

..09). We conclude that, at doses that are well tolerated, R115777 markedly inhibits the FTase target and has antitumor activity in MDS...

..Our findings suggest that the alterations in B lymphocytes in the form of increased apoptosis can be seen in MDS and support the concept that immune modulation plays a role in the pathophysiology of MDS...

..The combination of vorinostat and idarubicin is generally tolerable and active in patients with advanced leukaemia and should be studied in the front-line setting...

..To investigate the activity of a novel dioxolane L-nucleoside analog, troxacitabine (L-(-)-OddC, BCH-4556), in patients with refractory leukemia...

..An overview of current treatment modalities in Ph-positive ALL will be provided and the rationale for new therapies will be discussed...

..The importance of this down-modulation in the efficacy of current therapy with rituximab needs further investigation...

..0002, Cox proportional hazard model). A multivariate model based on Cox-2 and degree of splenomegaly was developed for survival in patients with early CP CML. Agents that inhibit Cox-2 activity merit investigation in patients with CP CML...

..Myeloproliferative neoplasm blast phase is associated with a dismal prognosis. Responses to chemotherapy can be achieved but are not durable. Long-term survivors had all received SCT either as first therapy or in first remission...

..In CLL, elevated serum β-2 microglobulin (β2M) levels were associated with more rapid disease progression and shorter survival (OS)...

..INCB018424 is a potent and selective Janus kinase 1 (JAK1) and JAK2 inhibitor...

..Because the results of standard regimens have been disappointing, high-dose chemotherapeutic regimens were investigated recently. In the absence of randomized trials, the relative merits of various treatment regimens are unknown...

..Grade 3 toxicities included arrhythmia (n=1) and transient ischemic attack (n=1). Ten patients (30%) had no side-effects. CONCLUSIONS: Low-dose IL-11 has activity in patients with BMF and is generally well tolerated...

..Hepatic venoocclusive disease (VOD) has been reported in patients who have undergone stem cell transplantation (SCT) after Mylotarg therapy. Outside of the SCT setting, VOD has been associated very rarely with cytotoxic therapy...

..Interleukin-11 (IL-11) is a thrombopoietic cytokine that attenuates postchemotherapy thrombocytopenia at doses of 50 microg/kg/d subcutaneously. Very little is known about the activity of IL-11 in patients with bone marrow failure states...

..g., thalidomide), tyrosine kinase inhibitors (e.g., imatinib mesylate), farnesyl transferase inhibitors (e.g., R115777), and other agents are reviewed, in addition to the potential roles of autologous and allogeneic SCT...

..The incidence and outcome of secondary leukemia in the setting of active ovarian carcinoma is reviewed...

..The median survival of patients with chromosome 8 abnormalities was 12 months compared with 40 months of those without (P=0.17). Novel therapies for patients with GS are required...

..To investigate the toxicity profile, activity, and pharmacokinetics of a novel L-nucleoside analog, troxacitabine (BCH-4556), in patients with advanced leukemia...

..Decreased CD81 expression is a sensitive and specific marker for residual pre-B-ALL, even in a background of hematogones, making CD81 a useful addition to a panel for MRD detection by FC...

..SU5416 is a small-molecule RTK inhibitor (RTKI) that targets VEGFR-2, c-kit, and fms-related tyrosine kinase Flk2...

..One transient partial response was observed. The only severe extramedullary toxicities observed were Grade 3 myalgias and arthralgias. CONCLUSION: The study paclitaxel regimen was ineffective in refractory adult ALL...

..0017). In conclusion the hyper CVXD regimen has a relatively high response rate, significant toxicity and a moderate impact on survival in RS...

..Efficacy of rituximab was also significant in this group of patients...

..Median increase above baseline in CD4(+) cell count was similar (q.d. group, +144 cells/mm(3); b.i.d. group, +146 cells/mm(3)), and the incidences of adverse events, disease progression, and HIV-associated conditions were comparable...

..Baseline viral load and some genotypic and phenotypic markers of resistance correlated with HIV RNA response...