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Amy Billett

Publications and source records attributed to Amy Billett.

7 recordsLinked to original sources

Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation: a pediatric oncology group study.

PURPOSE: Prognosis and outcome of children with isolated CNS relapse of acute lymphoblastic leukemia (ALL) has depended on duration of first complete remission (CR1). This study intensified systemic therapy by delaying CNS radiation for 12 months and tailored CNS radiation by CR1 duration. PATIENTS AND METHODS: Seventy-six children with first isolated CNS relapse of ALL were treated with systemic chemotherapy that effectively penetrates into the CSF and intrathecal chemotherapy for 12 months. Patients with CR1 of less than 18 months received craniospinal radiation (24 Gy cranial/15 Gy spinal), whereas those with CR1 of 18 months or more received cranial radiation only (18 Gy), followed by maintenance chemotherapy. Additionally, asymptomatic patients were enrolled in a thiotepa up-front therapeutic window. RESULTS: Seventy-four (97.4%) of 76 eligible patients achieved a second remission. Overall 4-year event-free survival (EFS) for the 71 precursor B-cell patients was 70.1% +/- 5.8%. CR1 duration and National Cancer Institute (NCI; National Institutes of Health, Bethesda, MD) risk group at initial diagnosis predicted outcome. Patients with CR1 of less than 18 months and 18 months or more had a 4-year EFS of 51.6% +/- 11.3% and 77.7% +/- 6.4% (P = .027), respectively. NCI high- versus standard-risk 4-year EFS was 51.4% +/- 10.8% and 80.2% +/- 6.3% (P = .0018), respectively. A significant difference in EFS between standard risk/CR1 of at least 18 months and both high risk/CR1 of less than 18 months and high risk/CR1 of at least 18 months groups was detected (P = .0068 and .0314, respectively). Response rate to thiotepa was 78%. Most relapses involved the bone marrow, and three second malignancies were reported. CONCLUSION: Twelve months of intensive systemic chemotherapy with reduced dose cranial radiation (18 Gy) is highly effective for children with isolated CNS relapse and CR1 of 18 months or more. Novel strategies are needed for patients with CR1 of less than 18 months.

Adolescent↗

Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research.

The best treatment approach for children with B-precursor acute lymphoblastic leukemia (ALL) in second clinical remission (CR) after a marrow relapse is controversial. To address this question, we compared outcomes in 188 patients enrolled in chemotherapy trials and 186 HLA-matched sibling transplants, treated between 1991 and 1997. Groups were similar except that chemotherapy recipients were younger (median age, 5 versus 8 years) and less likely to have combined marrow and extramedullary relapse (19% versus 30%). To adjust for time-to-transplant bias, treatment outcomes were compared using left-truncated Cox regression models. The relative efficacy of chemotherapy and transplantation depended on time from diagnosis to first relapse and the transplant conditioning regimen used. For children with early first relapse (< 36 months), risk of a second relapse was significantly lower after total body irradiation (TBI)-containing transplant regimens (relative risk [RR], 0.49; 95% confidence interval [CI] 0.33-0.71, P < .001) than chemotherapy regimens. In contrast, for children with a late first relapse (> or = 36 months), risks of second relapse were similar after TBI-containing regimens and chemotherapy (RR, 0.92; 95% CI, 0.49-1.70, P = .78). These data support HLA-matched sibling donor transplantation using a TBI-containing regimen in second CR for children with ALL and early relapse.

Adolescent↗

Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group.

PURPOSE: Nelarabine (compound 506U78), a water soluble prodrug of 9-b-d-arabinofuranosylguanine, is converted to ara-GTP in T lymphoblasts. We sought to define the response rate of nelarabine in children and young adults with refractory or recurrent T-cell disease. PATIENTS AND METHODS: We performed a phase II study with patients stratified as follows: stratum 1: > or = 25% bone marrow blasts in first relapse; stratum 2: > or = 25% bone marrow blasts in > or = second relapse; stratum 3: positive CSF; stratum 4: extramedullary (non-CNS) relapse. The initial nelarabine dose was 1.2 g/m2 daily for 5 consecutive days every 3 weeks. There were two dose de-escalations due to neurotoxicity on this or other studies. The final dose was 650 mg/m2/d for strata 1 and two patients and 400 mg/m2/d for strata 3 and four patients. RESULTS: We enrolled 121 patients (106 assessable for response) at the final dose levels. Complete plus partial response rates at the final dose levels were: 55% in stratum 1; 27% in stratum 2; 33% in stratum 3; and 14% in stratum 4. There were 31 episodes of > or = grade 3 neurologic adverse events in 27 patients (18% of patients). CONCLUSION: Nelarabine is active as a single agent in recurrent T-cell leukemia, with a response rate more than 50% in first bone marrow relapse. The most significant adverse events associated with nelarabine administration are neurologic. Further studies are planned to determine whether the addition of nelarabine to front-line therapy for T-cell leukemia in children will improve survival.

Adolescent↗

Prognostic factors for children with Hodgkin's disease treated with combined-modality therapy.

PURPOSE: Evaluation of pretreatment factors to identify children at high risk for relapse after combined-modality therapy for Hodgkin's disease. PATIENTS AND METHODS: From 1990 to 2000, 328 pediatric patients with clinical stage I to IV Hodgkin's disease were treated with chemotherapy and low-dose involved-field radiotherapy on prospective, collaborative, risk-adapted protocols at three institutions. Pretreatment factors were analyzed by univariate and multivariate analysis for prognostic significance for 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: With a median follow-up of 59 months (range, 8 to 125 months), the 5-year DFS and OS for all patients were 83% and 93%, respectively. Several factors were associated with inferior DFS and OS by univariate analysis. By multivariate analysis, male sex; stage IIB, IIIB, or IV disease; bulky mediastinal disease; WBC more than 13.5 x 10(3)/mm3; and hemoglobin less than 11.0 g/dL were significant for inferior DFS. A prognostic index was developed incorporating the five significant factors from the multivariate analysis, assigning each a score of 1. The 5-year DFS and OS for children with a prognostic score of 0 to 1 were 94% and 99%; score 2, 85% and 96%; score 3, 71% and 92%; and score 4 or 5, 49% and 72%, respectively. There was a significant difference in DFS among each of these groups, with significantly worse OS in those with a score of 4 to 5. CONCLUSION: A prognostic index that was based on five pretreatment factors correlated with inferior DFS by multivariate analysis stratified patients by outcome; this may be useful in assigning children with Hodgkin's disease to risk-adapted therapy.

Adolescent↗

Chemotherapy error reduction: a multidisciplinary approach to create templated order sets.

More than 48,000 newly diagnosed cancer patients can expect to have some adverse events related to their care each year. Historically, 20% of these adverse events have been medication related, and two thirds have been thought to be preventable. Since the majority of these errors occurred during the order writing process, the prioritized changes made at the joint pediatric program for Children's Hospital, Boston, and Dana-Farber Cancer Institute have been the initiation of templated orders and the development of a computerized order entry system. The goal of this initiative was to decrease errors related to chemotherapy administration by creating legible, complete, clearly defined order sets, and at the same time, to make order writing and reviewing more efficient. Chemotherapy templates were created using a consistent format and a rigorous multidisciplinary review process. Each order set includes the following: identification of the patient and cycle of chemotherapy to be given, criteria necessary to receive chemotherapy, chemotherapy orders with modifications if appropriate, and supportive care orders. Templated order sets have reduced the duplication of work efforts by significantly reducing the number of changes made during the order verification process; orders are more complete, and standardization has occurred.

Academies and Institutes↗

Evaluating process changes in a pediatric hospital medication system.

This article describes a process change designed to increase the safety of prescribing and interpreting complex order sets. All chemotherapy orders written for pediatric oncology patients at a major teaching hospital in the Eastern United States and the affiliated ambulatory clinic from June 1998 through February 2000 (n = 1792) were reviewed to evaluate a new process for communication of chemotherapy orders. The multidisciplinary check (MDC) is a forum where all disciplines simultaneously review and change complex order sets. Evaluation of the MDC included monthly completion rate and classification of changes made to orders at MDC. Over the study period, 96% of eligible orders received a multidisciplinary check, and 44% were changed. The most common change was to clarify discrepancies between the order and the protocol. Changes were made to avoid medication errors in 99 of 451 orders. Changes to avoid medication errors were more likely to involve nonchemotherapy medications. The MDC is an efficient and feasible process to increase safety at the beginning of the medication system.

Antineoplastic Agents↗