There is a need to improve pediatric palliative care. Recurring themes in the family interviews suggest useful issues to consider in the development of a palliative care program.
There was no overall difference in skeletal toxicity by corticosteroid type; dexamethasone was associated with more infections and, in older children, increased incidence of osteonecrosis and fracture. There was no difference in asparaginase-related toxicity by EC-Asnase dosing method. Dexamethasone and ID EC-Asnase were each associated with superior EFS. Monitoring NSAA during treatment with EC-Asnase may be an effective strategy to improve outcome in pediatric ALL.
Summary Background Doxorubicin chemotherapy is associated with cardiomyopathy. Dexrazoxane reduces cardiac damage during treatment with doxorubicin in children with acute lymphoblastic leukaemia (ALL). We aimed to establish the long-term effect of dexrazoxane on the subclinical state of cardiac health in survivors of childhood high-risk ALL 5 years after completion of doxorubicin treatment. Methods Between January, 1996, and September, 2000, children with high-risk ALL were enrolled from nine centres in the USA, Canada, and Puerto Rico. Patients were assigned by block randomisation to receive ten doses of 30 mg/m² doxorubicin alone or the same dose of doxorubicin preceded by 300 mg/m² dexrazoxane. Treatment assignment was obtained through a telephone call to a centralised registrar to conceal allocation. Investigators were masked to treatment assignment but treating physicians and patients were not; however, investigators, physicians, and patients were masked to study serum cardiac troponin-T concentrations and echocardiographic measurements. The primary endpoints were late left ventricular structure and function abnormalities as assessed by echocardiography; analyses were done including all patients with data available after treatment completion. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00165087. Findings 100 children were assigned to doxorubicin (66 analysed) and 105 to doxorubicin plus dexrazoxane (68 analysed). 5 years after the completion of doxorubicin chemotherapy, mean left ventricular fractional shortening and end-systolic dimension Z scores were significantly worse than normal for children who received doxorubicin alone (left ventricular fractional shortening: −0·82, 95% CI −1·31 to −0·33; end-systolic dimension: 0·57, 0·21–0·93) but not for those who also received dexrazoxane (−0·41, −0·88 to 0·06; 0·15, −0·20 to 0·51). The protective effect of dexrazoxane, relative to doxorubicin alone, on left ventricular wall thickness (difference between groups: 0·47, 0·46–0·48) and thickness-to-dimension ratio (0·66, 0·64–0·68) were the only statistically significant characteristics at 5 years. Subgroup analysis showed dexrazoxane protection (p=0·04) for left ventricular fractional shortening at 5 years in girls (1·17, 0·24–2·11), but not in boys (−0·10, −0·87 to 0·68). Similarly, subgroup analysis showed dexrazoxane protection (p=0·046) for the left ventricular thickness-to-dimension ratio at 5 years in girls (1·15, 0·44–1·85), but not in boys (0·19, −0·42 to 0·81). With a median follow-up for recurrence and death of 8·7 years (range 1·3–12·1), event-free survival was 77% (95% CI 67–84) for children in the doxorubicin-alone group, and 76% (67–84) for children in the doxorubicin plus dexrazoxane group (p=0·99). Interpretation Dexrazoxane provides long-term cardioprotection without compromising oncological efficacy in doxorubicin-treated children with high-risk ALL. Dexrazoxane exerts greater long-term cardioprotective effects in girls than in boys. Funding US Nat...
For 10 winters, 608 children five years old or younger who were hospitalized with respiratory syncytial virus (RSV) infection were prospectively studied to evaluate the relation between their immune status and the severity of their infection. Forty-seven had been immunocompromised by chemotherapy, steroid therapy, or a primary immunodeficiency disorder. Among the immunocompromised children, those receiving chemotherapy for cancer and those with immunodeficiency disease had more severe RSV disease, with pneumonia occurring at all ages, and a higher mortality rate. Children receiving long-term steroid therapy did not appear to have more severe clinical manifestations than normal children. Viral shedding, however, was significantly greater and more prolonged in the children receiving steroid therapy, and particularly in those receiving chemotherapy or with an immunodeficiency disease. Giant-cell pneumonia was documented in one child with leukemia. Over half the immunocompromised children acquired the RSV infection nosocomially. These findings indicate that children receiving chemotherapy for cancer and those with immunodeficiency disease are at risk for complicated or fatal infections from RSV and should be considered for antiviral and other therapies as they become available. Efforts should also be made to protect compromised children if hospitalization cannot be avoided.
The Dana-Farber Cancer Institute (DFCI) Childhood ALL Consortium Protocol 95-01 was designed to minimize therapy-related morbidity for children with newly diagnosed ALL without compromising efficacy. Patients participated in randomized comparisons of (1) doxorubicin given with or without dexrazoxane, a cardioprotectant (high-risk patients), (2) intensive intrathecal chemotherapy and cranial radiation (standard-risk patients), and (3) Erwinia and Escherichia coli asparaginase (all patients). Between 1996 and 2000, 491 patients (aged 0-18 years) were enrolled (272 standard risk and 219 high risk). With a median of 5.7 years of followup, the estimated 5-year event-free survival (EFS) for all patients was 82% ؎ 2%. Dexrazoxane did not have a significant impact on the 5-year EFS of high-risk patients (P ؍ .99), and there was no significant difference in outcome of standardrisk patients based on type of central nervous system (CNS) treatment (P ؍ .26).Compared with E coli asparaginase, Erwinia asparaginase was associated with a lower incidence of toxicity (10% versus 24%), but also an inferior 5-year EFS (78% ؎ 4% versus 89% ؎ 3%, P ؍ .01). We conclude that (1) dexrazoxane does not interfere with the antileukemic effect of doxorubicin, (2) intensive intrathecal chemotherapy is as effective as cranial radiation in preventing CNS relapse in standard-risk patients, and (3) onceweekly Erwinia is less toxic than E coli asparaginase, but also less efficacious.
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