Hagop Kantarjian

..To assess these new guidelines, a cross-sectional survey of US hematologists and/or oncologists was conducted in December 2010 through an online survey...

..We assessed the efficacy and toxicity of sapacitabine, a novel oral cytosine nucleoside analogue, in elderly patients with AML...

..The long-term outcome of patients with chronic phase chronic myeloid leukemia treated with imatinib after failure of interferon alpha therapy has not been detailed...

..Monoclonal antibodies targeting surface markers in acute lymphocytic leukemia (CD19, CD20 and CD22) are showing promising results and are reviewed...

..CD22 is highly expressed in patients with ALL. Inotuzumab ozogamicin is a CD22 monoclonal antibody conjugated to the toxin calecheamicin. We did a phase 2 study to assess the efficacy of this antibody...

..Evidence of monoasters in all but the 4 mg/day dose group provided proof of mechanism for AZD4877. This study was terminated due to lack of efficacy. (ClinicalTrials.gov identifier NCT00486265)...

..Imatinib therapy minimized the impact of known prognostic factors and Sokal risk in CP-CML and accentuated the impact of age in AP- and BP-CML...

..Overall, dasatinib continues to show faster and deeper responses compared with imatinib, supporting first-line use of dasatinib in patients with newly diagnosed CML-CP. This study was registered at ClinicalTrials.gov: NCT00481247...

....

..The G/G genotype of the single-nucleotide polymorphism (SNP) rs1617640 in the erythropoietin (EPO) promoter has been shown to be associated with decreased EPO expression. We examined the association of rs1617640 genotype with MDS...

..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...

..Sapacitabine is an oral deoxycytidine nucleoside analog with a unique mechanism of action that is different from cytarabine...

..Myelofibrosis is associated historically with a poor prognosis in patients with chronic myelogenous leukemia (CML). Its significance in the recent era of effective therapy with imatinib mesylate is unknown...

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

..Even with all the information we have learned, there is still a need to determine the optimal dosing schedule and the development of alternative dosing forms...

..0001); the survival advantage was confirmed by multivariate analysis (hazard ratio, 0.19; P <.0001)...

..In conclusion, high-dose imatinib induced higher rates of complete cytogenetic response and of molecular response in patients with newly diagnosed chronic phase CML...

..This phase II study assessed clofarabine monotherapy in older adults (>or= 60 years of age) with untreated acute myeloid leukemia (AML) and at least one unfavorable baseline prognostic factor...

....

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

..0035) compared with placebo. Grade 3 rash and arthralgia each were reported in 1 romiplostim-treated patient (4%). This study suggests romiplostim may provide clinical benefits in MDS patients during azacitidine therapy...

..Because early allogeneic stem cell transplantation (SCT) may be associated with a better outcome, early parameters predicting for subsequent cytogenetic responses would optimize the treatment decision-making...

..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...

..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...

..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...

....

..These results could be used in assessing the efficacy of new treatments aimed at improving CR durations and survival post salvage therapy...

....

..88%; P = 0.27) and failure-free survival rates (69 vs. 77%; P = 0.34) were also not different. We conclude that the previously established poor prognostic significance of marrow fibrosis in CML is less relevant with imatinib therapy...

....

..The prognosis of patients with chronic myelogenous leukemia (CML) after failure of imatinib mesylate therapy is not well documented...

..Many approved and investigational MDS therapies caused or exacerbated preexisting thrombocytopenia. The incidence of severe bleeding in MDS was greater than reported in current guidelines...

..In summary, nilotinib is highly active and safe in patients with CML-CP after imatinib failure or intolerance. This clinical trial is registered at http://clinicaltrials.gov as ID no. NCT00109707...

..Ongoing and future studies will examine the use of clofarabine in elderly patients with AML for whom standard regimens are too toxic, and in MDS intravenous and oral forms of the drug...

..Response rates in chronic myeloid leukemia (CML) are now reported based on the cumulative incidence of a single-time best response. The study aim was to examine the significance of different response criteria for CML on imatinib therapy...

....

..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...

..Treatment guidelines propose dose escalation based on clinical assessments of disease response...

..The clinical significance of increasing levels of QPCR in patients in CGCR is uncertain...

..Dasatinib represents a safe and effective therapy for CP-CML resistant to conventional imatinib doses with improved cytogenetic and molecular response rates and progression-free survival relative to high-dose imatinib...

..Review the state-of-art knowledge of the biology and therapy of chronic myelogenous leukemia (CML)...

..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...

..Decitabine indirectly depletes methylcytosine and causes hypomethylation of target gene promoters...

..Data with a minimum of 2 years of follow-up were available for the current study of dasatinib and high-dose imatinib in CP-CML resistant to imatinib at daily doses from 400 mg to 600 mg...

....

..Further clinical trials are needed to characterize the efficacy and safety profile of these new agents and to determine which agents improve the long-term prognosis for patients with CML who have shown resistance to imatinib...

..Preclinical in vitro studies have shown that nilotinib (AMN107), a new BCR-ABL tyrosine kinase inhibitor, is more potent than imatinib against CML cells by a factor of 20 to 50...

..We conclude that a low-dose, dose-intensity schedule of decitabine optimizes epigenetic modulation and clinical responses in MDS...

..In this study, the authors update their experience with decitabine in patients with MDS and analyze the cytogenetic response patterns and prognostic factors associated with decitabine therapy...

..The comparative efficacy of these 2 forms of treatment in MDS is unknown. The objective of the current study was to compare the efficacy and toxicity profiles of decitabine and intensive chemotherapy in MDS...

..001). These results demonstrate that dasatinib 140 mg once daily has similar efficacy to dasatinib 70 mg twice daily but with an improved safety profile. This trial is registered at www.clinicaltrials.gov as #CA180-035...

..The purpose of our investigation was to evaluate the response and minimal residual disease by quantitative competitive PCR (QC-PCR) studies in patients with chronic myeloid leukemia (CML) treated with imatinib mesylate...

..The objectives of this study were to define the prognosis for adult patients with ALL after first salvage through multivariate analyses of patient and disease characteristics...

..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...

..This new research includes dose intensive anthracyclines, novel agents, STI571 for Philadelphia chromosome-positive ALL, and risk-oriented strategies...

..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)...

..Chronic myelogenous leukemia (CML) is caused by the BCR-ABL tyrosine kinase, the product of the Philadelphia chromosome. Imatinib mesylate, formerly STI571, is a selective inhibitor of this kinase...

..Future CML therapy might include earlier use of these agents to help more patients achieve complete molecular response and may be a path to a CML cure...

..Both therapies may be suitable for younger patients. The authors reviewed current data to assist in prioritizing these modalities in an individual patient...

..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...

....

..This article lists some of the questions related to the current treatment programs for ALL and notes the remaining articles in this issue that address those questions...

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

..This study indicates that nilotinib is effective, with a manageable safety profile, and can provide favorable long-term benefits for patients with CML-CP after imatinib failure...

..Different definitions of progression-free survival (PFS) and event-free survival (EFS) may result in perceived differences in outcomes with tyrosine kinase inhibitor (TKI) therapies in chronic myelogenous leukemia (CML)...

..To assess the safety and efficacy of romiplostim, a peptibody that increases platelet production, for treatment of thrombocytopenic patients with myelodysplastic syndromes (MDS)...

..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)...

..We present data from the Evaluating Nilotinib Efficacy and Safety in clinical Trials-newly diagnosed patients (ENESTnd) study after a minimum follow-up of 24 months...

..Cephalotoxine esters, including homoharringtonine (HHT), have shown encouraging activity in leukemia in initial studies in China and in later studies in the U.S...

..CONCLUSIONS: MTA was moderately effective and associated with significant toxicity in patients with refractory AML...

..This review focuses on supportive care modalities, the approved agents indicated for the treatment of MDS and future directions for the treatment of MDS, including agents under clinical investigation...

..The patient then developed myelodysplastic syndrome and solitary central nervous system relapse of ALL...

..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...

..This risk is discernible as early as 3 months into imatinib therapy by molecular analysis and may provide the rationale to institute therapies that render higher rates of early response...

....

..CSA inclusion in gemtuzumab ozogamicin-based regimens is feasible. MFAC is an effective regimen for refractory AML...

..Homoharringtonine (HHT) is a cephalotaxus alkaloid that inhibits the synthesis of proteins leading to apoptosis. Intravenous HHT has demonstrated activity in patients with chronic myeloid leukemia (CML) after failure with interferon...

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

..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...

..SBT is still a rare event, probably less common than that observed with IFN-alpha therapy. Continuous monitoring of patients treated with imatinib is mandatory...

..A phase I study of cloretazine combined with cytarabine (1-beta-d-arabinofuranosylcytosine, ara-C) was conducted in patients with refractory disease...

..Seven patients were treated with regimens designed for AML. Complete remission (CR) rates of 78% and 57% were noted respectively. The overall survival probability at 2 years was 60%...

..LBH589 is a novel histone deacetylase inhibitor that inhibits proliferation and induces apoptosis in tumor cell lines. In this phase I study, LBH589 was administered i.v. as a 30-minute infusion on days 1 to 7 of a 21-day cycle...

..In contrast, high VEGF-R1 levels did not correlate with a specific CML phase, characteristic, or outcome. Our findings support VEGF-R2 over-expression as an independent prognostic indicator for shortened survival in patients with CML...

..Its potential role alone or in combinations should be further explored in this condition...

..Ongoing studies will better determine their mechanism of action and the role of combination with other agents, defining their place in the therapeutic arsenal of hematologic disorders...

..CONCLUSIONS: As(2)O(3) is effective and well tolerated therapy for patients with recurrent APL. Molecular remission may be achieved at the time of CR in the majority of patients, and remissions are durable...

..The inclusion of CSA in a gemtuzumab ozogamicin-containing regimen is feasible. The MDAC regimen was associated with significant toxicity in a cohort of patients with very advanced AML...

..The possible mechanism of response is discussed. This observation may lead to a better understanding of the pathophysiology of HES, and may provide a new form of effective therapy for the disease...

..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...

..Combination strategies are currently being investigated in preliminary clinical studies and may prove to be useful. Overall, there are an increasing number of treatment options now available for patients with CML...

..SM is rare and has no effective standard of care. Collaboration among academic centers to accrue enough patients to evaluate novel therapeutic strategies is needed...

..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...

..Forodesine has biologic activity in CLL; pharmacodynamic parameters suggest that an alternate dosing schedule and/or higher doses to achieve greater intracellular dGTP may be beneficial in this patient population...

..The incidence, dynamics, and management of cytopenias were investigated in patients with chronic myeloid leukemia in chronic phase (CP CML) who received dasatinib therapy after imatinib failure...

..CONCLUSIONS: The addition of Mylotarg to idarubicin and ara-C is feasible. MIA has significant activity in patients with refractory AML. Hepatotoxicity and VOD are significant toxicities of Mylotarg-based combinations...

..Median survival was 5 months (range, 2 - 20 months). This outpatient regimen is effective and well tolerated and perhaps superior to single-agent imatinib for patients in myeloid BP...

..Our data suggest that HSCT is preferable to chemotherapy alone in these patients with poor prognoses, with particular benefits noted in patients under age 50 years...