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Resume La crainte d’effets indesirables des traitements se developpe beaucoup, pas toujours avec pertinence, parallelement a l’expansion des reseaux sociaux, comme on l’a vu dans la pandemie de la COVID-19 avec ses vaccins. Elle donne toute sa valeur aux essais randomisees contre placebo… Par ailleurs, des campagnes, qui se sont averees injustifiees, s’opposent a l’utilisation de nouvelles formulations medicamenteuses ou des traitements generiques, faisant reflechir au role de l’effet nocebo. Il est propose ici d’etudier les effets placebo et nocebo et les bases scientifiques sur lesquelles ils reposent.

Resume Introduction Le Plan Cancer 2014–2019 insiste sur l’importance de la collaboration entre tous les acteurs de la recherche clinique dans la lutte contre le cancer, dont les intergroupes et groupes cooperateurs. Cette enquete avait pour objectif de definir le profil des investigateurs du reseau des Groupes cooperateurs en oncologie et d’identifier certains facteurs qui pouvaient faciliter ou freiner leur activite de recherche clinique. Methodes Un questionnaire a ete envoye a tous les investigateurs ayant participe en 2014 a une etude promue par l’un des 10 membres du reseau des Groupes cooperateurs en oncologie. Il portait sur leur profil, et leur activite de recherche ainsi que sur la structuration de la recherche clinique au sein de leur etablissement. Resultats D’apres les resultats des 366 medecins repondants, les etudes des Groupes cooperateurs en oncologie ont represente une part importante de l’activite de recherche clinique des investigateurs en France en 2014. Ces groupes participent a l’ouverture de centres dans toutes les regions francaises. Une forte activite de recherche clinique des medecins (inclusions de patients > 10) est fortement associee au nombre d’attaches de recherche clinique ou de techniciens d’etudes cliniques (plus de 2 equivalents temps plein (ETP), OR = 11,16 [3,82–32,6] compare a 0 ETP) ainsi qu’a l’exercice de cette activite dans un centre hospitalier universitaire par rapport a un centre hospitalier (OR = 2,15 [1,20–3,83]). Conclusion Cette enquete a permis d’identifier des elements susceptibles de renforcer l’activite de recherche clinique des investigateurs afin de permettre ainsi a un nombre croissant de patients de beneficier de l’innovation therapeutique.

French National Cancer Institute (INCA) and the Fondation Francaise pour la Recherche contre le Myelome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myelome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myelome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization

The French Cancer Plan 2014-2019 stresses the importance of strengthening collaboration between all stakeholders involved in the fight against cancer, including cancer cooperative groups and intergroups. This survey aimed to describe the basics characteristics and clinical research activity among the Cancer Cooperative Groups (Groupes coopérateurs en oncologie). The second objective was to identify facilitators and barriers to their research activity.A questionnaire was sent to all the clinicians involved in 2014 as investigators in a clinical trial sponsored by one of the ten members of the Cancer Cooperative Groups network. The questions were related to their profile, research activity and the infrastructure existing within their healthcare center to support clinical research and related compliance activities.In total, 366 investigators responded to our survey. The academic clinical trials sponsored by the Cancer Cooperative Groups represented an important part of the research activity of the investigators in France in 2014. These academic groups contributed to the opening of many research sites throughout all regions in France. Factors associated with a higher participation of investigators (more than 10 patients enrolled in a trial over a year) include the existing support of healthcare professionals (more than 2 clinical research associate (CRA) OR=11.16 [3.82-32.6] compared to none) and the practice of their research activity in a University Hospital Center (CHU) rather than a Hospital Center (CH) (OR=2.15 [1.20-3.83]).This study highlighted factors that can strengthen investigator clinical research activities and subsequently improve patient access to evidence-based new cancer therapies in France.

Les recommandations de la Societe de Reanimation en Langue Francaise (SRLF) [1], publiees en 2002, concernant les limitations et arrets de therapeutiques actives en reanimation adulte, sont a ce jour une initiative unique qui a modifie les pratiques professionnelles des services de reanimation. Dans un contexte different, de nombreuses situations posent au quotidien, dans les services d’hematologie, le probleme de la proportionnalite des soins et d’une eventuelle obstination deraisonnable, encore appelee communement acharnement therapeutique. En hematologie comme dans d’autres disciplines, cette conduite therapeutique peut etre cause de souffrance chez les malades, leurs familles et les soignants eux-memes, et souleve de graves problemes ethiques. C’est pourquoi le premier objectif du groupe Ethique de la Societe Francaise d’Hematologie (SFH), cree par son conseil d’administration en fevrier 2004, a ete de proposer a la discipline une reflexion et des recommandations. Ce texte a ete redige en s’inspirant du texte de la SRLF [1], des reflexions et de l’experience des membres du groupe et des donnees de la litterature. Il sera presente aux membres du conseil d’administration de la SFH et diffuse au sein de la discipline « hematologie ». Ce projet est apparu particulierement necessaire avec l’apparition de nouveaux textes legislatifs (en particulier la loi du 4 mars 2002), l’avis n° 60 du Comite Consultatif National d’Ethique du 27 janvier 2000 intitule « Fin de vie, arret de vie, euthanasie », la publication des recommandations de la Conference de consensus de l’ANAES des 14 et 15 janvier 2004 sur l’Accompagnement des patients en fin de vie et de leurs proches et la proposition de loi n° 1882 du 30 novembre 2004 relative aux droits des malades et a la fin de vie. Ce texte est propose comme une incitation a la reflexion plutot que comme une serie de recommandations qui s’ajouteraient aux textes officiels actuels ou en cours d’elaboration.

This multicentre prospective randomised trial compared the efficacy and safety of two doses of thalidomide in patients with relapsed or refractory myeloma. The study was designed to test the non-inferior efficacy and to confirm the better tolerability of low-dose thalidomide as compared to a higher dose. Four hundred patients were randomly assigned to receive either 100 or 400 mg/day of thalidomide. Dexamethasone treatment was added in both arms for patients with stable disease or treatment failure at 12 weeks. The primary endpoint was 1-year overall survival (OS). Thalidomide 100 mg/day was better tolerated than 400 mg/day with less high-grade somnolence, constipation, nausea/vomiting and peripheral neuropathy (P < 0.001, P = 0.007, P = 0.03 and P = 0.007, respectively). In the per-protocol population (PP), the estimated 1-year OS rates were of 74.5% (n = 149) and 67.3% (n = 156) in the 400 and 100 groups, respectively. The upper limit of the difference between these rates was of 15.6% higher than the non-inferiority acceptable limit of 12.75%, and the hypothesis of non-inferiority of 100 could not be established (P = 0.14). On the other hand, when intent-to-treat (ITT) population was analysed, the non-inferiority was demonstrated because the 1-year OS rates were of 72.8% (n = 195) and 68.8% (n = 205) in the same groups, leading to an upper limit of the difference of 11.49% lower than the non-inferiority acceptable limit. In addition, in patients alive 12 weeks postrandomisation and those who received thalidomide plus dexamethasone, there were no significant differences in response rates, time to progression, progression-free survival and OS between the two groups. Collectively, low-dose thalidomide 100 mg/day has significant activity in advanced myeloma with an improved safety profile and can be a good salvage therapy in combination with dexamethasone.

Purpose This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT). Patients and Methods Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m2 intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day 21) for eight cycles (6 months), and then on days 1, 8, 15, and 22 with a 20-day rest period (day 23 to day 42) for four cycles (6 months). Results Median time to progression (primary end point) was significantly longer with VTD than TD (19.5 v 13.8 months; hazard ratio, 0.59; 95% CI, 0.44 to 0.80; P = .001), the complete response plus near-complete response rate was higher (45% v 21%; P = .001), and the median duration of response was longer (17.9 v 13.4 months; P = .04). The 24-month survival rate was in favor of VTD (71% v 65%; P = .093). Grade 3 peripheral neuropathy was more frequent with VTD (29% v 12%; P = .001) as were the rates of grades 3 and 4 infection and thrombocytopenia. Conclusion VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity.

hma.2011.0608 Auteur(s) : Chantal Bauchetet, Dominique Bordessoule, Philippe Casassus, Joel Ceccaldi, Morgane Cheminant, Christian Bastard, Philippe Colombat, Diane Damotte, Eric Fiat, Dominique Jaulmes, Jean-Pierre Jouet, Sandra Malak, Genevieve Margueritte, Sarah Morin, Alice Polomeni, Henri Rochant, Jean-Jacques Sotto JJSotto@chu-grenoble.fr, Marc Zandecki, Robert Zittoun Commission d’ethique de la Societe francaise d’hematologie Tires a part : J. Sotto Notre pratique quotidienne [...]

Peripheral T-Cell lymphomas (PTCL) are relatively rare diseases but appear to be highly aggressive and display worse remission and survival rates than B-cell lymphomas. Despite unsatisfactory results with the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen, it remains the reference front-line therapy in these diseases, but has not been challenged in phase III trials. The Groupe Ouest Est d'Etude des Leucemies et Autres Maladies du Sang (GOELAMS) devised an alternative therapeutic schedule including etoposide, ifosfamide, cisplatin alternating with doxorubicin, bleomycin, vinblastine, dacarbazine (VIP-reinforced-ABVD; VIP-rABVD) and compared it to CHOP/21 as front-line treatment in non-cutaneous PTCL. All newly diagnosed patients were eligible. The primary objective was to improve the 2-year event-free survival (EFS) rate. Secondary objectives were to compare the response rate, overall survival, and toxicities as well as identify prognostic factors. Eighty-eight patients were identified between 1996 and 2002. Both arms were well balanced for patients' characteristics in terms of histological and clinical presentation. No significant difference was observed between the two arms in terms of 2-year EFS. Anaplastic large cell lymphoma type and Ann Arbor stage I-II were identified as two independent favourable prognostic factors influencing survival. VIP-rABVD was not superior to CHOP/21 in terms of EFS as first-line treatment of PTCL, confirming that CHOP/21 remains the reference regimen in these lymphomas.

Purpose Until recently, melphalan and prednisone were the standards of care in elderly patients with multiple myeloma. The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years. This randomized, placebo-controlled, phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma. Patients and Methods Between April 2002 and December 2006, 232 previously untreated patients with myeloma, age 75 years or older, were enrolled and 229 were randomly assigned to treatment. All patients received melphalan (0.2 mg/kg/d) plus prednisone (2 mg/kg/d) for 12 courses (day 1 to 4) every 6 weeks. Patients were randomly assigned to receive 100 mg/d of oral thalidomide (n = 113) or placebo (n = 116), continuously for 72 weeks. The primary end point was overall survival. Results After a median follow-up of 47.5 months, overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo (median, 44.0 v 29.1 months; P = .028). Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group (median, 24.1 v 18.5 months; P = .001). Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group: grade 2 to 4 peripheral neuropathy (20% v 5% in the melphalan and prednisone plus placebo group; P < .001) and grade 3 to 4 neutropenia (23% v 9%; P = .003). Conclusion This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.

Background and Objectives T-lymphoblastic lymphoma is an infrequent disease usually treated as T-acute lymphoblastic leukemia with an induction chemotherapy course and sequential reinduction and maintenance chemotherapy. The T-LBL/ALL-GOELAL02 study evaluated the impact of randomized reinduction chemotherapy against intensified conditioning followed by autologous stem cell transplantation (ASCT), after an induction regimen of the type used for acute lymphoblastic leukemia (ALL).Design and Methods Patients with favorable characteristics were randomized to receive chemotherapy or ASCT. Patients with unfavorable characteristics (bone marrow involvement and age over 35 years old or leukocytosis >30 × 109/L or failure to achieve medullar complete remission [CR] after one induction course) received a second induction course and ASCT.Results Among 45 patients, the CR rate was 71% after induction and 87% after a second induction course. Within the group of 27 patients with favorable characteristics, ten received ASCT and 17 chemotherapy. Ten patients in the group with unfavorable characteristics received ASCT. The 7-year overall survival and progression-free survival rates were 64 and 65%, respectively. Surprisingly, CR obtained after only two induction courses was associated with improved overall survival (p=0.04). None of the known prognostic factors significantly affected survival.Interpretation and Conclusions Randomized maintenance or high-dose therapy (HDT) and ASCT or intensified HDT according to initial presentation gave similar overall and relapse-free survival rates. However, HDT allowed sparing of mediastinal irradiation and shortened treatment duration.

International audience; A 1-year prospective cohort study of all episodes of Escherichia coli bacteraemia in two French university hospitals was conducted to assess simultaneously the influence of host and bacterial determinants on the initial severity and outcome of E. coli sepsis. Clinical data (community-acquired/nosocomial infection, immune status, underlying disease, primary source of infection, severity sepsis scoring and outcome), phylogenetic groups (A, B1, D and B2), nine virulence factors (VFs) (papC, papGII, papGIII, sfa/foc, hlyC, cnf1, iucC, fyuA and iroN) and the antibiotic susceptibility of isolates were investigated. All VFs except iucC were significantly more prevalent (p

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin4 mg/l and high hemoglobin (Hb)/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.

In patients with multiple myeloma (MM) not eligible for high-dose therapy and autologous stem cell transplantation (ASCT), the 2 following options are recommended as part of front-line treatment and approved based on data from randomized phase III trials: melphalan/prednisone/thalidomide (MPT), or

Dexamethasone alone increases life expectancy in patients with relapsed multiple myeloma (MM); however, no large randomized study has compared dexamethasone and dexamethasone-based regimens with standard melphalan-prednisone in newly diagnosed MM patients ineligible for high-dose therapy. In the Intergroupe Francophone du Myelome (IFM) 95-01 trial, 488 patients aged 65 to 75 years were randomized between 4 regimens of treatment: melphalan-prednisone, dexamethasone alone, melphalan-dexamethasone, and dexamethasone-interferon alpha. Response rates at 6 months (except for complete response) were significantly higher among patients receiving melphalan-dexamethasone, and progression-free survival was significantly better among patients receiving melphalan (P < .001, for both comparisons), but there was no difference in overall survival between the 4 treatment groups. Moreover, the morbidity associated with dexamethasone-based regimens was significantly higher than with melphalan-prednisone, especially for severe pyogenic infections in the melphalan-dexamethasone arm and hemorrhage, severe diabetes, and gastrointestinal and psychiatric complications in the dexamethasone arms. Overall, these results indicated that dexamethasone should not be routinely recommended as first-line treatment in elderly patients with MM. In the context of the IFM 95-01 trial, the standard melphalan-prednisone remained the best treatment choice when efficacy and patient comfort were both considered. These results might be useful in the context of future combinations with innovative drugs.

Mastocytosis (M) is a clonal myeloid-disabling disorder for which no curative therapy is currently available. Cladribine (2-chlorodeoxyadenosine [2-CdA]) is a synthetic purine analog cytoreductive treatment, for which efficacy is mostly reported in advanced M. Here we report, with a long-term follow-up period (>10 years) efficacy and safety in 68 adult patients with M (36 [53%] had indolent M and 32 [47%] had advanced M) treated by 2-CdA (0.14 mg/kg in infusion or subcutaneously, days 1-5; repeated at 4-12 weeks until 1 to 9 courses). Median 2-CdA courses number was 3.7 (1-9). The overall response rate was 72% (complete remission [R]/major/partial R: 0%/47%/25%) and according to indolent/advanced M was 92% (major/partial R: 56%/36%) and 50% (major/partial R: 37.5%/12.5%), respectively. Clinical improvement was observed for 10 of 11 mediator release and 6 of 7 mast cell infiltration-related symptoms including urticaria pigmentosa and organomegaly (P < .02). Serum tryptase levels decreased (P = .01). Median durations of response were 3.71 (0.1-8) and 2.47 (0.5-8.6) years for indolent and aggressive M, respectively. The most frequent grade 3/4 toxicities were lymphopenia (82%), neutropenia (47%), and opportunistic infections (13%). 2-CdA appears to provide a significant efficacy with some toxicity in various M subtypes, mostly in indolent M, refractory to multiple symptomatic therapies.

The combination of high levels of beta2-microglobulin (beta2-m) and chromosome 13 deletion allows identification of a high-risk subgroup of patients with de novo multiple myeloma (MM). In this population of patients, we have evaluated the impact of a murine anti-interleukin 6 (anti-IL-6) monoclonal antibody (BE-8) as part of the second conditioning regimen in a multicenter prospective randomized trial of tandem autologous stem cell transplantation (ASCT). Conditioning for the first ASCT was accomplished with melphalan 200 mg/m2 and for the second one with melphalan 220 mg/m2 plus dexamethasone with or without BE-8 infusion. This trial included 219 patients, of whom 166 were randomized, 85 without BE-8 (arm A) and 81 with BE-8 (arm B). The median overall survival (OS) and event-free survival (EFS) times of the whole group of patients were 41 and 30 months, respectively. Response rates, OS, and EFS were not different between the 2 arms of the trial. OS at 54 months was 46% in arm A and 51% in arm B (P = .90); median EFS was 35 months in arm A and 31 in arm B (P = .39). In high-risk patients the dose intensity of melphalan at 420 mg/m2 led to encouraging results, but the addition of anti-IL-6 monoclonal antibody to the second conditioning regimen did not improve either OS nor EFS.

Resume Introduction. – Les manifestations neuropsychologiques de la mastocytose systemique se resument principalement a des troubles cognitifs et des desordres affectifs. Exegese. – Nous rapportons deux observations de malades atteints de mastocytose systemique sans hypereosinophilie, ayant presente un accident vasculaire cerebral ischemique sur dissection des arteres cervicales. Nous discutons cette association decrite pour la premiere fois. Conclusion. – Nous suggerons de rajouter la mastocytose systemique au nombre des facteurs endogenes impliques dans les dissections des arteres cervicales.

Resume Propos. – Les mastocytoses systemiques sont des maladies rares, caracterisees par une proliferation mastocytaire au sein de differents organes. Les manifestations cliniques sont de deux types : celles liees au relargage des mediateurs mastocytaires et celles liees a l’envahissement des differents organes par les mastocytes pathologiques, ces dernieres definissant les formes agressives de la maladie. Jusque recemment, le traitement n’etait que symptomatique et sans effet sur le syndrome tumoral. Actualites et points forts. – Des progres ont ete faits ces dernieres annees dans la comprehension de la maladie avec la mise en evidence d’une mutation du proto-oncogene c-kit et l’assimilation des mastocytoses systemiques a un syndrome myeloproliferatif. Perspectives et projets. – De nouvelles approches therapeutiques fondees sur l’experience acquise dans le traitement de certains syndromes myeloproliferatifs sont en cours de developpement. Dans cette optique, l’association interferon–cytarabine d’une part et la cladribine d’autre part, constituent des voies prometteuses. Enfin, une nouvelle famille de molecules actives sur la proteine c-kit, les inhibiteurs de tyrosine kinase, a recemment demontre avec l’imatinib mesylate une grande efficacite dans le traitement des tumeurs stromales gastro-intestinales (GIST) comportant une mutation de c-kit. Par analogie, il est possible d’esperer une reponse chez les malades porteurs d’une mutation de c-kit sensible a ces inhibiteurs.

Systemic mastocytosis (SM) is characterized by proliferation of mast cells in various organs, which may release a wide variety of mediators, thereby explaining the broad clinical spectrum of disease manifestations. The potentially life-threatening systemic symptoms and tumoral proliferation are poorly controlled despite the use of several cytotoxic chemotherapies and/or symptomatic treatments. Twenty consecutive adult SM patients with histologically confirmed bone marrow (BM) involvement received interferon-alpha subcutaneously (1-5 million units/m2/d, with progressive dose intensification over the first month of treatment) and were evaluated after 6 months of therapy. Seven of them had previously received symptomatic treatments, including steroids, which were ineffective. Among the 13 patients treated for at least 6 months, seven partial and six minor responses, mainly concerning vascular congestion and skin lesions, were obtained, while BM infiltration remained unchanged in 12 patients. The significant reduction of mast-cell mediator levels after 6 months of treatment was not predictive of clinical remission. The rate of depression was unexpectedly high (seven patients; 35%). Two patients died soon after starting therapy (one myocardial infarction, one septic shock). Six months of interferon-alpha may relieve vascular congestion in adults with SM, probably by inhibiting mast-cell degranulation.

High-dose therapy has become a common treatment for myeloma. The objective of this study (Intergroupe Francophone du Myélome [IFM] 9502 trial) was to compare in a prospective and randomized trial the 2 most widely used conditioning regimens before autologous stem cell transplantation in newly diagnosed symptomatic patients younger than 65 years old: 8 Gy total body irradiation plus 140 mg/m(2) melphalan (arm A) versus 200 mg/m(2) melphalan (arm B). A total of 282 evaluable patients were compared--140 in arm A and 142 in arm B. Baseline characteristics and disease response to 4 cycles of the VAD regimen performed before randomization and autologous stem cell transplantation were identical in the 2 treatment arms. In arm B, hematologic recovery was significantly faster for both the duration of neutropenia and thrombocytopenia, transfusion requirements were also significantly lower, and the median duration of hospitalization was significantly shorter. In arm A, the incidence of severe mucositis was significantly increased. The median duration of event-free survival was similar in both arms (21 vs 20.5 months, P =.6), but the 45-month survival was 65.8% in arm B versus 45.5% in arm A (P =.05). This difference might be attributed in part to better salvage regimens after relapse in arm B compared with arm A. We conclude that 200 mg/m(2) melphalan is a less toxic and at least as effective conditioning regimen when compared with 8 Gy total body irradiation with 140 mg/m(2) melphalan. This regimen should be considered as the standard of care before autologous stem cell transplantation in multiple myeloma.

Admission of patients with hematological malignancies to intensive care unit (ICU) raises recurrent ethical issues for both hematological and intensivist teams. The decision of transfer to ICU has major consequences for end of life care for patients and their relatives. It also impacts organizational human and economic aspects for the ICU and global health policy. In light of the recent advances in hematology and critical care medicine, a wide multidisciplinary debate has been conducted resulting in guidelines approved by consensus by both disciplines. The main aspects developed were (i) clarification of the clinical situations that could lead to a transfer to ICU taking into account the severity criteria of both hematological malignancy and clinical distress, (ii) understanding the process of decision-making in a context of regular interdisciplinary concertation involving the patient and his relatives, (iii) organization of a collegial concertation at the time of the initial decision of transfer to ICU and throughout and beyond the stay in ICU. The aim of this work is to propose suggestions to strengthen the collaboration between the different teams involved, to facilitate the daily decision-making process, and to allow improvement of clinical practice.

Background. Primary bone lymphoma (PBL) is a rare entity that has only been reviewed in one prospective and small retrospective studies, from which it is difficult to establish treatment guidelines. We prospectively evaluated high-dose or conventional anthracycline-cyclophosphamide dose and radiotherapy for PBL.Patients and Methods. The GOELAMS prospective multicenter study (1986–1998) enrolled adults with localized high-grade PBL according to age and performance status (PS). Patients Results. Among the 26 patients included (VCAP: 19; VCEP-bleomycin: 7), 39% had poor PS ≥2. With a median follow-up of 8 years, overall survival, event-free survival, and relapse-free survival were 64%, 62%, and 65%, respectively, with no significant difference between treatment groups. Poor PS was significantly associated with shorter OS and EFS.Conclusions. Our results confirm the efficacy of our age-based therapeutic strategy. High-doses anthracycline-cyclophosphamide did not improve the outcome. VCEP-bleomycin is effective and well tolerated for old patients. The intensification must be considered for patients with PS ≥2, a poor prognostic factor.

The epidemiology and clinical outcome of acute myeloid leukaemia in human immunodeficiency virus (HIV)-infected adults is poorly documented. We retrospectively surveyed all French haematology centres for adult acute myeloid leukaemia (AML) cases diagnosed between January 1990 and July 1996 who were found to be HIV-seropositive before or at the time of AML diagnosis. Medical charts were reviewed to determine the stage of HIV infection, the characteristics of AML and the response of AML to chemotherapy. Sixteen cases of AML (13 men, three women) were reported by 12 haematology units. Based on assumptions on the size, age and sex distribution of the HIV-infected population in France, the estimated risk of AML in 1990 to 1996 among HIV-infected adults was twice that of the general population (standardized incidence ratio = 2.05; 95% confidence interval, 1.17-3.34). Two other cases occurring before 1990 were spontaneously notified to the authors and were included in the clinical analysis. At AML diagnosis, the median CD4+ cell count was 275 x 106/l and nine patients had acquired immune deficiency syndrome (AIDS). Fifteen patients were scheduled for remission-induction therapy of AML. No deaths were related to AML treatment. Complete remission was obtained in 11 out of 15 patients. Three patients were long-term survivors: two remain alive in complete remission at 8 years and 9 years, respectively, and the third died of AIDS at 8 years. A CD4+ cell count above 200 x 106/l at AML diagnosis was predictive of longer survival (log-rank test: P = 0.004). Like many other malignancies, the incidence of AML appears to be increased in HIV-infected patients. Our results show a twofold higher incidence, although this needs to be confirmed in a specifically designed prospective epidemiological study. Such patients, especially those with CD4+ cell counts above 200 x 106/l at AML diagnosis, should receive remission-induction therapy, which can confer long-term survival.

To better define the overall characteristics and risk factors for dying of adult pneumococcal endocarditis (PE) focusing on the echocardiographic diagnosis, the impact of surgery, and emergence of penicillin resistance, the medical and microbiologic charts of adult PE cases observed between 1991 and 1998 in university and general hospitals were reviewed through a nationwide retrospective study in France. Thirty cases of PE (22 men, 8 women; median age, 53 yr; range, 27-87 yr) were collected and validated. Twenty patients (66.7%) had no known predisposing cardiopathy; 4 had a bioprosthetic valve. The primary focus of infection was pneumonia in 10 (33.3%), and meningitis was noted in 12 (40.0%). Half the patients suffered from chronic alcoholism. Echocardiography detected vegetation(s) in 29 cases (96.7%), valvular perforation in 6 (20.0%), and/or valve ring abscess in 4 (13.3%). The most frequent complications were congestive heart failure (n = 19), large arterial emboli (n = 8), and focal abscesses (n = 7). Five strains were penicillin-resistant. Twenty (66.7%) patients underwent valve replacement, 12 of them during the first month. The overall mortality rate was 24.1%. According to a multivariate analysis, the risk factors independently associated with dying were age > or = 65 yr and septic shock, while cardiac surgery was protective (p < 0.01). In conclusion, PE is usually fulminant and causes severe valve damage and embolic complications; its short-term prognosis might be improved by early valve replacement.

Autologous stem cell transplantation (ASCT) in the front line treatment of non-Hodgkin's lymphoma (NHL) remains controversial. Anaplastic large-cell lymphoma (ALCL) is known to have its own clinical and biological features. The outcome of ALCL patients treated with high-dose chemotherapy and ASCT as part of their first-line therapy was analysed in 202 intermediate or high-grade NHL patients in a prospective randomized trial. First-line chemotherapy comprised two alternating anthracycline-containing regimens. Responding patients were autografted after a BEAM (BCNU, cytarabine, etoposide and melphalan) regimen. Patients with bulky or residual masses were irradiated. Fifteen patients with ALCL were identified by morphological and immunological features (CD30 was expressed in 14 out of 15 patients, three patients expressed B-cell markers, five patients expressed T-cell markers and seven patients did not express cell markers). Anaplastic lymphoma kinase (ALK) expression was confirmed in seven cases. The median age was 39 years with a predominant male sex ratio (2.75). Thirteen patients were stage >/= III and six presented with two or more adverse prognostic factors. According to the international age-adjusted prognostic index, the expected complete remission (CR), event-free survival (EFS) and overall survival (OS) rates were 69%, 71% and 69%. Two deaths were observed (one due to interstitial pneumonitis, one due to pulmonary carcinoma). All patients entered CR, no relapse occurred and EFS and survival reached 87% with a follow-up of more than 5 years. These results differ significantly from those observed in the other 176 lymphoma patients: event-free survival was only 53 +/- 5% and OS reached 60 +/- 4% with a median follow-up of 56 months (P = 0.006). Intensified chemotherapy with autologous stem cell support appeared effective in the treatment of ALCL, offering patients the real chance of a cure.

We report the occurrence of invasive aspergillosis (IA) in nonallografted patients with multiple myeloma (MM) who were treated at hematology or oncology centers in Europe during 1984‐1996. Thirty-one cases met the criteria for definitive (21 [68%]) or probable (10 [32%]) IA. Of these cases, 23 (74%) were reported during 1992‐1996. Twenty-nine cases (94%) occurred in patients with Durie-Salmon stage 3 MM, and 2 (6%) occurred in patients with Durie-Salmon stage 2 MM. The median time between MM and IA diagnoses was 8 months (range, 1‐75 months). Sixteen patients (51%) had a neutrophil count

This prospective study, based on declaratory data, evaluates the appropriateness of red blood cell transfusion prescriptions in a university hospital. Local recommendations written after data collection and the analysis of prescriptions using a blinded method limited the bias related to the declaratory data. The results show that the rate of unjustified prescriptions is 4.2% (95% CI: 2.2%; 6.2%). This rate is statistically (P = 0.032) lower in the department of surgery (1.3%) than in the department of medicine (5.7%). This rate tends to decrease according to the experience of the prescriber (P = 0.06) and varies significantly according to the hemoglobin levels (P = 0.03). The logistic regression, integrating these three parameters, confirms that only the hemoglobin level is significantly related (P < 0.003) to the appropriateness of RBC transfusions. This study also highlights problems not linked to prescriptions, and the hospital created a quality assurance program as a result.

A prospective study of autologous bone marrow or peripheral blood stem cell transplantation after intensive chemotherapy in myelodysplastic syndromes

Objective To retrospectively analyze the clinical symptoms, laboratory findings, and outcomes in patients with microscopic polyangiitis (MPA) who were enrolled in various clinical trials conducted by the French Vasculitis Study Group. Methods A cohort of 85 patients meeting the Chapel Hill criteria for MPA participated in the study. Seventy-one of them were included in prospective therapeutic trials. Eighty-one diagnoses were biopsy proven. In the other patients, diagnosis was based on clinical findings. Results Forty-seven men and 38 women, with a mean ± SD age of 56.8 ± 14.6 years, met the criteria for MPA. Their main clinical symptoms were renal manifestations (78.8%), weight loss (72.9%), skin involvement (62.4%), fever (55.3%), mononeuritis multiplex (57.6%), arthralgias (50.6%), myalgias (48.2%), hypertension (34.1%), lung involvement (24.7%; alveolar hemorrhage 11.8%), and cardiac failure (17.6%). The mean ± SD serum creatinine level before treatment was 2.59 ± 2.96 mg/dl; 47 patients had renal insufficiency (serum creatinine >1.36 mg/dl). Eight patients underwent dialysis at the time of diagnosis, and long-term dialysis was necessary for 10 patients. Antineutrophil cytoplasmic antibodies (ANCA) were present in 38 of 51 patients (74.5%), of whom 33 had a perinuclear staining pattern (pANCA) and 5 had a cytoplasmic pattern. Antibodies to proteinase 3 were present in 4 patients and antibodies to myeloperoxidase were detected in 31, as determined by enzyme-linked immunosorbent assay. Of the 30 patients who underwent renal and celiac angiography, 4 had microaneurysms. Of the 29 patients (34.1%) who had relapses, 8 died during or after the relapse. During followup, 28 of the 85 patients (32.9%) died. The mean ± SD duration of followup of the group was 69.9 ± 60.6 months. Deaths were less frequent when patients had been treated with steroids and immunosuppressive drugs (13 patients [24.1%]) than with steroids alone (15 patients [48.4%]) (P < 0.01). The 5-year survival rate was 74%. Conclusion This study demonstrated that MPA is a multisystemic disease in which renal symptoms are frequent, but the disease is also associated with general symptoms, arthritis, mononeuritis multiplex, and other manifestations that are also seen in various vasculitides. The rarity of abnormal angiogram findings and the high frequency of pANCA are characteristic of MPA. In most cases, the outcome is comparable with those of other systemic vasculitides, but relapses are frequent.

Churg-Strauss syndrome (CSS) is a systemic vasculitis characterized by the presence of asthma, hypereosinophilia, and necrotizing vasculitis with extravascular eosinophil granulomas. In this retrospective study of 96 patients between 1963 and 1995, we analyzed clinical manifestations, identified prognostic factors, and assessed the long-term outcome. CSS was diagnosed when asthma, hypereosinophilia > 1,500/mm3 or > 10%, and clinical manifestations consistent with systemic vasculitis, with or without histologic evidence, were present. Asthma was the most frequently observed manifestation at presentation, with mononeuritis multiplex the second. Other common manifestations were weight loss, fever, myalgia, skin involvement, paranasal sinusitis, arthralgia, pulmonary infiltrate, and gastrointestinal involvement. Mean eosinophilia at presentation was 7.193 +/- 6.706/mm3; ANCA, present in 20 of 42 (47.6%) patients, predominantly gave the perinuclear labeling pattern. All the patients were treated with corticosteroids alone or in combination with cyclophosphamide or plasma exchanges. Clinical remission was obtained in 91.5%; 22 (25.6%) patients relapsed. Twenty-three patients died during follow-up: 11 of these deaths were directly due to vasculitis. The presence of severe gastrointestinal tract or myocardial involvement was significantly associated with a poor clinical outcome. The long-term prognosis of CSS is good and does not differ from that of polyarteritis nodosa, although most patients need low doses of oral corticosteroids for persistent asthma, even many years after clinical recovery from vasculitis.

Acute promyelocytic leukaemia (APL) is characterized by t(15;17)(q22;q21) which results in the formation of two chimaeric genes, PML/RAR alpha and RAR alpha/PML, thought to play a role in leukaemogenesis. We report a case of a patient with APL apparently lacking the t(15;17) but with t(1;17) translocation identified by fluorescence in situ hybridization (FISH). Chromosome 15 seemed intact but PML/RAR alpha fusion transcript was detected by molecular analysis. The patient achieved complete remission with all-trans retinoic acid treatment associated with chemotherapy. This case illustrates the usefulness of combined cytogenetics, FISH and molecular biology in cases with no evident t(15;17) to predict response to treatment.

Background: The International Prognostic Index (IPI) is widely used to predict outcome of patients with aggressive lymphomas. Our goal was to assess the prognostic value of this index for low-grade lymphoma. Patients and methods: One hundred eighty-two patients with disseminated (stage III or IV) low-grade lymphoma were enrolled in a prospective multicenter trial. According to the initial features, treatment either was started immediately or was deferred until indicated by disease progression. Patients received the same polychemotherapy regimen, given monthly for six cycles. They were assigned to one of four risk groups according to the number of presenting risk factors: low-risk (0 or 1), low-intermediate-risk (2). high-intermediate-risk (3), high-risk groups (4). Results: Survival curves (Kaplan-Meier method) demonstrated a high significant difference for the four groups (logrank : P < 0.0001). Median survival for the low-risk group has yet to be reached, while that for the three other groups are, respectively, 65, 34, and 12 months. Conclusions: In this study, the IPI has been found to be an important prognostic tool in low-grade lymphoma and may be used in the selection of appropriate therapeutic approaches for individual patients.

In 2011, the Oncologie 93 health network set up support groups for children with a parent suffering from cancer. A psychologist and a health care manager give information to the children and listen to their difficulties. Then, parents and children can open up with each other helping them to overcome the ordeal of the disease.

Background The median survival of patients with myeloma after conventional chemotherapy is three years or less. Promising results have been reported with high-dose therapy supported by autologous bone marrow transplantation. We conducted a randomized study comparing conventional chemotherapy and high-dose therapy. Methods Two hundred previously untreated patients under the age of 65 years who had myeloma were randomly assigned at the time of diagnosis to receive either conventional chemotherapy or high-dose therapy and autologous bone marrow transplantation. Results The response rate among the patients who received high-dose therapy was 81 percent (including complete responses in 22 percent and very good partial responses in 16 percent), whereas it was 57 percent (complete responses in 5 percent and very good partial responses in 9 percent) in the group treated with conventional chemotherapy (P

Resume L'itraconazole est un nouvel antifongique triazole particulier par son activite sur Aspergillus. Ses indications sont : l'aspergillose broncho-pulmonaire allergique, les aspergillomes pulmonaires symptomatiques inoperables et l'aspergillose pulmonaire chronique necrosante. Bien que le traitement de reference des aspergilloses de l'immunodeprime reste l'amphotericine B, quelques publications ont rapporte des resultats encourageants de l'itraconazole prescrit de premiere intention, en particulier chez le neutropenique. Il est, dans ces indications, le plus souvent utilise en relais de l'amphotericine B lorsque celle-ci est inefficace ou mal toleree ou lorsque la persistance de l'immunodepression rend necessaire un traitement d'entretien. Du fait de la biodisponibilite incertaine de l'itraconazole, l'utilisation d'une dose de charge et la surveillance reguliere des taux seriques en cours de traitement sont indispensables. Les nouvelles formes galeniques (solution orale et forme intra-veineuse) ainsi que des essais comparatifs reposeront le probleme des indications de l'itraconazole chez le neutropenique.

Recent studies have provided direct evidence for genetic variegation in subclones for various cancer types. However, little is known about subclonal evolutionary processes according to treatment and subsequent relapse in multiple myeloma (MM). This issue was addressed in a cohort of 24 MM patients treated either with conventional chemotherapy or with the proteasome inhibitor, bortezomib. As MM is a highly heterogeneous disease associated with a large number of chromosomal abnormalities, a subset of secondary genetic events that seem to reflect progression, 1q21 gain, NF-κB-activating mutations, RB1 and TP53 deletions, was examined. By using high-resolution single-nucleotide polymorphism arrays, subclones were identified with nonlinear complex evolutionary histories. Such reordering of the spectrum of genetic lesions, identified in a third of MM patients during therapy, is likely to reflect the selection of genetically distinct subclones, not initially competitive against the dominant population but which survived chemotherapy, thrived and acquired new anomalies. In addition, the emergence of minor subclones at relapse appeared to be significantly associated with bortezomib treatment. These data support the idea that new strategies for future clinical trials in MM should combine targeted therapy and subpopulations' control to eradicate all myeloma subclones in order to obtain long-term remission.