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Resume Objectif Evaluer les performances diagnostique et pronostique de la TEP au 18-FDG lors du bilan avant chimio-hyperthermie intra-peritoneale (CHIP). Patientes et methodes Trente-huit patientes atteintes de cancer ovarien de stade IIIC (11 primaires et 27 recidivants), ayant eu une CHIP, ont ete incluses dans cette etude retrospective monocentrique. Les examens TEP pre-CHIP ont ete relus a l’aveugle, puis ont ete compares aux resultats chirurgicaux et histologiques et au suivi des patientes. Resultats Trente-deux patientes avaient une carcinose peritoneale selon les resultats chirurgicaux et histologiques et 19 selon la TEP. La TEP n’a montre aucun foyer sus-diaphragmatique suspect. Les sensibilite et specificite etaient calculees a 56,2 et 100 %. Onze patientes parmi 14 faussement TEP negatives avaient uniquement des lesions peritoneales infracentimetriques. Il y avait significativement plus de patientes traitees par chimiotherapie dans le groupe TEP negative ( p = 0,02), dont 13 appartenant aux faux negatifs. Malgre un taux d’evenements legerement plus eleve dans le groupe TEP positive pour la survie sans evenements (68 % vs 64 % dans le groupe TEP negative) et globale (26,3 % vs 17,6 %), l’analyse des courbes de survie n’a pas montre de difference significative (respectivement, p = 0,62 et 0,59). Conclusion La TEP/TDM a montre une excellente specificite et une sensibilite moindre lors du bilan avant CHIP, essentiellement due a la presence de lesions de petite taille et au traitement par chimiotherapie precedent la CHIP. Il n’a pas ete observe de valeur pronostique significative de la TEP, mais celle-ci reste utile dans la detection des metastases a distance avec un impact sur la prise en charge therapeutique.

Background: Treatment with escalated BEACOPP achieved a superior time to treatment failure over ABVD in patients with disseminated Hodgkin lymphoma. However, recent clinical trials have failed to confirm BEACOPP overall survival (OS) superiority over ABVD. In addition, the gain in low-risk patients is still a matter of debate. Patients and methods: We randomly compared ABVD (8 cycles) with BEACOPP (escalated 4 cycles ≥baseline 4 cycles) in low-risk patients with an International Prognostic Score (IPS) of 0-2. The primary end point was event-free survival (EFS). This parallel group, open-label phase 3 trial was registered under #RECF0219 at French National Cancer Institute. Results: One hundred and fifty patients were randomized in this trial (ABVD 80, BEACOPP 70): 28 years was the median age, 50% were male and IPS was 0-1 for 64%. Complete remission rate was 85% for ABVD and 90% for BEACOPP. Progression or relapses were more frequent in the ABVD patients than in the BEACOPP patients (17 versus 5 patients). With a median follow-up period of 5.5 years, seven patients died: six in the ABVD arm and one in the BEACOPP arm (HL 3 and 0, 2nd cancer 2 and 1, accident 1 and 0). The EFS at 5 years was estimated at 62% for ABVD versus 77%, for BEACOPP [hazards ratio (HR) = 0.6, P = 0.07]. The progression-free survival (PFS) at 5 years was 75% versus 93% (HR = 0.3, P=0.007). The OS at 5 years was 92% versus 99% (HR = 0.18, P = 0.06). Conclusion: Fewer progressions/relapses were observed with BEACOPP, demonstrating the high efficacy of the more intensive regimen, even in low-risk patients. However, additional considerations, balancing treatment-related toxicity and late morbidity due to salvage may help with decision-making with regard to treatment with ABVD or BEACOPP. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Le role de l’angiogenese est reconnu comme important dans les tumeurs solides, et ce n’est que recemment que les memes phenomenes ont ete decrits dans les hemopathies malignes. L’expression des peptides angiogeniques comme le vascular endothelial growth factor (VEGF) et le basic fibroblast growth factor (bFGF) est correlee avec la presentation clinique des lymphomes non hodgkiniens a grandes cellules. La densite en microvaisseaux dans le myelome multiple est un marqueur independant de survie. Tous ces resultats ont encourage le developpement de medicaments bloquant de maniere large les cytokines proangiogeniques, comme le lenalidomide, mais aussi d’agents cibles anti-VEGF. Cette revue reprend les connaissances sur l’angiogenese qui permettent de nouvelles ouvertures sur la physiologie et le traitement des hemopathies malignes. La problematique est maintenant de combiner les chimiotherapies avec ces nouvelles molecules pour obtenir lesmeilleurs resultats possibles et de les positionner par rapport a la greffe de moelle.

Background Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly known as agranular CD4+/CD56+ haematodermic neoplasm (CD4/CD56 HN), is a rare distinct form of lymphoma-like entity known of dermatologists because of its marked predilection for cutaneous involvement, and its aggressive behaviour. Moreover, the association or the evolution to an acute leukaemia entity that still expresses CD4 and CD56 markers is almost systematic. This new described entity of ‘CD4+/CD56+ leukaemia’ or ‘leukaemia of plasmacytoid dendritic cell lineage’ has a poor prognostic and may lead to include haematopoietic stem cell transplantation in the treatment strategy as early as possible. Report of cases We report here four cases presenting with skin lesions and haematological signs. One of the patients underwent allogeneic stem cell transplantation, with a relapse-free survival of 40 months. We discuss the diagnosis features as well as the treatment options. Conclusion A collaborative work between dermatologists and onco-haematologists is essential to give patients the best chance of complete and long-term response.

Introduction: Clinical evolution of classical Hodgkin lymphoma (cHL) cannot be always predicted by clinical, biological or radiological parameters. Given the high treatment related morbidity of clinical trials it should be interesting to get other prognostic markers to predict cHL patients evolution. Some immunohistochemical (IHC) markers have been already published as prognostic in cHL but they are still matter to debate. We have tested 13 IHC markers in the LYSA H3/4 trial of cHL which compares patients with stage III to IV cHL in a phase III who were assigned to either doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD, 8 courses) to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisons (escBEACOPPx4 & BEACOPP x4) without radiation therapy, in order to determine if some of these markers could predict different progression free survival (PFS) or overall survival (OS). Methods: The H3/4 trial includes both high (n=549) and low risk (n=150) patients, and we obtained all biological data for 165 patients (106 high & 59 low risk). We performed 13 IHC markers (CD20, CD3, CD68, CD163, CD117, TiA1, FoxP3, ICOS, CD10, CXL13, PD1, PDL1 & EBER probe) on Tissue Micro Arrays (TMA) performed for these 165 patients. Most of these markers were evaluated on the micro-environment cells of the cHL (absolute number of cells stained when they are few or percentage of cells stained on TMA spots when they are numerous). For PDL1 and EBER, we evaluated the number of both micro-environmental cells and Reed-Sternberg (RS) cells stained with this antibody. The results of this IHC study were compared with the clinical data base of these patients. For each variable different cut-offs were studied on PFS and OS. Results: Patients characteristics were similar to those of the total population: median age (31 y), male sex (66%), nodular sclerosis histology (83.3%), stage IV (61%), B symptoms (73%), IPS>2 (66%), bulky disease (26.5%), bone marrow involvement (16%). Half of the patients received ABVD or escBEACOPP. 82.4% achieved a CR/Cru at the end of treatment and we observed 23 relapses and 14 deaths with a five-year median follow up. IHC study revealed a marked expression of tumor associated macrophages (TAM) and lymphocytes markers but none of them were associated with PFS or OS by statistical evaluation. By contrast, we found that a low count of TiA1+ cells in cHL microenvironment (median ≤29)) and a high number of RS cells PDL1+ (=100)) were significantly associated in a multivariate analysis with a worse PFS (TiA1: HR;95% CI=5.33; [1.62;17.52] and PDL1: HR;95%CI = 5.01; [1.39;18.05]). We also found that the association of a higher number of PDL1 RS+ and TAM CD68+ was statistically significant in patients of the high group risk in multivariate analysis. EBER expression on RS cells or on micro-environmental cells was not statistically associated with PFS or OS. But, the association of a higher number of EBER RS+ cells and TAM CD68+ was statistically significant in both high or low risk groups. The association of EBER and CD68 on micro-environmental cells was not statistically significant. Conclusion: In this large and unselected series of advanced cHL, we do not find prognostic significance of TAM CD68/CD163+ nor of other lymphoid markers tested nor of EBER expression. But, we showed that a low count of TiA+ cells in the micro-environment of cHL and a high level of PDL1 RS+ cells expression cells are predictive of a worse PFS in this study. We found also that there is a significant association between the number of PDL1 RS+ cells and TAM CD68+ in the high risk group and between EBER RS+ and TAM CD68+ cells in both groups. These results suggest that IHC markers could be helpful to predict evolution in cHL patients. Disclosures Casasnovas: Roche: Consultancy; takeda: Consultancy; merck: Consultancy; MSD: Consultancy; Gilead Sciences: Consultancy; Janssen: Consultancy; Roche: Research Funding; Gilead Sciences: Research Funding; Roche: Honoraria; Takeda: Honoraria; Merck: Honoraria; MSD: Honoraria; Gilead Sciences: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Coiffier:NOVARTIS: Membership on an entity's Board of Directors or advisory committees; CELGENE: Consultancy, Membership on an entity's Board of Directors or advisory committees; MORPHOSYS: Membership on an entity's Board of Directors or advisory committees; MUNDIPHARMA: Membership on an entity's Board of Directors or advisory committees; CELLTRION: Membership on an entity's Board of Directors or advisory committees.

Resume Depuis quelques annees, Internet est devenu un outil indispensable pour tous types d'information. La place qu'il prend dans la medecine et notamment dans l'oncohematologie est croissante. Les donnees delivrees par Internet sont de sources diverses et variees, allant de sites officiels a des blogs tenus par des patients. L'infection par le virus de l'immunodeficience acquise (VIH) etant tres mediatisee ces dernieres annees, nous prendrons l'exemple de la maladie de Hodgkin associee au VIH pour confronter les donnees issues d'Internet et celles issues d'articles scientifiques. L'information issue d'Internet est globalement de bonne qualite, mais des donnees non actualisees et erronees sont regulierement retrouvees. Cela confirme que la consultation specialisee par un medecin referent doit rester la principale source d'information pour le patient.

Hodgkin's and non-Hodgkin's lymphomas are frequent and represent a heterogenic group of haematologic diseases. Prognostic factors allow to classify patients into homogeneic risk groups, to adapt treatment proposal to disease's risk and, in some cases, to avoid over-treatment. For all lymphomas, the first step is to determine the stage of the disease in Ann Arbor's classification, using physical examination, radiological and functional imaging. However, this classification is not optimal to predict disease evolution. Specific scores corresponding to the histological subtype of the lymphoma have been determined: IPI (international prognostic index) for aggressive lymphomas, FLIPI (follicular lymphoma international prognostic index) for indolent lymphomas and IPS (international prognostic score) for advanced Hodgkin's lymphomas. Functional imaging by PET (position emission tomography) is of prognostic significance in aggressive and Hodgkin lymphomas to evaluate early response to treatment, before autografting and at the end of the treatment. Several kinds of molecular prognostic markers have been studied: circulating rates of proteins, over expression of genes, presence of specific cells in the tumour... But these factors are not yet used in clinical practice, as they have not been validated on large cohorts and their interactions with other prognostic factors and between them are not well known. Although molecular biology has made some recent progress, only classical prognostic factors (physical examination, radiological and functional imaging) are used by now.

L’interferon alpha est etudie en hematologie depuis la fin des annees 1960. Il est utilisable dans de nombreuses indications mais, depuis l’avenement des therapies ciblees, il semble necessaire de revoir la litterature pour faire le point sur ses indications. L’activite immunomodulatrice de l’interferon lui a confere une indication en premiere ligne dans le traitement des lymphomes folliculaires, y compris en combinaison avec le rituximab. En revanche, sa mediocre tolerance limite actuellement son utilisation. Pour les lymphomes de bas grade associes aux infections virales, l’interferon associe a des molecules antivirales garde tout son interet. Pour les lymphomes T, l’absence de consensus therapeutique permet de proposer l’interferon en deuxieme ou troisieme ligne. Pour la leucemie myeloide chronique, l’interferon a ete supplante par l’imatinib en traitement d’induction, mais des essais sont en cours en traitement d’entretien. Pour conclure, les indications de l’interferon en hematologie se restreignent peu a peu, mais de nouvelles voies de recherche semblent prometteuses notamment dans les leucemies.

Resume Le Zevalin® (yttrium-90 ibritumomab-tiuxetan) est la premiere radio-immunotherapie autorisee en France dans le traitement des lymphomes malins non hodgkiniens (LMNH). Il est indique, en routine clinique, chez l’adulte, dans le traitement des LMNH folliculaires en rechute ou refractaires incluant les LMNH refractaires au rituximab, avec des taux de reponse de l’ordre de 70 a 80 %. Depuis trois ans, 13 patients ont etes traites par Zevalin® a Nice. A partir de leur etude retrospective, nous avons discute les differentes perspectives de ce traitement. La majorite de nos patients ont ete evalues par tomographie d’emission de positons au 18-fluorodesoxyglucose (TEP–FDG), parallelement, nous avons donc rapporte nos resultats sur cet aspect. Bien que nous manquions de recul, notre experience confirme l’efficacite et la tolerance du Zevalin® dans le traitement des LMNH multirecidivants, en particulier folliculaires, y compris refractaires au rituximab. Il apparaitrait egalement interessant chez les personnes âgees et en cas d’antecedent d’autogreffe de cellules souches. L’indication proposee dans le cadre de l’Autorisation de mise sur le marche (AMM) n’est probablement pas la plus favorable puisque l’efficacite du Zevalin® semble etre meilleure en cas de volume tumoral reduit et quand il est utilise plus precocement dans la sequence therapeutique. Les benefices seront donc vraisemblablement plus significatifs en premiere ligne therapeutique et en consolidation apres un traitement par chimio-immunotherapie ainsi qu’en conditionnement d’autogreffe. Nous avons souligne l’interet d’une evaluation TEP–FDG post-therapeutique precoce, un a deux mois apres traitement par Zevalin® dans un but pronostique. Cette indication reste encore a etre evaluee dans des etudes menees a plus large echelle.

La leucemie a cellules dendritiques est une nouvelle entite de leucemie aigue coexprimant les marqueurs CD4(+) CD56(+) derivee des cellules dendritiques plasmocytoides. II s’agit d’une entite extremement rare dont les premiers cas ont ete decrits entre 1994 et 1999 chez des patients presentant des nodules et tumeurs cutanees de couleur rouge violacees, le plus souvent disseminees. Ces premiers cas ont ete initialement rapportes sous le terme de lymphomes Natural Killer (NK) ou de lymphomes blastiques NK. L’atteinte cutanee peut etre isolee au debut, mais une atteinte extracutanee, le plus souvent medullaire, sanguine et ganglionnaire apparait dans tous les cas apres quelques mois. Le Groupe Francais d’E tude des Lymphomes Cutanes (GFELC) a pose les bases de cette pathologie en 1999 et lui a donne le nom provisoire d’hematodermie CD4(+) CD56(+). Onconsidere actuellement que cette hematodermie derive de precurseurs des cellules dendritiques plasmocytoides. Elle a ete recemment caracterisee par le Groupe d’Etude Immunologique des Leucemies (GEIL) et denommee leucemie CD4(+) CD56(−) ou leucemie derivee des cellules dendritiques plasmocytoides (LpDC). Si les circonstances de decouverte et les aspects cliniques de cette entite ont ete rapportes, il n’existe pas encore de criteres diagnostiques specifiques au plan biologique. On sait toutefois que la de finition de cette entite inclut l’absence d’expression de marqueurs forts des lignees myeloides, lymphoides B et T. Nous rapportons ici un cas de LpDC de couvert dans le service d’hematologie clinique du CHU de Nice qui a ete bien documente aussi bien sur le plan clinique, biologique qu’anatomopathologique.

Objectives: Rasburicase (Fasturtec®) is used to prevent or treat hyperuricemia associated with chemotherapy. We developed a capillary zone electrophoresis method to measure urinary allantoin, the degradation product of uric acid by rasburicase. Design and methods: Electrophoresis was performed using a P/ACE 5500 system (Beckman) with a fused silica capillary tube and a UV–visible detector set at 214 nm. Urine samples from 10 patients with non-Hodgkin’s lymphoma were analyzed to validate the technique. Results: Using a sodium tetraborate running buffer, urinary allantoin was separated from related compounds and internal standard in less than 30 min. The method was linear up to 1.25 g/L (quantification limit: 30 mg/L); precision was below 10%. The total amount of allantoin excreted in patients treated by rasburicase ranged from 1.5 g to 7.9 g/4 days. Conclusion: This CZE assay is a simple, rapid and reproducible method to measure allantoin in urine. Different elimination profiles have been found in patients treated with rasburicase.

Background. The standard Q-TWiST approach defines a series of health states and weights each state’s duration according to its quality of life (QOL) to calculate quality-adjusted lifetimes. However, a fixed weight may not adequately reflect time variations in QOL. Methods. To account for measurements derived from irregular visits and informative missing data, the authors estimated the mean QOL profile using a mixed-effect growth curve model for the response, combined with a logistic regression model for the drop-out process. Results. Using data from a clinical study of lymphoma patients, the authors demonstrated better readaptation to normal life for patients younger than 30. Sensitivity analyses and computer simulations demonstrated that modeling the drop-out probability as a function of the QOL measurements is necessary if conditioning by health state is not possible. Conclusion. Our model-based approach is useful to analyze studies with incomplete QOL data, especially when approximate QOL assessment by...

M. Rummel (Abstract 3) a eu les honneurs de la seance pleniere du dimanche apres-midi. Il presentait l’analyse finale de la phase 3 allemande StiL NHL1 randomisant R-bendamustine (R pour rituximab) vs R-CHOP en premiere ligne dans les lymphomes folliculaires, mais aussi dans d’autres lymphomes indolents (zone marginale) et les lymphomes du manteau. Il n’y avait pas demaintenance par rituximab apres la fin de chimiotherapie. Les resultats avaient deja ete tres remarques lors de l’ASH 2009. Avecmaintenant un recul de quatre ans, sur 514 patients, lamediane de PFS (survie sans progression) etait de 69,5 vs 31,2 mois (p = 0,001). Cet avantage du R-bendamustine persistait egalement dans tous les sous-groupes pronostiques ou sous-types histologiques. En revanche, il n’y avait pas de difference significative en survie. Compte tenu du tres bon profil de toxicite (pas d’alopecie) et de l’absence d’exces de seconds cancers (20 vs 23 cas), le R-bendamustine semble pouvoir etre remonte en tete de la longue liste des traitements disponibles.

La bendamustine est un agent cytotoxique qui combine des effets antimetabolites et alkylants. Cette particularite lui confere une moindre resistance croisee avec les autres agents cytotoxiques. En France, cet agent est uniquement utilisable dans le cadre de l’autorisation temporaire d’utilisation (ATU), pour le traitement des lymphomes indolents, de la leucemie lymphoide chronique (LLC) et du myelo memultiple. Nous presentons ici nos premiers resultats concernant cinq patients ayant une LLC refractaire, traites par bendamustine sur la premiere annee d’ATU en 2008. Ils semblent confirmer que ce traitement est efficace pour les LLC en rechute. Cependant, les LLC transformees en lymphome non-hodgkinien ou les leucemies prolymphocytaires semblent moins sensibles. Par ailleurs, du fait de sa bonne tolerance, la bendamustine peut fournir une excellente plateforme pour la combinaison avec d’autres agents efficaces dans les hemopathies lymphoides comme le rituximab, le lenalidomide ou le bortezomib.

Plasma cell leukemia is an aggressive variant of multiple myeloma affecting 4% of all cases of the latter. It is characterized by the presence of at least 20% plasma cells circulating in the peripheral blood, equivalent to an absolute number greater than 2,000/mm3. Plasma cell leukemia exits in two forms: primary or de novo plasma cell leukemia (60%) and the secondary form, which consists of a leukemia transformation of a multiple myeloma (40% plasma cell leukemia and 1% multiple myeloma). The disease is rare and has poor prognosis, as there is no effective therapy except the standard melphalan–prednisone combination. We report here on a case of primary plasma cell leukemia diagnosed in the Nice University Hospital’s Onco-hematology Department, which achieved complete response (CR) after eight cycles of bortezomib-cexamethasone followed by maintenance treatment with bortezomib.

La leucemie a plasmocytes est une variante agressive du myelome multiple qui concerne 4% de ces derniers. Elle se definit par la presence d’au moins 20% de plasmocytes circulants dans la formule sanguine, soit 2 000/mm3 de sang. Il existe deux formes de leucemie a plasmocytes: les primaires ou leucemie a plasmocytes de novo (60 %) et les secondaires qui sont une transformation leucemique d’un myelome multiple (40% des leucemies a plasmocytes et 1% des myelomes multiples). Il s’agit dans tous les cas d’une entite rare et de pronostic sombre, d’autant plus qu’il n’existe pas de therapeutique efficace connue en dehors du classique schema melphalan-prednisone. Nous rapportons ici un cas de leucemie a plasmocytes primaire decouvert en consultation dans le service d’oncohematologie clinique du CHU de Nice qui a ete mis en remission complete grâce a huit cycles de bortezomib-dexamethasone puis traitement d’entretien par bortezomib.

Resume Chez les patients traites pour maladie de Hodgkin, les tumeurs radio-induites representent la premiere cause de deces apres 10 ans. Ce risque ne doit plus etre ignore. La premiere tumeur radio-induite a ete decrite des 1902, ce risque a cependant ete ensuite sous-evalue. Les radiations ionisantes ont alors ete utilisees pour des affections diverses, tant malignes que benignes. Depuis, de nombreuses etudes epidemiologiques ont permis de mieux evaluer les risques des traitements. A partir d'une revue de la litterature, nous avons compare les risques relatifs de developper une tumeur radio-induite en fonction du type de tissu, de la dose, de l'âge et des maladies associees. Les organes les plus sensibles a la transformation semblent etre la thyroide, le systeme nerveux central, le sein, l'os et le poumon, ce dernier principalement chez les fumeurs. Le nombre de tumeurs radio-induites augmente, dans la plupart des cas, avec la dose. Les risques sont plus importants pour les irradiations de l'enfant et de l'adulte jeune et majeurs pour les patients traites pour retinoblastome. Si le risque de tumeur induite ne doit pas modifier la place de la radiotherapie dans le traitement des tumeurs malignes, une reflexion sur les volumes et les doses doit etre entreprise pour en limiter l'incidence. Pour les affections benignes, l'indication d'une radiotherapie doit etre posee avec une extreme prudence, surtout chez les patients jeunes.

Substantial progress has been made in understanding the role of autotransplantation in aggressive non-Hodgkin's lymphoma. At present, the clinical indications for high-dose therapy include patients with relapsed or poor prognosis disease. Hematopoietic reconstitution with peripheral stem cells has rendered transplantation less toxic but the optimal preparative regimen remains to be found. It should combine a high antitumor activity with acceptable toxicity to normal tissues. The literature, on combinations of drugs with or without total body irradiation, was reviewed with regard to this objective. BEAM, CBV and ICE, the most common chemotherapy regimens can be considered safe as they cause low transplant-related morbidity. The combination of fractionated TBI and etoposide or cyclophosphamide was not found to be superior. However, it must be kept in mind that comparisons were made on registry data or retrospectively. In every case, relapse of the residual primary disease argue for the need for more effective strategies such as tandem transplantation or sequential high-dose chemotherapy with stem-cell support. To obtain an objective evaluation, these new preparative regimens need to be tested in controlled trials with treatment groups stratified for known prognostic factors.

Les lymphomes diffus a grandes cellules B (LDGCB ou DLBCL) sont la forme la plus frequente des lymphomes malins non hodgkiniens. Ils representent environ un tiers de l’ensemble des lymphomes. Cette entite regroupe des formes agressives, caracterisees a la fois par une evolution spontanee rapide et severe, et une possibilite de guerison apres traitement. Ce sont des entites anatomopathologiques variees. Outre cette variete histologique, l’etude en biologie moleculaire des genes exprimes dans les LDGCB a permis d’extraire et d’isoler des profils d’expression genique specifiques a des sous-groupes de LDGCB. Les strategies therapeutiques developpees jusqu’a present sont concues pour etre applicables a une entite homogene, meme si depuis peu emergent des essais therapeutiques specifiques testes en situation de rechute [1].

Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly known as agranular CD4(+) /CD56(+) haematodermic neoplasm (CD4/CD56 HN), is a rare distinct form of lymphoma-like entity known of dermatologists because of its marked predilection for cutaneous involvement, and its aggressive behaviour. Moreover, the association or the evolution to an acute leukaemia entity that still expresses CD4 and CD56 markers is almost systematic. This new described entity of 'CD4(+) /CD56(+) leukaemia' or 'leukaemia of plasmacytoid dendritic cell lineage' has a poor prognostic and may lead to include haematopoietic stem cell transplantation in the treatment strategy as early as possible.We report here four cases presenting with skin lesions and haematological signs. One of the patients underwent allogeneic stem cell transplantation, with a relapse-free survival of 40 months. We discuss the diagnosis features as well as the treatment options.A collaborative work between dermatologists and onco-haematologists is essential to give patients the best chance of complete and long-term response.

The expression of the Bombyx cytoplasmic actin A3 gene and its response to 20-hydroxyecdysone are studied after transfection in hormone responsive Drosophila cells and are compared to the expression of homologous resident genes. The host cells accumulate correct transcripts of the Bombyx gene in a gene dosage dependent way. The relative amount of endogenous cytoplasmic actin mRNAs is decreased in transfected cells, whether the transgene is integrated into the genome or not. When 20-hydroxyecdysone is added to the culture medium, the accumulation of the foreign mRNA is decreased whereas those of endogenous cytoplasmic actin transcripts are increased. These results are discussed in terms of competition for transcription and regulatory factors.

A cytoplasmic actin gene from Bombyx mori introduced into Drosophila melanogaster by P-element mediated transformation, is efficiently transcribed in larvae, pupae and adults of the host. The exogenous mRNA has the same size as the one observed in the Bombyx cells and the intron located within the coding region is properly excised, indicating a correct recognition of the exogenous sequences by the Drosophila transcriptional and splicing machineries. The expression of the Bombyx gene in Drosophila tissues was determined by transforming flies with a hybrid gene in which a large part of the Bombyx actin coding sequences was replaced by those of the bacterial lac Z gene. This chimaeric gene is specifically and highly expressed, from the embryo to the adult of the transgenic lines, in tissues of endodermal origin, the midgut and its derivatives, i.e. gastric caeca, the outer layer of the proventriculus, and in the Malpighian tubules. This gene is also expressed, at a lower level, in germ cells but restricted to the sixteen cell cysts during previtel-logenesis. The expression of the Bombyx gene during development of transgenic flies was compared to that of the two Drosophila endogenous cytoplasmic actin genes and the results are discussed.

Peripherally inserted central catheters (PICC) have the advantage of limiting the risk of accidents during installation and are easy to remove. Its use in oncology remains debated because of possible infectious complications. We analyzed 52 PICC in patients with hematological tumor from Nice Hospital. An installation failure was noted in 5.8% of cases. After a follow-up of 15 months, the complication rate was 26.9%, mainly mechanical complications: obstruction (13.5%) or accidental removal (9.6%). The organic complications such as infection or thrombophlebitis represented 3.8%. The median duration was 26 days [2-291]. The longest duration was associated with PICC for chemotherapy (median: 58 days). Frequent blood samples (above: 2 week) were associated with lower duration (median: 23 days). In conclusion, PICC represent a simple and effective alternative to intra-venous central devices in onco-hematology. However, physicians have to focus on short-course treatment.

In recent years, Internet has become an indispensable tool for all types of information. Its importance has increased in medicine and particularly in human malignancies. The data issued by the Internet are many and varied sources ranging from official websites to patient's blogs. HIV infection is an infection highly publicized in recent years, we take the case of Hodgkin's disease associated with HIV to compare data from the Internet and scientific articles. The information from the Internet is mostly good but not updated and erroneous data are regularly found. This confirms that the consultation by a specialist doctor referral should remain the main source of information for the patient.

HDAC, by modifiing relations between DNA and histones, are major proteins of the epigenetic regulation. They play part in the signal transduction and in many cellular processes: cell cycle control, apoptosis, protein degradation, angiogenesis, invasion and cell motility. In several models of cancer HDAC inhibitors (HDACIs) are able to up regulate tumor suppressing gene (p53, p21, pRB...) and to down regulate oncogenes (SRC, HIF-Ialpha,HER2...). Many inhibitors are currently in clinical development and promising results have been reported in cutaneous T cell lymphoma, Hodgkin's disease and non-hodgkin lymphoma. Combination with chemotherapy and molecular targeted agents seem to be effective in myeloma, lung cancer and myeloïd neoplasms. In this review, we focus on recent biologic and clinical data that highlitght the anti-neoplastic role of HDACIs.

Bone metastases from epithelial ovarian carcinoma are rare, usually discovered postmortem. The survival of these patients is poor. Furthermore, only two cases of endometrioid ovarian carcinoma with metastasis to the skeletal structures have been described in the literature.We present the case of a 58-year-old woman with a lytic metastasis in the left iliac ramus from endometrioid ovarian carcinoma that occurred seven years after the initial diagnosis.A review of the literature since 1966 on bone metastasis of ovarian cancer is also presented. In patients suffering from a neoplasm that rarely metastasises to bone, histological proof should be obtained to diagnose uncommon sites of disease relapse.

Hodgkin's and non-Hodgkin's lymphomas are frequent and represent a heterogenic group of haematologic diseases. Prognostic factors allow to classify patients into homogeneic risk groups, to adapt treatment proposal to disease's risk and, in some cases, to avoid over-treatment. For all lymphomas, the first step is to determine the stage of the disease in Ann Arbor's classification, using physical examination, radiological and functional imaging. However, this classification is not optimal to predict disease evolution. Specific scores corresponding to the histological subtype of the lymphoma have been determined: IPI (international prognostic index) for aggressive lymphomas, FLIPI (follicular lymphoma international prognostic index) for indolent lymphomas and IPS (international prognostic score) for advanced Hodgkin's lymphomas. Functional imaging by PET (position emission tomography) is of prognostic significance in aggressive and Hodgkin lymphomas to evaluate early response to treatment, before autografting and at the end of the treatment. Several kinds of molecular prognostic markers have been studied: circulating rates of proteins, over expression of genes, presence of specific cells in the tumour... But these factors are not yet used in clinical practice, as they have not been validated on large cohorts and their interactions with other prognostic factors and between them are not well known. Although molecular biology has made some recent progress, only classical prognostic factors (physical examination, radiological and functional imaging) are used by now.

International audience; Purpose To determine the safety and the efficacy of paclitaxel and capecitabine as second-line combination chemotherapy after failure of platinum regimens in advanced gastric cancer. Methods Patients with histologically proven gastric cancer and measurable metastatic disease received capecitabine 825 mg/m2 twice daily (1,650 mg/m2 per day) on days 1–14 and paclitaxel 175 mg/m2 by intravenous infusion on day 1 every 3 weeks until disease progression or unacceptable toxicities. Results Between June 2003 and October 2005, 26 patients, of median age 59 years (range 41–84 years) were included in the study and were treated by paclitaxel/capecitabine combination. Overall response rate was 34.6% (95%CI = 17.2–55.7%) with one complete response and 42.3% (95%CI = 17.2–55.7%) of patients achieved a stable disease. Median progression-free survival was 4.5 months (95%CI = 4–4.5 months). Median overall survival was 7.5 months (95%CI = 6–10 months). Cumulated overall survival including cisplatin regimens was 15.5 months (95%CI = 11–18 months). Grade 3/4 adverse events included alopecia (30.8%), neutropenia (11.5%), hand foot skin reaction (11.5%), neuropathy (11.5%), arthralgias (7.5%), and anemia (3.8%). Conclusions Paclitaxel and capecitabine combination was safe and effective in advanced gastric cancer after failure of cisplatin regimens. The cumulated overall survival of 15.5 months suggests a particular interest of taxanes in second-line treatment after failure of platinum salts.

Objectifs Dans le lymphome VIH negatif, la TEP/TDM au 18FDG (TEP-FDG) est reconnue comme etant un important facteur pronostique apres 2–3 cycles de chimiotherapie pour la survie. Cependant, des etudes equivalentes doivent etre realisees dans le lymphome associe au VIH afin de proposer une strategie de desescalade therapeutique. Patients et methodes Dix-neuf patients (pts) consecutifs presentant un lymphome associe au VIH ont beneficie d’une TEP intermediaire dans notre service pour une maladie de Hodgkin (8), un LBDGC (6) ou un lymphome de Burkitt (5). Il y avait 13 hommes, âge moyen 48 ans [28-65], taux de CD4 moyen 350/mm 3 , charge virale negative chez 12 pts, stades III–IV chez 12 pts. Sans connaitre l’issue therapeutique, nous avons retrospectivement mesure les parametres quantitatifs suivant : DSUVmax, DSULmax et DMTV ( cut-off 66 %). Les criteres qualitatifs en 5 points de Deauville (1–3 versus 4–5) et le rapport SULmax/hepatic SULmean ont aussi ete etudies. Resultats Avec une mediane de suivi a 3 ans, la survie globale etait de 70 % (60 % pour les LNH et 83 % pour les MH). Les parametres quantitatifs etaient statistiquement significatifs : la survie globale a 3 ans etait de 87 % lorsque DSUVmax > 66 % contre 33 % lorsque DSUVmax p p p = 0,55). Les criteres qualitatifs de Deauville n’etaient pas significatifs (survie globale a 3 ans 81 % versus 44 %, p = 0,11). Toutefois, le rapport SULmax/hepaticSULmean p Conclusions Dans le lymphome associe au VIH, les parametres quantitatifs DSUVmax et DSULmax de la TEP-FDG intermediaire ont montre une meilleure valeur predictive pour la survie globale que les criteres de Deauville. S’ils ne sont pas realisables (en l’absence de TEP initiale), le rapport SULmax/hepaticSULmean semble prometteur. Ces resultats doivent etre confirmes sur une population plus large en tenant compte des sous types de lymphomes associes au VIH avant de guider une desescalade therapeutique.

Rituximab has greatly improved standard cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, but prospects remain poor in patients with adverse risk factors. We need to know whether the addition of rituximab also improves the efficacy of more intensive treatments and how to use molecular profiling to guide us in introducing other novel agents.

Intermediate or unfavourable stage Hodgkin's lymphoma (HL) definition relies upon at least three different scoring systems defined by cooperative groups (EORTC, GHSG and Canadian-ECOG). We aimed to investigate their efficacy and their correlation with International Prognostic Score (IPS) for advanced HL.We studied a population of 1156 patients with localized stage HL treated prospectively within GELA centres in H8 (518 patients) and H9 (638 patients) protocols. Median age: 30 yr, 18%, Female 50%; stage I: 25%; stage II: 75%. According to scoring systems 70% had 0-1 EORTC factors; 60% 0-1 GHSG factors and 82% 0-1 Canadian factors. The IPS for advanced stages was available only in H9 study with 64% 0-1 factor.Survival curves according to each of the different scoring systems could significantly discriminate the subgroup populations. When a multivariate Cox analysis was performed for overall survival (OS) including all the scoring system variables: age45 yr, sex male, Haemoglobin10.5 g/dL, lymphocytes600/microL, B symptoms with elevated ESR, extra nodal sites did retain an independent significant value. Probability of OS was 99%, 98%, 92%, 82% and 73% for patients with 1-5 factors, respectively P0.0001.These factors are similar for most of them with those described in the IPS when stages III and IV are replaced by extra nodal localization. This new score should be validated in other prospective trials, as it will simplify the Hodgkin prognostic scoring systems for localized and advanced stages.

THE PATHOPHYSIOLOGY of most autoimmune diseases is often poorly understood. EXPERIMENTAL CONSIDERATIONS and clinical experience suggest that high doses immunoablation followed by stem cell transplantation is a therapeutic option to consider for certain severe autoimmune disorders. THE CONCEPT OF RESTORING NORMAL IMMUNE REACTIVITY must in part br true since current results of 466 transplants (445 autologous, 21 allogeneic) patients suffering from various autoimmune diseases show a beneficial outcome in approximately 2/3 of the patients. TO IMPROVE THE EFFICACY AND SAFETY OF SUCH AN AGGRESSIVE PROCEDURE in patients with potentially affected vital organs by the underlying autoimmune disease, it is especially important to follow international consensus guidelines and to centrally collect clinical data for in depth analysis in the EBMT International Stem Cell Project for Autoimmune Disease in Basel, Switzerland. PHASE III STUDIES ARE RUNNING FOR SYSTEMIC SCLEROSIS (Astis, Autologous Stem cell Transplantation International Rheumatoid Arthritis Trial) started in 2003. A STUDY PROJECT IS PLANNED FOR MULTIPLE SCLEROSIS (Astims, Autologous Stem cell Transplantation International Multiple Sclerosis).

The optimal treatment for patients with advanced Hodgkin's disease (HD) responding to initial chemotherapy (CT) and an intensive salvage therapy for those who fail to respond completely after initial treatment were evaluated prospectively.The Groupe d'etudes des Lymphomes de l'Adulte H89 trial compared two cycles of CT with (sub)total nodal irradiation (RT) as consolidation treatments for patients with stage IIIB/IV HD with a complete response (CR) or good partial response (PR) after six cycles of CT. Early salvage therapy, including intensified cytoreductive CT and high-dose CT with autologous stem-cell transplantation, was integrated into the trial for patients who had failed to respond completely or relapsed after initial treatment.The study does not demonstrate any advantage of RT over CT as consolidation treatment at the time of CT-induced CR or good PR. Early intensive therapy improves the outcomes of patients with PR and those who relapsed with unfavourable factors. This strategy remains unsatisfactory for patients with primary refractory disease and chemoresistant disease.Based on first intensification of conventional-dose CT, in the next trial (EORTC-GELA Intergroup Study), four escalated bleomycin-etoposide-doxorubicin-cyclophosphamide-procarbazine-prednisone (BEACOPP) followed by four baseline BEACOPP are compared with the eight doxorubicin-bleomycin-vinblastine-dacarbazine standard with no RT for patients who achieve CR/CR-uncertain after initial CT.

To compare a short intensified regimen followed by sequential consolidation therapy (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone [ACVBP]) to the standard regimen of methotrexate, bleomycin, cyclophosphamide, and etoposide (m-BACOD) in patients with low-risk aggressive lymphoma.A total of 752 patients with intermediate- or high-grade lymphoma and no adverse prognostic factors (Eastern Cooperative Oncology Group performance status of 2 to 4,/= two extranodal sites of disease, tumor burden/= 10 cm in largest dimension, bone marrow or CNS involvement, Burkitt's or lymphoblastic subtypes) were registered. Of 673 eligible patients, 332 received ACVBP and 341 received m-BACOD.The complete remission rate was identical (86%) in the two groups. With a median follow-up duration of 7 years, the 5-year failure-free survival (FFS) rate was 65% in the ACVBP group and 61% in the m-BACOD group (P =.16). The 5-year overall survival rate was 75% in the ACVBP group and 73% in the m-BACOD group (P =.47). ACVBP was responsible for more severe and life-threatening infections (P.01), but m-BACOD caused more pulmonary toxicity (P.001). The number of treatment-related deaths did not differ between the two regimens. A multivariate analysis indicated that ACVBP was associated with a longer FFS in patients with two or three risk factors of the International Prognostic Index.In this population of patients with low-risk aggressive lymphoma, toxicities of the regimens are different, but the rates of response and survival are identical. The survival advantage of ACVBP over standard regimen in patients with advanced disease is suggested by this analysis but remains to be assessed in prospective studies specifically designed for this purpose.

Following injury, tissue repair process takes place involving inflammation, granulation tissue formation and scar constitution. Granulation tissue develops from the connective tissue surrounding the damaged area and contains vessels, inflammatory cells, fibroblasts and myofibroblasts. Myofibroblasts play an important role in many tissue injuries and fibrocontractive diseases. The process of normal wound repair after tissue injury follows a closely regulated sequence including the activation and the proliferation of fibroblastic cells. In pathological situations, the normal resolution stages are abrogated and the proliferation of myofibroblasts continues, inducing excessive accumulation of extracellular matrix. The differentiation of fibroblastic cells into myofibroblasts is an early event in the development of tissue fibrosis. Myofibroblastic cells express smooth muscle cytoskeletal markers (alpha-smooth muscle actin in particular) and participate actively in the production of extracellular matrix. The evaluation of myofibroblast differentiation in renal biopsies would be useful for histopathologists to appreciate the intensity of tissue injury and particularly to predict the long term outcome of some nephropathies. Immunohistochemical studies for alpha-smooth muscle actin should be made systematically in renal tissue biopsies. Myofibroblastic differentiation appears to play a significant role in the progression of renal failure and seems to be a useful marker of progressive disease.

Amongst men, prostatic adenocarcinoma is the most common cancer and the second most frequent cause of deaths. Widespread PSA measurement have led to earlier diagnosis. Recent clinical trials have tried to show an improvement in the prognosis. Early stages are mainly treated surgically even if local control results are similar with radiotherapy. Radiotherapy is the main stay of treatment for more locally advanced disease, either conventionally or conformational. Adjuvant hormonotherapy has been shown to improve survived as opposed to neoadjuvant hormonotherapy which only has local effects. The treatment of metastatic disease is palliative with the use of antiandrogens. In case of relapse, a second line of hormonotherapy or a chemotherapy is given. However the problem is the lack of effective drugs. Response rates to the main drug treatment are around 10 to 20%. New therapeutic approaches are now based on antimicrotubules agents but it is difficult to evaluate their efficacity. Further clinical trials will provide more information about improvement in survival rates and in quality of life.

Although the first radiation-induced solid tumor was reported as early as 1902, the risk of second tumor has been underestimated by radiation oncologists who treated large numbers of patients with either benign or malignant diseases. Since then, numerous epidemiological studies yielded better knowledge of the risks of radiation-induced malignancies. For instance, radiation-induced tumors are the first cause of death 10 years after treatment for Hodgkin's disease. We present here a literature review of the risks of radiation-tumors in various organs, related to the irradiation dose, age, and associated diseases. The most sensitive organs are the thyroid, central nervous system, breast, bone, and lung, especially in smokers. Higher risks are observed with increasing doses, the shape of the dose-response curve depending on the tumor type, when the irradiation is performed in children or young adults and in patients with retinoblastomas. The risk of radiation-induced tumors should lead the radiation oncology committee to reconsider the dose and technique of irradiation and to reduce the use of ionizing radiation in benign diseases.

The objectives of this study were to evaluate the outcome after polychemotherapy for patients with primary cutaneous large-cell lymphomas (PCLL) and to validate the recently proposed immunohistologic classification of cutaneous lymphomas. Among 140 patients with positive skin biopsies included in the LNH87 protocol (for treatment of aggressive lymphomas), 49 patients met the criteria of PCLL. Characteristics were: sex ratio M/F, 2.3; age 18 to 83 years (median, 52), peripheral lymph nodes, n=22; diffuse disease, n=12; median tumor size, 4.5 cm; elevated lactate dehydrogenase, n=9; ECOG: 0/1, n=49. Histology was: follicular center B cell, n=23; B-lymphoblastic, n=1; anaplastic large-cell lymphoma, n=14 (T cell phenotype n=8); CD30- T cell lymphoma, n=11. All patients received polychemotherapy: under 70 years, ACVBP (three to four cycles and consolidation for 6 months) n=25; mBACOD (eight cycles) n=16; over 70 years, C(T)VP (six cycles) n=8. Radiation therapy was not included in the protocol. With a median follow-up of 5 years, 24/49 patients had relapsed, with 20 skin relapses. Event-free (EFS) and overall survival (OS) at 5 years were, respectively, 50 and 77%. Significant adverse prognostic factors were: histology (CD30- T cell lymphoma) and diffuse cutaneous disease (10% of skin). The presence of nodal involvement was only significant for EFS. When compared to 140 non-cutaneous lymphoma patients included in the same trial and fully matched for the main clinical characteristics, OS was similar. In conclusion, PCLL behaves like other localized B or T cell extranodal lymphomas with the same prognostic factors (LDH, ECOG, age) except for CD30+ PCLL which have a very good prognosis.

Background The optimal treatment for patients with advanced Hodgkin's disease (HD) responding to initial chemotherapy (CT) and an intensive salvage therapy for those who fail to respond completely after initial treatment were evaluated prospectively. Patients and methods The Groupe d'etudes des Lymphomes de l'Adulte H89 trial compared two cycles of CT with (sub)total nodal irradiation (RT) as consolidation treatments for patients with stage IIIB/IV HD with a complete response (CR) or good partial response (PR) after six cycles of CT. Early salvage therapy, including intensified cytoreductive CT and high‐dose CT with autologous stem‐cell transplantation, was integrated into the trial for patients who had failed to respond completely or relapsed after initial treatment. Results The study does not demonstrate any advantage of RT over CT as consolidation treatment at the time of CT‐induced CR or good PR. Early intensive therapy improves the outcomes of patients with PR and those who relapsed with unfavourable factors. This strategy remains unsatisfactory for patients with primary refractory disease and chemoresistant disease. Conclusion Based on first intensification of conventional‐dose CT, in the next trial (EORTC–GELA Intergroup Study), four escalated bleomycin–etoposide–doxorubicin–cyclophosphamide–procarbazine–prednisone (BEACOPP) followed by four baseline BEACOPP are compared with the eight doxorubicin–bleomycin–vinblastine–dacarbazine standard with no RT for patients who achieve CR/CR‐uncertain after initial CT.