Bendamustine and rituximab combination in the management of chronic lymphocytic leukemia-associated autoimmune hemolytic anemia: A multicentric retrospective study of the French CLL intergroup (GCFLLC/MW and GOELAMS)
Quinquenel A.,Reims University Hospital Center |
Quinquenel A.,University of Reims Champagne Ardenne |
Willekens C.,CHRU Lille |
Dupuis J.,Hopital Henri Mondor |
And 9 more authors.
American Journal of Hematology | Year: 2015
We report our experience on bendamustine and rituximab (BR) combination in 26 patients with chronic lymphocytic leukemia (CLL) complicated by autoimmune hemolytic anemia (AIHA). At the time of BR initiation, 88% of the patients had already been treated for AIHA and CLL was progressive regardless of AIHA in all patients but one. Overall response rates were 81% for AIHA and 77% for CLL. Median time to next treatment was 28.3 months and 26.2 months for AIHA and CLL, respectively. BR therapy may represent a good and safe therapeutic option in this setting where adequate control of CLL seems important for long-term AIHA response. © 2014 Wiley Periodicals, Inc.
Arfe E.,Cadre de Sante |
Bombail M.,IUCT Oncopole
Revue de l'Infirmiere | Year: 2015
The therapeutic education program set up at the Institut Universitaire du Cancer (University Cancer Institute) in Toulouse accompanies the treatment pathway of breast cancer patients. It includes nine collective workshops. From work organization to application, professionals and patients are closely involved. © 2015 Elsevier Masson SAS.
Kamel S.,St Vincents Hospital |
Horton L.,St Vincents Hospital |
Ysebaert L.,IUCT Oncopole |
Levade M.,University Paul Sabatier |
And 15 more authors.
Leukemia | Year: 2015
The BTK (Bruton's tyrosine kinase) inhibitor ibrutinib is associated with an increased risk of bleeding. A previous study reported defects in collagen- and adenosine diphosphate (ADP)-dependent platelet responses when ibrutinib was added ex vivo to patient samples. Whereas the collagen defect is expected given the central role of BTK in glycoprotein VI signaling, the ADP defect lacks a mechanistic explanation. In order to determine the real-life consequences of BTK platelet blockade, we performed light transmission aggregometry in 23 patients receiving ibrutinib treatment. All patients had reductions in collagen-mediated platelet aggregation, with a significant association between the degree of inhibition and the occurrence of clinical bleeding or bruising (P=0.044). This collagen defect was reversible on drug cessation. In contrast to the previous ex vivo report, we found no in vivo ADP defects in subjects receiving standard doses of ibrutinib. These results establish platelet light transmission aggregometry as a method for gauging, at least qualitatively, the severity of platelet impairment in patients receiving ibrutinib treatment. © 2015 Macmillan Publishers Limited.
PubMed | Institute Paoli Calmettes, Caen University Hospital Center, Nantes University Hospital Center, University Paris - Sud and 4 more.
Type: Journal Article | Journal: Haematologica | Year: 2016
The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m
PubMed | TC Electronic, Hopital Saint Louis, CHRU de Lille, Hopital denfants de la Timone and 11 more.
Type: Journal Article | Journal: Bulletin du cancer | Year: 2016
In the attempt to harmonize clinical practices between different centers belonging to the Francophone society of bone marrow transplantation and cellular therapy (SFGM-TC), our society set up the sixth annual series of workshops which brought together practitioners from all member centers and took place in September2015in Lille. Here, we report our recommendations regarding diagnosis and disease status coding in the ProMISe database used by the SFGM-TC.
PubMed | Groupe hospitalier Pellegrin, CHRU de Lille, CHRU de Montpellier, CHRU de Strasbourg and 6 more.
Type: Journal Article | Journal: Bulletin du cancer | Year: 2016
In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its sixth annual workshop series in September 2015 in Lille. This event brought together practitioners from across the country. Our article discusses the updates and modifications for the 2016 version of the national patient follow-up care logbook.
PubMed | Bergonie Institute, Leon Berard Center, Paoli Calmettes Institute, Antoine Lacassagne Center and 7 more.
Type: | Journal: European journal of cancer (Oxford, England : 1990) | Year: 2016
Malignant peripheral nerve sheath tumors (MPNST) are a rare subtype of soft tissue sarcoma. They can arise in irradiated fields, in patients with type 1 neurofibromatosis (NF1), or sporadically. MPNST exhibit an aggressive behaviour, and their optimal management remains controversial. An unsolved issue is whether NF1-related and sporadic forms of MPNST have a different prognosis, and should be managed differently.Adult and paediatric patients with histologically confirmed MPNST treated between 1990 and 2013 in French cancer centres of the GSF/GETO network, were included in this retrospective study.A total of 353 patients (37% with NF1 and 59% with sporadic tumours) were analysed. Median age at diagnosis was 42 years (range 1-94). The majority of tumours developed in the limbs, were deep-seated and of high grade. Two hundreds and ninety four patients underwent a curative intent surgery. Among them, 60 patients (21%) had neoadjuvant treatment (mainly chemotherapy), and 173 (59%) had adjuvant treatment (mainly radiotherapy). For operated patients, median progression free and overall survival (OS) were 26.3 months and 95.8 months, respectively. In multivariate analysis, poor-prognosis factors for OS were high grade, deep location, locally advanced stage at diagnosis, and macroscopically incomplete resection (R2). NF1 status was not negatively prognostic, except in the recurrence or metastatic setting, where NF1-related MPNST patients treated with palliative chemotherapy showed worse survival than patients with sporadic forms.To our knowledge, our series is the largest study of patients with MPNST reported to date. For operated patients, we showed a worse prognosis for NF1-related MPNST, due to different clinical features at diagnosis, more than NF1 status itself. The French sarcoma group is now conducting correlative analyses on these patients, using the latest molecular tools.
PubMed | CAS Wuhan Institute of Virology, University Paul Sabatier, Hopital Necker Enfants Malades, French Institute of Health and Medical Research and IUCT Oncopole
Type: Journal Article | Journal: PLoS pathogens | Year: 2016
Congenital infection by human cytomegalovirus (HCMV) is a leading cause of permanent sequelae of the central nervous system, including sensorineural deafness, cerebral palsies or devastating neurodevelopmental abnormalities (0.1% of all births). To gain insight on the impact of HCMV on neuronal development, we used both neural stem cells from human embryonic stem cells (NSC) and brain sections from infected fetuses and investigated the outcomes of infection on Peroxisome Proliferator-Activated Receptor gamma (PPAR), a transcription factor critical in the developing brain. We observed that HCMV infection dramatically impaired the rate of neuronogenesis and strongly increased PPAR levels and activity. Consistent with these findings, levels of 9-hydroxyoctadecadienoic acid (9-HODE), a known PPAR agonist, were significantly increased in infected NSCs. Likewise, exposure of uninfected NSCs to 9-HODE recapitulated the effect of infection on PPAR activity. It also increased the rate of cells expressing the IE antigen in HCMV-infected NSCs. Further, we demonstrated that (1) pharmacological activation of ectopically expressed PPAR was sufficient to induce impaired neuronogenesis of uninfected NSCs, (2) treatment of uninfected NSCs with 9-HODE impaired NSC differentiation and (3) treatment of HCMV-infected NSCs with the PPAR inhibitor T0070907 restored a normal rate of differentiation. The role of PPAR in the disease phenotype was strongly supported by the immunodetection of nuclear PPAR in brain germinative zones of congenitally infected fetuses (N = 20), but not in control samples. Altogether, our findings reveal a key role for PPAR in neurogenesis and in the pathophysiology of HCMV congenital infection. They also pave the way to the identification of PPAR gene targets in the infected brain.
PubMed | CNRS Institute of Pharmacology and Structural Biology, Besancon University Hospital Center, Cliniques Universitaires Saint Luc, Institute Bergonie and 10 more.
Type: | Journal: Human pathology | Year: 2016
In contrast to long bone osteosarcoma, mandibular osteosarcoma is highly heterogeneous and morphologically overlaps with benign tumors, obscuring diagnosis and treatment selection. Molecular characterization is difficult due to the paucity of available specimens of this rare disease. We aimed to characterize the spectrum of mandibular osteosarcoma using immunohistochemistry and molecular techniques (quantitative polymerase chain reaction and sequencing) and compare them with benign fibro-osseous lesions. Forty-nine paraffin-embedded mandible osteosarcoma tissue samples were collected retrospectively and compared with 10 fibrous dysplasia and 15 ossifying fibroma cases. These were analyzed for molecular markers thought to differ between the different diseases and subtypes: MDM2 (murine double-minute type 2) overexpression, GNAS (guanine nucleotide-binding protein/ subunit) mutations, and amplification of MDM2 and/or RASAL1 (RAS protein activator like 1). Five fibroblastic high-grade osteosarcoma subtypes showed MDM2 amplification, including 2 with a microscopic appearance of high-grade osteosarcoma with part low-grade osteosarcoma (differentiated/dedifferentiated osteosarcoma) and MDM2 overexpression. The other 3 contained a coamplification of MDM2 and RASAL1, a signature also described for juvenile ossifying fibroma, with no overexpression of MDM2. These were of the giant cell-rich high-grade osteosarcoma, with areas mimicking juvenile ossifying fibroma (ossifying fibroma-like osteosarcoma). Our results show that some diagnosed high-grade osteosarcomas are differentiated/dedifferentiated osteosarcomas and harbor an overexpression and amplification of MDM2. In addition, juvenile ossifying fibromas can potentially evolve into giant cell-rich high-grade osteosarcomas and are characterized by a RASAL1 amplification (osteosarcoma with juvenile ossifying fibroma-like genotype). Thus, the presence of a RASAL1 amplification in ossifying fibroma may indicate a requirement for closer follow-up and more aggressive management.
PubMed | Toulouse University Hospital Center, French Institute of Health and Medical Research and IUCT Oncopole
Type: Journal Article | Journal: Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology | Year: 2016
Oncocytic tumors of the adrenal cortex are rare, mostly nonfunctioning and benign.Report virilizing oncocytic adrenocortical carcinoma in a 50-year-old woman.She presented a recent and progressive virilization syndrome, associated with high blood pressure. Hormonal evaluation showed elevated serum testosterone and delta-4-androstenedione levels, normal urinary free cortisol level and incomplete suppression of cortisol at the 1mg dexamethasone suppression test. CT scan of the abdomen revealed a 35mm left adrenal mass.The patient underwent a left adrenalectomy, and the histological study showed a 3cm oncocytic adrenocortical carcinoma with signs of malignancy.Immunohistochemical study revealed that tumor cells expressed the steroidogenic enzymes involved into androgen synthesis (3HSD and P450c17), P450 aromatase and luteinizing hormone (LH) receptors. Post-operatively, signs of virilization improved rapidly, serum testosterone and delta-4-androstenedione levels returned to normal, as did the dexamethasone suppression test. During follow-up CT-scan and 18-FDG PET/CT showed a right ovary mass, corresponding to a follicular cyst associated with hyperthecosis. The patient is alive with no recurrence 48 months after adrenal surgery.Oncocytic adrenocortical carcinomas, although extremely rare, should be considered in women with a virilization syndrome. In this woman immunohistochimical studies revealed the presence of steroidogenic enzymes involved into androgen synthesis and aromatization, and LH receptors could be implicated in this pathology.