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1.
Blood Adv ; 3(13): 1981-1988, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31270080

RESUMO

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a phosphatase known to be a tumor suppressor gene in T-cell acute lymphoblastic leukemia (T-ALL). Because the full clinicobiologic characteristics of PTPN2 loss remain poorly reported, we aimed to provide a comprehensive analysis of PTPN2 deletions within a cohort of 430 patients, including 216 adults and 214 children treated according to the GRAALL03/05 (#NCT00222027 and #NCT00327678) and the FRALLE2000 protocols, respectively. We used multiplex ligation-dependent probe amplification to identify an 8% incidence of PTPN2 deletion, which was comparable in adult (9%) and pediatric (6%) populations. PTPN2 deletions were significantly associated with an αß lineage and TLX1 deregulation. Analysis of the mutational genotype of adult T-ALL revealed a positive correlation between PTPN2 deletions and gain-of-function alterations in the IL7R/JAK-STAT signaling pathway as well as PHF6 and WT1 mutations. Of note, PTPN2 and PTEN (phosphatase and tensin homolog) deletions were mutually exclusive. Regarding treatment response, PTPN2-deleted T-ALLs were associated with a higher glucocorticoid response and a trend for improved survival in children, but not in adults, with a 5-year cumulative incidence of relapse of 8% for PTPN2-deleted pediatric cases vs 26% (P = .177).

2.
Bull Cancer ; 2018 Sep 17.
Artigo em Francês | MEDLINE | ID: mdl-30236479

RESUMO

Acute lymphoblastic leukemia (ALL) is the first cause of cancer in children. Five-year overall survival is greater than 90% but leukemia remains a major cause of death from cancer in children. A new class of immunotherapy based on a chimeric antigen receptor "CAR" targeting the CD19 on the B leukemic cells and that is transduced in an autologous or allogenic T lymphocyte will allow to transform the prognosis of refractory or relapsed B-ALL. Overall response rates range from 60 to 90% in phase I-II studies in patients with second relapse or more or with refractory disease. Persistent remissions and even cures have been observed. These very good results could lead to use this treatment in first line for patients with very high-risk disease. However, CAR T cells production, costs and adverse events management represent major issues for the future of this therapeutic. The occurrence of CD19 negative relapses has led to develop bispecific CAR T cells. Allogeneic CAR would permit to obtain a "CAR garage" off the shelf available from the diagnosis. Perspectives for CAR T cells are immense but will involve technological progresses around the CAR conception and production, leading to further improved results in leukemias (ALL but also AML) and lymphomas and hopefully the emergence of efficacy in childhood solid tumors.

3.
J Pediatr Hematol Oncol ; 40(2): 85-92, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29300240

RESUMO

In children, nasopharyngeal carcinoma (NPC) is a very rare tumor, mostly Epstein-Barr Virus related and quite always diagnosed at a locally advanced stage. With current protocols associating induction cisplatin-based chemotherapy and concomitant chemoradiotherapy, prognosis is excellent with overall survival higher than 85%. However, long-term toxicities are frequent. Improvement in radiation therapy modalities like intensity-modulated radiation therapy and new strategies with radiation dose adaptation to chemotherapy response have been introduced to reduce acute and long-term toxicities. Actually, 2 main questions remain: is it possible to pursue a therapeutic deescalation in children with low-risk NPC or very good response to induction chemotherapy in order to reduce the risk of late effects? Could an immunologic maintenance treatment improve prognosis of children with high-risk NPC? International collaborative groups and prospective trials including biological studies are necessary to answer these questions to improve childhood NPC treatment and knowledge.

4.
Bull Cancer ; 105 Suppl 2: S147-S157, 2018 Dec.
Artigo em Francês | MEDLINE | ID: mdl-30686353

RESUMO

CAR T CELLS: CURRENT INDICATIONS IN CHILDREN AND PERSPECTIVES: Acute lymphoblastic leukemia (ALL) is the first cause of cancer in children. Five-year overall survival is greater than 90% but leukemia remains a major cause of death from cancer in children. A new class of immunotherapy based on a chimeric antigen receptor "CAR" targeting the CD19 on the B leukemic cells and that is transduced in an autologous or allogenic T lymphocyte will allow to transform the prognosis of refractory or relapsed B-ALL. Overall response rates range from 60 to 90% in phase I-II studies in patients with second relapse or more or with refractory disease. Persistent remissions and even cures have been observed. These very good results could lead to use this treatment in first line for patients with very high-risk disease. However, CAR-T cells production, costs and adverse events management represent major issues for the future of this therapeutic. The occurrence of CD19 negative relapses has led to develop bispecific CAR-T cells. Allogeneic CAR would permit to obtain a "CAR garage" off the shelf available from the diagnosis. Perspectives for CAR-T cells are immense but will involve technological progresses around the CAR conception and production, leading to further improve results in leukemias (ALL but also AML) and lymphomas and hopefully to the emergence of efficacy in childhood solid tumors. Cet article fait partie du numéro supplément Les cellules CAR-T : une révolution thérapeutique ? réalisé avec le soutien institutionnel des partenaires Gilead : Kite et Celgene.


Assuntos
Antígenos CD19/imunologia , Imunoterapia Adotiva/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos Quiméricos , Adolescente , Especificidade de Anticorpos , Linfócitos B/imunologia , Criança , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Glioblastoma/terapia , Humanos , Imunoterapia Adotiva/efeitos adversos , Linfoma/terapia , Neuroblastoma/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos Quiméricos/imunologia , Recidiva
5.
Bull Cancer ; 104(3): 267-280, 2017 Mar.
Artigo em Francês | MEDLINE | ID: mdl-27989630

RESUMO

Carcinomas are rare tumors of the adolescent-young adult (AYA) with a different spectrum from those of adults. The most common sites outside of the thyroid is the nasopharynx, salivary gland, colon-rectum and ovaries. If nasopharyngeal carcinoma or salivary gland tumors are good prognosis, others are more reserved prognosis, such as digestive carcinomas, gynecological or midline. The revelation modes are non-specific and depend on the location: mass, tumor syndrome, pain, impaired general condition. The unusual of pediatric carcinomas led to propose a systematic oncogenetic exploration. The medical history of the family, the symptoms and the type of the carcinoma should guide the analysis. In the absence of guidance, analysis of TP53 gene and, for carcinomas of the expanded spectrum of the hereditary non-polyposis colorectal cancer (HNPCC) syndrome, the search for mutation of MMR genes (mismatch repair) seems essential. Because of the rarity of these diseases and the absence of homogeneous recommendations, members of the rare tumors committee of the SFCE recommended for the management of these AJA, an histological review by a pathologist familiar with carcinomas of the adult, a double discussion between pediatric and adult oncologists, analysis of adult standards with adaptation to pediatric data, especially in terms of risk of side effects. An advice to a national opinion (by a member of FRACTURE group) or European (group EXPERT) is sometimes necessary in the most complex situations.


Assuntos
Carcinoma/diagnóstico , Carcinoma/terapia , Neoplasias/diagnóstico , Neoplasias/terapia , Adolescente , Fatores Etários , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Carcinoma/genética , Carcinoma/patologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Feminino , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Masculino , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/terapia , Neoplasias/genética , Neoplasias/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Prognóstico , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/terapia , Fatores Sexuais , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/terapia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/terapia , Adulto Jovem
8.
Pediatr Nephrol ; 27(3): 497-502, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22167562

RESUMO

BACKGROUND: Congenital abnormalities of the kidney and the urinary tract (CAKUT) are among the most frequent causes of antenatal consultation. In this retrospective study we evaluated the outcome of children for whom antenatal consultation was performed between 2006 and 2011 in one single pediatric nephrology center, with a particular focus on the outcome of children whose parents declined a therapeutic abortion. CASE-DIAGNOSIS/TREATMENT: Thirty-four cases of isolated CAKUT were found. Of these, 19 terminations of pregnancies (TOP) were proposed, and ten TOP were refused for these patients. Among the ten infants whose parents refused an abortion, five died in the first month of life. Their median creatinine level at 3 days of life was 56 (range 25-316) µmol/L. For the five surviving patients, the median age at the time of analysis was 29 months, at which time all had a normal serum creatinine with a variable degree of proteinuria.Oligohydramnios was found in three of the patients who died. However, two of the five surviving patients also had oligohydramnios. CONCLUSION: In ten patients for whom TOP was proposed for severe CAKUT and refused, five had normal serum creatinine at a median age of 29 months. No one predictive factor seems to have sufficient specificity to motivate a therapeutic abortion proposal, suggesting the need of long-term follow-up studies.


Assuntos
Rim/anormalidades , Diagnóstico Pré-Natal , Sistema Urinário/anormalidades , Aborto Induzido , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Oligo-Hidrâmnio/etiologia , Gravidez , Estudos Retrospectivos
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