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Your search keyword '"Fogelstrand, Linda"' showing total 4 results
Start Over Author "Fogelstrand, Linda" Topic pediatrics
4 results on '"Fogelstrand, Linda"'

1. Paediatric Strategy Forum for medicinal product development for acute myeloid leukaemia in children and adolescents: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

Author

Pearson ADJ, Zwaan CM, Kolb EA, Karres D, Guillot J, Kim SY, Marshall L, Tasian SK, Smith M, Cooper T, Adamson PC, Barry E, Benettaib B, Binlich F, Borgman A, Brivio E, Capdeville R, Delgado D, Faller D, Fogelstrand L, Fraenkel PG, Hasle H, Heenen D, Kaspers G, Kieran M, Klusmann JH, Lesa G, Ligas F, Mappa S, Mohamed H, Moore A, Morris J, Nottage K, Reinhardt D, Scobie N, Simko S, Winkler T, Norga K, Reaman G, and Vassal G

Subjects
Adolescent, Age of Onset, Child, Child, Preschool, Drug Development methods, Drug Development standards, Drug Development trends, Europe epidemiology, Humans, International Agencies organization & administration, International Agencies trends, International Cooperation, Leukemia, Myeloid, Acute epidemiology, Medical Oncology trends, Pediatrics trends, Survival Analysis, United States epidemiology, United States Food and Drug Administration organization & administration, United States Food and Drug Administration trends, Antineoplastic Agents classification, Antineoplastic Agents isolation & purification, Antineoplastic Agents therapeutic use, Drug Development organization & administration, Leukemia, Myeloid, Acute drug therapy, Medical Oncology organization & administration, Pediatrics organization & administration
Abstract

Purpose: The current standard-of-care for front-line therapy for acute myeloid leukaemia (AML) results in short-term and long-term toxicity, but still approximately 40% of children relapse. Therefore, there is a major need to accelerate the evaluation of innovative medicines, yet drug development continues to be adult-focused. Furthermore, the large number of competing agents in rare patient populations requires coordinated prioritisation, within the global regulatory framework and cooperative group initiatives., Methods: The fourth multi-stakeholder Paediatric Strategy Forum focused on AML in children and adolescents., Results: CD123 is a high priority target and the paediatric development should be accelerated as a proof-of-concept. Efforts must be coordinated, however, as there are a limited number of studies that can be delivered. Studies of FLT3 inhibitors in agreed paediatric investigation plans present challenges to be completed because they require enrolment of a larger number of patients than actually exist. A consensus was developed by industry and academia of optimised clinical trials. For AML with rare mutations that are more frequent in adolescents than in children, adult trials should enrol adolescents and when scientifically justified, efficacy data could be extrapolated. Methodologies and definitions of minimal residual disease need to be standardised internationally and validated as a new response criterion. Industry supported, academic sponsored platform trials could identify products to be further developed. The Leukaemia and Lymphoma Society PedAL/EUpAL initiative has the potential to be a major advance in the field., Conclusion: These initiatives continue to accelerate drug development for children with AML and ultimately improve clinical outcomes., Competing Interests: Conflict of interest statement PA is an employee of Sanofi. BB is an employee of Celgene. FB is an employee of Servier. AB is an employee of Jazz Pharmaceuticals. RC is an employee of Novartis. DD is an employee of Astellas Pharma Global Development, Inc. DF is an employee of Takeda Pharmaceuticals. LF has participated in advisory boards for Astellas. PGF is an employee of Sanofi. MK is an employee of BMS. SYK is an employee of AbbVie. SM is an employee of Helsinn Healthcare. HM is an employee FORMA Therapeutics. JM is an employee of Amgen. LVM has participated in advisory boards for AstraZeneca, Merck, Tesaro, Bayer and Celgene. JN is an employee, Janssen Research & Development. ADJP has participated in advisory boards for Novartis, Takeda, Merck, Lilly and Celgene. SS is an employee of Roche/Genentech. TW is an employee of Agios Pharmaceuticals. CMZ has received institutional research funding from Pfizer, Daiichi-Sankyo, BMS and Celgene. Consultancy was provided for Agios, Takeda, Janssen, Sanofi, Servier, AbbVie and Forma therapeutics. Travel support was obtained from Jazz Pharmaceuticals., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Published
2020
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2. Duplex sequencing uncovers recurrent low-frequency cancer-associated mutations in infant and childhood KMT2A-rearranged acute leukemia

Author

Pilheden, Mattias, Ahlgren, Louise, Hyrenius-Wittsten, Axel, Gonzalez-Pena, Veronica, Sturesson, Helena, Hansen Marquart, Hanne Vibeke, Lausen, Birgitte, Castor, Anders, Pronk, Cornelis Jan, Barbany, Gisela, Pokrovskaja Tamm, Katja, Fogelstrand, Linda, Lohi, Olli, Norén-Nyström, Ulrika, Asklin, Johanna, Chen, Yilun, Song, Guangchun, Walsh, Michael, Ma, Jing, Zhang, Jinghui, Saal, Lao H, Gawad, Charles, Hagström-Andersson, Anna K, Tampere University, BioMediTech, and Department of Paediatrics

Subjects
Cancer och onkologi, 3123 Gynaecology and paediatrics, Cancer and Oncology, 3122 Cancers, Pediatrik, 3111 Biomedicine, Medical Genetics, Pediatrics, Medicinsk genetik
Abstract

Infant acute lymphoblastic leukemia (ALL) with KMT2A-gene rearrangements (KMT2A-r) have few mutations and a poor prognosis. To uncover mutations that are below the detection of standard next-generation sequencing (NGS), a combination of targeted duplex sequencing and NGS was applied on 20 infants and 7 children with KMT2A-r ALL, 5 longitudinal and 6 paired relapse samples. Of identified nonsynonymous mutations, 87 had been previously implicated in cancer and targeted genes recurrently altered in KMT2A-r leukemia and included mutations in KRAS, NRAS, FLT3, TP53, PIK3CA, PAX5, PIK3R1, and PTPN11, with infants having fewer such mutations. Of identified cancer-associated mutations, 62% were below the resolution of standard NGS. Only 33 of 87 mutations exceeded 2% of cellular prevalence and most-targeted PI3K/RAS genes (31/33) and typically KRAS/NRAS. Five patients only had low-frequency PI3K/RAS mutations without a higher-frequency signaling mutation. Further, drug-resistant clones with FLT3 D835H or NRAS G13D/G12S mutations that comprised only 0.06% to 0.34% of diagnostic cells, expanded at relapse. Finally, in longitudinal samples, the relapse clone persisted as a minor subclone from diagnosis and through treatment before expanding during the last month of disease. Together, we demonstrate that infant and childhood KMT2A-r ALL harbor low-frequency cancer-associated mutations, implying a vast subclonal genetic landscape. publishedVersion

Published
2022
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3. The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia.

Author

Chen, Dongfeng, Zheng, Junxiong, Gerasimcik, Natalija, Lagerstedt, Kristina, Sjögren, Helene, Abrahamsson, Jonas, Fogelstrand, Linda, and Mårtensson, Inga-Lill

Subjects
LYMPHOBLASTIC leukemia treatment, PROTEIN expression, CELLULAR signal transduction, B cell receptors, HEALTH outcome assessment
Abstract

Precursor-B cell receptor (pre-BCR) signaling represents a crucial checkpoint at the pre-B cell stage. Aberrant pre-BCR signaling is considered as a key factor for B-cell precursor acute lymphoblastic leukemia (BCP-ALL) development. BCP-ALL are believed to be arrested at the pre-BCR checkpoint independent of pre-BCR expression. However, the cellular stage at which BCP-ALL are arrested and whether this relates to expression of the pre-BCR components (IGHM, IGLL1 and VPREB1) is still unclear. Here, we show differential protein expression and copy number variation (CNV) patterns of the pre-BCR components in pediatric BCP-ALL. Moreover, analyzing six BCP-ALL data sets (n = 733), we demonstrate that TCF3-PBX1 ALL express high levels of IGHM, IGLL1 and VPREB1, and are arrested at the pre-B stage. By contrast, ETV6-RUNX1 ALL express low levels of IGHM or VPREB1, and are arrested at the pro-B stage. Irrespective of subtype, ALL with high levels of IGHM, IGLL1 and VPREB1 are arrested at the pre-B stage and correlate with good prognosis in high-risk pediatric BCP-ALL (n = 207). Our findings suggest that BCP-ALL are arrested at different cellular stages, which relates to the expression pattern of the pre-BCR components that could serve as prognostic markers for high-risk pediatric BCP-ALL patients. [ABSTRACT FROM AUTHOR]

Published
2016
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4. Residual disease detected by flow cytometry is an independent predictor of survival in childhood acute myeloid leukaemia; results of the NOPHO- AML 2004 study.

Author

Tierens, Anne, Bjørklund, Elizabeth, Siitonen, Sanna, Marquart, Hanne Vibeke, Wulff ‐Juergensen, Gitte, Pelliniemi, Tarja‐Terttu, Forestier, Erik, Hasle, Henrik, Jahnukainen, Kirsi, Lausen, Birgitte, Jonsson, Olafur G., Palle, Josefine, Zeller, Bem, Fogelstrand, Linda, and Abrahamsson, Jonas

Subjects
ACUTE myeloid leukemia, TUMORS in children, FLOW cytometry, PEDIATRICS, HEALTH outcome assessment
Abstract

Early response after induction is a prognostic factor for disease outcome in childhood acute myeloid leukaemia ( AML). Residual disease ( RD) detection by multiparameter flow cytometry ( MFC) was performed at day 15 and before consolidation therapy in 101 patients enrolled in the Nordic Society of Paediatric Haemato-Oncology AML 2004 study. A multicentre laboratory approach to RD analysis was used. Event-free survival ( EFS) and overall survival ( OS) was significantly different in patients with and without RD at both time points, using a 0·1% RD cut-off level. RD-negative and -positive patients after first induction showed a 5-year EFS of 65 ± 7% and 22 ± 7%, respectively ( P < 0·001) and an OS of 77 ± 6% ( P = 0·025) and 51 ± 8%. RD-negative and -positive patients at start of consolidation therapy had a 5-year EFS of 57 ± 7% and 11 ± 7%, respectively ( P < 0·001) and an OS of 78 ± 6% and 28 ± 11%) ( P < 0·001). In multivariate analysis only RD was significantly correlated with survival. RD before consolidation therapy was the strongest independent prognostic factor for EFS [hazard ratio ( HR):5·0; 95% confidence interval ( CI):1·9-13·3] and OS ( HR:7·0; 95% CI:2·0-24·5). In conclusion, RD before consolidation therapy identifies patients at high risk of relapse in need of intensified treatment. In addition, RD detection can be performed in a multicentre setting and can be implemented in future trials. [ABSTRACT FROM AUTHOR]

Published
2016
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