Xavier Thomas

..0002). Trisomy 8 in addition to favorable karyotype maintained a good clinical outcome, while trisomy 8 in addition to unfavorable cytogenetics showed the worst prognosis...

..These agents may be potentially administered at different times of leukemia therapy: before or instead of chemotherapy, as maintenance therapy, prior to allogeneic stem cell transplant (SCT) or after relapse following SCT...

..We conclude that most adult patients with recurring AML could not be rescued using current available therapies, although allogeneic SCT remains the best therapeutic option at this stage of the disease...

..This agent should provide a unique opportunity to treat selected ALL patient subpopulations...

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..CR proportion was significantly higher in patients with a first CR duration > or =6 months when compared with those from a control trial using standard-dose mitoxantrone (90 vs 70%, p=0.03)...

..In a first report, we have shown that priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) may enhance complete remission (CR) rate and event-free survival (EFS) in younger adults with acute myeloid leukemia (AML)...

..This article reviews the results of important trials in which TSC was used as an induction regimen in de novo, relapsed, or refractory acute myelogenous leukemia or as postremission therapy...

..All these special issues are addressed in this review of the literature...

..New therapeutic approaches are warranted to improve the outcome in this age group of ALL patients...

..04). There were no significant differences between the three groups in terms of disease-free survival...

..The data reported in this review are derived from the medical literature and from the experience of the authors...

..We analyzed the benefits of a risk-adapted postremission strategy in adult lymphoblastic leukemia (ALL), and re-evaluated stem-cell transplantation (SCT) for high-risk ALL...

..New strategies are required that specifically target the malignant stem cell population...

..Advantages of these therapeutic alternatives to native L-asparaginase and their results as part of preliminary clinical trials in adults have been outlined in this review...

..It is anticipated that these studies will serve to define the optimal roles of FTIs in patients with these hematologic malignancies and provide insight into effective methods by which to combine FTIs with other agents...

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..Leukemic relapse remains a major therapeutic challenge. Adult ALL with CNS recurrence remains of poor prognosis and is generally associated with a systemic and medullary relapse...

..Here we review the results of timed-sequential chemotherapy, used as induction regimen in de novo, relapsed or refractory AML or used as post-remission therapy, and compare them with those from other types of regimens...

..We evaluate the outcome of this post-remission approach after complete remission (CR) and consolidation in elderly patients included in the EORTC-GIMEMA AML-13 trial...

..Priming of leukemic cells with hematopoietic growth factors is a means of enhancing the efficacy of chemotherapy in younger adults with AML...

..Leukemic relapse remains a major therapeutic problem and CNS involvement at the time of relapse occurs in 1-15% of cases. Adult ALL with CNS recurrence remains of poor prognosis and is generally associated with a systemic relapse...

..New challenges have emerged with respect to induction of resistance to imatinib via ABL mutations. Several novel kinase inhibitors with significantly more potent anti-leukemic activity than imatinib are currently being developed...

..General therapeutic options for adult patients with acute leukemia are reviewed and specific new treatment strategies are described...

..With a better understanding of the disease, more target-specific therapies could be designed. The aim of this review is to highlight new pharmacotherapies and those emerging drug treatments for patients with adult ALL...

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..Current studies are underway to better define the role of clofarabine in younger and elderly patients with AML, and also explore development strategies for an oral formulation...

..To test the value of the combination of pefloxacin and vancomycin as gastro-intestinal tract decontamination for the prevention of infections in patients with chemotherapy-induced neutropenia...

..It is a potential marker of prognosis in patients with leukemia...

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..Identification of valuable factors that can facilitate therapeutic decision-making between intensive chemotherapy and investigational treatment strategies is warranted...

..The persistence of normal residual hematopoiesis and intense leukemic cells mitotic activity were both factors of favorable outcome, while BM fibrosis did not display any prognostic value...

..Molecular monitoring for the PML-RARalpha fusion protein permits prompt intervention for early molecular relapse ultimately improving chances of prolonged remission...

..The questions relating to the pathogenesis of cardiac failure are discussed. We also discuss the prophylactic measures required for such treatment-related side effects...

..AP24534 could be the next treatment of choice in hematological malignancies with Philadelphia-positive chromosome, particularly Ph(+) ALL known for its frequent occurrence of T315I mutation...

..We conclude that the pejorative overall outcome in elderly ALL points to the need for new therapeutic trials taking into account the specific characteristics of ALL in this age group...

..This study demonstrates that TSC did not produce any benefit when used as consolidation therapy in younger adults compared with HDAraC. This trial was registered at www.clinicaltrials.gov as #NCT00880243...

..New treatment options, needed to be developed to further improve on the therapeutic perspectives for adult patients with ALL, and therapeutic schedules of main cooperative groups are also reviewed...

..Results in adults who experience a relapse after conventional chemotherapy support the use of autologous HSCT as salvage therapy if such patients achieve a subsequent CR...

..In conclusion, more prolonged ambulatory treatment should be preferred to intensive chemotherapy as postremission therapy in elderly patients with AML reaching CR after standard intensive remission induction...

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..Both TCR and genotypic stratification can therefore contribute to risk-adapted management of adult T-ALLs...

..We recommend its consideration before allo-HSCT in the donor-recipient selection parameters...

..The aim of the present study was to analyze the decisional value of poor risk factors in 416 elderly patients treated in the ALFA-9803 trial in order to derive a decisional index...

..This retrospective analysis points to a somewhat heterogenous group of AML in terms of biological features and outcome, and warrants a larger multicenter study with study in molecular biology to clarify treatment effects further...

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..Allogeneic SCT in first CR is the current best treatment option in adults with the disease. New strategies must be tested during early phases of therapy to increase the rate of BCR-ABL(-) remissions...

..CONCLUSION: We conclude that ATRA in combination with Ida and Ara-C can be administered safely to high-risk AML patients. However, in this setting, ATRA did not offer any advantage when compared to chemotherapy alone...

..The impact of initial characteristics on prognosis has been addressed previously in elderly patients; however, very few data are available regarding the prognostic value of immunophenotypic characteristics in this setting...

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..The response rate observed in this heavily pretreated group of patients suggests the requirement to enhance the response rate either by combining tipifarnib with other active agents or determining factors that are predictive of response...

..The eight survivors (15%), including two patients with unfavorable or intermediate karyotype, remained in first complete remission 50+ to 119+ months after transplantation and are probably cured...

..All other patients displayed a poor outcome. This suggests their orientation at an earlier time to alternate therapeutic programs based on investigational drugs...

..In this investigation, the authors attempted to express the results in terms of the proportion of long-term disease-free survivors and in terms of lifetime in patients who developed recurrent disease or died...

..7; 95% confidence interval, 1.08-6.7; and 2.9; 95% confidence interval, 1.01-8.2; with P = .034 and .05, for abnormal karyotype and FLT3-ITD, respectively)...

..Chemotherapy treatment during the second or third trimester may not require termination of pregnancy, because as remission of AL and delivery of a normal infant are likely to be obtained...

..Better supportive care strategies may improve overall survival in patients undergoing chemotherapy for acute myeloid leukemia...

..There is no standard post-remission therapy in older patients with acute myeloid leukemia...

..4% for PMC (P < 0.0001 and P < 0.0001). Multivariate analysis only showed a significant impact of chimaerism status on OS, as well as acute and chronic graft-versus-host disease on EFS, with a trend for conditioning regimen...

..This analysis suggests that predictive factors may be split into tolerance factors and haematological factors. Determination of such factors is crucial to adapt postremission therapeutic strategies in acute lymphoblastic leukaemia...

..5; intermediate index, 2.5-20; high index, 20 or more). In multivariate analysis, the WBC index was the only prognostic factor for DFS (P =.003), complete remission duration (P =.002), and overall survival (P =.04)...

..The study objectives were: 1) to report on invasive aspergillosis patients in a hematology department; and 2) to estimate its incidence according to the hematologic diagnosis...

..003). CD20 expression thus appears to be associated with a worse outcome, which reinforces the interest of evaluating rituximab combined to chemotherapy in CD20-positive adult BCP-ALL. ClinicalTrials.gov ID, NCT00222027...

..We suggest that hypodiploidy with 30 to 39 chromosomes or near-triploidy should be regarded as a new high-risk factor in the risk stratification of adult ALL protocols...

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..Other expected adverse events were comparable to those observed with E. colil-ASNase and there was also no difference between the three doses of GRASPA(®) ...

..All other patients displayed a very poor outcome and must be oriented after failure of first-line therapy to alternate therapeutic programs based on investigational drugs...

..Our results suggest that dCK and cN-II mRNA expression in leukaemic blasts at diagnosis is correlated with clinical outcome and may play a functional role in the resistance to ara-C in patients with AML...

..These results demonstrate that the expression of high levels of high Km 5NT in blast cells is correlated with outcome in patients with AML...

..In NN patients, FLT3-ITD was the main bad-prognosis factor for second CR achievement and survival, leading to consider SCT earlier, at least in FLT3-ITD patients with a donor...

..Patient's age and response to induction treatment are two independent infection risk factors, and need more attention during future clinical trials linked to antifungal prophylaxis...

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..The large field of monoclonal antibodies will be also approached focusing on antibodies developed in leukemias...

..This might suggest a benefit of initial leukapheresis in the treatment of AML presenting with hyperleukocytosis...

..To our knowledge, this is the first description of a mini-allograft in an APL patient achieving molecular remission after As2O3 therapy...

..It was associated with severe infections during aplasia. Leukemogenic compounds favoring complex karyotypic abnormalities could also be involved...

..Of interest, the reduced relapse risk after ASCT translated in better disease-free survival in the 300 rapid responders who reached CR after the first induction course...

..We conclude that PBSC mobilization with G-CSF alone initiated in steady state is a feasible, safe, and suitable procedure for harvesting cells in sight of autologous transplantation in adult acute myeloid leukemia...

..Only T cell lineage ALL outcomes have improved over the years. The results suggest a time (3 years) at which it becomes reasonable to speak of potential cure, provided the patient is in CR...

..The very poor overall outcome in elderly patients with Ph+ ALL may be significantly improved by the introduction of imatinib mesylate into current treatment regimens...

..5 months (range, 1-14 months) in the IDA and MIT arms respectively. We conclude that CBP at a cumulative dosage of 1 g/m2 together with intercalating agents (IDA/MIT) has antileukemic efficacy in elderly patients...

..A multivariate analysis demonstrated a significantly worse survival rate after transplantation for female recipients, advanced disease and acute leukemia before transplantation...

..In conclusion, although similar to published studies in elderly patients with ALL, this study is inferior to our previous one. INF, given as a single drug, has a modest role if any in the treatment of older persons with ALL...

..EPO-beta-ATRA combination appears a possible therapeutic option in anemia of MDS having failed an ESA alone, but not in patients with high endogenous EPO level, and does not improve neutropenia and thrombocytopenia...

..Distinctive subgroups can be identified according to prognostic factors related to survival. A larger multicenter study with well-defined diagnostic criteria is warranted to further clarify treatment effects...

..Recently, 2 groups reported that WT1 mutations occur in approximately 10% of normal karyotype AMLs and are an independent predictor of poor outcome in this subgroup of patients with AML...

..The objective of the study was to assess the impact of the relocation of an adult hematological intensive care unit on invasive aspergillosis (IA) incidence...

..In conclusion, we show herein that upon allogeneic reaction, TNFbeta secretion contributes, in concert with IFNgamma, to increase or restore surface molecules involved in AML blast interaction with T cells...

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..We thus propose a risk classification that includes in the favorable subgroup all patients from the intermediate subgroup displaying CEBPA mutations when not associated with FLT3-ITD...

..To compare pediatric and adult therapeutic practices in the treatment of acute lymphoblastic leukemia (ALL) in adolescents...

..These results suggest that expression of 5NT and reduced hENT1 in leukemic blasts at diagnosis are correlated with clinical outcome and may play a role in resistance mechanisms to ara-C in patients with AML...

..In multivariate analysis, shorter OS was related to DNA POL positivity. These results suggest that expression of DNA POL, 5NT and hENT1 at diagnosis may be resistance mechanisms to ara-C in AML patients...

..However, the median DFS was short requiring the rapid completion of effective intensive postremission therapy...

..We propose that TLX1(+) T-ALLs be defined as cases expressing TLX1/ABL ratios greater than 1 and/or demonstrating TLX1 rearrangement. Therapeutic modification should be considered for those patients...

..Resistance to this inhibition may occur. We investigated the role of the K247R polymorphism in persistent sensitivity...