D Campana

..We noted the presence of CD34+ cells expressing CD13 but lacking CD33, a subset of cells not yet well characterized. In this report we describe the prevalence and the immunophenotype of this cell subset...

..This review summarizes recent advances in the application of minimal residual disease (MRD) testing in childhood acute lymphoblastic leukemia (ALL)...

....

..Here we review the relative advantages and disadvantages of flow cytometry for MRD studies, as well as results obtained in correlative studies with treatment outcome...

....

..This article discusses practical issues related to MRD methodologies and the evidence supporting the use of MRD for risk assignment in clinical trials...

....

..The presence of cells expressing these phenotypes in patients who are in clinical remission is associated with an increased risk of relapse...

..In this review, we discuss methodologic aspects and clinical results of flowcytometric detection of MRD in patients with acute leukemia...

..This article discusses the methodologies available for productive MRD testing and the clinical significance of the results...

..The time points at which MRD testing is performed and the threshold levels that trigger treatment intensification vary according to the methodology available, the results of preclinical correlative studies, and protocol design...

....

..The treatment described here produces high cure rates in children with lymphoblastic lymphoma without the use of prophylactic cranial irradiation...

..The next main challenge is to further increase cure rates while improving quality of life for all patients...

..These results indicate that studies of gene expression with cDNA arrays can aid the discovery of leukemia markers. (Blood. 2001;97:2115-2120)..

..For all patients, 5-year event-free survival and overall survival estimates were 44.1+/-5.4 and 50.0+/-5.5%. Our results suggest that cladribine in combination with continuous-infusion cytarabine is effective therapy for childhood AML...

..We here review the principles and methodologies for designing chimeric receptors and delivering them into immune cells, as well as some of the potential complications associated with this form of cell therapy...

..The immune system and overall growth and development were otherwise normal in this patient, suggesting that BLNK function is highly specific...

..These results establish direct contact with stroma as a survival requirement of normal B lymphoblasts and show marked heterogeneity in stromal dependency among B-lineage leukemic cells...

..Furthermore, they suggest that Igalpha does not play a critical role in B-cell development until it is expressed, along with mu heavy chain, as part of the pre-BCR...

....

....

..Pediatric acute lymphoblastic leukemia (ALL) is the prototype for a drug-responsive malignancy. Although cure rates exceed 80%, considerable unexplained interindividual variability exists in treatment response...

....

..We conclude that anti-CD19 chimeric receptors containing 4-1BB are a powerful new tool for T-cell therapy of B-lineage ALL and other CD19+ B-lymphoid malignancies...

..These results indicate that BLNK deficiency is a rare occurrence in childhood B-lineage ALL and is unlikely to be a common leukemogenic event as previously proposed...

..022); overt recurrence of AML within the subsequent 6 months was significantly more likely in the former group. The assay described here holds promise for guiding the choice of post-remission treatment options in children with AML...

..Thus, this new assay would enable most treatment centers to identify a high proportion of children with ALL who have an excellent early treatment response and a high likelihood of cure...

..These data suggest that with contemporary treatment, patients with the t(1;19) and TCF3/PBX1 fusion have a favorable overall outcome but increased risk of CNS relapse...

..We conclude that Tec is expressed and can be stimulated throughout human B-cell differentiation, implying that this tyrosine kinase plays a role in B-cell development and activation...

....

..The use of the two methods in tandem ensures MRD monitoring in all patients...

..This article discusses the relative merits of the available MRD assays and the significance of MRD in relation to clinical and biologic features of the disease, and treatment outcome...

..Thus, approximately half of the children with ALL achieve profound clearance of leukemic cells after 2 to 3 weeks of remission-induction chemotherapy, and these patients have an excellent treatment outcome...

..Therefore, this gene is a strong candidate for inclusion in gene expression arrays specifically designed for leukemia diagnosis...

..Thus, clotrimazole is cytotoxic to ALL cells at concentrations achievable in vivo...

..0% +/- 1.3% (n = 6) in KOPN55bi. CD32 ligation also reduced cell recovery in five of seven CD32(+) primary leukemia samples. Thus, FcgammaRIIA mediates signals that suppress the growth of lymphoid leukemia cells...

..Ultimately, treatment based on biological features of leukaemic cells, host genetics, and the amount of residual disease should improve cure rates further...

..In the interim, prospective clinical trials have provided valuable clues that are further increasing the cure rate of childhood acute lymphoblastic leukemia...

..Identifying the genetic and environmental factors that influence the clinical phenotype may enhance patient care and our understanding of normal B cell development...

..Prophylactic cranial irradiation has been a standard treatment in children with acute lymphoblastic leukemia (ALL) who are at high risk for central nervous system (CNS) relapse...

..01% or more at the end of the 6-week remission induction phase. Our results suggest the efficacy of early intensification of intrathecal chemotherapy and provide the basis for studies omitting cranial irradiation altogether...

....

..Our goal was to use the information to further refine therapy and advance cure rates...

..We reviewed the outcome of older adolescents (age 15 to 18 years) treated in four consecutive Total Therapy studies to determine if recent improved treatment extended to this high-risk group...

..In the analysis of a paediatric leukaemia data set, PROMISE effectively identifies genomic features that exhibit a biologically meaningful pattern of association with multiple endpoint variables...

..We also suggest that hematopoietic stem cell transplantation is often not required for cure of these patients...

..The authors evaluated the response rate, toxicity, and pharmacokinetics of topotecan given before standard induction therapy for childhood acute lymphoblastic leukemia (ALL) in first relapse...

..Incorporation of the expression levels of these genes into existing strategies of risk classification could improve clinical management...

..We conclude that MRD assays should be used to guide the selection of postremission therapy in patients with ALL in first relapse...

..Other clinically informative uses of MRD testing include the detection of early relapse and the evaluation of the efficacy of new antileukemic agents...

..1. These findings indicate that expression of the functional lambda5/14.1 is critical for B cell development in the human...

..These results provide what we believe to be a new basis for understanding asparaginase resistance in ALL and indicate that MSC niches in the bone marrow can form a safe haven for leukemic cells...

..047). Thus, low levels of MRD (0.001%-< 0.01%) at the end of remission induction therapy have prognostic significance in childhood ALL, suggesting that patients with this finding should be monitored closely for adverse events...

..The transfected mRNA conferred powerful cytotoxicity to T cells against CD19+ targets from the same donor. These results demonstrate that this method can be applied to generate autologous T lymphocytes directed toward malignant cells...

..Recent genomewide analyses have identified a high frequency of DNA copy-number abnormalities in ALL, but the prognostic implications of these abnormalities have not been defined...

..We suggest that the methods described here should have many applications in studies of NK cell biology and NK cell-based therapies...

..A strong correlation between flow cytometric measurements of MRD during clinical remission and treatment outcome has been demonstrated, suggesting that these assays should be incorporated into treatment protocols...

..Thus, the single platform of expression profiling should enhance the accurate risk stratification of pediatric ALL patients...

..We studied leukaemic cells, collected at diagnosis, to identify cases with ETP features and determine their clinical outcome...

..Summarized are current efforts for NK cell immunotherapy for cancer and future perspectives...

..Our findings indicate that enforced expression of signaling receptors by NK cells might circumvent inhibitory signals, providing a novel means to enhance the effectiveness of allogeneic stem cell transplantation...

..Measurements of disease dissemination at diagnosis might provide useful prognostic information, which can be further refined by monitoring response to therapy through blood testing...

..We sought to identify the most sensitive tumor subtypes, clarify the molecular interactions regulating cytotoxicity, and determine NK antitumor potential in vivo...

..007). These results indicate that peripheral blood may be used to monitor MRD in patients with T-lineage ALL and that peripheral blood MRD may provide strong prognostic information in patients with B-lineage ALL...

..2%). Blast phenotypes were stable in culture and at relapse, and were useful for MRD monitoring in patients. Marker combinations for childhood ALL are also applicable to adult cases...

..Current knowledge indicates that MRD studies using well-tested methodologies are clinically useful and should be incorporated into the clinical management of patients with acute leukaemia...

..04). The GSTM1 non-null and TYMS 3/3 genotypes are plausibly linked to drug resistance. Polymorphisms interact to influence antileukemic outcome and represent determinants of response that can be used to optimize therapy...

..We conclude that both MRD assays yield generally concordant results. Their combined use should enable MRD monitoring in virtually all patients and prevent false-negative results due to clonal evolution or phenotypic shifts...

..The proposed studies will further characterize the antileukemic activity of BAY 36-1677 and identify synergistically interacting compounds. ..

..The development of new automated MRD assays and the identification of new markers of leukemia should improve residual disease evaluation and thereby improve risk-directed therapy selection for every child with ALL. ..

..Success in this endeavor could radically improve remission studies in these patients by overcoming the practical and ethical constraints posed by sequential bone marrow aspirations ..

..The research proposed should not only spur clinical studies of immune cells in patients with refractory ALL but also facilitate the development of effective cell therapies for other neoplasms. ..

..Studies in this aim will determine whether higher levels of blood MRD and of circulating leukemic stem cells correlate with a higher risk of relapse. ..

..The research proposed should not only spur clinical studies of immune cells in patients with refractory ALL but also facilitate the development of effective cell therapies for other neoplasms. ..

..The techniques established in this project should be applicable to in vitro models for testing of antileukemic agents...

..Establishing a drug sensitivity assay with prognostic relevance could lead to improved rationales for drug selection in individual patients with ALL. ..

..The studies proposed in this application should meet that need and demonstrate the feasibility of clinical management decisions based on MRD detection in children with ALL. ..

..Studies in this aim will determine whether higher levels of blood MRD and of circulating leukemic stem cells correlate with a higher risk of relapse. ..