Susan O'Brien

..EXPERT OPINION: Rituximab, the prototype anti-CD20 mAb, forms the core of CIT in CLL. The success of rituximab and ofatumumab has led investigators to evaluate other anti-CD20 mAbs in the treatment of CLL...

..25% in controls. Elacytarabine has monotherapy activity in patients with advanced AML. This study provides proof-of-concept that lipid esterification of nucleoside analogues is clinically relevant...

..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...

..These naturally occurring compounds are well tolerated, and they inhibit survival signals in the microenvironment necessary for tumor development, making them well suited for evaluation as maintenance therapy for CLL...

....

..We evaluated whether oblimersen would improve response to chemotherapy in patients with relapsed or refractory CLL...

..53; P = .05), was observed in patients with fludarabine-sensitive disease. We evaluated long-term survival and poststudy CLL therapy among all randomly assigned patients...

..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...

..Further evaluation in less heavily pretreated patients and in combination with other therapeutic agents is warranted. This trial has been registered with http://clinicaltrials.gov under identifier NCT00600964...

..This suggests a novel mechanism of indirect infection-associated lymphomagenesis whereby chronic local antigen stimulation would lead to the emergence of ectopic B-cell lymphoma...

..To determine the maximum-tolerated dose (MTD), efficacy, safety, and pharmacokinetics of oblimersen sodium in patients with advanced chronic lymphocytic leukemia (CLL)...

..Further understanding of the in-vitro mechanisms involved in tumor cell killing by MoAb will be important in maximizing the efficacy of this approach...

..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...

..Ongoing trials will help confirm the role of ofatumumab in CLL, in addition to the effect of this agent in combination with chemotherapies and other MoAbs...

..However, important questions still have not been answered. For example, which patients may be cured with imatinib and which patients should still be offered transplant early in the course of their disease?..

..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...

..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...

..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...

..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...

..Efficacy and toxicity profile of orally administered clofarabine were evaluated in patients with higher-risk myelodysplastic syndrome (MDS)...

..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...

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

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

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

..The objectives of this study were to update the long-term experience with imatinib in patients who had accelerated-phase CML and to compare outcomes with historic experience...

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

..These data further indicate that plasma may be a good target to evaluate for minimal residual disease using cCD52/cCD20 levels...

..The overall 4-week mortality rate was 9%. In conclusion, BIDFA is active and safe in heavily pretreated patients with myeloid malignancies...

..Outcomes in chronic myeloid leukemia have improved with tyrosine kinase inhibitor treatment. However, little is known about outcomes of chronic myeloid leukemia in adolescent and young adult patients...

..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...

..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...

..However, survival does not appear to be improved compared with other regimens. Modifications of this combination in AML therapy of older patients warrant further evaluation...

....

..We hypothesized, therefore, that combination of an HDACi with a proapoptotic agent, such as the Bcl-2 homology domain-3 mimetic GX15-070, could result in enhanced antileukemia activity...

..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...

..The purpose of this study was to assess the incidence, presenting characteristics, and treatment outcomes of Richter's syndrome (RS) and factors predicting response and survival...

..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...

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

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

..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...

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

..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...

..These results suggest that achievement of a MCyR without concomitant CHR is associated with poor outcome...

..Mutation scoring can predict outcome in CML-chronic phase with imatinib failure treated with second-generation TKIs and can help in therapy selection. More complex prognostic models will be required for advanced stages of disease...

..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...

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

..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...

..We continue to use criteria for active disease to initiate therapy. Multivariable analysis was performed to identify prognostic factors independently associated with time to first treatment for patients with CLL...

..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...

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

..In conclusion, imatinib dose escalation can induce sustained responses in a subset of patients with cytogenetic failure and a previous cytogenetic response to standard-dose imatinib...

..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...

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

..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...

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

..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...

..v. ITRA) reduced the incidence of probable/proven fungal infections in this group of patients, and compare the results with those of a historic control group treated with fluconazole plus itraconazole capsules (F+I)...

..This scoring system could serve to advise patients of their prognosis and treatment options, as well as to evaluate the benefit of newer alternate options...

..In this patient cohort, p53-IHC is an important determinant of complete remission and overall survival, but not remission duration, in patients with CLL receiving FCR...

..Response rates and survival are comparable with historic high-risk FCR-treated patients. CFAR may be a useful frontline regimen to achieve CR in patients with 17p deletion before allogeneic stem cell transplantation...

..Further studies are required to determine whether there might be a minimum adequate dose of these agents...

..The EPI is reproducible and useful...

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

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

..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...

..These results suggest that patients receiving 2TKI with no cytogenetic response at 3 to 6 months should be considered for alternative therapies...

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

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

..CONCLUSION: Further assessment of ABT-751, especially in combination with other agents, in patients with acute leukemias is warranted...

..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...

..No objective response occurred. Acceleration of disease occurred in four patients. While well-tolerated, Enbrel did not have anti-myeloma activity as administered on this study...

..Those agents targeting vascular endothelial growth factor are also briefly reviewed...

..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...

..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...

..Gemtuzumab ozogamicin-based combinations should not be prescribed outside the research setting until further data is available...

..Further development of rational therapies and improvements in the outcome of patients with MDS are likely to emerge from an increased understanding of the pathophysiology of these diseases...

..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...

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

..AG-01736 had minimal biologic or clinical activity in this elderly patient population...

..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...

..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...

....

..Use of second-generation TKI after failure to 2 TKIs may induce responses, but these are usually not durable except in some CP patients. New treatment options are needed...

..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...

..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...

..The recommended phase II regimen is Triapine 105 mg/m2/day followed by ara-C 600 mg/m2/day for 5 consecutive days every 3-6 weeks...

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

..Grade 3 or 4 toxicities included stomatitis (4%), hand-foot syndrome (18%), and skin rash (12%). Four patients (13%) responded. Troxacitabine-based combinations merit study in IM-resistant CML...

..A major impact of Iseganan on reducing stomatitis, UOM, or its clinical sequelae in patients receiving stomatotoxic therapy was not detected on this study...

..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...

..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...

..Dasatinib is a 325-fold more potent inhibitor of Bcr-Abl than imatinib and has been associated with high rates of durable responses in patients with CML in chronic phase (CP) after imatinib failure...

..8, P < .001). Our results suggest that postremission interventions should be targeted toward patients with unmutated IgV(H) status...

..CONCLUSIONS: The combination of imatinib mesylate and anagrelide was safe and was associated with an 89% CHR rate in patients with CML in chronic phase and persistent thrombocythemia...

..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...

..These data indicate that the combination of troxacitabine and IM has significant preclinical activity in advanced CML and that clinical evaluation of this combination is warranted...

..Our study provides the first evidence that rapamycin derivatives inhibit AKT signaling in primary AML cells both in vitro and in vivo, and supports the therapeutic potential of mTOR inhibition strategies in leukemias...

..008). Multivariate analysis showed that VEGF was not independent of the synthesis stage (P =.09). These data suggest that VEGF plays a role in the biology of CML and that VEGF inhibitors should be investigated in CML...