J E Cortes

..We herein summarize the preclinical and clinical experience of bosutinib in CML...

..The continued study of these phenomena will help us to understand better the pathogenesis of CML and improve the long-term treatment of patients with CML...

..Emerging CML therapies, some of which have different mechanisms of action from those of tyrosine kinase inhibitors, have shown promising results and could offer an alternative to these patients as monotherapy or in combination...

..In conclusion, high-dose imatinib induces complete cytogenetic responses in most patients with chronic-phase CML after interferon failure. This is accompanied by a high rate of molecular remission...

..Cytopenias were noted in the majority of patients, and were manageable with dose interruptions/reductions. Dasatinib is associated with a promising rate of response in this high-risk population...

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..Three of 4 nonresponders failed to respond to an increase in dose. Toxicity was minimal. We conclude that imatinib therapy is effective for HES...

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

..R115777 showed clinical activity in patients with CML and MF. The effect on VEGF needs to be further investigated to determine whether this might be a possible mechanism of action of R115777...

..However, based on the current data, imatinib blood-level testing seems to be a useful aid when making clinical decisions in CML...

..Some of these approaches are expected to improve the outcomes of patients with CML...

..Long-term clinical outcome data have established imatinib 400 mg/d as standard front-line treatment for newly diagnosed patients with chronic myeloid leukemia (CML)...

..If this is successful, complete eradication of disease may become a reality for the majority of patients with CML...

..Although most patients with chronic myeloid leukemia (CML) in chronic phase respond well to front-line therapy with imatinib, some patients do not achieve the desirable end point, and others may eventually lose response or are intolerant...

..c-kit is expressed in most patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) and PDGF has been implicated in the pathogenesis of myeloproliferative disorders (MPD)...

..Future studies should consider CMML as a separate entity to promote a better understanding and identify more effective therapy for patients with this disease...

..The continued understanding of the biology of CML and mechanisms of resistance to imatinib and the ability to develop target-specific therapies should lead to the increased probability of cure for most patients who have CML...

..This article describes the natural history of CML and its prognostic factors,with emphasis on changes due to the emergence of imatinib...

..To investigate the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of BMS-214662, a farnesyl transferase (FTase) inhibitor, in patients with acute leukemias and high-risk myelodysplastic syndromes (MDS)...

..To determine the clinical significance of molecular response and relapse among patients with chronic myelogenous leukemia (CML) treated with imatinib...

..The in vitro evidence of antileukemia and transient hematological improvements observed in some patients warrants further investigation of bortezomib in acute leukemias, probably in combination with other agents...

..Myelosuppression occurs in up to 50% of patients with chronic myeloid leukemia (CML) who are treated with imatinib and > or = Grade 3 myelosuppression is reported in approximately 10% of patients...

..Thus there is a need for developing approaches to overcome and prevent resistance to imatinib...

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..It is very possible that these agents will soon find their way to the ranks of established agents for the management of myeloid malignancies..

..These trials were registered at www.clinicaltrials.gov as #CA180006 and #CA180015...

..Lonafarnib can inhibit the proliferation of imatinib-resistant cells and increases imatinib-induced apoptosis in vitro in cells from imatinib-resistant patients...

..In this study, there was no marked increase in development of T315I...

..To evaluate the safety and efficacy of initial treatment with imatinib mesylate 800 mg/d (400 mg twice daily) versus 400 mg/d in patients with newly diagnosed chronic myeloid leukemia in chronic phase...

..Treatment recommendations have been developed for management of patients with chronic myeloid leukemia (CML)...

..This study in adults evaluated safety of and compared efficacy of rasburicase alone with rasburicase followed by oral allopurinol and with allopurinol alone in controlling plasma uric acid...

..The p53 antisense oligonucleotide cenersen has been shown to sensitize acute myeloid leukemia (AML) stem cells to DNA damaging agents...

..The implications of rising BCR-ABL1 transcript levels and caveats of molecular monitoring are also described...

..Dasatinib is effective therapy for chronic myeloid leukemia (CML) after imatinib failure. In this study, we investigate the efficacy of dasatinib as initial therapy for patients with CML in early chronic phase...

..In the current study, the authors investigated the use of CsA in the management of anemia or thrombocytopenia of presumed autoimmune etiology associated with CLL...

..This study is registered at http://www.clinicaltrials.gov as NCT00471497...

..Many of these agents are already showing promising results in the clinic. This manuscript reviews some of these agents, particularly those for which clinical data are already available...

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..Interferon alpha (IFN ?) is efficacious in CML likely due to its immunomodulatory properties, and is synergistic in vitro with imatinib and granulocyte macrophage-colony stimulating factor (GM-CSF)...

..These data suggest bosutinib is effective and tolerable in patients with chronic phase imatinib-resistant or imatinib-intolerant CML. This trial was registered at http://www.clinicaltrials.gov as NCT00261846...

..Patients with less than complete cytogenetic response to second -line therapy or beyond should be considered to have benefit from therapy and the value of this considered in the context of which alternative options are available...

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..In this review, we analyze the current status of therapy of CML, and we discuss some of the most relevant clinical questions that we face today...

..It is unlikely that, as given here, either FA or TA is, in general, superior to IA, highlighting the need for new treatments...

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

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

..We conclude that addition of ATRA +/- G-CSF to FAI had no effect on CR rate, survival, EFS, or EFS in CR in poor prognosis, newly diagnosed AML or high-risk MDS...

..0014) and returned to 50% at the end of the first 28-day cycle (P=0.016). 5-azacitidine is relatively well tolerated and results in induction of global hypomethylation in patients with MF, but results in limited clinical activity...

..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...

..01). In conclusion, the addition of intensive chemotherapy may improve survival in patients with CML who have not obtained an adequate cytogenetic response on an IFN-alpha-based regimen...

..T-cell lymphoid blastic phase (BP) transformation is rare in chronic myelogenous leukemia (CML). 2-amino-9-beta-D-arabinosyl-6-methoxy-9H-guanine (GW506U78), a prodrug of arabinosylguanine (ara-G), is effective in T-cell leukemias...

..Our data suggest that lipoATRA is an effective means of producing molecular CR in newly diagnosed APL...

..In summary, the CAT regimen is well tolerated and has significant anti-leukemia activity which warrants further investigation...

..Nonetheless, the rates and duration of PCR negativity produced by lipoATRA monotherapy suggest that lipoATRA is a superior anti-APL agent than oral ATRA...

..In conclusion, P-loop mutations were not associated with poor outcome, suggesting that the prognosis of patients who fail imatinib is multifactorial...

..Myelosuppression and infection remain the most significant complications of therapy in CLL...

..These findings suggest that inhibition of ZAP70 signaling pathway and suppression of Th1 cytokine synthesis by CD4+ T cells required the presence of IM at the time of T-cell activation through the T-cell receptor...

..Here, we propose a treatment algorithm for imatinib-resistant patients based on BCR-ABL mutation status and patient history...

..The association of treatment response with survival was evaluated by multivariate and landmark analyses...

..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...

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..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...

..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...

..2 months (95% CI 13-18). In summary, this analysis indicates that it is possible to identify patients with lower risk MDS and poor prognosis who may benefit from early intervention...

..More research is needed to define the intensity and duration of treatment and the role of cranial irradiation in the treatment of isolated CNS relapses...

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..Grade III/IV toxicities were mainly cytopenias and neutropenic fever. Combination of rATG, cyclosporine and G-CSF is safe and effective as first-line treatment of AA and has significant activity in low-risk MDS...

..On the basis of these results, ABL1 kinase inhibitors warrant clinical investigation in patients with NUP214-ABL1-positive T-cell malignancies...

..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...

..The diagnosis of AML-M6 does not impart by itself a worse prognosis, and treatment decisions on this disease should be guided by well known AML prognostic factors...

..Our data establish EXEL-0862 as a solid candidate for the targeted treatment of patients with FIP1L1-PDGFR-alpha-positive HES...

..To evaluate the efficacy and safety of the combination of topotecan and cytarabine in patients with myelodysplastic syndromes (MDSs) and chronic myelomonocytic leukemia (CMML)...

..AmBisome was better tolerated than ABLC but was associated with mild abnormalities in liver function tests at the end of therapy...

..The results show that PEG IFN-alpha-2b is easier to deliver (once weekly), better tolerated, and perhaps more effective than IFN-alpha...

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

..02), with overall survival rates of 91%, 69%, and 75%, respectively (P=0.13). In conclusion, patients with more than one BCR-ABL1 mutation fare worse than those with no or one mutation...

..The influence of these cellular proteins and caspase-3 activity on apoptosis in CML is complex and merits further investigation...

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..1 microg/ml, with the lowest limit of quantitation being 0.2 microg/ml. This method is suitable for routine analysis of UCN-01 in human plasma at concentration from 0.2 to 30 microg/ml...

..ClinicalTrials.gov Identifier: NCT00217646)...

..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...

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..Troxacitabine-based therapy had significant antileukemic activity in extramedullary myeloid leukemias and warrants further investigation in this clinical situation...

..001). Competitive quantitative polymerase chain reaction (QPCR) studies at 9 months showed a median QPCR value (ratio of BCR-ABL/ABL transcripts x 100) of 0.59% overall and of 0.24% (range, 0.001%-29.5%) for complete cytogenetic response...

..Although molecular monitoring has a clear role in assessing residual disease and determining the risk of disease progression in patients with CML, the importance of cytogenetic monitoring should not be ignored...

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

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

..Intervention with hematopoietic growth factors in patients with CML who are treated with imatinib should be investigated...

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..A median of 5 post-CR courses have been given to date with 3 patients having currently received 8 post-CR courses, and 4 patients receiving 7 post-CR courses. Mylotarg appears active in APL, and repeated administration is feasible...

..This phenomenon should be considered when evaluating toxicity from chemotherapy, particularly when using new and investigational agents...

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

..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...

..We report 16 patients with CML who developed VZV infection during imatinib mesylate therapy...

..Patterns of KD mutations in Philadelphia chromosome (Ph)-positive acute lympho- blastic leukemia (ALL) are less well studied...

..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...

..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...

..We conclude that EXEL-0862 is active against KIT activation loop mutants and is a promising candidate for the treatment of patients with SM and other KIT-driven malignancies harboring active site mutations...

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