Jeffrey E Rubnitz

..To the authors' knowledge, the impact of age relative to that of other prognostic factors on the outcome of patients treated in recent trials is unknown...

..The development of molecularly targeted agents, some of which are already in clinical trials, holds great promise for the future...

..Despite the efficacy of the cladribine and cytarabine regimen in treating newly diagnosed acute myeloid leukemia (AML) in a previously reported study, the combination was not effective for relapsed or refractory childhood AML...

..More important, we must develop alternative treatment approaches, such as agents that target specific leukemia-associated abnormalities and agents that selectively eradicate leukemic stem cells...

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

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..We propose to further investigate the efficacy of KIR-mismatched NK cells in a phase II trial as consolidation therapy to decrease relapse without increasing mortality in children with AML...

..We therefore sought to determine if detection of relapse by blood counts before the onset of symptoms provided any clinical benefit...

..Despite improvements in supportive care, death due to treatment toxicity remains a significant problem for children treated for acute leukemia...

..In addition, gene expression profiling may improve the genetic classification of leukaemia and identify clinically important subgroups. It may also lead to the identification of new targets for novel antileukaemic agents...

..Outcome after recurrence of childhood acute myeloid leukemia (AML) is poor. We performed this study to identify prognostic factors for recurrence and for survival after recurrence of AML...

..The association between race and outcome of treatment for childhood acute myeloid leukemia (AML) has not been adequately studied...

..Several novel therapeutic agents targeted to molecular lesions of leukemic cells are under investigation...

..To determine the molecular characteristics, clinical features, and treatment outcomes of children with acute lymphoblastic leukemia (ALL) and the t(11;19)(q23,p13.3) translocation...

..Molecular techniques are also used to detect minimal residual disease and genetic polymorphisms that are important in optimizing drug therapy...

..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...

..To prospectively determine the prognostic significance of the TEL-AML1 fusion in children with acute lymphoblastic leukemia (ALL)...

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..Additional studies are required to determine whether serial MBL measurements may be valuable for this purpose...

..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...

..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...

..Response can now be assessed by minimal residual disease (MRD) monitoring with flow cytometry or polymerase chain reaction (PCR). We determined the relation among the results of these approaches and their prognostic value...

..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...

..Further, the systemic clearance of methotrexate, teniposide, etoposide, and cytarabine did not differ with BMI (P > .3). We conclude that BMI does not affect the outcome or toxicity of chemotherapy in this patient population with ALL...

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..10; P = .01) at the time of transplantation. We concluded that transplantation has improved over time and should be considered for all children with very high-risk leukemia, regardless of matched donor availability...

..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...

..To assess the toxicity, pharmacokinetics, and pharmacodynamics of multikinase inhibitor sorafenib in combination with clofarabine and cytarabine in children with relapsed/refractory leukemia...

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

..The percentage of myeloperoxidase (MPO)-positive blast cells is associated with prognosis in adult acute myeloid leukemia (AML), but this association is unsubstantiated in pediatric AML...

..The prognosis after recurrence of pediatric acute myeloid leukemia (AML) is poor, and effective salvage regimens are urgently needed...

..Treatment results for acute lymphoblastic leukemia (ALL) clearly have improved over the past decade, but black children have not fared as well as white children in large national trials...

..9% versus 78% +/- 3.1% (P = .08). These data suggest that CD20 expression is not associated with inferior outcome in pediatric patients treated with contemporary regimens...

..16 can be included in the low-risk arm of treatment protocols. We cannot make similar recommendations for patients with T-lineage ALL because of the small number of cases (n = 3) in this study...

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

..97; P =.03) and the t(9;11) (relative risk of relapse, 0.32; 95% confidence interval, 0.16 to 0.64; P =.002). CONCLUSION: We conclude that the t(9;11) is the most favorable genetic factor for patients with AML treated at our institution...

..Surprisingly, AMLs containing partial tandem duplications of MLL failed to cluster with MLL chimeric fusion gene cases, suggesting a significant difference in their underlying mechanism of transformation...

..Treatment outcome for black patients with cancer has been significantly worse than for their white counterparts. We determined whether recent improved treatment had narrowed the gap in outcome between black and white pediatric patients...

..Little is known about the incidence of secondary neoplasms after 15 to 20 years in children and adolescents who were treated for acute lymphoblastic leukemia...

..However, the optimal G-CSF dosage for patients with AML has not been determined. To the authors' knowledge, G-CSF dosages have not been compared in a randomized AML study...

..Although MRD before HCT is a strong prognostic factor, its impact has diminished and should not be regarded as a contraindication for HCT...

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..Traumatic or bloody lumbar puncture (LP) reduces the diagnostic value of the procedure and may worsen the outcome of patients with acute lymphoblastic leukemia (ALL). Little is known about the risk factors for traumatic and bloody LP...

..The prognostic significance of age among pediatric patients with acute myeloid leukemia (AML) was investigated...

..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...

..To the authors' knowledge, no recently published study has evaluated the management and clinical course in this regard, especially in relation to pediatric patients...

..Investigation for SEL in leukemia or lymphoma patients with difficult lumbar punctures is warranted. Placement of an Ommaya reservoir may facilitate safe CNS-directed therapy in severely affected patients...

..The aim of this study was to determine whether antibiotic prophylaxis during periods of neutropenia reduced streptococcal (S. viridans) sepsis and overall bacterial sepsis...

..Therefore, the clinical usefulness of MR imaging as a screening tool for AVNB in this set of patients remains uncertain...

..They also suggest that dose intensification of etoposide and addition of 2-CDA may also offer an advantage. This study underscores the dependence of the prognostic impact of cytogenetic features on the efficacy of treatment...

..The effect of body mass index (BMI) on the treatment outcomes of children with acute myeloid leukemia (AML) is unclear and needs further evaluation...

..We investigated a treatment strategy combining sorafenib, a multikinase inhibitor with limited single-agent activity in AML, and cytarabine, a key component of AML chemotherapy...

..Life-threatening pulmonary complications that coincide with cell lysis during early chemotherapy and that mimic systemic inflammatory response syndrome (SIRS) have been reported in patients with acute myeloid leukemia (AML)...

..These results suggest that t(8;21)-positive AML represents a heterogeneous disease with variable outcome. The reported favorable outcome for t(8;21)-positive AML in other studies may be due to the use of high-dose cytarabine...

..Allogeneic transplantation during remission offers the best chance of cure; in the absence of remission, transplantation offers no advantage over chemotherapy alone. (Blood. 2001;97:3727-3732)..

..CNS involvement had no adverse prognostic significance, and patients with CNS2 status had similar outcome to CNS1 patients in this large group of pediatric patients with AML, treated at a single institution...

..4-fold). Collectively, these findings indicate that etoposide can inhibit hOCTN2 function, potentially disturb carnitine homeostasis, and that this phenomenon can contribute to treatment-related toxicities...

..Our findings demonstrates the feasibility of measuring HRQoL in adolescents with OS or AML (and their parents) at the time of diagnosis, and thus their HRQoL ratings can be used to inform their cancer care from diagnosis forward...

..We report the successful use of levetiracetam monotherapy after Phenobarbital load in a neonate with leukemia and localization-related epilepsy...

..Future studies should focus on improving treatments for primary AML while preventing second malignancies...

..These data indicate that contamination of CSF with circulating leukemic blast cells during diagnostic lumbar puncture can adversely affect the treatment outcome of children with ALL and is an indication to intensify intrathecal therapy...

..Patients with thrombocytopenia are at risk for spontaneous or procedure-related hemorrhage. Whether such patients can safely undergo lumbar puncture (LP) without prophylactic platelet transfusion is unknown...

..To investigate the incidence of and risk factors for late sequelae of treatment in patients who survived for more than 10 years after the diagnosis of childhood acute myeloid leukemia (AML)...

..This report is the first to describe new partner breakpoints at 2p23 and 6p22 for MLL and CBFA2 genes, respectively, and concurrent rearrangements of these genes in a patient with secondary MDS...

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..0+/-9.6% for those with late relapse and 20.0+/-8.0% for those with early relapse. We conclude that low-dose etoposide administered orally has a cytoreductive effect in relapsed ALL...

..We conclude that subtype-specific therapies are needed to replace the 'one size fits all' strategy of the past two decades...

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

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

..To reassess the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia (ALL)...

..In conclusion, the prognostic impact of overt testicular disease has diminished. Irradiation appears to provide no survival advantage to this patient population...

..To investigate the role of ontogeny in sorafenib metabolism to the equipotent active metabolite sorafenib N-oxide...

..We also show a relatively high incidence of ABCG2 mRNA expression in non-Down associated M7 AML, which may contribute to the relatively poor prognosis of the M7 AML subtype...

..These data indicate that the malignant clone was not present before therapy, arose early during chemotherapy, and was able to proliferate even during exposure to antileukemic therapy...

..These data reflect a remarkably low burden of genomic alterations within pediatric de novo AML, which is in stark contrast to most other human malignancies...

..With the increasing population of immunocompromised children, it is essential for timely management that clinicians have a high index of suspicion for this unusual presentation of aspergillosis...

..Pediatric patients with or without hyperglycemia during remission induction for ALL have similar clinical outcome. Occurrence of hyperglycemia does not warrant alteration of the antileukemic regimen...

..05). Seven patients (35%) had recurrent urolithiasis. Patients with ALL are at risk of developing calcium renal stones during chemotherapy, especially when a glucocorticoid is included...

..These data suggest that expression of CBFA2T3-GLIS2 directly contributes to leukemogenesis...

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..The fungus was identified by DNA sequencing using both the internal transcribed spacer and D1/D2 region of the 28S ribosomal DNA gene...

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..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...

..Incorporating knowledge of this gene rearrangement into treatment decisions serves as a paradigm for translating molecular discoveries into clinically meaningful data to direct patient care and improve outcome...