Ra Larson

..Nilotinib continues to demonstrate superior efficacy in all key response and outcome parameters compared with imatinib for the treatment of patients with newly diagnosed CML-CP...

..In phase 2, ezatiostat was administered on 2 dose schedules: 600 mg/m2 IV on days 1 to 5 or days 1 to 3 of a 21-day treatment cycle...

..Down-regulation of the miR-181 family contributes to an aggressive leukemia phenotype through mechanisms associated with the activation of pathways of innate immunity mediated by toll-like receptors and interleukin-1beta...

..The rationale, pharmacology, and clinical experience to date with these agents in the treatment of patients with refractory acute leukemia are reviewed, with a highlight on ALL...

..In this study, the authors analyzed the efficacy and safety of gemtuzumab ozogamicin (GO) (Mylotarg), an antibody-targeted chemotherapy for CD33-positive acute myeloid leukemia (AML)...

..However, Allo-HCT is recommended in CR1 for patients with high-risk ALL, for those in a second CR (CR2) and for certain other subsets of patients with this disease...

..These results suggest that an adequate plasma concentration of imatinib is important for a good clinical response. This study is registered at http://clinicaltrials.gov as NCT00333840...

..Philadelphia (Ph) chromosome (BCR/ABL)-positive ALL is particularly common among older patients. The availability of specific tyrosine kinase inhibitors is changing the prognosis for this challenging subset...

..However, it is necessary to assess each patient's disease individually and to evaluate prognostic factors, other treatment options, and the appropriateness and timing of transplantation...

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..Establishing the molecular pathways involved in t-AML may facilitate the identification of selectively expressed genes that can be exploited for the development of targeted therapies...

..Most importantly, the molecular and genetic differences that appear to determine the phenotype and the outcome of these patients need to be investigated further...

..These protocols have enrolled all adult patients older than 15 years with ALL, without an upper age restriction, and did not exclude Philadelphia (Ph) chromosome-positive patients...

..We compared the efficacy of fludarabine with that of chlorambucil in the primary treatment of chronic lymphocytic leukemia...

..Mylotarg is an effective treatment for older patients with CD33-positive AML in first relapse and has acceptable toxicity...

..Homozygotes and heterozygotes (who are at risk for treatment-induced mutation or loss of the remaining wild-type allele in their hematopoietic stem cells) may be particularly vulnerable to leukemogenic changes induced by carcinogens...

..7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome...

..Therapy-related leukemias with 11q23 or 21q22 rearrangements, inv(16) or t(15;17), have a more favorable response to treatment and a clinical course similar to their de novo counterparts...

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..Cladribine has modest clinical activity and considerable toxicity in a very selected group of patients with fludarabine-refractory CLL lacking pre-treatment neutropenia and thrombocytopenia...

..CMV prophylaxis with pre-transplant ganciclovir and high-dose valacyclovir after engraftment appears effective in preventing the excessive incidence of CMV infection after alemtuzumab-based conditioning regimens...

..The development of a transcription map will facilitate the molecular cloning of a myeloid leukemia suppressor gene on 5q...

..8 megabases. This cytogenetic map of 5q31, together with the molecular characterization of the critical region, will facilitate the identification of a putative tumor-suppressor gene in this band...

..These data support an association between pre-transplant disease burden and poor outcome after SCT...

..The Cancer and Leukemia Group B is presently evaluating the efficacy of this regimen in a large phase II trial (CALGB study 19802)...

..Additional studies are currently evaluating gemtuzumab ozogamicin in combination with, or as an alternative to, other standard AML chemotherapy...

..We conclude that this two-step approach to autologous transplantation produces good CD34+ mobilization and that this approach has cured some patients. Results in patients with APL are especially promising...

..Clearly, over the past 25 years, molecular biology and biotechnology has provided the hematologist/oncologist novel bullets in their arsenal that will allow treatment by design in leukemia...

..We suggest that patients with core-binding factor AML should be screened for mutKIT at diagnosis for both prognostic and therapeutic purposes, given that activated KIT potentially can be targeted with novel tyrosine kinase inhibitors...

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..This article describes the development, pharmacology, toxicity and clinical activity of nelarabine, as well as discusses its potential role in the treatment of T-cell haematological malignancies...

..In this report, we present the results of that effort...

..In conclusion, within the limitation of this historical comparison, there is a survival advantage from first-line therapy with imatinib over IFN/Ara-C...

..Based on these results, we caution against interchanging BM with PB sampling for MRD monitoring during treatment of CML since this may lead to misinterpretation of treatment results...

..Patients with complex > or = 5 appear to benefit minimally from current treatment and are better suited for investigational therapy or supportive care...

..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...

..Ultimately, this knowledge could influence initial treatment strategies with the goal of decreasing the incidence of this serious complication...

..Cancer and Leukemia Group B (CALGB) 9720 evaluated subcutaneous low-dose recombinant interleukin-2 (rIL-2) maintenance immunotherapy as a strategy for prolonging remission in older patients with acute myeloid leukemia (AML)...

..RAS mutations occur in 12% to 27% of patients with acute myeloid leukemia (AML) and enhance sensitivity to cytarabine in vitro. We examined whether RAS mutations impact response to cytarabine in vivo...

..Although the combination of oblimersen and IM is safe and feasible, we did not observe clinical benefit in these patients with imatinib-resistant CML using these doses and schedule...

..No correlation was observed between the development of DLT and pharmacokinetics. The RTPD is 1,750 mg. XK469R induced hematological responses in patients with refractory leukemia at tolerable doses...

..No patient has yet required transplantation. With median follow-up of 18 months, all patients remain in CCyR and 9 of 16 (54%) have undetectable BCR-ABL in the most recent blood and marrow sample...

..The primary objective of the study was to establish the maximum tolerated dose of 3-AP when given in combination with a fixed dose of cytarabine...

..In conclusion, nilotinib is an effective and well-tolerated treatment in imatinib-resistant and -intolerant CML-AP. This trial is registered at www.clinicaltrials.gov as NCT00384228...

..To validate ERG overexpression as an adverse predictor and assess its prognostic value in the context of other molecular markers in cytogenetically normal (CN) -acute myeloid leukemia (AML)...

..Based on these observations, a prospective study for AYAs with ALL using the more successful approach of the CCG has been initiated...

..The 1-year overall survival was 28% (95% CI, 15%, 43%). Nelarabine is well tolerated and has significant antitumor activity in relapsed or refractory T-ALL and T-LBL...

..5-7.7 years). Intensive consolidation therapy that included autologous peripheral stem-cell transplantation during CR1 may have contributed to the better outcome of this historically poor-prognosis group of CN-AML patients with MLL-PTD...

..We found only a borderline difference in median survival of patients with an initial t-MDS diagnosis compared with patients with an initial t-AML diagnosis...

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..To study the impact of repetitive (three to four courses) versus a single course of high-dose cytarabine (HDAC) consolidation therapy on outcome of patients with acute myeloid leukemia (AML) and inv(16)(p13q22) or t(16;16)(p13;q22)...

..RAS and FLT3 mutations, which are thought to stimulate the proliferation of leukemia cells, appear to be less common in t-MDS/t-AML than in de novo AML, whereas TP53 mutations are more frequent...

..02). It will be of interest to see if newly diagnosed t(9;22)-positive adult ALL patients with these and other secondary aberrations respond differently to treatment regimens that include imatinib mesylate...

..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...

..Quality of life (QOL) outcomes in patients with chronic myeloid leukemia (CML) were evaluated in an international phase III study...

..7, 2.6, and 2.2. We conclude that high BAALC expression predicts an adverse prognosis and may define an important risk factor in AML with normal cytogenetics...

..01) using a landmark analysis at 18 months. This intermittent schedule of rIFNalpha-2b/ara-C has a high response rate in patients with CML with acceptable toxicity...

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

..0001). Median survival time after diagnosis of t-MDS/t-AML was 8 months; survival at 5 years was less than 10%. These data confirm and extend previous associations between clinical, morphologic, and cytogenetic findings in t-MDS/t-AML...

..Establishing the molecular pathways involved in t-AML may facilitate the identification of selectively expressed genes that can be exploited for the development of urgently needed targeted therapies...

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..Rituximab administered concurrently with fludarabine in previously untreated CLL patients demonstrates marked clinical efficacy and acceptable toxicity. Phase 3 studies using this combination approach for patients with CLL are warranted...

..Expression of NKG2D ligands by leukemic cells was detected in the majority of cases tested and should be assessed for correlation with response to IL-2 in future studies...

..A series of patients enrolled onto an intergroup CLL trial were examined for this complication...

..Confirmation of these findings will require a prospective randomized trial comparing fludarabine and rituximab to fludarabine...

..To our knowledge, ours is the first relatively large study evaluating the usefulness of CRc attained immediately following induction chemotherapy...

..1), and p53 mutations. To date, the impact of these same prognostic factors have not been examined relative to treatment outcome with chemoimmunotherapy...

..This article describes the development, pharmacology, toxicity and clinical activity of clofarabine, as well as discuss its potential role in the treatment of acute leukaemia...

..To test the prognostic significance of ETS-related gene (ERG) expression in cytogenetically normal primary acute myeloid leukemia (AML)...

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..Therefore, we sought to determine whether these two cytogenetic groups should also be considered separate entities from a clinical standpoint...

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..We sought to determine if flavopiridol has activity in previously treated CLL using two schedules of administration...

..Herein, we investigated the feasibility of this approach in untreated elderly AML patients by administering oblimersen sodium (G3139), an 18-mer phosphorothioate antisense to Bcl-2, during induction and consolidation treatments...

..Toxicity was greater with multiagent chemotherapy. These 2 postremission regimens produced similar outcomes...

..Tipifarnib, an orally bioavailable inhibitor of farnesyl transferase, has activity in hematologic malignancies, but the dose required to achieve the proposed biologic end point, inhibition of farnesylation, is unknown...

..Evaluate the outcome of induction and postremission therapy in adults younger than 60 years with normal cytogenetics acute myeloid leukemia (AML)...

..Clinical rather than pharmacokinetic end points were used to develop two induction therapies containing drugs susceptible to Pgp-mediated efflux and associated with comparable toxicities at the maximum-tolerated doses...

..Acute myeloid leukemia (AML) with t(6;11)(q27;q23) is a well established but rare entity, and few studies have reported the full clinical, hematologic, and outcome data of patients with this disease...

..Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs...