Michael Keating

..Significant responses were not seen with any of these treatment regimens. We conclude that cyclosporine therapy may be beneficial for T-LGL leukemia patients. New treatment modalities are needed for these patients...

..A chemoimmunotherapy program consisting of fludarabine, cyclophosphamide, and rituximab (FCR) was developed with the goal of increasing the complete remission (CR) rate in previously untreated CLL patients to >/= 50%...

..Ofatumumab (Arzerra; Genmab/GlaxoSmithKline) - a fully human cytolytic monoclonal antibody that is specific for CD20 - was approved by the US FDA for the treatment of chronic lymphocytic leukaemia in October 2009...

..Alemtuzumab induced significant responses in these patients with clinical benefit in the majority and with acceptable toxicity in a high-risk group...

..Because high response rates and few complications are observed in previously untreated patients, the use of alemtuzumab earlier in therapy may provide optimum benefit to patients...

..Fludara-refractory patients are a poor prognosis group and need more effective therapeutic regimens and well-designed infection prophylactic regimens...

..The combination of clofarabine with ara-C is safe and active. Cellular pharmacology data support the biochemical modulation strategy...

..To examine the efficacy and safety of the combination of alemtuzumab and pentostatin in patients with T-cell neoplasms...

..Multivariate analyses were conducted to assess the independent prognostic effect of therapy (imatinib versus other) on survival...

..Topotecan-cytarabine regimens have shown encouraging results in higher-risk MDS. The aim of this study was to analyze the long-term results with topotecan-cytarabine versus other intensive chemotherapy regimens in higher-risk MDS...

..There was no correlation between CD33 intensity and response to therapy or overall survival in 35 patients treated with protocols including Mylotarg. These data demonstrate variation in CD33 intensity between various leukemias...

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

..The authors analyzed the outcome of patients with AML undergoing second salvage therapy, and identified prognostic factors associated with response and survival...

..Four patients (7%) developed hepatic venoocclusive disease (VOD). CONCLUSIONS: The MFAC regimen may merit further study in patients with AML if measures to avoid and/or treat VOD can be incorporated into the regimen...

..The purpose of this study was to improve the complete remission (CR) rate for previously treated patients and evaluate the quality of bone marrow response...

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..03). This increased only in responders (median, 1.8-fold; P =.008) after the second clofarabine infusion. In summary, clofarabine is active in acute leukemias and MDS; cellular pharmacokinetics may have prognostic significance...

..The objective of the current analysis was to determine whether improvements in treatment have had an impact on survival for patients with CLL...

..This was most likely because approximately 90% of patients receiving IFN-alpha plus ara-C changed to imatinib therapy after a median of 8 months into therapy...

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

..The recent availability of modern immunophenotypic and molecular tools has allowed a better distinction of this disorder from its B-cell counterpart and other mature T-cell leukemias...

..The current analysis updated the long-term results with the original hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) program, with a median follow-up time of 63 months...

..Identifying pretreatment patient characteristics or prognostic factors associated with clinical outcomes is important for counseling patients, conducting clinical research, and evaluating trial results...

..Patients receiving imatinib should be advised to practice adequate contraception...

..4 months (range, 1-39). Late relapses in AML are infrequent, with poor response to therapy. Karyotype at relapse is frequently different, raising the question of second AML versus relapse with the original clone...

..CONCLUSIONS: The current results suggest, that for patients with P-AML, bone marrow TA is a highly significant prognostic factor...

..These data suggest that VEGF expression, rather than the expression of its receptors, is the determining factor in the biological behaviour of AML and MDS, and that VEGFRs are differentially expressed in AML and MDS...

..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...

..These data support the conclusion that PB plasma is enriched by tumor-specific DNA and can replace BM cells for studying genomic abnormalities...

..In patients with MDS, it was recently demonstrated that epigenetic therapy with hypomethylating agents improved survival. Much therapeutic progress has been witnessed in leukemia and MDS, and much more is expected to occur soon...

..However, the profound immunosuppression caused by alemtuzumab has been associated with infectious complications...

..004). In conclusion, this agent was highly effective for prophylaxis of CMV reactivation in patients receiving alemtuzumab. This trial was registered at www.ClinicalTrials.gov as #NCT00562770...

..This prognostic model may help patients and clinicians in clinical decision making as well as in clinical research and clinical trial design...

..In summary, the prognosis of most patients (72%) ≥ 70 years of age with AML is poor with intensive chemotherapy (8-week mortality ≥ 30%; median survival < 6 months)...

..The compound is being evaluated currently in Phase II and III clinical trials. Here we characterized the effects and mechanisms of action of bortezomib in cells obtained from patients with chronic lymphocytic leukemia (CLL)...

..95 mg/L had significantly shorter survival than those with lower values. Plasma TPO and beta2-M may be useful for the prediction of clinical behavior in CLL and may replace the need for the determination of IgV(H) mutation status...

..The observation that patients can be cured of APL without the use of chemotherapy should encourage further study of 'targeted' therapy in APL and in other leukemias...

..Decitabine is a hypomethylating agent that has shown encouraging preliminary anti-CML activity. This study evaluated the activity and toxicity of decitabine in different phases of CML...

..02). CONCLUSIONS: The current study data suggest that TA plays a role in the propagation of CP-CML and that the potential of telomerase inhibitors in patients with CML should be explored, even in those with early phase disease...

..The role of IL-8 inhibitors in the treatment of patients with CLL should be explored...

..Encouraging activity was observed in acute leukemia...

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

..Median survival duration has not been reached (range, 2+-64+ months). Treatment with cladribine followed by rituximab is effective tk;4and may increase CR rate. This study was registered at www.clinicaltrials.gov as NCT00412594...

..CONCLUSIONS: Enbrel was well tolerated, but no responses were noted in these immunosuppressed patients with refractory hematologic malignancies...

..Thus, we adapted this approach as consolidation therapy in patients with CLL responding to chemoimmunotherapy...

..Guidelines for reporting adverse events in leukemia studies should be revisited...

..Our results show that NPI-0052 is a more effective proapoptotic agent than bortezomib in isolated CLL cells and suggest that the chemical properties of NPI-0052 might also make it an effective therapeutic agent in CLL patients...

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

..Herein, we review the clinical and pathological features of mature T-cell leukemias...

..Delaying SCT until the disease demonstrates resistance to other strategies (e.g., imatinib mesylate or interferon-alpha) entails the risk of the development of a sudden blastic phase, which may not permit enough time to perform a SCT...

..Although 13q deletion as the sole abnormality has been found to confer a favorable prognosis, there are little data as to whether there is a difference in prognostic value between monoallelic versus biallelic deletion of 13q...

..Such a combination strategy may be an effective therapeutic regimen and have potential clinical application in leukemia...

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

..Further studies are needed to establish the clinical relevance of this approach in comparison with other techniques...

..Thus, Aurora-A kinase overexpression in chronic lymphocytic leukemia may be involved in the genesis of chromosomal abnormalities and is a potential target for therapeutic intervention...

..Because Stat3 is constitutively activated in CLL and sequence analysis revealed that the ROR1 promoter harbors gamma-interferon activation sequence-like elements typically activated by Stat3, we hypothesized that Stat3 activates ROR1...

..Early clinical trials show that forodesine has promise as a single agent for the treatment of relapsed/refractory hematologic malignancies, and combination therapies might be warranted to improve clinical results...

..The frequent 2p25.3 gain involving the ACP1 and MYCN genes may help define the critical region of 2p that contributes to pathogenesis of CLL together with other chromosomal abnormalities...

..This type of relatively nontoxic regimen is being investigated in elderly patients who may not tolerate standard combination chemoimmunotherapies...

..CD79b is a relatively newly characterized B-cell marker that is expressed in a minority of chronic lymphocytic leukemia (CLL) cases...

..Our results illustrate differences in proliferation and apoptosis between acute and chronic leukemias and MDS. These differences may have diagnostic and therapeutic implications...

..These results demonstrate a potent graft-versus-leukaemia effect that can overcome the adverse prognostic effect of ZAP-70 expression...

..However, these neoplasms also differ from CLL cytologically and in their immunophenotype...

..Thus, we can classify cases with 95% accuracy based on the expression of as few as three genes...

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..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...

..We review the evolution of modern chemoimmunotherapy for CLL, and discuss current research directions for further refining the potency of these regimens...

..Leukemic CD20 expression differed significantly between FISH subtypes. Patients with trisomy 12 CLL showed strong leukemic cell CD20 expression and had a high rate of response to rituximab-based therapy...

..To test whether nelarabine is an effective agent for indolent leukemias and to evaluate whether there is a relationship between cellular pharmacokinetics of the analog triphosphate and clinical responses...

..Serum beta(2) microglobulin (beta2M) is prognostic in other hematologic malignancies; therefore, we evaluated its prognostic significance in acute myeloid leukemia (AML)...

..According to our experience, lenalidomide given as a continuous treatment has antitumor activity in heavily pretreated patients with CLL...

..We conducted a phase I-II trial of oxaliplatin, fludarabine, cytarabine, and rituximab (OFAR) in these diseases...

..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...

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..In the current study, the authors addressed this question by matching MS patients with analogous AML patients and comparing their clinical outcomes...

..To determine its antitumor activity in combination with cyclophosphamide, we initiated a Phase II trial of the two agents in patients with advanced chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL)...

..We assessed whether characteristics of patients with CLL and SLL differ in ways other than the absolute lymphocyte count (ALC) and evaluated treatment outcomes and prognostic factors...

..In these cases, histologic confirmation is always recommended, not only to differentiate HL transformation from other entities but also for subclassification of HL...

..Our findings support a role of fludarabine-mediated DNA repair inhibition as a mechanism critical for the cytotoxic synergy of the 2 drugs...

..This technique may be a useful adjunct to flow cytometry and other methods when an extensive phenotype of the leukaemia cell is desired for clinical trials, research and prognostic factor analysis...

..In this study, the authors assessed the incidence, presenting characteristics, and outcomes of patients with CLL/SLL who developed Hodgkin lymphoma (HL)...

..There was one episode of septic shock in a patient with Grade 4 neutropenia. CONCLUSIONS: (90)Y ibritumomab tiuxetan had no significant antitumor activity and hematologic toxicity was severe in these heavily pretreated patients with RS...

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..Human antimouse antibody (HAMA) and/or human antiricin antibody (HARA) development was documented in 2 patients. Anti-B4 blocked ricin was well tolerated but had limited activity in patients with residual CLL after chemotherapy...

..The clinical significance of circulating antigen in patients receiving monoclonal antibody therapy directed against CD20 and/or CD52 warrants study...

..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...

..The use of PS-341 should be explored in patients with chronic myelogenous leukemia resistant to IM. Trials of combinations of PS-341 and IM require cautious design...

..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...

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..Available data thus indicate that rituximab can be an effective therapy in a wide range of CD20+ lymphoid disorders...

..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...

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..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...

..Our findings suggest that UCN-01 may be a good candidate for combination strategies of cancer treatment...

..CONCLUSIONS: Plasma VEGF levels have prognostic significance in patients with AML. The lack of clinical relevance of VEGF levels in patients with MDS suggests some biologic difference between AML and MDS...

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..FACPGM had very limited activity and significant toxicity in a cohort of patients with heavily pretreated refractory lymphoproliferative disorders...

..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...

..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...