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Article ; Online: Nouvelle AMM : crizotinib dans le lymphome anaplasique à grandes cellules systémique ALK positif en pédiatrie.

Meurillon, Roxane / Leruste, Amaury

2023 Volume 110, Issue 3, Page(s) 250–251

Title translation	Drug approval: Crizotinib for relapsed or refractory, ALK-positive, systemic anaplastic large cell lymphoma in pediatrics.
MeSH term(s)	Child ; Humans ; Crizotinib/therapeutic use ; Lymphoma, Large-Cell, Anaplastic/drug therapy ; Drug Approval ; Receptor Protein-Tyrosine Kinases ; Pediatrics ; Protein Kinase Inhibitors/therapeutic use ; Lung Neoplasms ; Antineoplastic Agents/therapeutic use
Chemical Substances	Crizotinib (53AH36668S) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Protein Kinase Inhibitors ; Antineoplastic Agents
Language	French
Publishing date	2023-02-06
Publishing country	France
Document type	Letter
ZDB-ID	213270-9
ISSN	1769-6917 ; 0007-4551
ISSN (online)	1769-6917
ISSN	0007-4551
DOI	10.1016/j.bulcan.2022.12.011
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Article ; Online: Nouvelles AMMs : le blinatumomab en monothérapie dans le traitement de consolidation après première rechute des LAL Ph-CD19+ chez l’enfant de plus de un an.

Coppin, Robin / Leruste, Amaury

Bulletin du cancer

2022 Volume 109, Issue 4, Page(s) 391–392

Title translation	Blinatumomab as monotherapy in consolidation treatment after first relapse of Ph-CD19+ ALL in children over one year old.
MeSH term(s)	Antibodies, Bispecific/therapeutic use ; Antigens, CD19/therapeutic use ; Antineoplastic Agents/therapeutic use ; Child ; Humans ; Infant ; Neoplasm Recurrence, Local ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Recurrence
Chemical Substances	Antibodies, Bispecific ; Antigens, CD19 ; Antineoplastic Agents ; blinatumomab (4FR53SIF3A)
Language	French
Publishing date	2022-02-17
Publishing country	France
Document type	Letter
ZDB-ID	213270-9
ISSN	1769-6917 ; 0007-4551
ISSN (online)	1769-6917
ISSN	0007-4551
DOI	10.1016/j.bulcan.2022.01.003
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Article ; Online: CAR-T cells for pediatric brain tumors: Present and future.

Leruste, Amaury / Beccaria, Kevin / Doz, François

Bulletin du cancer

2021 Volume 108, Issue 10S, Page(s) S109–S116

Abstract: Chimeric Antigen Receptor T (CAR-T) cells are currently approved for B cell malignancies only, in children and adults. Despite a lack of robust evidence to approve such cellular immunotherapy for pediatric solid tumors, there is a growing interest for ... ...

Abstract	Chimeric Antigen Receptor T (CAR-T) cells are currently approved for B cell malignancies only, in children and adults. Despite a lack of robust evidence to approve such cellular immunotherapy for pediatric solid tumors, there is a growing interest for this approach in the treatment of pediatric brain tumors. Following the identification of tumor antigens as targets, the first clinical trials demonstrated some degree of clinical and biological responses to CAR-T cells for such tumor types. Additionaly, several preclinical studies have recently identified new attractive targets and antigen combination strategies, along with a superior tumor trafficking following locoregional administration. We review here the preclinical and clinical knowledge at the basis of the current clinical development of CAR-T cells for pediatric brain tumors.
MeSH term(s)	Antigens, Neoplasm/immunology ; Blood-Brain Barrier ; Brain Neoplasms/genetics ; Brain Neoplasms/immunology ; Brain Neoplasms/therapy ; Child ; Clinical Trials as Topic ; Humans ; Immunologic Memory ; Immunotherapy, Adoptive/adverse effects ; Immunotherapy, Adoptive/methods ; Immunotherapy, Adoptive/trends ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes/transplantation ; Tumor Microenvironment/immunology
Chemical Substances	Antigens, Neoplasm ; Receptors, Chimeric Antigen
Language	English
Publishing date	2021-12-17
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	213270-9
ISSN	1769-6917 ; 0007-4551
ISSN (online)	1769-6917
ISSN	0007-4551
DOI	10.1016/j.bulcan.2021.06.002
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Article ; Online: Checkpoint Immunotherapy in Pediatrics: Here, Gone, and Back Again.

Long, Adrienne H / Morgenstern, Daniel A / Leruste, Amaury / Bourdeaut, Franck / Davis, Kara L

American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

2022 Volume 42, Page(s) 1–14

Abstract: The role of immune checkpoint inhibitors (ICIs) in the treatment of pediatric cancers continues to evolve. Such therapies function by augmenting existing antitumor T-cell responses that have been rendered ineffective by inhibitory pathways. Although ICIs ...

Abstract	The role of immune checkpoint inhibitors (ICIs) in the treatment of pediatric cancers continues to evolve. Such therapies function by augmenting existing antitumor T-cell responses that have been rendered ineffective by inhibitory pathways. Although ICIs have proven highly effective for adult cancers, initial phase I/II clinical trials using single-agent ICIs against unselected pediatric cancers have been overall disappointing. With the exception of pediatric classic Hodgkin lymphoma, responses to ICIs have been infrequent, likely stemming from an inherent difference in the immunogenicity of childhood cancers, which, on average, have far fewer neoantigens than adult cancers. Recently, however, hope has reemerged that certain subsets of children with cancer may benefit from ICI therapies. In preliminary studies, patients with both pediatric hypermutated and SMARCB1-deficient cancers have had impressive responses to ICI therapies, likely as a result of underlying biologies that enhance neoantigen expression and tumoral inflammation. Dedicated trials are ongoing to fully evaluate the efficacy of ICIs for patients with these subsets of pediatric cancer.
MeSH term(s)	Child ; Hodgkin Disease ; Humans ; Immune Checkpoint Inhibitors ; Immunologic Factors ; Immunotherapy ; Pediatrics
Chemical Substances	Immune Checkpoint Inhibitors ; Immunologic Factors
Language	English
Publishing date	2022-05-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2431126-1
ISSN	1548-8756 ; 1548-8748
ISSN (online)	1548-8756
ISSN	1548-8748
DOI	10.1200/EDBK_349799
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Article ; Online: Immune responses in genomically simple SWI/SNF-deficient cancers.

Leruste, Amaury / Chauvin, Céline / Pouponnot, Celio / Bourdeaut, Franck / Waterfall, Joshua J / Piaggio, Eliane

Cancer

2020 Volume 127, Issue 2, Page(s) 172–180

MeSH term(s)	Animals ; Combined Modality Therapy/methods ; DNA Helicases/deficiency ; DNA Helicases/genetics ; DNA-Binding Proteins/deficiency ; DNA-Binding Proteins/genetics ; Disease Models, Animal ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immunity ; Mice ; Mutation ; Neoplasms/drug therapy ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/radiotherapy ; Nuclear Proteins/deficiency ; Nuclear Proteins/genetics ; Polymorphism, Single Nucleotide ; SMARCB1 Protein/deficiency ; SMARCB1 Protein/genetics ; Transcription Factors/deficiency ; Transcription Factors/genetics ; Treatment Outcome
Chemical Substances	DNA-Binding Proteins ; Immune Checkpoint Inhibitors ; Nuclear Proteins ; PBRM1 protein, human ; SMARCB1 Protein ; SMARCB1 protein, human ; Transcription Factors ; SMARCA4 protein, human (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-)
Keywords	covid19
Language	English
Publishing date	2020-10-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.33172
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Article ; Online: Controversies on the possible role of immune checkpoint inhibitors in pediatric cancers: balancing irAEs and efficacy.

Nigro, Olga / Ferrari, Andrea / Casanova, Michela / Orbach, Daniel / Leruste, Amaury / Gatz, Susanne A / Frappaz, Didier / Massimino, Maura

Tumori

2021 Volume 107, Issue 4, Page(s) 276–281

Abstract: Pediatric cancers are not the equivalent of adult cancers occurring at a younger age and the prospect of immunotherapy in children has not been received with the same enthusiasm as in the adult setting. Although most pediatric malignancies are considered ...

Abstract	Pediatric cancers are not the equivalent of adult cancers occurring at a younger age and the prospect of immunotherapy in children has not been received with the same enthusiasm as in the adult setting. Although most pediatric malignancies are considered immunologically cold, we are learning more about PD-L1 expression, tumor mutational burden, and microsatellite instability in several pediatric cancers. The side effects of immunotherapy are an important consideration. Immune checkpoint inhibitors (ICIs) engender a unique constellation of inflammatory toxicities known as immune-related adverse events (irAEs). Three early-phase trials-KEYNOTE-051, iMATRIX, and ADVL1412-were the first to describe irAEs in pediatric patients and ICIs were well tolerated. There was concern about unknown late irAEs in pediatric patients, as they have much more time to develop than in adult or elderly patients. Academic clinicians, biopharmaceutical companies, and parents' advocates concluded that no benefit could be expected from further monotherapy trials employing other ICIs with the same mechanism of action until more scientific knowledge becomes available. On the other hand, ICIs could be useful in combination with other therapies to prevent the functional inactivation of several pathways in the hostile microenvironment. Future clinical studies on ICIs in children need to build on strong biological premises, taking into account the distinctive immunobiology of pediatric cancers vis-à-vis ICI-responsive adult cancers. We need to gain and share experiences of new therapies for managing pediatric patients with cancer, clarifying to what extent we can extrapolate the data obtained in adults.
MeSH term(s)	Child ; Drug-Related Side Effects and Adverse Reactions/etiology ; Drug-Related Side Effects and Adverse Reactions/pathology ; Humans ; Immune Checkpoint Inhibitors/adverse effects ; Immunotherapy/adverse effects ; Neoplasms/drug therapy ; Neoplasms/immunology ; Prognosis
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2021-04-20
Publishing country	United States
Document type	Editorial
ZDB-ID	280962-x
ISSN	2038-2529 ; 0300-8916
ISSN (online)	2038-2529
ISSN	0300-8916
DOI	10.1177/03008916211010214
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Article ; Online: Epstein-Barr Virus in Childhood and Adolescent Classic Hodgkin Lymphoma in a French Cohort of 301 Patients.

Pereira, Victor / Boudjemaa, Sabah / Besson, Caroline / Leblanc, Thierry / Rigaud, Charlotte / Leruste, Amaury / Garnier, Nathalie / Lambilliotte, Anne / Simonin, Matthieu / Curtillet, Catherine / Bonneau-Lagacherie, Jacinthe / Coulomb, Aurore / Landman-Parker, Judith

Journal of pediatric hematology/oncology

2022 Volume 44, Issue 8, Page(s) e1033–e1038

Abstract: Objective: The aim was to analyze the role of Epstein-Barr virus (EBV) in the bioclinical characteristics of patients treated for classic Hodgkin lymphoma (cHL) in France.: Methods: Biopathologic data of 301 patients treated for a cHL in/or according ...

Abstract	Objective: The aim was to analyze the role of Epstein-Barr virus (EBV) in the bioclinical characteristics of patients treated for classic Hodgkin lymphoma (cHL) in France. Methods: Biopathologic data of 301 patients treated for a cHL in/or according to the EuroNet PHL-C1 trial between November 2008 and February 2013 were centrally reviewed. Results: Median age at diagnosis was 14 (3 to 18) years and the F/M ratio 0.86, 0.47 before 10 years and 0.9 from 11 to 18. CHL subtypes were nodular sclerosis for 266/301 (88%) patients, mixed cellularity for 22/301 (7%), lymphocyte rich for 2/301 (1%), and 11/301 were unclassified. EBV positivity by in situ hybridization was observed for 68/301 (23%) patients, significantly associated with mixed cellularity subtype and male sex, particularly overrepresented in boys below 10 years: 15/23 (65%) versus 28/139 among other male patients (20%). EBV viral load was detectable in 22 of 108 (22%) tested cases and was overrepresented in EBV cHL (13/28) versus non-EBV cHL (9/80) patients. Detailed semiquantitative histologic analysis showed a high number of B-cell residual follicles in EBV cHL relative to EBV-negative HL. Conclusion: Distribution of EBV cHL in children and adolescents is associated with young age and male sex, suggesting a specific physiopathology and may require a differential therapeutic approach.
MeSH term(s)	Child ; Humans ; Adolescent ; Male ; Herpesvirus 4, Human/genetics ; Hodgkin Disease/pathology ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/epidemiology ; Immunohistochemistry ; In Situ Hybridization ; Lymphoma, Non-Hodgkin/complications
Language	English
Publishing date	2022-01-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1231152-2
ISSN	1536-3678 ; 1077-4114 ; 0192-8562
ISSN (online)	1536-3678
ISSN	1077-4114 ; 0192-8562
DOI	10.1097/MPH.0000000000002403
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Article: Immune responses in genomically simple SWI/SNF-deficient cancers

Leruste, Amaury / Chauvin, Céline / Pouponnot, Celio / Bourdeaut, Franck / Waterfall, Joshua J / Piaggio, Eliane

Cancer

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #33079397
Database	COVID19

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Article ; Online: Rituximab in addition to LMB-based chemotherapy regimen in children and adolescents with primary mediastinal large B-cell lymphoma: results of the French LMB2001 prospective study.

Dourthe, Marie Emilie / Phulpin, Aurélie / Auperin, Anne / Bosq, Jacques / Couec, Marie-Laure / Dartigues, Peggy / Ducassou, Stéphane / Garnier, Nathalie / Haouy, Stéphanie / Leblanc, Thierry / Leruste, Amaury / Paillard, Catherine / Rigaud, Charlotte / Simonin, Mathieu / Patte, Catherine / Minard-Colin, Véronique

Haematologica

2022 Volume 107, Issue 9, Page(s) 2173–2182

Abstract: Primary mediastinal large B-cell lymphoma (PMLBL) is a rare entity predominantly affecting adolescents and young adults. Recently, an international phase II trial in pediatric patients using dose-adjusted etoposide, doxorubicin, and cyclophosphamide with ...

Abstract	Primary mediastinal large B-cell lymphoma (PMLBL) is a rare entity predominantly affecting adolescents and young adults. Recently, an international phase II trial in pediatric patients using dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) failed to reproduce excellent survival reported in some adult studies. The optimal therapy regimen needs to be determined in this disease. The French prospective LMB2001 trial included all patients ≤18 years with mature B-cell lymphoma treated in French centers. For patients with PMLBL, treatment included four to eight courses of Lymphomes Malins B (LMB)-based chemotherapy without radiotherapy. From 2008, rituximab was added before each chemotherapy course. From 09/2001 to 03/2012, 42 patients with PMLBL were registered. The median age was 15 years (range, 8-18). Twenty-one patients were treated with chemotherapy plus rituximab. The median follow-up was 7.1 years (interquartile range, 5.8-11.1). Five-year event-free and overall survival were 88.1% (95% confidence interval (CI): 75.0-94.8) and 95.2% (95% CI: 84.0-98.7) for the whole population. The 5-year EFS was 81.0% (95% CI: 60.0-92.3) and 95.2% (95% CI: 77.3-99.2) (hazard ratio =0.24; 95% CI: 0.03- 2.2) and 5-year overall survival was 90.5% (95% CI: 71.1-97.3) and 100% for patients treated without and with rituximab, respectively. Only one of 21 patients treated with rituximab and LMB-based chemotherapy had local early treatment failure but achieved prolonged complete remission with second-line chemotherapy and radiotherapy. Intensive LMBbased chemotherapy with rituximab achieved excellent survival in children/adolescents with PMLBL. Further international prospective studies are required to confirm these results in this population.
MeSH term(s)	Adolescent ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Child ; Cyclophosphamide ; Doxorubicin/adverse effects ; Etoposide ; Humans ; Lymphoma, Large B-Cell, Diffuse/pathology ; Prednisone/therapeutic use ; Prospective Studies ; Rituximab ; Vincristine/adverse effects ; Young Adult
Chemical Substances	Rituximab (4F4X42SYQ6) ; Vincristine (5J49Q6B70F) ; Etoposide (6PLQ3CP4P3) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2022-09-01
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2021.280257
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Article ; Online: GH and Childhood-onset Craniopharyngioma: When to Initiate GH Replacement Therapy?

Nguyen Quoc, Adrien / Beccaria, Kévin / González Briceño, Laura / Pinto, Graziella / Samara-Boustani, Dinane / Stoupa, Athanasia / Beltrand, Jacques / Besançon, Alix / Thalassinos, Caroline / Puget, Stéphanie / Blauwblomme, Thomas / Alapetite, Claire / Bolle, Stéphanie / Doz, François / Grill, Jacques / Dufour, Christelle / Bourdeaut, Franck / Abbou, Samuel / Guerrini-Rousseau, Léa /

Leruste, Amaury / Brabant, Séverine / Cavadias, Iphigénie / Viaud, Magali / Boddaert, Nathalie / Polak, Michel / Kariyawasam, Dulanjalee

The Journal of clinical endocrinology and metabolism

2023 Volume 108, Issue 8, Page(s) 1929–1936

Abstract: Context: Craniopharyngioma is a benign brain tumor with frequent local recurrence or progression after treatment. GH replacement therapy (GHRT) is prescribed in children with GH deficiency resulting from childhood-onset craniopharyngioma.: Objective: ...

Abstract	Context: Craniopharyngioma is a benign brain tumor with frequent local recurrence or progression after treatment. GH replacement therapy (GHRT) is prescribed in children with GH deficiency resulting from childhood-onset craniopharyngioma. Objective: To evaluate whether a shorter delay of GHRT initiation after childhood-onset craniopharyngioma completion therapy increased the risk of a new event (progression or recurrence). Methods: Retrospective, observational, monocenter study. We compared a cohort of 71 childhood-onset patients with craniopharyngiomas treated with recombinant human GH (rhGH). Twenty-seven patients were treated with rhGH at least 12 months after craniopharyngioma treatment (>12-month group) and 44 patients before 12 months (<12-month group), among which 29 patients were treated between 6 and 12 months (6-12 month group). The main outcome was the risk of tumor new event (progression of residual tumor or tumor recurrence after complete resection) after primary treatment in the >12-month group and in the <12 month or in the 6- to 12-month group patients. Results: In the >12-month group, the 2- and 5-year event-free survivals were respectively 81.5% (95% CI, 61.1-91.9) and 69.4% (95% CI, 47.9-83.4) compared with 72.2% (95% CI, 56.3-83.1) and 69.8% (95% CI, 53.8-81.2) in the <12-month group. The 2- and 5-year event-free survivals were the same in the 6- to 12-month group (72.4%; 95% CI, 52.4-85.1). By log-rank test, the event-free survival was not different between groups (P = .98 and P = .91).The median time for event was not statistically different.In univariate and multivariate analysis, the risk of craniopharyngioma new event was not associated with the GHRT time delay after craniopharyngioma treatment. Conclusions: No association was found between GHRT time delay after childhood-onset craniopharyngioma treatment and an increased risk of recurrence or tumor progression, suggesting GH replacement therapy can be initiated 6 months after last treatment for craniopharyngiomas.
MeSH term(s)	Humans ; Child ; Craniopharyngioma/pathology ; Retrospective Studies ; Pituitary Neoplasms/drug therapy ; Pituitary Neoplasms/epidemiology ; Pituitary Neoplasms/pathology ; Neoplasm Recurrence, Local/etiology ; Human Growth Hormone/adverse effects ; Hormone Replacement Therapy/adverse effects
Chemical Substances	Human Growth Hormone (12629-01-5)
Language	English
Publishing date	2023-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgad079
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