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ABSTRACT: Since 1975, there has been a dramatic increase in the survival rates of pediatric and older cancer patients, but adolescent and young adult (AYA) patients ages 15 to 40 years have not had a similar improvement. Data indicate a direct correlation between increased cure rates and clinical trial enrollment.
The authors previously published data indicating inferior clinical trial enrollment when AYA patients were treated at an adult oncology center versus a pediatric oncology center. To address this deficit, a joint pediatric and adult AYA Oncology Program was established in July 2006 with the primary objective of improving outcomes by increasing therapeutic clinical trial enrollment in this population. Patients who were referred to that program from July 2006 through June 2010 were examined retrospectively to establish whether clinical trial enrollment increased compared with historic controls.
Fifty-seven patients were referred to the program from 2006 to 2010 (range, 12-16 new patients per year). Eight patients were referred for consultation only and were not treated at the University of Pittsburgh Cancer Institute or Children's Hospital of Pittsburgh. Five of 22 patients (23%) who received treatment at the pediatric cancer center were enrolled onto a clinical trial, whereas 9 of 27 patients (33%) patients who received treatment at the adult cancer center were enrolled. There was superior trial participation compared with the previous 3 years for those shared AYA patients who were treated at the adult center (P < .001).
Data from this study demonstrated that establishing a unified AYA oncology program can lead to improved clinical trial enrollment for patients who are treated at medical oncology centers.
Cancer 12/2011; 118(14):3614-7. · 4.77 Impact Factor
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Rachael F Grace,
Carolyn M Bennett, A Kim Ritchey,
Michael Jeng,
Courtney D Thornburg,
Michele P Lambert,
Michelle Neier,
Michael Recht,
Manjusha Kumar,
Victor Blanchette,
Robert J Klaassen,
George R Buchanan,
Margaret Heisel Kurth,
Diane J Nugent,
Alexis A Thompson,
Kimo Stine,
Leslie A Kalish,
Ellis J Neufeld
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ABSTRACT: Treatment choice in pediatric immune thrombocytopenia (ITP) is arbitrary, because few studies are powered to identify predictors of therapy response. Increasingly, rituximab is becoming a treatment of choice in those refractory to other therapies.
The objective of this study was to evaluate univariate and multivariable predictors of platelet count response to rituximab. After local IRB approval, 565 patients with chronic ITP enrolled and met criteria for this study in the longitudinal, North American Chronic ITP Registry (NACIR) between January 2004 and October 2010. Treatment response was defined as a post-treatment platelet count ≥ 50,000/µl within 16 weeks of rituximab and 14 days of steroids. Treatment response data were captured both retrospectively at enrollment and then prospectively.
Eighty (14.2%) patients were treated with rituximab with an overall response rate of 63.8% (51/80). Univariate correlates of response to rituximab included the presence of secondary ITP and a positive response to steroids. In multivariable analysis, response to steroids remained a strong correlate of response to rituximab, OR 6.8 (95% CI 2.0-23.0, P = 0.002). Secondary ITP also remained a strong predictor of response to rituximab, OR 5.6 (95% CI 1.1-28.6, P = 0.04). Although 87.5% of patients who responded to steroids responded to rituximab, 48% with a negative response to steroids did respond to rituximab.
In the NACIR, response to steroids and presence of secondary ITP were strong correlates of response to rituximab, a finding not previously reported in children or adults.
Pediatric Blood & Cancer 06/2011; 58(2):221-5. · 1.89 Impact Factor
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ABSTRACT: The American Society of Pediatric Otolaryngology recommends pre-operative coagulation testing only when indicated by history or physical exam. Nevertheless, many surgeons test all children scheduled for tonsillectomy and/or adenoidectomy (T&A). Studies of pre-operative screening have had conflicting results. A decision analysis model was constructed to address the costs and health outcome states of pre-operative screening strategies in children.
A 14-day Markov model evaluated three strategies: (1) test all children for coagulation disorders; (2) test only those children with a pertinent history; and (3) perform no pre-operative testing. A literature search and a review of national databases estimated probabilities, costs, and utility data. Parameters then were varied widely in sensitivity analyses. Using a societal perspective and a cycle length of 1 day, we compared the strategies based on total costs and quality-adjusted life years (QALYs).
Total costs for the strategies were $3,200 for testing all children, $3,083 for testing only those with a history finding, and $3,077 for not testing. Total utilities were 0.02579, 0.02654, and 0.02659 QALYs, respectively. Cost-effectiveness ratios were most sensitive to variation in the cost of post-operative care and the probability of post-operative bleeding. The strategy of not testing was dominant in all sensitivity analyses.
Our results demonstrate that not performing preoperative testing is the most cost-effective strategy. This was persistent in sensitivity analyses, indicating that the model was robust. These data may be helpful to institutions and organizations to formulate policies regarding pre-operative coagulation for children without previous diagnoses of bleeding disorders.
Pediatric Blood & Cancer 12/2010; 55(6):1153-9. · 1.89 Impact Factor
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ABSTRACT: The central nervous system (CNS) has long been recognized as a site, indeed a sanctuary, for leukemic cells. Although few (<5%) patients with acute lymphoblastic leukemia (ALL) actually present with overt CNS leukemia, without prophylactic CNS-directed treatment, over 50% will develop CNS disease. However, with modern CNS prophylaxis, the incidence of CNS relapse has been reduced to 6% or less. Although great progress has been made, we continue to struggle with management of CNS leukemia. This commentary will address issues of CNS leukemia treatment at diagnosis and at relapse. Topics that will be addressed include (1) CNS 2 status at diagnosis-definition and treatment; (2) CNS leukemia at diagnosis--treatment with radiation therapy; (3) isolated relapse of leukemia in the CNS--treatment of early and late relapse; and (4) opportunities for future research in CNS relapse of ALL.
Pediatric Hematology and Oncology 05/2010; 27(5):329-32. · 0.89 Impact Factor
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ABSTRACT: The primary objective in the treatment of acute pediatric idiopathic thrombocytopenic purpura (ITP) is to rapidly increase the platelet count.
We built a decision analytic model to evaluate the cost-utility of four commonly used treatment strategies: intravenous immunoglobulin G (IVIG) 0.8 g/kg, anti-D 75 mcg/kg, methylprednisolone (30 mg/kg for 3 days), and prednisone (4 mg/kg/day for 4 days). In our baseline model, all children were hospitalized upon presentation, and discharged once the platelet count reached > or =20,000. We performed a literature search to estimate time to platelet count > or =20,000 for each strategy, as well as the probability of side effects. We obtained cost data and quality of life measures from institutional and published data sources.
Total cost of one-time treatment for a 20 kg child was US dollars 786 with prednisone, US dollars 1,346 with methylprednisolone, US dollars 2,035 with anti-D, and US dollars 2,492 with IVIG. The strategies of IVIG and methylprednisolone were less effective and more expensive than anti-D and prednisone, respectively. Although anti-D caused the most rapid rise in platelet counts, the incremental cost-utility ratio (costs incurred by using anti-D instead of prednisone divided by health benefit of using anti-D instead of prednisone) was US dollars 7,616 per day of severe thrombocytopenia avoided, primarily due to the much higher medication cost of anti-D. Utilizing an outpatient model, the cost difference between anti-D and prednisone was even more striking.
The clinical benefit of anti-D is offset by a substantial cost increase. Although often overlooked in favor of newer agents, a brief course of high-dose prednisone is an inexpensive and effective treatment for acute ITP.
Pediatric Blood & Cancer 02/2007; 48(2):173-80. · 1.89 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Journal of Clinical Oncology 08/2006; 24(19):3142-9. · 18.37 Impact Factor
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Pediatric Blood & Cancer 08/2004; 43(1):4-7. · 1.89 Impact Factor
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ABSTRACT: This study examined whether chronic stress impairs the immune system's capacity to respond to hormonal signals that terminate inflammation. Fifty healthy adults were studied; half were parents of cancer patients, and half were parents of healthy children. Parents of cancer patients reported more psychological distress than parents of healthy children. They also had flatter diurnal slopes of cortisol secretion, primarily because of reduced output during the morning hours. There was also evidence that chronic stress impaired the immune system's response to anti-inflammatory signals: The capacity of a synthetic glucocorticoid hormone to suppress in vitro production of the pro-inflammatory cytokine interleukin-6 was diminished among parents of cancer patients. Findings suggest a novel pathway by which chronic stress might alter the course of inflammatory disease.
Health Psychology 12/2002; 21(6):531-41. · 3.87 Impact Factor
