EFS and survival appear to be directly related to histologic response to neoadjuvant chemotherapy.

Conventional therapy for childhood acute lymphoblastic leukemia (ALL) includes prednisone and oral 6-mercaptopurine. Prior observations suggested potential advantages for dexamethasone over prednisone and for intravenous (IV) over oral 6-mercaptopurine, which remain to be validated. We report the results of a randomized trial of more than 1000 subjects that examined the efficacy of dexamethasone and IV 6-mercaptopurine. Children with National Cancer Institute standard-risk ALL were randomly assigned in a 2 ؋ 2 factorial design to receive dexamethasone (6 mg/m 2 /d) for 28 days in induction, plus taper, compared with prednisone (40 mg/m 2 /d). The second randomized assignment was for daily oral or weekly IV 6-mercaptopurine during consolidation. During maintenance, 5 days of the randomized steroid was given monthly, at the same dose, and all patients received daily oral 6-mercaptopurine. During delayed intensification, all patients received a dexamethasone dosage of 10 mg/m 2 /d for 21 days, with taper. Intrathecal (IT) methotrexate was the sole central nervous systemdirected therapy. Patients randomly assigned to receive dexamethasone had a 6-year isolated central nervous systemrelapse rate of 3.7% ؎ 0.8%, compared with 7.1% ؎ 1.1% for prednisone (P ‫؍‬ .01). There was also a trend toward fewer isolated bone marrow relapses with dexamethasone. The 6-year event-free survival (EFS) was 85% ؎ 2% for dexamethasone and 77% ؎ 2% for prednisone (P ‫؍‬ .002). EFS was similar with oral or IV 6-mercaptopurine; however, patients assigned to IV 6-mercaptopurine had decreased survival after relapse. (Blood. 2003;101:3809-3817)

Continuous nevirapine may be associated with increased toxicity among HIV-1-infected pregnant women with CD4 cell counts greater than 250 cells/microL, as has been observed in non-pregnant women.

Background The prognostic value of histologic response for osteosarcoma may have changed with induction chemotherapy schedules over time. We hypothesized that the increased intensity of induction therapy provided on INT0133 compared to the Children’s Cancer Group study CCG-782 would diminish the impact of histologic response on the risk of events after definitive surgery. Methods Retrospective analysis was performed for patients aged <22 with newly diagnosed nonmetastatic osteosarcoma enrolled on CCG-782 and INT0133. Clinical factors were evaluated for association with response and outcome. Good response was defined as <5% viable tumor at resection. Associations of response, study, and post-definitive surgery event-free survival (EFS-DS)were determined using Cox proportional hazard models. EFS-DS was estimated by Kaplan–Meier methodology. Results Data were available for 814 patients (206 CCG-782, 608 INT0133). For good responders, 10-year EFS-DS (±SE) was 75.4% ± 7.7% for CCG-782 and 70.8% ± 3.1% for INT0133. For poor responders, 10-year EFS-DS was 39.9% ± 4.9% for CCG-782 and 58.4% ± 3.1% for INT0133. Histologic response predicted outcome across studies (P < 0.0001). Significant interaction between study and histologic response was observed for EFS-DS (P = 0.011). Using proportional hazards regression, INT0133 poor responders had less risk of events compared to CCG-782 poor responders (relative hazard ratio (RHR) = 0.6:1), but good responders on INT0133 had a greater risk of events compared to CCG-782 good responders (RHR = 1.53:1). Conclusion We observed an inverse relationship between the predictive value of tumor necrosis and intensity of induction therapy, raising questions about the true prognostic value of histologic response. This highlights the need for novel markers to develop strategies for treatment in future trials.

The effect of the state of nutrition of 18 children with Stage IV neuroblastoma at diagnosis and during initial therapy, was evaluated with respect to treatment delays, drug dosage alterations, tumor response, days to first event (relapse or death), and survival. All patients received similar therapy (CCSG protocol CCG 371). Based on nutrition staging at diagnosis, nine were classified as malnourished; four were randomized to receive total parenteral nutrition (TPN) and four peripheral parenteral nutrition plus enteral nutrition for 28 days (through 2 chemotherapy courses), and one died before randomization. Nine were nourished at diagnosis; seven received a comprehensive enteral nutrition program and two received TPN. By life‐table analysis, the duration of remission was significantly greater in the nourished than the malnourished (P < 0.01) and a trend towards improved survival was evident at one year (P = 0.08). The median length of survival for children nourished at diagnosis was approximately 12 months, whereas those malnourished had a median survival of only 5 months. Nine children remained nourished or were becoming renourished during the first 21 days of therapy, and one of these had treatment delays and decreased drug dosages. Seven were becoming malnourished or remained malnourished during this period and six had treatment delays (P < 0.01). These data support the idea that nutrition staging at diagnosis and during initial treatment should be an integral part of protocol design and initial evaluation of children with Stage IV neuroblastoma.