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.

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.

MTX-related clinical neurotoxicity is transient, and most patients can receive subsequent MTX without recurrence of acute or subacute symptoms. All symptomatic patients and one in five asymptomatic patients develop leukoencephalopathy that can persist until the end of therapy. Polymorphisms in genes related to neurogenesis may contribute to susceptibility to MTX-related neurotoxicity.