Background We conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted in all children with newly diagnosed acute lymphoblastic leukemia. Methods A total of 498 evaluable patients were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission induction treatment. Continuous complete remission was compared between the 71 patients who previously would have received prophylactic cranial irradiation and the 56 historical controls who received it. Results The 5-year event-free and overall survival probabilities (95% confidence interval) for all 498 patients were 85.6% (79.9% to 91.3%) and 93.5% (89.8% to 97.2%), respectively. The 5-year cumulative risk of isolated central-nervous-system (CNS) relapse was 2.7% (1.1% to 4.2%), and that of any CNS relapse (isolated plus combined) was 3.9% (1.9% to 5.9%). The 71 patients had significantly better continuous complete remission than the 56 historical controls (P=0.04). All 11 patients with isolated CNS relapse remain in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blasts at diagnosis and a high level of minimal residual disease (≥ 1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the presence of the t(1;19)[TCF3-PBX1], any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to L-asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection. Conclusions With effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted in the treatment of childhood acute lymphoblastic leukemia.

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High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m2, is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury. This article provides comprehensive recommendations for prevention of toxicity from HDMTX, along with detailed treatment guidance to mitigate acute kidney injury and subsequent toxicity.

Although the field of pharmacogenetics has existed for decades, the implementation of, pharmacogenetic testing in clinical care has been slow. There are numerous publications, describing the barriers to clinical implementation of pharmacogenetics. Recently, several freely, available resources have been developed to help address these barriers. In this review we, discuss current programs that use preemptive genotyping to optimize the pharmacotherapy of, patients. Array-based preemptive testing includes a large number of relevant pharmacogenes, that impact multiple high-risk drugs. Using a preemptive approach allows genotyping results to, be available prior to any prescribing decision so that genomic variation may be considered as, an inherent patient characteristic in the planning of therapy. This review describes the common, elements among programs that have implemented preemptive genotyping and highlights key, processes for implementation, including clinical decision support.

St Jude Total Therapy Study XIIIB for childhood acute lymphoblastic leukemia (ALL) incorporated more stringent risk classification, early intensification of intrathecal chemotherapy, reinduction treatment, and the addition of dexamethasone to postremission therapy to increase the proportion of event-free survivors without jeopardizing their quality of life. Cranial irradiation was reserved for the 12% of patients who had T-cell ALL and a presenting leukocyte count of 100 ؋ 10 9 /L or more, or CNS-3 (5 or more leukocytes/L with identifiable blast cells in an atraumatic sample or the presence of cranial nerve palsy) status. Among the 247 consecutive patients enrolled in the study, 117 were classified as having lowerrisk leukemia and received mainly antimetabolite-based continuation therapy; the 130 cases with higher-risk leukemia received more intensive continuation chemotherapy with multiple drug pairs administered in weekly rotation. The 5-year event-free survival estimate was 80.8% ؎ 2.6% (SE); the 8-year rate was 78.6% ؎ 5.8%. The 5-year cumulative risk of an isolated central nervous system (CNS) relapse was 1.7% ؎ 0.8%, and that of isolated plus combined CNS relapse was 3.0% ؎ 1.1%. The 5-year cumulative risks of etoposide-related myeloid malignancies were 1.8% ؎ 1.3% in the lowerrisk patients who received a cumulative dose of 1.2 g/m 2 and 5.0% ؎ 2.0% in the higher-risk patients who received a cumulative dose of up to 14.4 g/m 2 (P ‫؍‬ .18). Independent adverse prognostic features included the presence of MLL-AF4 or BCR-ABL fusion gene and minimal residual leukemia of 0.01% 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.

Long-term central venous catheters (CVC) facilitate care for patients with chronic illnesses, but catheter occlusions and catheter-related thrombosis (CRT) are common complications. This review summarizes management of CVC and CRT. Mechanical CVC occlusions require cause-specific therapy; whereas, thrombotic occlusions usually resolve with thrombolytic therapy, such as alteplase. Prophylaxis with thrombolytic flushes may decrease CVC infections and CRT, but confirmatory studies and cost-effectiveness analysis are needed. Risk factors for CRT include previous catheter infections, malposition of the catheter tip, and prothrombotic states. CRT can lead to catheter infection, pulmonary embolism, and post-thrombotic syndrome. CRT is diagnosed primarily using Doppler ultrasound or venography and treated with anticoagulation for 6 weeks to a year, depending on the extent of the thrombus, response to initial therapy, and whether thrombophilic factors persist. Prevention of CRT includes proper positioning of the CVC and prevention of infections; anticoagulation prophylaxis is not recommended at present.

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