Hagop Kantarjian

..In conclusion, adaphostin showed significant and selective activity against CML and AML cells and its development for clinical testing is warranted...

..Identifying patients in whom a change to dasatinib or nilotinib is more appropriate than imatinib dose escalation is therefore important...

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

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

..A prospective historical control study evaluated the efficacy and safety of amphotericin B lipid complex (ABLC) in this patient population...

..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...

..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...

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..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...

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

..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...

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..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...

..This agent, therefore, combines low in vivo toxicity with formidable in vitro pro-apoptotic ROS-mediated activity, and may represent a novel OAD suitable for clinical development against a variety of hematological malignancies...

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

..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 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 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...

..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 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...

..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...

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

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

..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...

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

..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%...

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..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)...

..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...

..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...

..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...

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

..Although CFAR produced good response rates in this highly pretreated high-risk group of patients, there was no benefit in survival outcomes...

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

..Specific factors associated with poor prognosis have not been investigated in patients with hypocellular MDS...

..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...

..001) respectively; median OS was 45, 31 and 19 weeks (P = 0.04) respectively. The HCTCI score is predictive of early death rates and OS in older patients receiving AML induction therapy...

..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...

..As alkylating agents are important antileukemia drugs, a Phase I and pharmacokinetic study of VNP40101M was conducted in patients with refractory or relapsed leukemias or poor-risk myelodysplastic syndromes (MDS)...

..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 addition, both drugs inhibited the phosphorylation of PDGFR-alpha tyrosine kinase with equivalent efficacy. We conclude that AMN107 and imatinib are active and equipotent against cells expressing the FIP1L1-PDGFR-alpha fusion gene...

..ATRA plus ATO may serve as an alternative to chemotherapy in low-risk untreated APL (eg, in older patients) and, when combined with GO, may improve outcome in high-risk patients...

..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...

..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 objective of the current study was to evaluate the benefit of adding imatinib to the treatment sequence of patients with early chronic phase Ph-positive CML who received interferon alpha (IFN)-based regimens as frontline therapy...

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

..These results strongly support investigation of the clinical efficacy of AMN107 in 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...

..Therefore, higher kinase activity by mutation, transcriptional up-regulation or gene amplification appears required for lymphoid transformation by p210 BCR-ABL...

..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...

..The EPI is reproducible and useful...

..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...

..Sorafenib is an orally active multikinase inhibitor with potent activity against FLT3 and the Raf/ERK/MEK kinase pathway...

..The combination of chemotherapy with dasatinib is effective in achieving long-term remissions in patients with newly diagnosed Ph(+) ALL. This study was registered at www.ClinicalTrials.gov as NCT00390793...

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

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

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..In conclusion, a significant number of CD34+ cells can be safely collected in patients with CML who are on imatinib therapy, but CD34+ cell yields improve when imatinib is temporarily withheld...

..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...

..Although the T315I mutation is resistant to currently available TKIs, survival of patients with T315I remains mostly dependent on the stage of the disease, with many CP patients having an indolent course...

..CONCLUSIONS: The results of the current study suggest the superior potency of AMN107 compared with imatinib in Ph-positive ALL and support clinical trials of AMN107 in patients with Ph-positive ALL...

..We conclude that intense chemoimmunotherapy without stem cell transplantation is effective for untreated aggressive MCL...

..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...

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

..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...

..The importance of regular monitoring at experienced centers was highlighted...

..The mechanism underlying the association between high PE and poor clinical outcome is unclear, although it may be related to the possible PE reflection of tumor burden...

..In conclusion, clofarabine is an active agent in the treatment of acute leukemias and MDS, and cellular pharmacokinetics has prognostic significance...

..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...

..CONCLUSIONS: Although SU5416 had minimal clinical activity, signs of biological activity (decrease in plasma VEGF levels) suggest that angiogenic modulation may be of value in patients with MM...

..Similar to wild-type Bcr-Abl+ cells, inhibition of Jak2 by Ag490 treatment resulted in decrease of pSer Akt and c-Myc in imatinib-resistant cells. These results identify Jak2 as a potentially important therapeutic target for CML...

..Our results show that FLT3 inhibition is associated with clinical activity in AML patients harboring FLT3-activating mutations and indicate that CEP-701 holds promise as a novel, molecularly targeted therapy for this disease...

..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...

..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...

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

..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...

..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...

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

..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...

..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...

..We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML...

..These data suggest that the minimum needed to declare CR in AML be changed from 1500 to 1000...

..In conclusion, we show that obatoclax potently induces apoptosis and decreases leukemia cell proliferation and may be used in a novel therapeutic strategy for AML alone and in combination with other targeted agents and chemotherapeutics...

..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...

..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...

..In contrast, neither drug was effective against HMC-1.2 cells at the dose range tested. The present results suggest clinical potential for INNO-406 in KIT V560G-expressing malignancies...

..The outlook today for patients with CML is much brighter than that of a few years ago...

..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...

..Peripheral blood plasma was analyzed in this study because of previous detection of nucleic acids and proteins from tumor cells in plasma samples...

..Herein, we review some of these strategies, particularly those for which clinical data are currently available...

..Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy...

..In some patients, CCA/Ph-negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph-negative cells...

..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...

..0]). Therapy was discontinued in one patient because of diarrhea not responding to dose adjustments. CONCLUSIONS: Single-agent lonafarnib appears to have clinical activity in a small proportion of patients with CML refractory to imatinib...

..CONCLUSIONS: Activation of AME through t(3;21) defines a highly aggressive, therapy-related leukemic blast syndrome. Prior treatment with hydroxyurea or other antimetabolites is implicated as a contributory cause...