المؤلفون: Michael W. Bishop, Paul R. Hutson, Jacquelyn A. Hank, Paul M. Sondel, Wayne L. Furman, Michael M. Meagher, Fariba Navid, Victor M. Santana

المصدر: mAbs, Vol 12, Iss 1 (2020)

مصطلحات موضوعية: Neuroblastoma, osteosarcoma, GD2, hu14.18K322A, pharmacokinetics, Therapeutics. Pharmacology, RM1-950, Immunologic diseases. Allergy, RC581-607

الوصف: Hu14.18K322A is a humanized anti-GD2 monoclonal antibody with a single point mutation that reduces complement-mediated cytotoxicity, with a maximum tolerated dose (MTD) of 60 mg/m2 daily for 4 days in children with recurrent/refractory neuroblastoma. We report additional results of a Phase 1 trial to determine the MTD and safety profile of hu14.18K322A in patients with osteosarcoma, and of an alternative schedule of weekly hu14.18K322A administration in patients with neuroblastoma or osteosarcoma. Eligible patients with recurrent/refractory osteosarcoma received hu14.13K22A daily x4 every 28 days in a Phase 1 traditional 3 + 3 dose escalation design. Additional patients with osteosarcoma were then enrolled to receive hu14.18K322A once weekly for 4 weeks per course. Patients with recurrent/refractory neuroblastoma were also enrolled on the weekly schedule at 50 mg/m2/dose. Six patients with osteosarcoma treated on the daily schedule received a median of 2 (range 1–6) courses; the recommended daily dose was established as 60 mg/m2. Three patients had stable disease (SD) as best overall response. Five patients (3 neuroblastoma, 2 osteosarcoma) enrolled on the weekly schedule received a median of 1 (1–3) course; 2 achieved SD as best overall response. Pain, fever, hematologic toxicities, hyponatremia, and ocular/visual abnormalities were common toxicities among both schedules. Dose-limiting toxicities attributed to hu14.18K322A included anorexia and fatigue (n = 1). Pharmacokinetic profiles were similar between daily and weekly schedules. The recommended dose for patients with osteosarcoma receiving daily hu14.18K322A x4 is 60 mg/m2. Patients receiving the weekly schedule experienced similar pharmacokinetics and toxicity profile as the daily schedule.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1942-0862Test; https://doaj.org/toc/1942-0870Test

الوصول الحر: https://doaj.org/article/940c5599493e4765891a98b5a77da59bTest

المؤلفون: Pattamon Sutthatarn, Cara E. Morin, Jessica Gartrell, Wayne L. Furman, Max R. Langham, Teresa Santiago, Andrew J. Murphy

المصدر: Children, Vol 8, Iss 3, p 226 (2021)

مصطلحات موضوعية: diffuse nodular pulmonary ossification, fibrolamellar hepatocellular carcinoma, pulmonary calcification, Pediatrics, RJ1-570

الوصف: Pulmonary ossification (PO) is a rare finding, characterized by mature bone formation in the lung parenchyma. We report a 20-year-old female patient diagnosed with fibrolamellar hepatocellular carcinoma (FL-HCC) and bilateral diffuse nodular PO. The patient presented with a unifocal left liver mass and multiple bilateral pulmonary lesions, which were treated as metastatic disease. The patient received neoadjuvant chemotherapy, followed by left hepatectomy, and bilateral staged thoracotomies for clearance of the pulmonary disease. The histology of the pulmonary nodules demonstrated nodular type PO. We present the history, the course of treatment, imaging, and histologic findings of this rare disease process that could mimic metastatic pulmonary disease.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2227-9067/8/3/226Test; https://doaj.org/toc/2227-9067Test

الوصول الحر: https://doaj.org/article/1a1d89f447044ab793fd7811e8fab248Test

المؤلفون: Andrew M. Fleming, Andrew J. Murphy, Suraj Sarvode Mothi, Rodrigo B. Interiano, Amos Loh, Mary E. McCarville, Zachary Abramson, Sara A. Mansfield, Hafeez Abdelhafeez, Andrew M. Davidoff, Ankush Gosain, Jessica A. Gartrell, Wayne L. Furman, Max R. Langham

المصدر: Journal of Pediatric Surgery. 58:1081-1087

مصطلحات موضوعية: Pediatrics, Perinatology and Child Health, Surgery, General Medicine

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::6bb0f5ddd59bec87d39bb20d126f1e55Test
https://doi.org/10.1016/j.jpedsurg.2023.02.022Test

المؤلفون: Sanjeev A Vasudevan, Rebecka L Meyers, Milton J Finegold, Dolores López-Terrada, Sarangarajan Ranganathan, Stephen P Dunn, Max R Langham, Eugene D McGahren, Greg M Tiao, Christopher B Weldon, Marcio H Malogolowkin, Mark D Krailo, Jin Piao, Jessica Randazzo, Alexander J Towbin, M. BethMcCarville, Allison F O'Neill, Wayne L Furman, Carlos Rodriguez-Galindo, Howard M Katzenstein

المصدر: Journal of Pediatric Surgery. 57:251-256

مصطلحات موضوعية: Hepatoblastoma, Treatment Outcome, Chemotherapy, Adjuvant, Liver Neoplasms, Pediatrics, Perinatology and Child Health, Hepatectomy, Humans, Infant, Surgery, General Medicine, Child, Prognosis

الوصف: Hepatoblastoma (HB) requires surgical resection for cure, but only 20-30% of patients have resectable disease at diagnosis. Patients who undergo partial hepatectomy at diagnosis have historically received 4-6 cycles of adjuvant chemotherapy; however, those with 100% well-differentiated fetal histology (WDF) have been observed to have excellent outcomes when treated with surgery alone.Patients on the Children's Oncology Group non randomized, multicenter phase III study, AHEP0731, were stratified based on Evan's stage, tumor histology, and serum alpha-fetoprotein level at diagnosis. Patients were eligible for the very low risk stratum of surgery and observation if they had a complete resection at diagnosis and rapid central histologic review demonstrated HB with 100% WDF histology.A total of 8 eligible patients were enrolled on study between September 14, 2009 and May 28, 2014. Outcome current to 06/30/2020 was used in this analysis. The median age at enrollment was 22.5 months (range: 8-84 months) and the median AFP at enrollment was 714 ng/ml (range: 18-77,747 ng/mL). With a median follow-up of 6.6 years (range: 3.6-9.8 years), the 5-year event-free (EFS) and overall survival (OS) were both 100%.This report supports that HB with 100% WDF histology completely resected at diagnosis is curable with surgery only. The development of evidence-based surgical guidelines utilizing criteria based on PRETEXT group, vascular involvement (annotation factors), tumor-specific histology and corresponding biology will be crucial for optimizing which patients are candidates for resection at diagnosis followed by observation.Prognosis study, Level I evidence.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9f50dbbe16ee8366ab8232e88f11b628Test
https://doi.org/10.1016/j.jpedsurg.2022.05.022Test

المؤلفون: David Cullins, Barbara Rooney, Natasha Sahr, April Sykes, Mary Beth McCarville, Sara M Federico, Amanda Sooter, William E Janssen, Gwendolyn Anthony, Michael A Dyer, Alberto S Pappo, Wing H Leung, Wayne L Furman

المصدر: Journal for ImmunoTherapy of Cancer, Vol 8, Iss 1 (2020)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: BackgroundNatural killer (NK) cells are one of the main effector populations of immunotherapy with monoclonal antibody and cytokines, used in combination with chemotherapy to treat children with high-risk neuroblastoma on this phase II trial. However, the impact of chemoimmunotherapy on NK cell kinetics, phenotype, and function is understudied.MethodsWe prospectively examined NK cell properties from 63 children with newly diagnosed neuroblastoma enrolled in a phase II trial (NCT01857934) and correlated our findings with tumor volume reduction after 2 courses of chemoimmunotherapy. NK cell studies were conducted longitudinally during chemoimmunotherapy and autologous hematopoietic cell transplantation (autoHCT) with optional haploidentical NK cell infusion and additional immunotherapy.ResultsChemoimmunotherapy led to significant NK cytopenia, but complete NK cell recovery reliably occurred by day 21 of each therapy course as well as after autoHCT. Haploidentical NK cell infusion elevated the NK cell count transiently during autoHCT. NK cell cytotoxicity increased significantly during treatment compared with diagnosis. In addition, NK cells maintained their ability to respond to cytokine stimulation in culture longitudinally. Unsupervised cluster analysis of CD56bright NK cell count and tumor volume at diagnosis and after two courses of chemoimmunotherapy identified two patient groups with distinct primary tumor sizes and therapy responses.ConclusionAfter profound NK cytopenia due to chemoimmunotherapy, endogenously reconstituted NK cells exhibit enhanced NK cytotoxicity compared with pretherapy measurements. Our data suggest a relationship between CD56bright expression and tumor size before and after two courses of chemoimmunotherapy; however, future studies are necessary to confirm this relationship and its predictive significance.Trial registration numberNCT01857934.

العلاقة: https://jitc.bmj.com/content/8/1/e000176.fullTest; https://doaj.org/toc/2051-1426Test; https://doaj.org/article/61aa4de3291f4f04b11f55638ec3891cTest

الإتاحة: https://doi.org/10.1136/jitc-2019-000176Test
https://doaj.org/article/61aa4de3291f4f04b11f55638ec3891cTest

المؤلفون: Patrick A. Thompson, Marcio H. Malogolowkin, Wayne L. Furman, Jin Piao, Mark D. Krailo, Nadia Chung, Lindsay Brock, Alexander J. Towbin, Elizabeth B. McCarville, Milton J. Finegold, Sarangarajan Ranganathan, Stephen P. Dunn, Max R. Langham, Eugene D. McGahren, Gregory M. Tiao, Christopher B. Weldon, Allison F. O'Neill, Carlos Rodriguez‐Galindo, Rebecka L. Meyers, Howard M. Katzenstein

المصدر: Pediatric Blood & Cancer. 70

مصطلحات موضوعية: Oncology, Pediatrics, Perinatology and Child Health, Hematology

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::4947da926f304a072f2e9c49b2e1f60aTest
https://doi.org/10.1002/pbc.30365Test

المؤلفون: Wayne L. Furman, Alberto S. Pappo, Victor M. Santana, Rachel C. Brennan, Shenghua Mao, Jianrong Wu, William E. Janssen, Wing Leung, Catherine Y. Ng, Aaron Shafer, Michael Meagher, Paul Hutson, Jacquelyn A. Hank, Paul M. Sondel, Barry L. Shulkin, M. Beth McCarville, Sara M. Federico

الوصف: This figure demonstrates the relationship between prior treatment with chimeric or humanized 14.18 K322A antibody and A) the area under the concentration curve for the antibody (AUC); B elimination half-life of the antibody (T1/2 Beta); and C) the highest observed concentration of the antibody (Cmax). Although the data in panels A and B suggest that prior exposure to ch14.18 or hu14.18K322A tends to increase the AUC and the elimination half-life, there is no significant difference between prior treatment groups using the Kruskal-Wallis non-parametric test. The data in panel C do not suggest an association between prior exposure and the peak serum concentration of the hu14.18K322A antibody.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9dda4536ff96c433e250a2f403355bb7Test
https://doi.org/10.1158/1078-0432.22468175.v1Test

المؤلفون: Wayne L. Furman, Alberto S. Pappo, Victor M. Santana, Rachel C. Brennan, Shenghua Mao, Jianrong Wu, William E. Janssen, Wing Leung, Catherine Y. Ng, Aaron Shafer, Michael Meagher, Paul Hutson, Jacquelyn A. Hank, Paul M. Sondel, Barry L. Shulkin, M. Beth McCarville, Sara M. Federico

الوصف: Box and whisker plot showing absolute NK cells per mm3 in samples. NK cells were identified by flow cytometry as CD14 negative, CD56 positive, CD3 negative and percentage of total WBC was computed from flow cytometry results. Absolute WBC count was obtained using a Sysmex{trade mark, serif} KX-21 blood cell analyzer, and final absolute NK count was obtained by multiplying percent NK by absolute WBC. Sample identifiers and associated N are: DONOR (N=10) blood sample drawn at or before time of first NK cell donation; CS1_PRE (N=13), Patient blood drawn prior to first treatment course; CS1_14 (N=9); Patient on day +14 of first treatment course; CS1_21 (N=14), Patient on day +21 of first treatment course; CS2_NK_07 (N=11), Patient on day +7 following NK cell administration in second treatment course; CS2_NK_14 (N=11), Patient on day +14 following NK cell administration in second treatment course; CS3_14 (N=7), Patient on day +14 of third treatment course; CS3_21 (N=9), Patient on day +21 of third treatment course; CS4_NK_07 (N=9), Patient on day +7 following NK cell administration in fourth treatment course; CS4_NK_14 (N=10), Patient on day +14 following NK cell administration in fourth treatment course; CS5_14 (N=3), Patient on day +14 of fifth treatment course; CS5_21 (N=8), Patient on day +21 of fifth treatment course; CS6_PRE (N=1), Patient blood drawn prior to initiation of 6th treatment course; CS6_NK_07 (N=7), Patient on day +7 following NK cell administration in sixth treatment course; CS6_NK_14 (N=7), Patient on day +14 following NK cell administration in sixth treatment course. Central Point (ï�¯) - median; Box - Inner quartiles (25th percentile to 75th percentile) of data; Whiskers - non-outlier min and max data; Outliers (ï,¡) - data points outside of median {plus minus} inner quartile range; Extreme Outliers (*) - data points outside of median {plus minus} 1.5 X inner quartile range.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c62a93dddc4f296d3df3b810cfbce1b0Test
https://doi.org/10.1158/1078-0432.22468169.v1Test

المؤلفون: Wayne L. Furman, Alberto S. Pappo, Victor M. Santana, Rachel C. Brennan, Shenghua Mao, Jianrong Wu, William E. Janssen, Wing Leung, Catherine Y. Ng, Aaron Shafer, Michael Meagher, Paul Hutson, Jacquelyn A. Hank, Paul M. Sondel, Barry L. Shulkin, M. Beth McCarville, Sara M. Federico

الوصف: Human anti-human antibody (HAHA) level and peak hu14.18K322A serum level by course and prior antibody therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::120d7121dd373ab23a3e06c8088d7313Test
https://doi.org/10.1158/1078-0432.22468163Test

المؤلفون: Wayne L. Furman, Alberto S. Pappo, Victor M. Santana, Rachel C. Brennan, Shenghua Mao, Jianrong Wu, William E. Janssen, Wing Leung, Catherine Y. Ng, Aaron Shafer, Michael Meagher, Paul Hutson, Jacquelyn A. Hank, Paul M. Sondel, Barry L. Shulkin, M. Beth McCarville, Sara M. Federico

الوصف: Purpose: Anti-GD2 mAbs, acting via antibody-dependent cell-mediated cytotoxicity, may enhance the effects of chemotherapy. This pilot trial investigated a fixed dose of a unique anti-GD2 mAb, hu14.18K322A, combined with chemotherapy, cytokines, and haploidentical natural killer (NK) cells.Experimental Design: Children with recurrent/refractory neuroblastoma received up to six courses of hu14.18K322A (40 mg/m2/dose, days 2–5), GM-CSF, and IL2 with chemotherapy: cyclophosphamide/topotecan (courses 1,2), irinotecan/temozolomide (courses 3,4), and ifosfamide/carboplatin/etoposide (courses 5,6). Parentally derived NK cells were administered with courses 2, 4, and 6. Serum for pharmacokinetic studies of hu14.18K322A, soluble IL2 receptor alpha (sIL2Rα) levels, and human antihuman antibodies (HAHA) were obtained.Results: Thirteen heavily pretreated patients (9 with prior anti-GD2 therapy) completed 65 courses. One patient developed an unacceptable toxicity (grade 4 thrombocytopenia >35 days). Four patients discontinued treatment for adverse events (hu14.18K322A allergic reaction, viral infection, surgical death, second malignancy). Common toxicities included grade 3/4 myelosuppression (13/13 patients) and grade 1/2 pain (13/13 patients). Eleven patients received 29 NK-cell infusions. The response rate was 61.5% (4 complete responses, 1 very good partial response, 3 partial responses) and five had stable disease. The median time to progression was 274 days (range, 239–568 days); 10 of 13 patients (77%) survived 1 year. Hu14.18K322A pharmacokinetics was not affected by chemotherapy or HAHA. All patients had increased sIL2Rα levels, indicating immune activation.Conclusions: Chemotherapy plus hu14.18K322A, cytokines, and NK cells is feasible and resulted in clinically meaningful responses in patients with refractory/recurrent neuroblastoma. Further studies of this approach are warranted in patients with relapsed and newly diagnosed neuroblastoma. Clin Cancer Res; 23(21); 6441–9. ©2017 AACR.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7234f9e79e0bc385c497d16381d6d10fTest
https://doi.org/10.1158/1078-0432.c.6526859.v1Test