S Jeha

..Clofarabine is well tolerated and shows significant antileukemic activity in heavily pretreated children. Multicenter phase 2 trials in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are ongoing...

..These data confirm that rasburicase is effective and safe for the treatment and prophylaxis of children and adults with malignancy-associated hyperuricemia...

..To determine the efficacy and safety of clofarabine in pediatric patients with refractory or relapsed acute myeloid leukemia (AML)...

..Recent advances in genome-wide screening techniques, pharmacogenomic studies, and development of molecular therapeutics are ushering in an era of more refined personalized therapy...

..Ongoing trials are studying the benefits of clofarabine combinations in less heavily pretreated patients, and the use of different dose schedules in a variety of hematologic malignancies...

..A recombinant form of urate oxidase, rasburicase, is now available. In this chapter we will present an overview of rasburicase development and discuss the impact of rasburicase in the prevention and management of TLS...

..Ongoing studies are exploring the benefit of clofarabine combinations in less heavily pretreated patients and the use of different dose schedules in a variety of hematological malignancies...

..To evaluate the efficacy and safety of clofarabine, a novel deoxyadenosine analog, in pediatric patients with refractory or relapsed acute lymphoblastic leukemia (ALL)...

..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...

..Some have already been adopted into standard regimens, while others remain in early stages of development. This review summarizes the current status of these novel therapies as they get integrated into ALL regimens...

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

..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...

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..05) in both cohorts. Chromosome 5q33 has previously been associated with asthma and atopy. These data contribute to the growing body of evidence that there is an inherited component to predisposition to drug allergy...

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

..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...

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

..In this report we describe significant single agent activity of clofarabine in disseminated LCH refractory to salvage regimens, including cladribine...

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

..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...

..Because of the constant release of new drugs, health-care providers need to check the most recent references before making recommendations about drug interactions...

..It is the first new drug for paediatric leukaemia to be approved in more than a decade, and the only one to receive approval for paediatric use before adult use...

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..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...

..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...

..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...

..83; 95% confidence interval, 0.78-0.89; P=0.007). Antibodies were related to clinical allergy and to low systemic exposure to asparaginase, leading to lower risk of some adverse effects of therapy...

..Resolution of diffusion abnormalities did not preclude further toxicity and a large lesion could cause persisting symptoms...

..Encouraging activity was observed in acute leukemia...

..The remissions were sustained with repeated cycles of monotherapy for 47, 59, and 64 weeks, respectively...

..Novel schedules are being explored in lymphoproliferative disorders and solid tumors. Clofarabine is a new nucleoside analog with considerable activity and an acceptable safety profile in acute leukemias...

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..The 3-month cytogenetic response to imatinib mesylate refined the prognostic relevance of such studies in patients on imatinib mesylate therapy...

..03). This increased only in responders (median, 1.8-fold; P =.008) after the second clofarabine infusion. In summary, clofarabine is active in acute leukemias and MDS; cellular pharmacokinetics may have prognostic significance...

..Rituximab is used to primarily deplete normal B cells from HD lesions...

..This has translated into the recognition of several subgroups of ALL and the institution of risk-adapted therapies. New therapies are emerging based on the definition of specific cytogenetic-molecular abnormalities...

..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...

..Unlike in adults, VEGF and VEGF-R2 levels in pediatric AML patients did not correlate with survival. This data suggest that the role of VEGF and its receptor VEGF-R2 in pediatrics AML may be different from that in adult AML...

..The recommended phase II regimen is Triapine 105 mg/m2/day followed by ara-C 600 mg/m2/day for 5 consecutive days every 3-6 weeks...

..Ongoing and future studies will examine the use of clofarabine in elderly patients with AML for whom standard regimens are too toxic, and in MDS intravenous and oral forms of the drug...

..Imatinib mesylate, a specific Bcr-Abl tyrosine kinase inhibitor, has shown encouraging activity in chronic myelogenous leukemia (CML)...

..001). Competitive quantitative polymerase chain reaction (QPCR) studies at 9 months showed a median QPCR value (ratio of BCR-ABL/ABL transcripts x 100) of 0.59% overall and of 0.24% (range, 0.001%-29.5%) for complete cytogenetic response...

..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)...

..CONCLUSIONS: The current results suggest, that for patients with P-AML, bone marrow TA is a highly significant prognostic factor...

..003). These results indicate that differences in DNA methylation of specific molecular pathways may contribute to the prognostic differences known to occur between pediatric and adult patients with ALL...

..The results confirm that clofarabine should continue being dosed on a per-squaremeter or per-body-weight basis...

..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...

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