Institute dHematologie et Oncologie Pediatrique

Sainte-Foy-lès-Lyon, France

Institute dHematologie et Oncologie Pediatrique

Sainte-Foy-lès-Lyon, France

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Daikeler T.,University Paris Diderot | Daikeler T.,University of Basel | Labopin M.,CEREST TC European Group for Blood and Marrow Transplantation | Ruggeri A.,University Paris Diderot | And 25 more authors.
Blood | Year: 2013

To describe the incidence, risk factors, and treatment of autoimmune diseases (ADs) occurring after cord blood transplantation (CBT), we analyzed both CBT recipients reported to EUROCORD who had developed at least 1 new AD and those who had not. Fifty-two of 726 reported patients developed at least 1 AD within 212 days (range, 27-4267) after CBT. Cumulative incidence of ADs after CBT was 5.0% ± 1% at 1 year and 6.6% ± 1% at 5 years. Patients developing ADs were younger and had more nonmalignant diseases (P < .001). ADs target hematopoietic (autoimmune hemolytic anemia, n = 20; Evans syndrome, n = 9; autoimmune thrombocytopenia, n = 11; and immune neutropenia, n = 1) and other tissues (thyroiditis, n = 3; psoriasis, n = 2; Graves disease, n = 1; membranous glomerulonephritis, n = 2; rheumatoid arthritis, n = 1; ulcerative colitis, n = 1; and systemic lupus erythematosus, n = 1). Four patients developed 2 ADs (3 cases of immune thrombocytopenia followed by autoimmune hemolytic anemia and 1 Evans syndrome with rheumatoid arthritis). By multivariate analysis, the main risk factor for developing an AD was nonmalignant disease as an indication for CBT (P = .0001). Hematologic ADs were most often treated with steroids, rituximab, and cyclosporine. With a median follow-up of 26 months (range, 2-91), 6 of 52 patients died as a consequence of ADs. We conclude that CBT may be followed by potentially life-threatening, mainly hematologic ADs. © 2013 by The American Society of Hematology.


PubMed | Institute dhematologie et oncologie pediatrique, Gustave Roussy, Hospices civils de Lyon and University Pierre and Marie Curie
Type: Journal Article | Journal: Bulletin du cancer | Year: 2016

Ependymomas represent 10% of pediatric brain tumors. In the recent WHO 2016 classification, pathology is enriched by localization and molecular biology. Whatever the age, total removal by one or several looks when required remains a major prognostic factor. In children, focal radiation remains a standard, while the role of chemotherapy is matter of randomized studies. In infants, front line chemotherapy is the standard. Inclusion in the SIOP ependymomaII protocol is encouraged. In case of relapse, further surgery and radiation are advised, while inclusion in innovative trials including re-irradiation, and phaseI-II should be encouraged. A better understanding of underlying mechanisms of ependymoma cell will provide in the close future, the key to use targeted therapies at time of relapse, and very soon as first line therapy for some subgroups of patients.


Benezech S.,Institute Dhematologie Et Oncologie Pediatrique | Chabaud S.,Center Leon Berard | Chambon F.,Estaing University Hospital Center | Dijoud F.,Hopital Femme Mere Enfant | And 2 more authors.
Pathology and Oncology Research | Year: 2016

Metastatic status, histologic response, and quality of surgical resection are prognostic factors for osteosarcomas. Pathology reports sometimes describe peritumoral vascular invasion on surgical specimens after neoadjuvant chemotherapy but their prognostic significance as an independent parameter has never been reported. The aim of this study was to evaluate how the presence of this peritumoral vascular invasion could influence survival. We retrospectively analyzed histology, demographics, and outcomes of pediatric patients treated for osteosarcoma in our institutions between January 2007 and December 2012. A single pathologist analyzed the resection specimens after neoadjuvant chemotherapy. Fifty-one osteosarcomas were diagnosed over a 6-year period; nine had metastatic disease at diagnosis. Surgery was performed after neoadjuvant chemotherapy in all cases. We identified peritumoral vascular invasion in the surgical specimens in 15 cases. Two-year event-free survival (EFS) was 78 % (CI95%[64;93]) for patients without vascular invasion versus 48 % (CI95% [21;75]) in patients with vascular invasion, and 2-year overall survival (OS) was 94 % (CI95%[86;100]) for those without vascular invasion versus 79 % (CI95%[57;100]) for others. Multivariate analysis demonstrated correlation of metastatic status and presence of vascular invasion with survival. The histopathological description of peritumoral vascular invasion in surgical specimens of osteosarcoma after neoadjuvant chemotherapy can be considered a prognostic factor and could indicate modification of the postoperative therapeutic strategy. © 2016 Arányi Lajos Foundation


PubMed | Institute dHematologie et Oncologie Pediatrique, Center Leon Berard, Estaing University Hospital Center and Hopital Femme Mere Enfant
Type: Journal Article | Journal: Pathology oncology research : POR | Year: 2016

Metastatic status, histologic response, and quality of surgical resection are prognostic factors for osteosarcomas. Pathology reports sometimes describe peritumoral vascular invasion on surgical specimens after neoadjuvant chemotherapy but their prognostic significance as an independent parameter has never been reported. The aim of this study was to evaluate how the presence of this peritumoral vascular invasion could influence survival. We retrospectively analyzed histology, demographics, and outcomes of pediatric patients treated for osteosarcoma in our institutions between January 2007 and December 2012. A single pathologist analyzed the resection specimens after neoadjuvant chemotherapy. Fifty-one osteosarcomas were diagnosed over a 6-year period; nine had metastatic disease at diagnosis. Surgery was performed after neoadjuvant chemotherapy in all cases. We identified peritumoral vascular invasion in the surgical specimens in 15 cases. Two-year event-free survival (EFS) was 78% (CI95%[64;93]) for patients without vascular invasion versus 48% (CI95% [21;75]) in patients with vascular invasion, and 2-year overall survival (OS) was 94% (CI95%[86;100]) for those without vascular invasion versus 79% (CI95%[57;100]) for others. Multivariate analysis demonstrated correlation of metastatic status and presence of vascular invasion with survival. The histopathological description of peritumoral vascular invasion in surgical specimens of osteosarcoma after neoadjuvant chemotherapy can be considered a prognostic factor and could indicate modification of the postoperative therapeutic strategy.


Domenech C.,Institute DHematologie et Oncologie Pediatrique | Rabodonirina M.,Service de Parasitologie et de Pathologie Exotique | Bleyzac N.,Institute DHematologie et Oncologie Pediatrique | Pages M.-P.,University Claude Bernard Lyon 1 | Bertrand Y.,Institute DHematologie et Oncologie Pediatrique
Journal of Pediatric Hematology/Oncology | Year: 2011

Cryptosporidium is recognized as a cause of diarrhea associated with a high mortality in immunocompromised patients. We report on 2 pediatric cases of cryptosporidiosis during maintenance chemotherapy of acute lymphoblastic leukemia. The patients presented severe diarrheas, 1 of them was complicated by a cholangitis. Withdrawal of immunosuppressive treatments and adjunction of an adequate antiparasitic treatment cured the Cryptosporidium infection in both cases. © 2011 Lippincott Williams & Wilkins, Inc.


Butturini A.,Childrens Hospital Los Angeles | Butturini A.,University of Southern California | Frappaz D.,Institute dHematologie et Oncologie Pediatrique
Pediatric Blood and Cancer | Year: 2010

High-dose, myeloablative chemotherapy with hematopoietic stem cell rescue is used in children and young adults with brain tumors for which conventional therapy is either excessively toxic (e.g., radiotherapy in infants) or ineffective. Thus, the aims of such strategies are to improve both quantity and quality of life. Whether high-dose chemotherapy is less neurotoxic and more effective than other therapeutic approaches is still controversial. We will consider the difficulties in analyzing published data and the challenges of designing effective clinical trials that test high-dose chemotherapy in patients with brain tumors. © 2010 Wiley-Liss, Inc.


Baleydier F.,Institute dHematologie et Oncologie Pediatrique | Baleydier F.,Rockefeller University | Domenech C.,Institute dHematologie et Oncologie Pediatrique | Thomas X.,Hopital Edouard Herriot | Thomas X.,Rockefeller University
Bulletin du Cancer | Year: 2011

Cytogenetic, molecular and phenotyping features of malignant hematologic diseases succeeded in improving their management by a more accurate stratification of patients according to several groups of risk and by providing a rational for targeted therapy. Three major types of treatment (excluding cellular therapy) are currently available in onco-hematology: conventional chemotherapy, small molecules for targeted therapy and monoclonal antibodies. Conventional chemotherapy with optimization of doses and multidrug-based regimens allowed to substantially improve survival of patients and keeps a place of choice in treatment of these diseases. Targeted treatments came from the cytogenetic and molecular characterization of hemopathies. Thus, the kinase Bcr-Abl, as a result of the translocation t(9;22)(q34;q11), has been successfully targeted by tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia. Molecular abnormalities like internal-tandem duplication/point activating mutations in FLT3 in some acute myeloblastic leukemia or epigenetic dysregulations in some blood malignancies can also be targeted by small molecules. Hematopoietic malignant cells are phenotypically characterized by expression of cluster of differentiation (CD) on their surface. These CD are detected by flow cytometry using specific antibodies. Monoclonal antibodies targeting different CD have been developed for treatment. Rituximab, an anti-CD20 antibody, was the first monoclonal antibody successfully developed for treatment of malignant hematologic diseases. Since rituximab, many other monoclonal antibodies are being developed. Trends in malignant hematologic diseases presented here will include treatments, which have at least entered phase I/II clinical trials in adult or childhood leukemia. They include some novel drugs of conventional chemotherapy like secondgeneration nucleoside analogues. We will give an overview of the small molecules targeting the different cellular pathways and we will highlight those appearing as the most promising like novel TKIs. The large field of monoclonal antibodies will be also approached focusing on antibodies developed in leukemias. ©John Libbey Eurotext.


Dommange-Romero F.,Institute dHematologie et Oncologie Pediatrique | Collardeau-Frachon S.,Hospices Civils de Lyon | Hameury F.,Hospices Civils de Lyon
Bulletin du Cancer | Year: 2010

Pleuropulmonary blastoma is an extremely rare and aggressive thoracic tumour seen exclusively in children. The initial symptoms are respiratory and non specific and the chest X-ray done in that context reveals a thoracic mass. The chest CT scan then leads to the diagnosis of a cystic, mixt or solid mass. The diagnosis will be affirmed on anatomopathology of the tumour or biopsy. There are three different histological types: type I, cystic, type II, cystic and solid and type III, solid exclusively. Type I is less aggressive and its treatment is essentially surgical. Types II and III are highly aggressive and require surgery associated to polychemotherapy. In all cases, surgery is essential and should be the most complete possible. Extension and follow-up exams will include bone scan and brain imagery searching for metastasis as well as abdominal ultrasound searching associated renal lesions because 30% of pleuropulmonary blastoma are part of a familial predisposition syndrome. ©John Libbey Eurotext.


PubMed | Institute dhematologie et oncologie pediatrique
Type: Journal Article | Journal: Bulletin du cancer | Year: 2010

Pleuropulmonary blastoma is an extremely rare and aggressive thoracic tumour seen exclusively in children. The initial symptoms are respiratory and non specific and the chest X-ray done in that context reveals a thoracic mass. The chest CT scan then leads to the diagnosis of a cystic, mixt or solid mass. The diagnosis will be affirmed on anatomopathology of the tumour or biopsy. There are three different histological types: type I, cystic, type II, cystic and solid and type III, solid exclusively. Type I is less aggressive and its treatment is essentially surgical. Types II and III are highly aggressive and require surgery associated to polychemotherapy. In all cases, surgery is essential and should be the most complete possible. Extension and follow-up exams will include bone scan and brain imagery searching for metastasis as well as abdominal ultrasound searching associated renal lesions because 30% of pleuropulmonary blastoma are part of a familial predisposition syndrome.


PubMed | Institute dhematologie et oncologie pediatrique
Type: Journal Article | Journal: Bulletin du cancer | Year: 2011

Cytogenetic, molecular and phenotyping features of malignant hematologic diseases succeeded in improving their management by a more accurate stratification of patients according to several groups of risk and by providing a rational for targeted therapy. Three major types of treatment (excluding cellular therapy) are currently available in onco-hematology: conventional chemotherapy, small molecules for targeted therapy and monoclonal antibodies. Conventional chemotherapy with optimization of doses and multidrug-based regimens allowed to substantially improve survival of patients and keeps a place of choice in treatment of these diseases. Targeted treatments came from the cytogenetic and molecular characterization of hemopathies. Thus, the kinase Bcr-Abl, as a result of the translocation t(9;22)(q34;q11), has been successfully targeted by tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia and Ph+acute lymphoblastic leukemia. Molecular abnormalities like internal-tandem duplication/point activating mutations in FLT3 in some acute myeloblastic leukemia or epigenetic dysregulations in some blood malignancies can also be targeted by small molecules. Hematopoietic malignant cells are phenotypically characterized by expression of cluster of differentiation (CD) on their surface. These CD are detected by flow cytometry using specific antibodies. Monoclonal antibodies targeting different CD have been developed for treatment. Rituximab, an anti-CD20 antibody, was the first monoclonal antibody successfully developed for treatment of malignant hematologic diseases. Since rituximab, many other monoclonal antibodies are being developed. Trends in malignant hematologic diseases presented here will include treatments, which have at least entered phase I/II clinical trials in adult or childhood leukemia. They include some novel drugs of conventional chemotherapy like second-generation nucleoside analogues. We will give an overview of the small molecules targeting the different cellular pathways and we will highlight those appearing as the most promising like novel TKIs. The large field of monoclonal antibodies will be also approached focusing on antibodies developed in leukemias.

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