286 results on '"Miller TP"'
Search Results
2. A clinical analysis of two indolent lymphoma entities: mantle cell lymphoma and marginal zone lymphoma (including the mucosa-associated lymphoid tissue and monocytoid B-cell subcategories): a Southwest Oncology Group study
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Fisher, RI, primary, Dahlberg, S, additional, Nathwani, BN, additional, Banks, PM, additional, Miller, TP, additional, and Grogan, TM, additional
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- 1995
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3. Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: a prospective Southwest Oncology Group trial
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Miller, TP, primary, Grogan, TM, additional, Dahlberg, S, additional, Spier, CM, additional, Braziel, RM, additional, Banks, PM, additional, Foucar, K, additional, Kjeldsberg, CR, additional, Levy, N, additional, and Nathwani, BN, additional
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- 1994
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4. Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus (131)iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016.
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Press OW, Unger JM, Rimsza LM, Friedberg JW, Leblanc M, Czuczman MS, Kaminski M, Braziel RM, Spier C, Gopal AK, Maloney DG, Cheson BD, Dakhil SR, Miller TP, Fisher RI, Press, Oliver W, Unger, Joseph M, Rimsza, Lisa M, Friedberg, Jonathan W, and LeBlanc, Michael
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- 2013
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5. Phase 2 trial of combined cisplatin, etoposide, gemcitabine, and methylprednisolone (PEGS) in peripheral T-cell non-Hodgkin lymphoma: Southwest Oncology Group Study S0350.
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Mahadevan D, Unger JM, Spier CM, Persky DO, Young F, Leblanc M, Fisher RI, Miller TP, Mahadevan, Daruka, Unger, Joseph M, Spier, Catherine M, Persky, Daniel O, Young, Fay, LeBlanc, Michael, Fisher, Richard I, and Miller, Thomas P
- Abstract
Background: Patients with peripheral T-cell lymphomas (PTCLs) have inferior progression-free survival (PFS) and overall survival (OS) compared with patients who have aggressive B-cell non-Hodgkin lymphoma. Because PTCLs over express multidrug resistance gene 1/P-glycoprotein (MDR-1/P-gp), we devised platinum, etoposide, gemcitabine, and methylprednisolone (PEGS) with agents that are not substrates of the efflux pump. Gemcitabine was included because of its excellent single-agent activity in PTCL.Methods: Patients who had PTCL with stage II bulky disease, stage III or IV disease with extra-nodal, nodal, and transformed cutaneous presentations were eligible. Patients received intravenous cisplatin 25 mg/m(2) on days 1 through 4, etoposide 40 mg/m(2) on days 1 through 4, gemcitabine 1000 mg/m(2) on day 1, and methylprednisolone 250 mg on days 1 through 4 of a 21-day cycle for 6 cycles.Results: In total, 34 patients were enrolled, 33 were eligible, and 79% were newly diagnosed. Histologic types were PTCL not otherwise specified (n = 15), anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (n = 4), angioimmunoblastic T-cell lymphoma (n = 6), or other T-cell non-Hodgkin lymphomas (n = 8). Adverse events included 1 grade 5 infection with grade 3 or 4 neutropenia and 9 grade 4 hematologic toxicities. The overall response rate was 39% (47% in PTCL not otherwise specified, 33% in angioimmunoblastic T-cell lymphoma, 25% in ALK-negative and 38% in other T-cell non-Hodgkin lymphomas). The PFS rate at 2 years was 12% (95% confidence interval, 0.1%-31%), and the median PFS was 7 months. The OS rate at 2 years was 30% (95% confidence interval, 8%-54%), and the median OS was 17 months. Immunohistochemical analysis of P-gp expression revealed strong positivity in a subset of lymphoma cells (n = 6) and tumor endothelium (n = 25).Conclusions: Overall, PEGS was well tolerated, but OS was not considered promising given the design-specified targets. These results may serve as a benchmark for future comparisons for non-CHOP regimens. [ABSTRACT FROM AUTHOR]- Published
- 2013
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6. Racial differences in presentation and management of follicular non-Hodgkin lymphoma in the United States: Report from the National LymphoCare Study.
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Nabhan C, Byrtek M, Taylor MD, Friedberg JW, Cerhan JR, Hainsworth JD, Miller TP, Hirata J, Link BK, and Flowers CR
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- 2012
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7. Neural cell adhesion molecule-positive peripheral T-cell lymphoma: a rare variant with a propensity for unusual sites of involvement [see comments]
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Kern, WF, primary, Spier, CM, additional, Hanneman, EH, additional, Miller, TP, additional, Matzner, M, additional, and Grogan, TM, additional
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- 1992
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8. Multidrug-resistant myeloma: laboratory and clinical effects of verapamil as a chemosensitizer
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Salmon, SE, primary, Dalton, WS, additional, Grogan, TM, additional, Plezia, P, additional, Lehnert, M, additional, Roe, DJ, additional, and Miller, TP, additional
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- 1991
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9. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group.
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Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI, Bernstein, Steven H, Unger, Joseph M, Leblanc, Michael, Friedberg, Jonathan, Miller, Thomas P, and Fisher, Richard I
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- 2009
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10. Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014.
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Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ, Rimsza LM, Fisher RI, Miller TP, Southwest Oncology Group, Persky, Daniel O, Unger, Joseph M, Spier, Catherine M, Stea, Baldassarre, LeBlanc, Michael, McCarty, Matthew J, Rimsza, Lisa M, Fisher, Richard I, and Miller, Thomas P
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- 2008
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11. The impact of female hormone usage
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Miller Tp
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Text mining ,business.industry ,Internal Medicine ,Medicine ,business ,Bioinformatics ,Hormone - Published
- 1994
12. Cognitive and noncognitive symptoms in dementia patients: relationship to cortisol and dehydroepiandrosterone.
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Miller TP, Taylor J, Rogerson S, Mauricio M, Kennedy Q, Schatzberg A, Tinklenberg J, Yesavage J, Miller, T P, Taylor, J, Rogerson, S, Mauricio, M, Kennedy, Q, Schatzberg, A, Tinklenberg, J, and Yesavage, J
- Published
- 1998
13. The prognostic significance of the immunotype in diffuse large-cell lymphoma: a comparative study of the T-cell and B-cell phenotype
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Lippman, SM, Miller, TP, Spier, CM, Slymen, DJ, and Grogan, TM
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The clinical significance of immunophenotyping of the non-Hodgkin's lymphomas is controversial. Therefore, we conducted the present study of 103 consecutively accrued diffuse large-cell lymphoma (DLCL) patients to define, independently of histologic subtypes, the prognostic importance of phenotyping. We used an extensive panel of monoclonal antibodies to T- and B-cell antigens to assign all patients immunologically into the T-cell (20 patients) or B-cell group (83 patients). The only significant differences in pretreatment clinical variables between the two patient groups were the higher frequency of bulky disease (greater than 10 cm) in B-cell patients (P = .008) and more frequent skin involvement in the T-cell group (P less than or equal to .001). Multiagent doxorubicin-containing chemotherapy regimens were employed as initial therapy in over 83% of the patients in each group. Our study revealed that disease-free survival (DFS) was significantly shorter in the T-cell patients than in the B-cell DLCL patients (median DFS, 10.8 months for T-cell and 42.7 months for B- cell; P = .01, log rank). No patient with T-cell DLCL remained disease free for longer than 2 years, whereas 55% of the B-cell group were disease free at 2 years. Univariate and multivariate analyses of all major prognostic factors of DFS suggest that the T-cell phenotype indicates an incurable subset of DLCL patients. Although the B-cell group had a twofold advantage in median survival (35 months v 18 months), actuarial overall survival was not significantly different between the two patient groups (P = .23). Our results indicate the need for new approaches in the search for a curative treatment for T-cell DLCL.
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- 1988
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14. What should be the morphologic criteria for the subdivision of follicular lymphomas?
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Nathwani, BN, Metter, GE, Miller, TP, Burke, JS, Mann, RB, Barcos, M, Kjeldsberg, CR, Dixon, DO, Winberg, CD, and Whitcomb, CC
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The members of the Pathology Panel for Lymphoma Clinical Studies undertook a collaborative study with the hope of resolving some of the controversies regarding the criteria and methods for the subclassification of follicular lymphomas (FLs). A group of 105 patients with FL were subclassified by seven hematopathologists according to two methods. In the first method, cases were subclassified according to the Rappaport, Lukes and Collins, and Working Formulation systems. In each of these systems, FLs are subclassified by estimation of the different cell populations, without actual counting of cells. In the second method, precise counts of different cells were made according to the standard and modified Berard methods. With this counting method, diagnoses were independently derived, based on counts provided by the seven pathologists, for large cleaved (LC), small noncleaved (SNC), and large noncleaved (LNC) cells. To ascertain what method and which criteria are most useful in predicting survival, we made clinicopathologic correlations. When the subjective (first method) diagnoses were rendered, and when the consensus diagnoses of the seven pathologists were used, there were no significant differences in survival among patients with the different subtypes. On the other hand, when we used the counting method of Berard (second method) and the cut- off points for the cell counts suggested by him for the subclassification, we were able to divide the patient population into prognostic subgroups. Because the cut-off points proposed by Berard are not derived objectively, we made statistical comparisons of survival curves to determine cut-off points (and thus to establish objective criteria). We found that the patient population could be separated into at least two prognostic groups, for SNC and/or LNC and for SNC + LNC + LC cells. The cut-off points which we derived differed with cell type, however. Until the usefulness of these new cut-off points is established, we recommend that the cut-off points and the counting method of Berard be used for the subclassification of FL. Because the choice of treatment for the different subtypes of FL is totally dependent on the histologic diagnosis, and because of the variability among the diagnoses of pathologists, treatment planning is difficult.
- Published
- 1986
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15. Independent prognostic significance of a nuclear proliferation antigen in diffuse large cell lymphomas as determined by the monoclonal antibody Ki-67
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Grogan, TM, Lippman, SM, Spier, CM, Slymen, DJ, Rybski, JA, Rangel, CS, Richter, LC, and Miller, TP
- Abstract
To assess the prognostic significance of the growth fraction in diffuse large cell lymphoma (DLCL), we studied 105 DLCL patients with the monoclonal antibody Ki-67 applied to frozen tissue sections. Ki-67 detects a nuclear antigen associated with cell proliferation not found in resting cells. Ki-67 findings and other clinical prognostic factors were correlated with outcome using univariate and multivariate analyses in the proportional hazards model. High proliferative activity, defined as nuclear Ki-67 expression in greater than 60% of malignant cells (Ki- 67 greater than 60), was found to be a strong predictor of poor survival among these patients (P = .003, log-rank). The 19 patients with Ki-67 greater than 60% had a median survival of 8 months compared with a median survival of 39 months for the 86 patients with Ki-67 less than or equal to 60%. Examination of pretreatment clinical variables indicated the patient groups were similar with regard to age, sex, stage, B symptoms, tumor bulk, and lactate dehydrogenase (LDH). Both patient groups received comparable curative intent therapy and showed comparable complete response rate precluding treatment differences as modifying outcome. Multivariate analysis indicated Ki-67 is an independent predictor of survival (multivariate P = .006). Further statistical analysis using only B-cell DLCL patients treated with CHOP (63 patients) indicated that Ki-67 greater than 60 retained strong prediction of poor outcome (P = .002, log-rank) among this homogeneous group. We conclude that high proliferative activity (Ki-67 greater than 60) is an independent factor allowing laboratory prediction of probable poor outcome of DLCL.
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- 1988
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16. Initial chemotherapy for clinically localized lymphomas of unfavorable histology
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Miller, TP and Jones, SE
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Forty-five patients with localized non-Hodgkin's lymphoma of unfavorable histologic type (41 patients had diffuse histiocytic, 2 had nodular mixed, and 2 had minimally nodular histiocytic lymphoma) were treated with initial chemotherapy (28 patients), including cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP), or with initial CHOP followed by involved field radiotherapy (17 patients). Patients were clinically staged and found to have stage I (7 patients), stage IE (8), stage II (12), and stage IIE (18). Despite the presence of potentially adverse prognostic factors, including age older than 65 yr (11 patients), bulky disease (17), gastrointestinal involvement (9), and “B” symptoms (4), 44 of 45 patients (98%) achieved a complete response. Forty-two patients (93%) are alive with a median follow-up time of 41 mo (range 3–128 mo). Thirty-eight patients (84%) remain continuously free of disease. Neither the pretreatment clinical features nor the type of treatment significantly influenced the outcome for patients treated with initial chemotherapy. Patients who failed treatment relapsed at distant sites or in initially involved sites whether or not they received radiotherapy. Initial treatment for localized lymphomas of unfavorable histology with chemotherapy regimens of proven curative potential in advanced disease is a successful treatment strategy and obviates the need for extensive staging. The role of involved field radiotherapy following initial chemotherapy needs to be defined.
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- 1983
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17. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells.
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Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan WC, Fisher RI, Braziel RM, Rimsza LM, Grogan TM, Miller TP, LeBlanc M, Greiner TC, Weisenburger DD, Lynch JC, Vose J, Armitage JO, Smeland EB, Kvaloy S, and Holte H
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- 2004
18. Toxicity profile of high-dose methotrexate in young children with central nervous system tumors.
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Chavana AN, Taylor ZL, DeGroote N, Lindsay HB, Sauer HE, Mason EJ, Schafer ES, Miller TP, Castellino SM, Pommert L, O'Brien MM, Ramsey LB, Bernhardt MB, and Brown AL
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- Humans, Female, Male, Child, Preschool, Infant, Child, Follow-Up Studies, Retrospective Studies, Prognosis, Mucositis chemically induced, Neutropenia chemically induced, Methotrexate adverse effects, Methotrexate administration & dosage, Central Nervous System Neoplasms drug therapy, Antimetabolites, Antineoplastic adverse effects, Antimetabolites, Antineoplastic administration & dosage
- Abstract
High-dose methotrexate (HD-MTX) is used in the treatment of children with central nervous system (CNS) tumors; however, toxicity information is limited. We characterized toxicities following 102 administrations of HD-MTX (4.6-13.5 g/m
2 ) infused over 4 or 24 h in 38 children with a CNS tumor before 6 years of age (2010-2020). Delayed clearance of methotrexate occurred following 24% of infusions. Common Terminology Criteria for Adverse Events v5 grade 2-3 mucositis was observed in 47% of individuals, Grade 4 neutropenia in 76%, and grade 3-4 thrombocytopenia in 58%. No neurotoxicity was observed. HD-MTX can be safely used with supportive care and monitoring., (© 2024 Wiley Periodicals LLC.)- Published
- 2024
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19. Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards.
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Siegel RD, LeFebvre KB, Temin S, Evers A, Barbarotta L, Bowman RM, Chan A, Dougherty DW, Ganio M, Hunter B, Klein M, Miller TP, Mulvey TM, Ouzts A, Polovich M, Salazar-Abshire M, Stenstrup EZ, Sydenstricker CM, Tsai S, and Olsen MM
- Abstract
Purpose: To update the ASCO-Oncology Nursing Society (ONS) standards for antineoplastic therapy administration safety in adult and pediatric oncology and highlight current standards for antineoplastic therapy for adult and pediatric populations with various routes of administration and location., Methods: ASCO and ONS convened a multidisciplinary Expert Panel with representation of multiple organizations to conduct literature reviews and add to the standards as needed. The evidence base was combined with the opinion of the ASCO-ONS Expert Panel to develop antineoplastic safety standards and guidance. Public comments were solicited and considered in preparation of the final manuscript., Results: The standards presented here include clarification and expansion of existing standards to include home administration and other changes in processes of ordering, preparing, and administering antineoplastic therapy; the advent of immune effector cellular therapy; the importance of social determinants of health; fertility preservation; and pregnancy avoidance. In addition, the standards have added a fourth verification., Standards: Standards are provided for which health care organizations and those involved in all aspects of patient care can safely deliver antineoplastic therapy, increase the quality of care, and reduce medical errors.Additional information is available at www.asco.org/standards and www.ons.org/onf.
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- 2024
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20. Approach for defining human adenovirus infection and disease for central review adjudication in clinical studies.
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Fisher BT, Blumenstock J, Boge CLK, Shuster S, Seif AE, Green M, Michaels MG, Alexander JL, Ardura MI, Miller TP, Hijano DR, Muller WJ, Schuster JE, Green AM, Dulek DE, Kajon AE, and Danziger-Isakov L
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- Child, Humans, Reproducibility of Results, Transplantation, Homologous, Cohort Studies, Adenovirus Infections, Human diagnosis, Hematopoietic Stem Cell Transplantation, Adenoviruses, Human
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Background: Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials., Methods: A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were further refined through an iterative process and independently applied by two central review committees (CRCs) to 20 pediatric allo-HCT recipients with at least one HAdV-positive PCR., Results: Initial HAdV infection and disease definitions were developed and updated through an iterative process after reviewing clinical and virological details for 81 subjects with at least one positive HAdV PCR detected in a clinical specimen. Independent application of final definitions to 20 HAdV positive allo-HCT recipients by two CRCs yielded similar number of HAdV infection or disease events but with variation of degree of certainty for some events., Conclusions: Application of definitions by a CRC for a study of HAdV infection and disease is feasible and can provide consistency in the assignment of outcomes. Definitions need further refinement to improve reproducibility and to provide guidance on determining clinical improvement or worsening after initial diagnosis of HAdV infection or disease., (© 2024 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)
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- 2024
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21. An Interpretable Machine Learning Framework for Rare Disease: A Case Study to Stratify Infection Risk in Pediatric Leukemia.
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Al-Hussaini I, White B, Varmeziar A, Mehra N, Sanchez M, Lee J, DeGroote NP, Miller TP, and Mitchell CS
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Background : Datasets on rare diseases, like pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), have small sample sizes that hinder machine learning (ML). The objective was to develop an interpretable ML framework to elucidate actionable insights from small tabular rare disease datasets. Methods : The comprehensive framework employed optimized data imputation and sampling, supervised and unsupervised learning, and literature-based discovery (LBD). The framework was deployed to assess treatment-related infection in pediatric AML and ALL. Results : An interpretable decision tree classified the risk of infection as either "high risk" or "low risk" in pediatric ALL ( n = 580) and AML ( n = 132) with accuracy of ∼79%. Interpretable regression models predicted the discrete number of developed infections with a mean absolute error (MAE) of 2.26 for bacterial infections and an MAE of 1.29 for viral infections. Features that best explained the development of infection were the chemotherapy regimen, cancer cells in the central nervous system at initial diagnosis, chemotherapy course, leukemia type, Down syndrome, race, and National Cancer Institute risk classification. Finally, SemNet 2.0, an open-source LBD software that links relationships from 33+ million PubMed articles, identified additional features for the prediction of infection, like glucose, iron, neutropenia-reducing growth factors, and systemic lupus erythematosus (SLE). Conclusions : The developed ML framework enabled state-of-the-art, interpretable predictions using rare disease tabular datasets. ML model performance baselines were successfully produced to predict infection in pediatric AML and ALL.
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- 2024
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22. Prospective External Validation of the Esbenshade Vanderbilt Models Accurately Predicts Bloodstream Infection Risk in Febrile Non-Neutropenic Children With Cancer.
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Zhao Z, Patel PA, Slatnick L, Sitthi-Amorn A, Bielamowicz KJ, Nunez FA, Walsh AM, Hess J, Rossoff J, Elgarten C, Myers R, Saab R, Basbous M, Mccormick M, Aftandilian C, Richards R, Nessle CN, Tribble AC, Sheth Bhutada JK, Coven SL, Runco D, Wilkes J, Gurunathan A, Guinipero T, Belsky JA, Lee K, Wong V, Malhotra M, Armstrong A, Jerkins LP, Cross SJ, Fisher L, Stein MT, Wu NL, Yi T, Orgel E, Haeusler GM, Wolf J, Demedis JM, Miller TP, and Esbenshade AJ
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- Humans, Child, Prospective Studies, Fever diagnosis, Fever etiology, Anti-Bacterial Agents therapeutic use, Bacteremia diagnosis, Bacteremia epidemiology, Bacteremia microbiology, Infections, Neoplasms complications, Bacterial Infections, Sepsis diagnosis
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Purpose: The optimal management of fever without severe neutropenia (absolute neutrophil count [ANC] ≥500/µL) in pediatric patients with cancer is undefined. The previously proposed Esbenshade Vanderbilt (EsVan) models accurately predict bacterial bloodstream infections (BSIs) in this population and provide risk stratification to aid management, but have lacked prospective external validation., Materials and Methods: Episodes of fever with a central venous catheter and ANC ≥500/µL occurring in pediatric patients with cancer were prospectively collected from 18 academic medical centers. Variables included in the EsVan models and 7-day clinical outcomes were collected. Five versions of the EsVan models were applied to the data with calculation of C-statistics for both overall BSI rate and high-risk organism BSI (gram-negative and Staphylococcus aureus BSI), as well as model calibration., Results: In 2,565 evaluable episodes, the BSI rate was 4.7% (N = 120). Complications for the whole cohort were rare, with 1.1% (N = 27) needing intensive care unit (ICU) care by 7 days, and the all-cause mortality rate was 0.2% (N = 5), with only one potential infection-related death. C-statistics ranged from 0.775 to 0.789 for predicting overall BSI, with improved accuracy in predicting high-risk organism BSI (C-statistic 0.800-0.819). Initial empiric antibiotics were withheld in 14.9% of episodes, with no deaths or ICU admissions attributable to not receiving empiric antibiotics., Conclusion: The EsVan models, especially EsVan2b, perform very well prospectively across multiple academic medical centers and accurately stratify risk of BSI in episodes of non-neutropenic fever in pediatric patients with cancer. Implementation of routine screening with risk-stratified management for non-neutropenic fever in pediatric patients with cancer could safely reduce unnecessary antibiotic use.
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- 2024
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23. Applying machine learning to identify pediatric patients with newly diagnosed acute lymphoblastic leukemia using administrative data.
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Cao L, Huang YS, Getz KD, Seif AE, Ruiz J, Miller TP, Fisher BT, Aplenc R, and Li Y
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- Child, Humans, Predictive Value of Tests, Machine Learning, Databases, Factual, Algorithms, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis
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Case identification in administrative databases is challenging as diagnosis codes alone are not adequate for case ascertainment. We utilized machine learning (ML) to efficiently identify pediatric patients with newly diagnosed acute lymphoblastic leukemia. We tested nine ML models and validated the best model internally and externally. The optimal model had 97% positive predictive value (PPV) and 99% sensitivity in internal validation; 94% PPV and 82% sensitivity in external validation. Our ML model identified a large cohort of 21,044 patients, demonstrating an efficient approach for cohort assembly and enhancing the usability of administrative data., (© 2024 Wiley Periodicals LLC.)
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- 2024
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24. Missing the mark? Exploratory analysis of the 10-year-old cutoff as an independent marker of high-risk disease in pediatric B-ALL.
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George PE, DeGroote NP, Henderson M, Jordan K, Ziworitin-Ogola C, Castellino SM, and Miller TP
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- Child, Humans, Retrospective Studies, Risk Factors, Prognosis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
This single-center, retrospective study evaluated age as a risk factor for relapsed/refractory disease and/or death in 153 children with B-cell acute lymphoblastic leukemia. The study sample included children near the 10-year age cutoff for high-risk disease (6.0-13.9 years at diagnosis) and without other high-risk features (high white cell count, unfavorable cytogenetics). Children 10.0-13.9 years treated per high-risk protocols did not have inferior outcomes compared with children aged 6.0-9.9 years initiating treatment per standard-risk protocols. The study indicates that, in the era of cytogenetics, an age threshold of 10 years might not be an independent prognostic marker. Multicenter analyses are needed., (© 2023 Wiley Periodicals LLC.)
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- 2024
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25. Racial and ethnic disparities in acuity of presentation among children with newly diagnosed acute leukemia.
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Winestone LE, Getz KD, Li Y, Burrows E, Scheurer ME, Tam V, Gramatges MM, Wilkes JJ, Miller TP, Seif AE, Rabin KR, Fisher BT, and Aplenc R
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- Child, Humans, Racial Groups, Hospitals, Pediatric, Healthcare Disparities, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
We evaluated disparities in disease burden, organ dysfunction, vital signs, and timing of therapy in children newly presenting with acute leukemia. Among 899 patients with acute leukemia diagnosed at two large children's hospitals, a priori lab-based definitions of high disease burden, infection risk, renal dysfunction, and coagulopathy were applied to electronic health record data. Black patients with acute myeloid leukemia had increased prevalence of elevated white blood cell count and uric acid; Black patients with acute lymphoblastic leukemia demonstrated increased prevalence of coagulopathy. Black patients' presentation more frequently included multiple lab abnormalities consistent with advanced physiologic dysfunction. No differences were found in days to therapy initiation., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)
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- 2024
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26. Adolescents and young adults (AYAs) vs pediatric patients: survival, risks, and barriers to enrollment.
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Janardan SK and Miller TP
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- Humans, Child, Adolescent, Young Adult, Leukemia, Myeloid, Acute drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
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Adolescents and young adults (AYAs; ages 15-39 years) with acute lymphoblastic leukemia (ALL) have worse outcomes than pediatric patients with ALL. Multiple factors contribute to this differential survival. AYAs are more likely to have higher-risk leukemia biology than children with ALL. AYA patients have more choices for treatment facility and treatment protocol, as well as barriers to clinical trial enrollment, both of which can affect survival. AYAs must also navigate psychosocial factors inherent to their unique developmental stage. Furthermore, AYAs typically sustain more treatment-related toxicities than pediatric patients. Treatment on pediatric or pediatric-inspired ALL protocols at pediatric cancer centers has been associated with improved outcomes for AYAs with ALL, but there is still variation in the treatment that AYAs with ALL receive. Clinical trials focused on AYAs with ALL and individualized decision-making regarding choice of treatment facility and treatment protocol are needed to optimize the survival and long-term outcomes of this patient population., (Copyright © 2023 by The American Society of Hematology.)
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- 2023
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27. Acute and chronic kidney injury during therapy for pediatric acute leukemia: A report from the Leukemia Electronic Abstraction of Records Network (LEARN).
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Hsiao W, Li Y, Getz K, Cao L, Krause E, Ramos M, Lee J, Gramatges MM, Rabin KR, Scheurer ME, Aplenc R, Denburg M, and Miller TP
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- Child, Humans, Retrospective Studies, Hospital Mortality, Kidney, Electronics, Risk Factors, Acute Kidney Injury chemically induced, Acute Kidney Injury epidemiology, Renal Insufficiency, Chronic epidemiology, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute complications
- Abstract
Children with acute leukemia are at increased risk of kidney injury. Using electronic health record data from three centers between 2010 and 2018, this study retrospectively described acute kidney injury (AKI) and chronic kidney disease (CKD) prevalence in children with acute lymphoblastic or myeloid leukemia (ALL, AML) using Common Terminology Criteria for Adverse Events (CTCAE) and Kidney Disease Improving Global Outcomes (KDIGO) definitions. AKI during therapy was 25% (ALL) and 32% (AML) using CTCAE, versus 84% (ALL) and 74% (AML) using KDIGO. CKD prevalence was low and Grade 1/Stage 2. Further investigation is needed to optimally define kidney injury in acute leukemia., (© 2023 Wiley Periodicals LLC.)
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- 2023
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28. Supportive Care in Pediatric Oncology: Opportunities and Future Directions.
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Freedman JL, Beeler DM, Bowers A, Bradford N, Cheung YT, Davies M, Dupuis LL, Elgarten CW, Jones TM, Jubelirer T, Miller TP, Patel P, Phillips CA, Wardill HR, and Orsey AD
- Abstract
The optimization of outcomes for pediatric cancer patients relies on the successful advancement of supportive care to ease the treatment burden and mitigate the long-term impacts of cancer therapy. Advancing pediatric supportive care requires research prioritization as well as the development and implementation of innovations. Like the prevailing theme throughout pediatric oncology, there is a clear need for personalized or precision approaches that are consistent, evidence-based, and guided by clinical practice guidelines. By incorporating technology and datasets, we can address questions which may not be feasible to explore in clinical trials. Now is the time to listen to patients' voices by using patient-reported outcomes (PROs) to ensure that their contributions and experiences inform clinical care plans. Furthermore, while the extrapolation of knowledge and approaches from adult populations may suffice in the absence of pediatric-specific evidence, there is a critical need to specifically understand and implement elements of general and developmental pediatrics like growth, nutrition, development, and physical activity into care. Increased research funding for pediatric supportive care is critical to address resource availability, equity, and disparities across the globe. Our patients deserve to enjoy healthy, productive lives with optimized and enriched supportive care that spans the spectrum from diagnosis to survivorship.
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- 2023
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29. Clinical covariates that improve the description of high dose methotrexate pharmacokinetics in a diverse population to inform MTXPK.org.
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Taylor ZL, Miller TP, Poweleit EA, DeGroote NP, Pommert L, Awoniyi O, Board SG, Ugboh N, Joshi V, Ambrosino N, Chavana A, Bernhardt MB, Schafer ES, O'Brien MM, Castellino SM, and Ramsey LB
- Subjects
- Adolescent, Young Adult, Child, Humans, Antimetabolites, Antineoplastic pharmacokinetics, Retrospective Studies, Methotrexate, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
The MTXPK.org webtool was launched in December 2019 and was developed to facilitate model-informed supportive care and optimal use of glucarpidase following the administration of high-dose methotrexate (HDMTX). One limitation identified during the original development of the MTXPK.org tool was the perceived generalizability because the modeled population comprised solely of Nordic pediatric patients receiving 24-h infusions for the treatment of acute lymphoblastic leukemia. The goal of our study is to describe the pharmacokinetics of HDMTX from a diverse patient population (e.g., races, ethnicity, indications for methotrexate, and variable infusion durations) and identify meaningful factors that account for methotrexate variability and improve the model's performance. To do this, retrospectively analyzed pharmacokinetic and toxicity data from pediatric and adolescent young adult patients who were receiving HDMTX (>0.5 g/m
2 ) for the treatment of a cancer diagnosis from three pediatric medical centers. We performed population pharmacokinetic modeling referencing the original MTXPK.org NONMEM model (includes body surface area and serum creatinine as covariates) on 1668 patients, 7506 administrations of HDMTX, and 30,250 concentrations. Our results support the parameterizations of short infusion duration (<8 h) and the presence of Down syndrome on methotrexate clearance, the parameterization of severe hypoalbuminemia (<2.5 g/dL) on the intercompartmental clearance (Q2 and Q3), and the parameterization of pleural effusion on the volume of distribution (V1 and V2). These novel parameterizations will increase the generalizability of the MTXPK.org model once they are added to the webtool., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)- Published
- 2023
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30. High burden of clinically significant adverse events associated with contemporary therapy for pediatric T-cell acute lymphoblastic leukemia/lymphoma.
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Summers RJ, Monroig VM, DeGroote NP, West ZE, Katafias E, and Miller TP
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- Child, Humans, Retrospective Studies, Prospective Studies, Antineoplastic Combined Chemotherapy Protocols adverse effects, T-Lymphocytes, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Lymphoma drug therapy
- Abstract
Background: Despite improvements in survival for children with T-cell acute lymphoblastic leukemia and lymphoma (T-ALL/LLy), morbidity remains high. However, data are lacking regarding comprehensive descriptions of clinically relevant adverse events (AEs) experienced during early intensive chemotherapy., Procedure: This single-institution retrospective study evaluated children aged 1-21 years with T-ALL/T-LLy diagnosed from 2010 to 2020. Physician chart abstraction identified and graded 20 clinically relevant AEs. AE rates were analyzed by T-ALL or LLy, minimal residual disease status, induction steroid, and use of antimicrobial prophylaxis. Statistical comparisons used the Kruskal-Wallis test (continuous variables) and Chi-square or Fisher's exact test (categorical variables)., Results: The cohort included 120 patients (T-ALL: 88; T-LLy: 32). Most patients experienced AEs during induction (85 out of 120; 70.8%) and consolidation (89 out of 111; 80.2%). Nonsepsis infection was common in induction (26 out of 120; 21.7%) and consolidation (35 out of 111; 31.5%). Patients treated with dexamethasone during induction had significantly higher rates of nonsepsis infection and/or sepsis during consolidation than those who received prednisone (p < .01)., Conclusions: Clinically significant AEs are extremely common during induction and consolidation therapy for patients with T-ALL/LLy. Infectious AEs are particularly prevalent. These results can inform conversations with patients and families and aid in the development of toxicity-related aims in the next generation of, prospective clinical trials in T-ALL/LLy., (© 2023 Wiley Periodicals LLC.)
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- 2023
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31. Children's Oncology Group's 2023 blueprint for research: Cancer control and supportive care.
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Esbenshade AJ, Sung L, Brackett J, Dupuis LL, Fisher BT, Grimes A, Miller TP, Ullrich NJ, and Dvorak CC
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- Adolescent, Young Adult, Child, Humans, Medical Oncology, Delivery of Health Care, Vomiting, Quality of Life, Neoplasms drug therapy
- Abstract
The objective of the Cancer Control and Supportive Care (CCL) Committee in the Children's Oncology Group (COG) is to reduce the overall morbidity and mortality of therapy-related toxicities in children, adolescents, and young adults with cancer. We have targeted five major domains that cause clinically important toxicity: (i) infections and inflammation; (ii) malnutrition and metabolic dysfunction; (iii) chemotherapy-induced nausea and vomiting; (iv) neuro- and oto-toxicty; and (v) patient-reported outcomes and health-related quality of life. Subcommittees for each domain prioritize randomized controlled trials and biology aims to determine which strategies best mitigate the toxicities. The findings of these trials are impactful, informing clinical practice guidelines (CPGs) and directly leading to changes in the standard of care for oncology practice. With the development of new therapies, there will be new toxicities, and the COG CCL Committee is dedicated to developing interventions to minimize acute and delayed toxicities, lessen morbidity and mortality, and improve quality of life in pediatric and young adult patients with cancer., (© 2023 Wiley Periodicals LLC.)
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- 2023
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32. SARS-CoV-2 infections in patients enrolled on the Children's Oncology Group standard-risk B-cell acute lymphoblastic leukemia trial, AALL1731.
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Elgarten CW, Kairalla JA, Thompson JC, Miller TP, Wang C, Conway S, Loh ML, Raetz EA, Gupta S, Rau RE, Angiolillo A, Rabin KR, and Alexander S
- Abstract
Hematologic malignancy is a risk factor for severe coronavirus disease 2019 (COVID-19) in adults; however, data specific to children with leukemia are limited. High-quality infectious adverse event data from the ongoing Children's Oncology Group (COG) standard-risk B acute lymphoblastic leukemia/lymphoma (ALL/LLy) trial, AALL1731, were analyzed to provide a disease-specific estimate of SARS-CoV-2 infection outcomes in pediatric ALL. Of 253 patients with reported infections, the majority (77.1%) were asymptomatic or mildly symptomatic (CTCAE grade 1/2) and there was a single COVID-19-related death. These data suggest SARS-CoV-2 infection does not confer substantial morbidity among young patients with B-lymphoblastic leukemia/lymphoma (B-ALL/LLy)., Competing Interests: The authors declare they have no conflicts of interest., (© 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)
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- 2023
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33. Leveraging machine learning to identify acute myeloid leukemia patients and their chemotherapy regimens in an administrative database.
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Cao L, Huang YS, Wu C, Getz K, Miller TP, Ruiz J, Fisher BT, Seif AE, Aplenc R, and Li Y
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- Humans, Child, Predictive Value of Tests, Databases, Factual, Algorithms, Machine Learning, Leukemia, Myeloid, Acute drug therapy
- Abstract
Background: Administrative datasets are useful for identifying rare disease cohorts such as pediatric acute myeloid leukemia (AML). Previously, cohorts were assembled using labor-intensive, manual reviews of patients' longitudinal chemotherapy data., Methods: We utilized a two-step machine learning (ML) method to (i) identify pediatric patients with newly diagnosed AML, and (ii) among the identified AML patients, their chemotherapy courses, in an administrative/billing database. Using 2558 patients previously manually reviewed, multiple ML algorithms were derived from 75% of the study sample, and the selected model was tested in the remaining hold-out sample. The selected model was also applied to assemble a new pediatric AML cohort and further assessed in an external validation, using a standalone cohort established by manual chart abstraction., Results: For patient identification, the selected Support Vector Machine model yielded a sensitivity of 0.97 and a positive predictive value (PPV) of 0.97 in the hold-out test sample. For course-specific chemotherapy regimen and start date identification, the selected Random Forest model yielded overall PPV greater than or equal to 0.88 and sensitivity greater than or equal to 0.86 across all courses in the test sample. When applied to new cohort assembly, ML identified 3016 AML patients with 10,588 treatment courses. In the external validation subset, PPV was greater than or equal to 0.75 and sensitivity was greater than or equal to 0.82 for patient identification, and PPV was greater than or equal to 0.93 and sensitivity was greater than or equal to 0.94 for regimen identifications., Conclusion: A carefully designed ML model can accurately identify pediatric AML patients and their chemotherapy courses from administrative databases. This approach may be generalizable to other diseases and databases., (© 2023 Wiley Periodicals LLC.)
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- 2023
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34. Preventable harm because of outpatient medication errors among children with leukemia and lymphoma: A multisite longitudinal assessment.
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Wong CI, Vannatta K, Gilleland Marchak J, Quade EV, Rodgers IM, Reid CM, Dandoy CE, Billett AL, Miller TP, Vaughn S, Daraiseh NM, Liu S, Carle AC, and Walsh KE
- Subjects
- Child, Humans, Outpatients, Longitudinal Studies, Medication Errors prevention & control, Pharmaceutical Preparations, Lymphoma drug therapy, Leukemia drug therapy, Neoplasms drug therapy
- Abstract
Background: There is little longitudinal information about the type and frequency of harm resulting from medication errors among outpatient children with cancer. We aimed to characterize rates and types of medication errors and harm to outpatient children with leukemia and lymphoma over 7 months of treatment., Methods: We recruited children taking medications at home for leukemia or lymphoma from three pediatric cancer centers. Errors were identified by chart review, in-home medication review, observation of administration, and interviews. Physician reviewers confirmed error (Fleiss' κ = 0.95), harm (Fleiss' κ = 0.82), and suggested interventions. Generalized linear mixed models with random effects were used to account for clustering by site., Results: Among 131 children taking 1669 medications with 367 home visits, 408 errors were identified, including 242 with potential for harm and 39 with harm (1.0 harm per 1000 patient-days [95% CI, 0.1-9.8]). Ten percent of children were injured by errors and 42% had errors with potential for harm. Twenty-six percent of caregivers reported that miscommunication led to missed doses or overdoses at home. Children on >13 medications had significantly more serious medication errors than those on fewer medications (77% vs 61%; p = .05). Physician reviewers judged that improved communication among caregivers and between caregivers and clinicians may have prevented the most harm (66%)., Conclusions: In this longitudinal study, 10% children with leukemia or lymphoma experienced adverse drug events because of outpatient medication errors. Improvements addressing communication with and among caregivers should be codeveloped with families and based on human-factors engineering., Plain Language Summary: In this longitudinal study, medication errors in the clinic, pharmacy, or at home among children with leukemia or lymphoma over a 7-month period were common, and 10% suffered harm because of errors. Children on >13 medications had significantly more serious medication errors than those on fewer medications (77% vs 61%; p = .05). Physician reviewers judged that improved communication among caregivers and between caregivers and clinicians may have prevented the most harm (66%). Improvements addressing communication with and among caregivers should be codeveloped with families and based on human-factors engineering., (© 2023 American Cancer Society.)
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- 2023
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35. Multicenter study of pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorders.
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Afify ZAM, Taj MM, Orjuela-Grimm M, Srivatsa K, Miller TP, Edington HJ, Dalal M, Robles J, Ford JB, Ehrhardt MJ, Ureda TJ, Rubinstein JD, McCormack S, Rivers JM, Chisholm KM, Kavanaugh MK, Bukowinski AJ, Friehling ED, Ford MC, Reddy SN, Marks LJ, Smith CM, and Mason CC
- Subjects
- Child, Humans, Male, Female, Herpesvirus 4, Human, Prospective Studies, Retrospective Studies, Epstein-Barr Virus Infections complications, Epstein-Barr Virus Infections epidemiology, Lymphoproliferative Disorders diagnosis, Lymphoproliferative Disorders etiology, Lymphoma, Non-Hodgkin complications, Lymphoma, Large B-Cell, Diffuse pathology, Myeloproliferative Disorders complications, Organ Transplantation adverse effects
- Abstract
Background: Pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorder [EBV(-)M-PTLD] comprises approximately 10% of M-PTLD. No large multi-institutional pediatric-specific reports on treatment and outcome are available., Methods: A multi-institutional retrospective review of solid organ recipients diagnosed with EBV(-)M-PTLD aged ≤21 years between 2001 and 2020 in 12 centers in the United States and United Kingdom was performed, including demographics, staging, treatment, and outcomes data., Results: Thirty-six patients were identified with EBV(-)M-PTLD. Twenty-three (63.9%) were male. Median age (range) at transplantation, diagnosis of EBV(-)M-PTLD, and interval from transplant to PTLD were 2.2 years (0.1-17), 14 years (3.0-20), and 8.5 years (0.6-18.3), respectively. Kidney (n = 17 [47.2%]) and heart (n = 13 [36.1%]) were the most commonly transplanted organs. Most were Murphy stage III (n = 25 [69.4%]). Lactate dehydrogenase was elevated in 22/34 (64.7%) and ≥2 times upper limit of normal in 11/34 (32.4%). Pathological diagnoses included diffuse large B-cell lymphoma (n = 31 [86.1%]) and B-non-Hodgkin lymphoma (B-NHL) not otherwise specified (NOS) (n = 5 [13.9%]). Of nine different regimens used, the most common were: pediatric mature B-NHL-specific regimen (n = 13 [36.1%]) and low-dose cyclophosphamide, prednisone, and rituximab (n = 9 [25%]). Median follow-up from diagnosis was 3.0 years (0.3-11.0 years). Three-year event-free survival (EFS) and overall survival (OS) were 64.8% and 79.9%, respectively. Of the seven deaths, six were from progressive disease., Conclusions: EFS and OS were comparable to pediatric EBV(+) PTLD, but inferior to mature B-NHL in immunocompetent pediatric patients. The wide range of therapeutic regimens used directs our work toward developing an active multi-institutional registry to design prospective studies., Plain Language Summary: Pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorders (EBV(-)M-PTLD) have comparable outcomes to EBV(+) PTLD, but are inferior to diffuse large B-cell lymphoma in immunocompetent pediatric patients. The variety of treatment regimens used highlights the need to develop a pediatric PTLD registry to prospectively evaluate outcomes. The impact of treatment regimen on relapse risk could not be assessed because of small numbers. In the intensive pediatric B-non-Hodgkin lymphoma chemoimmunotherapy group, 11 of 13 patients remain alive in complete remission after 0.6 to 11 years., (© 2022 American Cancer Society.)
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- 2023
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36. Data standards in pediatric oncology: Past, present, and future.
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Wyatt KD, Noyd DH, Wood NM, Phillips CA, Miller TP, Rubin EM, Winestone LE, Waanders AJ, Perentesis JP, and Aplenc R
- Subjects
- Child, Humans, Medical Oncology, Forecasting, Patients, Oncology Nursing, Neoplasms therapy
- Abstract
In this commentary, we highlight the central role that data standards play in facilitating data-driven efforts to advance research in pediatric oncology. We discuss the current state of data standards for pediatric oncology and propose five steps to achieve an improved future state with benefits for clinicians, researchers, and patients., (© 2022 Wiley Periodicals LLC.)
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- 2023
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37. Burkitt lymphoma after solid-organ transplant: Treatment and outcomes in the paediatric PTLD collaborative.
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Afify Z, Orjuela-Grimm M, Smith CM, Dalal M, Ford JB, Pillai P, Robles JM, Reddy S, McCormack S, Ehrhardt MJ, Ureda T, Alperstein W, Edington H, Miller TP, Rubinstein JD, Kavanaugh M, Bukowinski AJ, Friehling E, Rivers JM, Chisholm KM, Marks LJ, and Mason CC
- Subjects
- Humans, Child, Infant, Child, Preschool, Adolescent, Cyclophosphamide therapeutic use, Rituximab therapeutic use, Prednisone therapeutic use, Treatment Outcome, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols adverse effects, Burkitt Lymphoma therapy, Burkitt Lymphoma drug therapy, Organ Transplantation adverse effects, Lymphoproliferative Disorders etiology
- Abstract
Burkitt lymphoma arising in paediatric post-solid-organ transplantation-Burkitt lymphoma (PSOT-BL) is a clinically aggressive malignancy and a rare form of post-transplant lymphoproliferative disorder (PTLD). We evaluated 35 patients diagnosed with PSOT-BL at 14 paediatric medical centres in the United States. Median age at organ transplantation was 2.0 years (range: 0.1-14) and age at PSOT-BL diagnosis was 8.0 years (range: 1-17). All but one patient had late onset of PSOT-BL (≥2 years post-transplant), with a median interval from transplant to PSOT-BL diagnosis of 4.0 years (range: 0.4-12). Heart (n = 18 [51.4%]) and liver (n = 13 [37.1%]) were the most frequently transplanted organs. No patients had loss of graft or treatment-related mortality. A variety of treatment regimens were used, led by intensive Burkitt lymphoma-specific French-American-British/Lymphomes Malins B (FAB/LMB), n = 13 (37.1%), and a low-intensity regimen consisting of cyclophosphamide, prednisone and rituximab (CPR) n = 12 (34.3%). Median follow-up was 6.7 years (range: 0.5-17). Three-year event-free and overall survival were 66.2% and 88.0%, respectively. Outcomes of PSOT-BL patients receiving BL-specific intensive regimens are comparable to reported BL outcomes in immunocompetent children. Multi-institutional collaboration is feasible and provides the basis of prospective data collection to determine the optimal treatment regimen for PSOT-BL., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2023
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38. Inclusion of a core patient-reported outcomes battery in adolescent and young adult cancer clinical trials.
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Roth ME, Parsons SK, Ganz PA, Wagner LI, Hinds PS, Alexander S, Bingen K, Bober SL, Brackett J, Cella D, Henry NL, Indelicato DJ, Johnson RH, Miller TP, Rosenberg SM, Schmitz KH, Thanarajasingam G, Reeve BB, and Salsman JM
- Subjects
- Adolescent, Humans, Young Adult, Quality of Life, Adult, Healthcare Disparities, Antineoplastic Agents toxicity, Neoplasms drug therapy, Clinical Trials as Topic, Patient Reported Outcome Measures
- Abstract
Disparities in care, treatment-related toxicity and health-related quality of life (HRQoL) for adolescents and young adults (AYAs, aged 15-39 years) with cancer are under-addressed partly because of limited collection of patient-reported outcomes (PROs) in cancer clinical trials (CCTs). The AYA years include key developmental milestones distinct from younger and older patients, and cancer interrupts attainment of critical life goals. Lack of consensus on a standardized approach to assess HRQoL and treatment-related toxicity in AYA CCTs has limited the ability to improve patient outcomes. The National Cancer Institute's Clinical Trials Network AYA PRO Task Force was assembled to reach consensus on a core set of PROs and foster its integration into AYA CCTs. Eight key considerations for selecting the core PRO AYA battery components were identified: relevance to AYAs; importance of constructs across the age continuum; prioritization of validated measures; availability of measures without licensing fees; availability in multiple languages; applicability to different cancer types and treatments; ability to measure different HRQoL domains and toxicities; and minimized burden on patients and sites. The Task Force used a modified Delphi approach to identify key components of the PRO battery. The Patient-Reported Outcomes Measurement Information System (PROMIS) and the PRO Common Terminology Criteria for Adverse Events Measurement System met all criteria and were selected to assess HRQoL and treatment toxicity, respectively. Investigators are rapidly incorporating the recommendations of the Task Force into AYA trials. Inclusion of a standardized assessment of HRQoL and treatment toxicities in AYA CCTs is a vital first step to develop interventions to improve health outcomes for AYAs diagnosed with cancer., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2023
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39. Characteristics and outcomes of pediatric oncology patients at risk for guardians declining transfusion of blood components.
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Stevenson J, DeGroote NP, Keller F, Brock KE, Bergsagel DJ, Miller TP, Cornwell P, Fasano R, Chonat S, and Castellino SM
- Subjects
- Humans, Child, Retrospective Studies, Blood Transfusion, Jehovah's Witnesses
- Abstract
Background: Transfusion of blood products is a necessary part of successful delivery of myelosuppressive regimens in pediatric cancer. There is a paucity of literature characterizing outcomes or management of pediatric patients with cancer when transfusion is declined., Aims: The objective of this paper is to describe the clinical characteristics, care, and outcomes of patients with cancer at risk for declining transfusion., Methods and Results: A retrospective cohort of patients aged 0-21 years with cancer managed at Children's Healthcare of Atlanta between 2006 and 2020 and with ICD-9 codes indicating risk of "transfusion refusal" or Jehovah's witness (JW) religion was identified. Demographics, disease, and management were abstracted. Descriptive statistics were performed to examine associations with transfusion receipt. Among 35 eligible patients identified as at risk for declining transfusion, 89% had primary guardians who identified as JW, and 45.7% identified as Black, non-Hispanic. Only 40% of guardians actively declined transfusion. Transfusion recipients had significantly lower hemoglobin (g/dl) and platelet counts (1000/μl) at initial presentation (9.6 vs. 11.9, p < .002 and 116.0 vs. 406.5, p = .001, respectively) and at nadir (5.9 vs. 8.7, p < .001 and ≤ 10 vs. 154, p < .001, respectively) than non-recipients. Legal intervention was required in 36.4% of those who ultimately received a transfusion., Conclusion: Among pediatric cancer patients whose medical record initially indicated a preference for no transfusion, 60% of guardians accepted blood products when prescribed for oncology care. Guidelines for systematic management and transfusion sparing approaches are needed to honor guardian's preferences when possible yet while maintaining equitable cancer outcomes in this population., (© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.)
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- 2023
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40. Absolute lymphocyte count recovery following initial acute myelogenous leukemia therapy: Implications for adoptive cell therapy.
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Molina JC, Li Y, Otto WR, Miller TP, Getz KD, Mccoubrey C, Ramos M, Krause E, Cao L, Gramatges MM, Rabin K, Scheurer M, Elgarten CW, Myers RM, Seif AE, Fisher BT, Shah NN, and Aplenc R
- Subjects
- Child, Young Adult, Humans, Infant, Prognosis, Lymphocyte Count, Immunotherapy, Adoptive, Retrospective Studies, Leukemia, Myeloid, Acute drug therapy, Hematopoietic Stem Cell Transplantation, Receptors, Chimeric Antigen
- Abstract
Background: An adequate absolute lymphocyte count (ALC) is an essential first step in autologous chimeric antigen receptor (CAR) T-cell manufacturing. For patients with acute myelogenous leukemia (AML), the intensity of chemotherapy received may affect adequate ALC recovery required for CAR T-cell production. We sought to analyze ALC following each course of upfront therapy as one metric for CAR T-cell manufacturing feasibility in children and young adults with AML., Procedure: ALC data were collected from an observational study of patients with newly diagnosed AML between the ages of 1 month and 21 years who received treatment between the years of 2006 and 2018 at one of three hospitals in the Leukemia Electronic Abstraction of Records Network (LEARN) consortium., Results: Among 193 patients with sufficient ALC data for analysis, the median ALC following induction 1 was 1715 cells/μl (interquartile range: 1166-2388), with successive decreases in ALC with each subsequent course. Similarly, the proportion of patients achieving an ALC >400 cells/μl decreased following each course, ranging from 98.4% (190/193) after course 1 to 66.7% (22/33) for patients who received a fifth course of therapy., Conclusions: There is a successive decline of ALC recovery with subsequent courses of chemotherapy. Despite this decline, ALC values are likely sufficient to consider apheresis prior to the initiation of each course of upfront therapy for the majority of newly diagnosed pediatric AML patients, thereby providing a window of opportunity for T-cell collection for those patients identified at high risk of relapse or with refractory disease., (© 2022 Wiley Periodicals LLC.)
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- 2023
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41. Infectious events in pediatric patients with acute lymphoblastic leukemia/lymphoma undergoing evaluation for fever without severe neutropenia.
- Author
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Patel PA, DeGroote NP, Jackson K, Cash T, Castellino SM, Jaggi P, Esbenshade AJ, and Miller TP
- Subjects
- Humans, Risk Factors, Fever complications, Acute Disease, Neutropenia chemically induced, Neutropenia epidemiology, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Sepsis, Lymphoma complications, Respiratory Tract Infections, Bacteremia
- Abstract
Background: Infections cause significant treatment-related morbidity during pediatric acute lymphoblastic leukemia/lymphoma (ALL/LLy) therapy. Fevers during periods without severe neutropenia are common, but etiologies are not well-described. This study sought to describe the bloodstream infection (BSI) and non-BSI risk in children undergoing therapy for ALL/LLy., Methods: Demographic and clinical data were abstracted for febrile episodes without severe neutropenia at two children's hospitals. Treatment courses were stratified by intensity. Multivariate logistic regression evaluated characteristics associated with infection., Results: There were 1591 febrile episodes experienced by 524 patients. Of these, 536 (34%) episodes had ≥1 infection; BSI occurred in 30 (1.9%) episodes. No BSIs occurred in episodes with a recent procedural sedation or cytarabine exposure. Presence of hypotension, chills/rigors, higher temperature, and infant phenotype were independently associated with BSI (p < .05). Of the 572 non-BSIs, the most common was upper respiratory infection (URI) (n = 381, 67%). Compared to episodes without infection, URI symptoms, higher temperature, absolute neutrophil count 500-999/μl, and evaluation during a low-intensity treatment course were more likely to be associated with a non-BSI (p < .05) and inpatient status was less likely to be associated with a non-BSI (p < .05)., Conclusions: The BSI rate in pediatric patients with ALL/LLy and fever without severe neutropenia is low, but one-third of the time, patients have a non-BSI. Future research should test if the need for empiric antibiotics can be tailored based on the associations identified in this study., (© 2022 American Cancer Society.)
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- 2022
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42. Improving infectious adverse event reporting for children and adolescents enrolled in clinical trials for acute lymphoblastic leukemia: A report from the Children's Oncology Group.
- Author
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Elgarten CW, Thompson JC, Angiolillo A, Chen Z, Conway S, Devidas M, Gupta S, Kairalla JA, McNeer JL, O'Brien MM, Rabin KR, Rau RE, Rheingold SR, Wang C, Wood C, Raetz EA, Loh ML, Alexander S, and Miller TP
- Subjects
- Acute Disease, Adolescent, Child, Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma etiology
- Abstract
Infections cause substantial morbidity for children with acute lymphoblastic leukemia (ALL). Therefore, accurate characterization of infectious adverse events (AEs) reported on clinical trials is imperative to defining, comparing, and managing safety and toxicity. Here, we describe key processes implemented to improve reporting of infectious AEs on two active phase III Children's Oncology Group (COG) ALL trials. Processes include: (a) identifying infections as a targeted toxicity, (b) incorporation of infection-specific case report form questions, and (c) physician review of AEs with real-time data cleaning. Preliminary assessment of these processes suggests improved reporting, as well as opportunities for further improvement., (© 2022 Wiley Periodicals LLC.)
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- 2022
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43. Rates of laboratory adverse events by course in paediatric leukaemia ascertained with automated electronic health record extraction: a retrospective cohort study from the Children's Oncology Group.
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Miller TP, Getz KD, Li Y, Demissei BG, Adamson PC, Alonzo TA, Burrows E, Cao L, Castellino SM, Daves MH, Fisher BT, Gerbing R, Grundmeier RW, Krause EM, Lee J, Lupo PJ, Rabin KR, Ramos M, Scheurer ME, Wilkes JJ, Winestone LE, Hawkins DS, Gramatges MM, and Aplenc R
- Subjects
- Adolescent, Child, Child, Preschool, Clinical Trials as Topic, Electronic Health Records, Female, Humans, Hypokalemia epidemiology, Infant, Infant, Newborn, Male, Retrospective Studies, Young Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leukemia, Myeloid, Acute drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Background: Adverse events are often misreported in clinical trials, leading to an incomplete understanding of toxicities. We aimed to test automated laboratory adverse event ascertainment and grading (via the ExtractEHR automated package) to assess its scalability and define adverse event rates for children with acute myeloid leukaemia and acute lymphoblastic leukaemia., Methods: For this retrospective cohort study from the Children's Oncology Group (COG), we included patients aged 0-22 years treated for acute myeloid leukaemia or acute lymphoblastic leukaemia at Children's Healthcare of Atlanta (Atlanta, GA, USA) from Jan 1, 2010, to Nov 1, 2018, at the Children's Hospital of Philadelphia (Philadelphia, PA, USA) from Jan 1, 2011, to Dec 31, 2014, and at the Texas Children's Hospital (Houston, TX, USA) from Jan 1, 2011, to Dec 31, 2014. The ExtractEHR automated package acquired, cleaned, and graded laboratory data as per Common Terminology Criteria for Adverse Events (CTCAE) version 5 for 22 commonly evaluated grade 3-4 adverse events (fatal events were not evaluated) with numerically based CTCAE definitions. Descriptive statistics tabulated adverse event frequencies. Adverse events ascertained by ExtractEHR were compared to manually reported adverse events for patients enrolled in two COG trials (AAML1031, NCT01371981; AALL0932, NCT02883049). Analyses were restricted to protocol-defined chemotherapy courses (induction I, induction II, intensification I, intensification II, and intensification III for acute myeloid leukaemia; induction, consolidation, interim maintenance, delayed intensification, and maintenance for acute lymphoblastic leukaemia)., Findings: Laboratory adverse event data from 1077 patients (583 from Children's Healthcare of Atlanta, 200 from the Children's Hospital of Philadelphia, and 294 from the Texas Children's Hospital) who underwent 4611 courses (549 for acute myeloid leukaemia and 4062 for acute lymphoblastic leukaemia) were extracted, processed, and graded. Of the 166 patients with acute myeloid leukaemia, 86 (52%) were female, 80 (48%) were male, 96 (58%) were White, and 132 (80%) were non-Hispanic. Of the 911 patients with acute lymphoblastic leukaemia, 406 (45%) were female, 505 (55%) were male, 596 (65%) were White, and 641 (70%) were non-Hispanic. Patients with acute myeloid leukaemia had the most adverse events during induction I and intensification II. Hypokalaemia (one [17%] of six to 75 [48%] of 156 courses) and alanine aminotransferase (ALT) increased (13 [10%] of 134 to 27 [17%] of 156 courses) were the most prevalent non-haematological adverse events in patients with acute myeloid leukaemia, as identified by ExtractEHR. Patients with acute lymphoblastic leukaemia had the greatest number of adverse events during induction and maintenance (eight adverse events with prevalence ≥10%; induction and maintenance: anaemia, platelet count decreased, white blood cell count decreased, neutrophil count decreased, lymphocyte count decreased, ALT increased, and hypocalcaemia; induction: hypokalaemia; maintenance: aspartate aminotransferase [AST] increased and blood bilirubin increased), as identified by ExtractEHR. 187 (85%) of 220 total comparisons in 22 adverse events in four AAML1031 and six AALL0923 courses were substantially higher with ExtractEHR than COG-reported adverse event rates for adverse events with a prevalence of at least 2%., Interpretation: ExtractEHR is scalable and accurately defines laboratory adverse event rates for paediatric acute leukaemia; moreover, ExtractEHR seems to detect higher rates of laboratory adverse events than those reported in COG trials. These rates can be used for comparisons between therapies and to counsel patients treated on or off trials about the risks of chemotherapy. ExtractEHR-based adverse event ascertainment can improve reporting of laboratory adverse events in clinical trials., Funding: US National Institutes of Health, St Baldrick's Foundation, and Alex's Lemonade Stand Foundation., Competing Interests: Declaration of interests SMC and PCA disclose relationships with the Children's Oncology Group as group and study chairs. MHD received funding from Alex's Lemonade Stand Foundation for this study and funding from Epic Systems. BTF and DSH have received funding from Pfizer and Merck. BTF has also received funding from Astellas. MMG, TPM, and PCA have received research funding from the National Institutes of Health and National Cancer Institute. KDG has received research funding from the US National Institutes of Health (NIH) and the National Heart, Lung, and Blood Institute. MMG's institution has a grant to receive funding from the Cancer Prevention Research Institute of Texas, Hyundai Hope on Wheels, the American Society of Clinical Oncology, Children's Cancer Cause, and the American Society of Clinical Investigation. DSH has received funding from Incyte, Eli Lilly, E R Squibb & Sons, Jazz Pharmaceuticals, Bayer, and AstraZeneca. PCA is currently employed by Sanofi. RWG has leadership roles on the board of the American Academy of Pediatrics and the American Board of Pediatrics., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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44. Automated Ascertainment of Typhlitis From the Electronic Health Record.
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Miller TP, Li Y, Masino AJ, Vallee E, Burrows E, Ramos M, Alonzo TA, Gerbing R, Castellino SM, Hawkins DS, Lash TL, Aplenc R, and Grundmeier RW
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- Adolescent, Adult, Algorithms, Anti-Bacterial Agents, Child, Child, Preschool, Humans, Infant, Infant, Newborn, Predictive Value of Tests, Young Adult, Electronic Health Records, Typhlitis
- Abstract
Purpose: Adverse events (AEs) on Children's Oncology Group (COG) trials are manually ascertained using Common Terminology Criteria for Adverse Events. Despite significant effort, we previously demonstrated that COG typhlitis reporting sensitivity was only 37% when compared with gold standard physician chart abstraction. This study tested an automated typhlitis identification algorithm using electronic health record data., Methods: Electronic health record data from children with leukemia age 0-22 years treated at a single institution from 2006 to 2019 were included. Patients were divided into derivation and validation cohorts. Rigorous chart abstraction of validation cohort patients established a gold standard AE data set. We created an automated algorithm to identify typhlitis matching Common Terminology Criteria for Adverse Events v5 that included antibiotics, neutropenia, and non-negated mention of typhlitis in a note. We iteratively refined the algorithm using the derivation cohort and then applied the algorithm to the validation cohort; performance was compared with the gold standard. For patients on trial AAML1031, COG AE report performance was compared with the gold standard., Results: The derivation cohort included 337 patients. The validation cohort included 270 patients (961 courses). Chart abstraction identified 16 courses with typhlitis. The algorithm identified 37 courses with typhlitis; 13 were true positives (sensitivity 81.3%, positive predictive value 35.1%). For patients on AAML1031, chart abstraction identified nine courses with typhlitis, and COG reporting correctly identified 4 (sensitivity 44.4%, positive predictive value 100.0%)., Conclusion: The automated algorithm identified true cases of typhlitis with higher sensitivity than COG reporting. The algorithm identified false positives but reduced the number of courses needing manual review by 96% (961 to 37) by detecting potential typhlitis. This algorithm could provide a useful screening tool to reduce manual effort required for typhlitis AE reporting., Competing Interests: Tamara P. MillerStock and Other Ownership Interests: Gilead Sciences, Thermo Fisher Scientific, AbbVie, United Health Group Aaron J. MasinoEmployment: AiCure Douglas S. HawkinsResearch Funding: Bayer (Inst), Lilly (Inst), Incyte (Inst), Jazz Pharmaceuticals (Inst), Pfizer (Inst) Timothy L. LashConsulting or Advisory Role: AmgenTravel, Accommodations, Expenses: Amgen Richard AplencExpert Testimony: Vorys, Sater, Seymour, and Pease LLPNo other potential conflicts of interest were reported.
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- 2022
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45. Incidence and risk factors for hypoglycemia during maintenance chemotherapy in pediatric acute lymphoblastic leukemia.
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Rosenfeld E, Getz KD, Miller TP, Seif AE, Fisher BT, Burrows E, Ramos MJ, De León DD, Aplenc R, Morales KH, and Guevara JP
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- Antineoplastic Combined Chemotherapy Protocols adverse effects, Child, Child, Preschool, Humans, Incidence, Infant, Maintenance Chemotherapy adverse effects, Retrospective Studies, Risk Factors, Chemical and Drug Induced Liver Injury etiology, Hypoglycemia chemically induced, Hypoglycemia epidemiology, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications
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Background: Fasting hypoglycemia is a recognized occurrence among pediatric patients with acute lymphoblastic leukemia (ALL) during maintenance therapy. Existing publications describing this finding are limited to small studies and case reports. Our objective was to determine the incidence of hypoglycemia during maintenance chemotherapy and to investigate the association of age, as well as other potential risk factors, with this outcome in pediatric patients with ALL., Procedure: This retrospective cohort study included individuals 1 to 21 years of age with ALL treated with antimetabolite-containing maintenance chemotherapy at a large children's hospital between January 2011 and December 2014. The primary endpoint was time to first documented episode of hypoglycemia during maintenance therapy, defined as single measurement of plasma glucose <60 mg/dL. Cox regression was used to evaluate the association with age and identify other potential risk factors., Results: We identified 126 eligible patients, of whom 63% were documented as White, non-Hispanic, 28% as non-White, non-Hispanic, and 9% as Hispanic. Twenty-eight children (22%) had documented hypoglycemia during maintenance therapy. Younger age at the start of maintenance and hepatotoxicity documented during chemotherapy prior to maintenance initiation were associated with hypoglycemia (adjusted HR age = 0.88; 95% CI, 0.78-0.99; adjusted HR prior hepatotoxicity = 3.50; 95% CI, 1.47-8.36)., Conclusions: Nearly one quarter of children in our cohort had hypoglycemia documented during maintenance chemotherapy. Younger age at maintenance initiation and hepatotoxicity during chemotherapy prior to maintenance initiation emerged as risk factors. These findings highlight the importance of counseling about the risk of, and monitoring for, hypoglycemia, particularly in young children., (© 2021 Wiley Periodicals LLC.)
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- 2022
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46. A report from the Leukemia Electronic Abstraction of Records Network on risk of hepatotoxicity during pediatric acute lymphoblastic leukemia treatment.
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Yi JS, Chambers TM, Getz KD, Miller TP, Burrows E, Daves MH, Lupo PJ, Scheurer ME, Aplenc R, Rabin KR, and Gramatges MM
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- Child, Electronics, Humans, Chemical and Drug Induced Liver Injury diagnosis, Chemical and Drug Induced Liver Injury epidemiology, Chemical and Drug Induced Liver Injury etiology, Drug-Related Side Effects and Adverse Reactions, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
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- 2022
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47. Challenges and Barriers to Adverse Event Reporting in Clinical Trials: A Children's Oncology Group Report.
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Miller TP, Marx MZ, Henchen C, DeGroote NP, Jones S, Weiland J, Fisher B, Esbenshade AJ, Aplenc R, Dvorak CC, and Fisher BT
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- Child, Humans, Self Report, Surveys and Questionnaires, Research Design
- Abstract
Objective: Adverse event (AE) reporting is crucial for determining safety of trials. Adverse events are captured manually by clinical research associates (CRAs) and research nurses (RNs), and prior studies show underreporting. It is necessary to understand AE reporting training, processes, and institution-level differences to improve AE capture., Methods: A 26-item questionnaire regarding AE reporting training, identification, tracking, and challenges was distributed to all Children's Oncology Group (COG) CRAs and RNs from February 15 to March 11, 2019, regardless of if they report AEs based on limitations of COG rosters. Results were tabulated. Institutions were grouped by self-reported full-time equivalents and compared using χ2 tests., Results: Of 1315 CRAs and 2703 RNs surveyed, 509 (12.7%) responded. Of those, 369 (64.9%) representing 71.8% of COG institutions report AEs. Only data from respondents who report AEs were collected and analyzed. There was a range in AE training; COG training modules were most common (79.7%). There was wide variability in AE ascertainment; only 51.2% use standardized approaches at their site. There was no standard AE tracking method; larger sites more commonly use spreadsheets (P = 0.002) and smaller sites more commonly use paper (P = 0.028). The greatest AE reporting challenges were differences between protocols (70%) and between AE definitions and documentation (53%). Half of the respondents endorsed 6 of 13 proposed tools for improving reporting including online AE reporting modules (75.3%), tip sheets for interpreting Common Terminology Criteria for Adverse Events definitions (67.5%), and standardized AE tracking forms (66.9%). Only half of the respondents reported that all colleagues at their site followed the same AE reporting practices, and there was no dominant AE tracking approach across the respondents., Discussion: There is wide variability in AE reporting training and practices. Numerous challenges exist, including differences between trials, challenges in interpreting AE definitions, and engaging clinicians., Conclusions: Respondents are eager for additional central resources. These results provide a roadmap for areas of potential improvement., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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48. Identifying relapses and stem cell transplants in pediatric acute lymphoblastic leukemia using administrative data: Capturing national outcomes irrespective of trial enrollment.
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Cahen VC, Li Y, Getz KD, Elgarten CW, DiNofia AM, Wilkes JJ, Winestone LE, Huang YV, Miller TP, Gramatges MM, Rabin KR, Fisher BT, Aplenc R, and Seif AE
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- Child, Humans, Recurrence, Risk Factors, United States, Hematopoietic Stem Cell Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Introduction: Our objectives were to design and validate methods to identify relapse and hematopoietic stem cell transplantation (HSCT) in children with acute lymphoblastic leukemia (ALL) using administrative data representing hospitalizations at US pediatric institutions., Methods: We developed daily billing and ICD-9 code definitions to identify relapses and HSCTs within a cohort of children with newly diagnosed ALL between January 1, 2004, and December 31, 2013, previously assembled from the Pediatric Health Information System (PHIS) database. Chart review for children with ALL at the Children's Hospital of Philadelphia (CHOP) and Texas Children's Hospital (TCH) was performed to establish relapse and HSCT gold standards for sensitivity and positive predictive value (PPV) calculations. We estimated incidences of relapse and HSCT in the PHIS ALL cohort., Results: We identified 362 CHOP and 314 TCH ALL patients in PHIS and established true positives by chart review. Sensitivity and PPV for identifying both relapse and HSCT in PHIS were > 90% at both hospitals. Five-year relapse incidence in the 10 150-patient PHIS cohort was 10.3% (95% CI 9.8%-10.9%) with 7.1% (6.6%-7.6%) of children underwent HSCTs. Patients in higher-risk demographic groups had higher relapse and HSCT rates. Our analysis also identified differences in incidences of relapse and HSCT by race, ethnicity, and insurance status., Conclusions: Administrative data can be used to identify relapse and HSCT accurately in children with ALL whether they occur on- or off-therapy, in contrast with published approaches. This method has wide potential applicability for estimating these incidences in pediatric ALL, including patients not enrolled on clinical trials., (© 2020 Wiley Periodicals LLC.)
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- 2021
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49. Presentation acuity, induction mortality, and resource utilization in infants with acute leukemia.
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Ibrahimova A, Winestone LE, Miller TP, Kettler K, Seif AE, Huang YS, Elgarten CW, Myers RM, Fisher BT, Aplenc R, and Getz KD
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- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Hospitals, Pediatric, Humans, Infant, Retrospective Studies, Leukemia, Myeloid, Acute drug therapy
- Abstract
Background: Treatment of infants with acute leukemia remains challenging, especially for acute lymphocytic leukemia (ALL). Infants have shown markedly higher rates of induction mortality compared with noninfants. There are limited data on presentation acuity and supportive care utilization in this age group., Methods: In retrospective analyses of patients treated for new onset ALL or acute myeloid leukemia (AML) at pediatric hospitals contributing to the Pediatric Health Information System, we compared presentation acuity, induction mortality, and resource utilization in infants relative to noninfants less than 10 years at diagnosis., Results: Analyses included 10 359 children with ALL (405 infants, 9954 noninfants) and 871 AML (189 infants, 682 noninfants). Infants were more likely to present with multisystem organ failure compared to noninfants for both ALL (12% and 1%, PR = 10.8, 95% CI: 7.4, 15.7) and AML (6% vs. 3%; PR = 2.0, 95% CI: 1.0, 3.7). Infants with ALL had higher induction mortality compared to noninfants, even after accounting for differences in anthracycline exposure and presentation acuity (2.7% vs. 0.5%, HR = 2.1, 95% CI: 1.0, 4.8). Conversely, infants and noninfants with AML had similar rates of induction mortality (3.2% vs. 2.1%, HR = 1.2, 95% CI: 0.3, 3.9), which were comparable to rates among infants with ALL. Infants with ALL and AML had greater requirements for blood products, diuretics, supplemental oxygen, and ventilation during induction relative to noninfants., Conclusions: Infants with leukemia present with higher acuity compared with noninfants. Induction mortality and supportive care requirements for infants with ALL were similar to all children with AML, and significantly higher than those for noninfants with ALL., (© 2021 Wiley Periodicals LLC.)
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- 2021
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50. Quantifying the difference in risk of adverse events by induction treatment regimen in pediatric acute lymphoblastic leukemia.
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West ZE, Castellino SM, Monroe C, Thomas AS, McCracken C, and Miller TP
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- Child, Cohort Studies, Humans, Induction Chemotherapy adverse effects, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma epidemiology
- Abstract
The differences in overall morbidity by induction treatment regimen for pediatric acute lymphoblastic leukemia (ALL) are unknown. We examined a cohort of children with ALL who received induction chemotherapy between January 2010 and May 2018. We evaluated 20 clinically relevant adverse events (AEs) and readmission and ICU admission rates. Outcomes were compared between standard 3- and 4-drug treatment regimens in multivariate analyses using Cox proportional hazard ratios. Among 486 eligible patients, the risks of sepsis (HR = 2.16, 95% CI = 1.11-4.19), hypoxia (HR = 2.08, 95% CI = 1.03-4.18), hyperbilirubinemia (HR = 2.48, 95% CI = 1.07-5.74), hyperglycemia (HR = 2.65, 95% CI = 1.29-5.42), thromboembolic event (HR = 4.50, 95% CI = 1.30-15.6), and hyponatremia (HR = 7.88, 95% CI = 1.26-49.4) were significantly higher during 4-drug induction. Despite no differences in readmission or ICU admission rates, 4-drug induction patients had greater total inpatient days (12 vs. 4 days; p <.0001). In conclusion, pediatric patients receiving 4-drug induction for ALL experience higher morbidity. These results inform care practices and patient guidance during induction therapy.
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- 2021
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