Efficacy of vinblastine in central nervous system Langerhans cell histiocytosis: a nationwide retrospective study

<p>Abstract</p> <p>Background</p> <p>Vinblastine (VBL) is the standard treatment for systemic Langerhans cell histiocytosis (LCH), but little is known about its efficacy in central nervous system (CNS) mass lesions.</p> <p>Methods</p> <p>A retrospective chart review was conducted. Twenty patients from the French LCH Study Group register met the inclusion criteria. In brief, they had CNS mass lesions, had been treated with VBL, and were evaluable for radiologic response.</p> <p>Results</p> <p>The median age at diagnosis of LCH was 11.5 years (range: 1-50). Intravenous VBL 6 mg/m²was given in a 6-week induction treatment, followed by a maintenance treatment. The median total duration was 12 months (range: 3-30). Eleven patients received steroids concomitantly. Fifteen patients achieved an objective response; five had a complete response (CR: 25%), ten had a partial response (PR: 50%), four had stable disease (SD: 20%) and one patient progressed (PD: 5%). Of interest, four out of the six patients who received VBL without concomitant steroids achieved an objective response. With a median follow-up of 6.8 years, the 5-year event-free and overall survival was 61% and 84%, respectively. VBL was well-tolerated and there were no patient withdrawals due to adverse events.</p> <p>Conclusion</p> <p>VBL, with or without steroids, could potentially be a useful therapeutic option in LCH with CNS mass lesions, especially for those with inoperable lesions or multiple lesions. Prospective clinical trials are warranted for the evaluation of VBL in this indication.</p

Traitement de la drépanocytose par hydroxyurée chez l'enfant (étude de la qualité de la vie)

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

311 Nonbacterial thrombotic (Libman-Sacks) endocarditis with mitral regurgitation in catastrophic antiphospholipid syndrome (a case study)

Antiphospholipid syndrome (APS) is one of several prothrombotic states in which thrombi occur within both the venous and arterial beds. A minority of patients with APS present with an acute and devastating syndrome characterized by multiple simultaneous vascular occlusions throughout the body. “Catastrophic APS” is defined by the clinical involvement of at least three different organ systems over a period of days or weeks with histological evidence of multiple occlusions of large or small vessels. We report the case of a 16-year-old girl referred to our paediatric cardiology unit for NHYA IV and a blowing systolic murmur at the apex radiating to the left axilla. Transthoracic echocardiography (TTE) revealed mitral valve leaflet thickening with vegetations (13mm) on the edges of both leaflets and moderate mitral regurgitation (MR) (image 1). The diagnosis of Libman-Sacks or non-bacterial thrombotic endocarditis secondary to antiphospholipid syndrome was suggested by repeated negative blood cultures along with persistently elevated anticardiolipin antibody titers. The condition deteriorated to acute thrombotic microangiopathy affecting multiple organs with arterial hypertension and thrombocytopenia. Anticoagulation with warfarin was peformed and aspirin, corticosteroids and ACE inhibitors were given. TTE follow-up after 1.5 years revealed no recurrence of MR with normal mitral valve leaflets.ConclusionIn catastrophic APS an aggressive therapeutic approach is warranted. Valve lesions may become more severe during long term follow-up

Profiles and seasonal distribution of airborne fungi in indoor and outdoor environments at a French hospital

International audienceA one-year prospective survey of fungal air contamination was conducted in outdoor air and inside two haematological units of a French hospital. Air was sampled with a portable Air System Impactor. During this period of survey, the mean viable fungal load was 122.1 cfu/m(3) in outdoor air samples, and 4.1 and 3.9 cfu/m(3) in samples from adult and pediatric haematology units, respectively. In outdoor samples, Cladosporium was the dominant genus (55%) while in the clinical units, Penicillium sp. (23 to 25%), Aspergillus sp. (15 to 23%) and Bjerkandera adusta (11 to 13%) were the most frequently recovered airborne fungi. The outdoor fungal load was far higher in autumn (168 cfu/m(3)), spring (110 cfu/m(3)) and summer (138 cfu/m(3)) than in winter (49 cfu/m(3)). In indoor air, fungal concentrations were significantly lower in winter (2.7 to 3.1 cfu/m(3)) than in summer (4.2 to 5.0 cfu/m(3)) in both haematology units. In the outdoor environment, Penicillium sp. and Aspergillus sp. were more abundant in winter while the levels of Cladosporium were lowest during this season. In the haematological units, the presence of Aspergillus sp. was stable during the year (close to 20%), Bjerkandera sp. was particularly abundant in winter (close to 30%); levels of Penicillium sp. were highest in autumn while levels of Cladosporium sp. were highest in spring and summer

Reduced fungal contamination of the indoor environment with the Plasmair system (Airinspace)

International audienc

Prospective survey of indoor fungal contamination in hospital during a period of building construction

International audienceAn 18-month survey of indoor fungal contamination was conducted in one haematology unit during a period of construction work. Air was sampled with a portable Air System Impactor and surfaces with contact Sabouraud plates. During this survey the mean concentration of viable fungi in air was 4.2 cfu/m(3) and that for surfaces was 1.7 cfu/plate. At the beginning of construction work, there were increases in airborne fungal spores (from 3.0 to 9.8 cfu/m(3)) in the unit, but concentrations did not exceed 10 cfu/m(3) during the 18-month period. The most frequently recovered airborne fungi were Penicillium spp. (27-38%), Aspergillus spp. (25%) and Bjerkandera adusta, a basidiomycete identified with molecular tools (7-12%). Blastomycetes accounted for more than 50% of the fungal flora on surfaces. Investigating the impact of a new air-treatment system (mobile Plasmair units), there were significant reductions in fungal contamination for the Plasmer -treated rooms, and in these rooms we observed the same level of fungal load whether construction work was in progress or not

Impact of early molecular response in children with chronic myeloid leukemia treated in the French Glivec phase 4 study

International audienceStudies in adults have shown that an early molecular response to imatinib predicts clinical outcome in chronic myeloid leukemia (CML). We investigated the impact of the BCR-ABL1 transcript level measured 3 months after starting imatinib in a cohort of 40 children with CML. Children with a BCR-ABL1/ABL ratio higher than 10% at 3 months after the start of imatinib had a larger spleen size and a higher white blood cell count compared with those with BCR-ABL1/ABL ≤10%. Children with BCR-ABL1/ABL ≤10% 3 months after starting imatinib had higher rates of complete cytogenetic response and major molecular response at 12 months compared to those with BCR-ABL1/ABL \textgreater10%. With a median follow-up of 71 months (range: 22 to 96), BCR-ABL1/ABL ≤10% correlated with better progression free survival. Thus, early molecular response at 3 months predicts outcome in children treated with imatinib for CML. The study was registered at www.clinicaltrials.gov as NCT00845221

Diversity of the clinical presentation of the MMR gene biallelic mutations

International audienceConstitutional mismatch repair-deficiency, due to biallelic mutations of MMR genes, results in a tumour spectrum characterized by leukaemias, lymphomas, brain tumours and adenocarcinomas of the gastro-intestinal tract, occurring mostly in childhood. We report here two families illustrating the phenotypic diversity associated with biallelic MMR mutations. In the first family, two siblings developed six malignancies including glioblastoma, lymphoblastic T cell lymphoma, rectal and small bowel adenocarcinoma with onset as early as 6 years of age. We showed that this dramatic clinical presentation was due to the presence of two complex genomic PMS2 deletions in each patient predicted to result into complete PMS2 inactivation. In the second family, the index case presented with an early form of Lynch syndrome with colorectal adenocarcinomas at ages 17 and 20 years, and urinary tract tumours at the age of 25 years. We identified in this patient two MSH6 mutations corresponding to a frameshift deletion and an in frame deletion. The latter was not predicted to result into complete inactivation of MSH6. These reports show that the clinical expression of biallelic MMR mutations depends on the biological impact of the second MMR mutation and that, in clinical practice, the presence of a second MMR mutation located in trans should also be considered in patients suspected to present a Lynch syndrome with an unusual early-onset of tumours