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International audience; Primary antibody deficiency (PAD) is characterized by a defective immunoglobulin production and recurrent infections, mostly involving respiratory and gastrointestinal tracts. Chronic or recurrent diarrhea is reported in up to 23%. Campylobacter infection is a common cause of infectious diarrhea, reported in 1.2% to 7.5% of patients with common variable immunodefi-ciency (CVID), the most frequent PAD. The aim of this study was to describe Campylobacter infection in patients with PAD included in a large nationwide study and analyze factors associ-ated with susceptibility to this pathogen. The DEFI (DEFicit Immunitaire) study is an ongoing large cross-sectional French multicentric study of adults with PAD, with retrospective collection of clinical data. All patients with a history of bacteriologically documented Campylobacter infection were identified, and clinical data were collected for each episode. Factors associated with recurrent infection were assessed as oddsratio (OR) and 95% confidence interval (CI), calculated by means of simple regression analysis. In patients with available material, strains of each episode were characterized using molecular analysis and compared (Table E1, available in this article’s Online Repository at www.jaci-inpractice.org). A com-parison of immunodeficiency-related characteristics of patients with and without Campylobacter infection was performed in the homogeneous group of patients with CVID. The control group included patients with CVID from DEFI centers who confirmed that patients did not develop Campylobacter infection after enrollment (Figure E1, available in this article’s Online Repository at www.jaci-inpractice.org). After correction for multiple comparisons, P

Objectives To demonstrate the bioequivalence between 2 intravenous immunoglobulin (IVIG) preparations, TEGELINE ® and ClairYg ® , a ready-to-use 5% IVIG, in primary immunodeficiency (PID). Secondary objectives were to assess the efficacy, safety and pharmacokinetics of ClairYg ® . Methods Twenty-two adult PID patients receiving stable doses of TEGELINE ® (5% lyophilized IVIG) were switched to ClairYg ® for 6 months. ClairYg ® was administered under the same conditions as TEGELINE ® , either every 3 or 4 weeks. The primary endpoint was mean average total IgG trough level at steady state with ClairYg ® versus TEGELINE ® . Clinical efficacy was also assessed in terms of infections and associated events. Results Bioequivalence was established with a mean average total IgG trough level at steady state being 8.05 g/L with TEGELINE ® and 9.17 g/L with ClairYg ® (i.e. geometric mean for the difference between ClairYg ® and TEGELINE ® was 1.136; [90% CI: 1.092–1.181] P 4–6 g/L) throughout the study. No patient was hospitalized for infection or had serious bacterial infections while receiving ClairYg ® . The median annualized infections rate per patient was similar for both products: 4.35 [0; 21.8] for TEGELINE ® and 4.30 [0; 15.1] for ClairYg ® . Infections were less common with higher IgG trough levels (> 8.16 g/L). ClairYg ® showed good safety, in particular good hepatic and renal tolerance, and did not induce hemolysis. ClairYg ® pharmacokinetics profile was comparable to that of TEGELINE ® . Conclusion ClairYg ® is safe and effective in the treatment of adult PID.

Introduction L’ibrutinib, inhibiteur irreversible et non specifique de la Bruton tyrosine kinase (BTK), voie du BCR, est utilise dans le traitement de nombreuses hemopathies lymphoides B. L’ibrutinib forme un lien covalent robuste avec la BTK et inhibe les voies de survie et multiplication cellulaires, empechant les cellules lymphomateuses d’adherer aux ganglions lymphatiques, environnement qui leur est favorable. Le traitement entraine une mort cellulaire lors de leur migration dans le sang, environnement qui ne leur est pas favorable. Parmi les effets indesirables connus (cytopenies, troubles digestifs, fibrillation auriculaire, thrombopathies…), on retrouve des complications infectieuses essentiellement bacteriennes, des voies respiratoires et urinaires. Concernant les atteintes cutanees, sont decrit principalement des rashs, un cas de panniculite et un cas d’abces cutanes multiples a Fusarium spp [1]. Observation Nous rapportons le cas d’un homme de 71 ans, diabetique de type 2, traite par ibrutinib depuis juillet 2015 en 2e ligne d’une maladie de Waldenstrom. Un traitement anterieur par 6 cures de rituximab–cyclophosphamide–dexamethasone avait ete initie devant des cytopenies severes (Hb a 4,8 g/L) sans syndrome tumoral associe, avec un echec primaire ayant conduit a l’introduction de l’ibrutinib. En mars 2017, il developpe un premier abces cutane en fosse iliaque gauche necessitant une mise a plat chirurgicale. Aucune documentation microbiologique n’est retrouvee. En juillet 2017, alors que le patient est toujours traite par ibrutinib, et presente une hypogammaglobulinemie a 5,9 g/L (et un pic IgM a 0,6 g/L) et une lymphopenie a 0,7 G/L, sans autre lesion cutanee, survenue d’un nouvel abces spontane paralombaire droit a Staphylococcus aureus meti sensible necessitant une mise a plat chirurgicale de la collection inguinale gauche precedemment operee, et de l’abces paralombaire droit. La recherche du portage de la leucocydine de Panton-Valentine s’avere negative. Devant l’absence d’autre etiologie, outre le diabete favorisant la susceptibilite aux infections, le traitement par ibrutinib est arrete en juillet 2017. L’evolution a ete partiellement favorable sous antibiotherapie, mise en place d’un VAC et soins quotidiens, avec retard de cicatrisation de l’abces inguinal gauche. Depuis son arret, il n’y a pas eu de nouvelle infection, pas de cytopenie, le pic est a 1,2 g/L. Conclusion Nous rapportons, via cette observation, le premier cas d’abces recidivants a S. aureus survenant au cours du traitement par ibrutinib. Le traitement peut etre responsable de complications infectieuses via une diminution de la phagocytose par les macrophages, du chimiotactisme, de l’adhesion et la migration des PNN, la secretion de cytokines pro-inflammatoires et la migration des cellules epitheliales vers le site infectieux.

Introduction L’hyperphosphoremie est un desordre hydroelectrolytique observe dans diverses situations : insuffisance renale aigue ou chronique, syndrome de lyse tumorale, rhabdomyolyse. Neanmoins, sa mesure peut etre faussee par des interferences analytiques, dont nous rapportons ici un exemple d’interet pour le clinicien. Methodes Quatre patients ont presente une hyperphosphoremie « isolee » dans un contexte de myelome multiple IgG, sans alteration du debit de filtration glomerulaire ni lyse tumorale. La technique standard de dosage du phosphore est la colorimetrie, basee sur la mesure de l’absorbance du complexe forme par le phosphore et le molybdate d’ammonium. Ce reactif peut interagir avec une immunoglobuline monoclonale. Pour s’affranchir de l’impact du composant monoclonal, chaque serum a ete deproteinise, par precipitation des proteines seriques a l’acide sulfosalicylique 1,57 M. L’analyse des plasmas a ete reiteree durant le suivi des patients. Resultats obtenus ou attendus Quatre patients (2 femmes et 2 hommes) âges de 55 a 78 ans, au diagnostic ou lors du suivi d’un myelome multiple avec un pic IgG important (kappa dans trois cas, lambda dans un cas) ont ete inclus. Tous les patients presentaient une hyperprotidemie superieure a 100 g/l, sans manifestation clinique d’hyperviscosite. Les valeurs initiales de phosphoremie, de phosphoremie apres deproteinisation, de protidemie et de pic sont presentees dans le Tableau 1 . Apres traitement, la diminution de la phosphoremie mesuree en colorimetrie etait parallele a celle de l’abondance du pic IgG, suggerant le lien direct entre le composant monoclonal et l’artefact de laboratoire. Conclusion La constatation d’une hyperphosphoremie isolee en presence d’un composant monoclonal IgG abondant doit conduire le clinicien et le biologiste a suspecter un artefact de laboratoire. Il convient de controler ce taux apres deproteinisation, devenue systematique dans notre centre lorsque la protidemie excede 100 g/l, permettant d’eviter des investigations et actions therapeutiques inutiles.

International audience; BACKGROUND:In 2014, the European Society for Immune Deficiencies (ESID) revised the common variable immunodeficiency (CVID) diagnosis criteria by incorporating new clinical and biological markers. The new definition appeared more restrictive but had not yet been evaluated in a large cohort of patients.OBJECTIVE:The objective of this study was to evaluate the impact of this new definition in a large cohort of patients with primary hypogammaglobulinemia.METHODS:Evaluation of 3 different CVID definitions (ESID/Pan-American Group for Immunodeficiency [PAGID] 1999, ESID 2014, DEFI 2015) in 521 patients included in the French DEFI study with a diagnosis of primary hypogammaglobulinemia.RESULTS:Using the ESID/PAGID 1999 definition, 351 patients were classified as CVID. The new ESID 2014 definition excluded 62 (18%) patients. Most of them (n = 56; 90%) had a less severe disease, whereas 6 (10%) presented with a severe disease with major T-cell defect. We propose different criteria (occurrence of opportunistic infection or very low naive CD4+ T-cell count) to define this population with severe T-cell defect. Sixty-two patients fulfilled these criteria, represented 20% of the initial CVID population but accounted for 77% of the deaths, with a 5-year overall survival of 67.6% (95% confidence interval, 51.0-79.6), and were considered as late onset combined immunodeficiency (LOCID).CONCLUSIONS:The new ESID definition for CVID still fails to exclude a large number of patients with severe T-cell defect. We propose a new definition (DEFI 2015) that excluded more patients with a T-cell defect and consider these patients as LOCID. This population has a poor outcome and should be considered as a distinct group requiring specific care.

Resume Introduction Le syndrome d’activation macrophagique ou syndrome hemophagocytaire est rare, il a parfois ete decrit en association avec la tuberculose. Observation Nous rapportons le cas d’un homme de 30 ans, migrant d’origine congolaise, qui a presente une pleuropneumopathie droite recidivante refractaire associe a un amaigrissement de 30 kg et de sueurs nocturnes. Ce tableau s’associait a une bicytopenie pour laquelle le myelogramme retrouvait une moelle de richesse normale. Le scanner thoracique notait de volumineuses adenopathies mediastinales. La biopsie d’un ganglion mediastinal concluait a une lymphadenite granulomateuse necrosante et la biopsie osteomedullaire evoquait un syndrome d’activation macrophagique associe. L’evolution fut favorable sous quadritherapie antituberculeuse et corticotherapie.

But de l’etude L’objectif de cette recherche est d’analyser les relations entre les caracteristiques individuelles des soignants et des services d’oncohematologie et les facteurs psychosociaux determinants de la sante au travail des soignants, dont le soutien social defini comme predicteur du coping, le stress, le coping et la qualite de vie au travail.

Le Groupe de reflexion sur l’accompagnement et les soins palliatifs en hematologie (GRASPH) fut cree en 1991 sur le concept de la demarche palliative qui affirme que la mise en place d’une demarche participative des equipes centrees sur le malade permet une meilleure prise en charge du patient et des proches. Ce concept, repris dans plusieurs textes officiels et plusieurs recommandations (Plan cancer [2003], rapport de Marie de Haennezel [2003], Conference de consensus sur l’accompagnement des personnes en fin de vie et de leurs proches [2004]), est detaille dans deux circulaires ministerielles des 19 fevrier 2002 et 9 juin 2004. La demarche palliative associe differents points de la demarche participative: formation interne aux unites de soins, mise en place d’un projet commun d’equipe, creation d’espaces de paroles pluriprofessionnels ou sont discutes les cas difficiles, soutien aux equipes. Depuis 1991, le GRASPH a diffuse la demarche palliative par le courrier du Groupe de reflexion sur l’accompagnement et les soins de support pour les patients en hematologie et oncologie (GRASSPHO), son site web, un congres national tous les deux ans, puis annuel, des formations nationales, la creation de groupes regionaux. En 2005, le groupe a integre les soins de support (definis comme l’ensemble des soins et soutiens necessaires aux personnes malades tout au long de la maladie, conjointement aux traitements specifiques) dans le concept de demarche participative des equipes transversales (douleur, soins palliatifs, psychooncologie, soutien social, nutrition, reeducation fonctionnelle...).

To decrease red blood cell (RBC) transfusion requirements during high-dose therapy (HDT) for hematological malignancies, we conducted a pilot study to assess the effect of recombinant human erythropoietin (rHuEpo) given during chemotherapy before HDT and autologous peripheral stem-cell transplantation (APSCT). The transfusion histories of 15 HDT and APSCT for hematological disease performed in 11 consecutive patients who received rHuEpo (10 000 U subcutaneously three times/week) were compared to those of 22 HDT and ASCT performed in 17 consecutive historical controls matched for hematological parameters. rHuEpo increased the hemoglobin (Hb) level from 10.3+/-2.3 g/dl at diagnosis to 12.9+/-2.2 g/dl at the time of HDT in 11 patients; no major adverse effects occurred. Compared to historical controls (95%, 21/22), RBC transfusion requirements were significantly lower for rHuEpo recipients (26%, 4/15) (P=0.00001) and rHuEpo responders (15%, 2/13) (P=0.000002). After HDT and APSCT, fewer RBC transfusions were needed: 3.3, 1.2 and 0.3 RBC units for controls, rHuEpo recipients and rHuEpo responders, respectively (P=0.006 and 0.00002). Therefore, rHuEpo should be administered before, and not after HDT and APSCT, to lower RBC transfusion requirements after HDT and APSCT.

Resume Propos. – Le diagnostic d’aspergillose pulmonaire invasive chez le patient neutropenique est difficile. Le scanner, le lavage bronchoalveolaire et l’histologie sont consideres comme des examens invasifs car ils representent un risque infectieux pour le patient immunodeprime. Methodes. – A partir d’une etude retrospective de 16 cas consecutifs d’aspergillose pulmonaire invasive dans un service d’hematologie, nous decrivons les signes cliniques et paracliniques non invasifs (radiographie, serologie, antigenemie) de cette mycose. Resultats. – En dehors de la fievre et des frissons, peu specifiques, les signes cliniques les plus precoces sont la toux et la polypnee, auxquels succedent dans l’ordre la douleur thoracique, la dyspnee, l’anomalie auscultatoire pulmonaire et enfin l’hemoptysie. Ces signes ont tous une sensibilite superieure a 56 %. La radiographie pulmonaire se modifie avant l’apparition d’anomalies auscultatoires ; elle montre volontiers des infiltrats alveolaires unilateraux. La serologie est peu sensible (25 %), mais a contribue au diagnostic precoce dans 16,6 % des cas. Conclusion. – Une meilleure connaissance des signes cliniques, radiologiques et serologiques d’aspergillose pulmonaire invasive pourrait aider le clinicien a poser l’indication d’examens consideres comme invasifs chez le patient neutropenique (tels qu’un scanner, une fibroscopie bronchique), afin d’etayer le diagnostic de cette infection.

Introduction L’existence d’une hypogammaglobulinemie et d’une lymphopenie chez l’adulte doit faire discuter un deficit immunitaire secondaire. Dans ce cadre, l’association a une hypoalbuminemie evoque des pertes excessives et fait rechercher un syndrome nephrotique, une dermatose etendue mais aussi une enteropathie exsudative. Nous rapportons un cas de maladie de Waldmann, cause rare d’enteropathie exsudative. Observation Un patient de 49 ans nous a ete adresse pour l’exploration d’une hypogammaglobulinemie a 3,9 g/L. Ses antecedents sont marques par un syndrome de Kallmann de Morsier, associant hypogonadisme hypogonadotrope et hyposmie, diagnostique a 13 ans, et substitue par Androtardyl ® . Lors de son suivi endocrinologique, sont decouvertes une hypogammaglobulinemie a 3,9 g/L et une lymphopenie a 690/mm 3 associees a une hypoalbuminemie a 29 g/L. Il n’y a ni composant monoclonal ni cryoglobulinemie. Les dosages ponderaux des immunoglobulines retrouvent des IgG diminuees a 400 mg/dL (665–1253) sans deficit en IgM a 67 mg/dL (54–163) ni en IgA a 164 mg/dL (99–325). Le dosage des sous-classes d’IgG montre un deficit en IgG1 et IgG3, respectivement a 2,25 g/L (4–10) et a 0,14 g/L (0,17–0,8). L’immunophenotypage lymphocytaire montrait une importante lymphopenie T globale touchant autant les cellules CD4+ (259/mm 3 ) et CD8+ (114/mm 3 ) avec une relative conservation des lymphocytes B (112/mm 3 ) et NK (113/mm 3 ). Les examens morphologiques ne montrent pas de syndrome tumoral. La serologie VIH est negative. L’existence d’une hypoalbuminemie oriente vers une cause secondaire a l’hypogammaglobulinemie. Le patient ne presente pas de proteinurie. En l’absence de toute symptomatologie digestive et notamment de diarrhee, nous avons tout de meme evoque l’enteropathie exsudative. Plusieurs dosages montrent une steatorrhee elevee autour de 14 g/24 h ( n Discussion La maladie de Waldmann est une maladie rare dont la prevalence est inconnue. Une revue de la litterature de 2010 estimait le nombre de cas rapportes a 84. Sa physiopathologie reste a eclaircir mais semble interesser la genetique de la lymphogenese. Elle est diagnostiquee le plus souvent chez l’enfant ou le jeune adulte devant un syndrome oedemateux allant des oedemes declives a un tableau d’anasarque, associe a une diarrhee chronique et une malabsorption. Toutefois des tableaux hypomorphes sans trouble du transit ont ete decrits, notamment chez l’adulte. Les lymphangiectasies intestinales engendrent une fuite de lymphe dans la lumiere intestinale, responsable d’une hypoalbuminemie, d’une hypogammaglobulinemie et d’une lymphopenie essentiellement T. Le diagnostic repose sur la visualisation des lymphangiectasies duodenales. Les etiologies secondaires des lymphangiectasies intestinales doivent etre eliminees afin de retenir la maladie de Waldmann. Le traitement repose sur un regime alimentaire pauvre en acides gras a longues chaines, pour limiter la pression dans les lymphatiques intestinaux et eviter leur rupture dans la lumiere digestive. L’alimentation est supplementee en acides gras a chaines moyennes, ceux-ci etant absorbes directement dans la circulation portale. Il n’existe a notre connaissance pas de lien entre la maladie de Waldmann et le syndrome de Kallmann de Morsier. Conclusion Notre observation rappelle qu’un tableau de deficit immunitaire, notamment a l’âge adulte, doit faire discuter une etiologie secondaire. L’enteropathie exsudative en fait partie et doit etre evoquee, a notre sens, meme en l’absence de diarrhee chronique. Les explorations chez ce patient ont permis de porter le diagnostic de maladie de Waldmann, dont le traitement repose sur l’exclusion des acides gras a chaines longues.

All trans-retinoic acid (ATRA) syndrome is a life-threatening complication of uncertain pathogenesis that can occur during the treatment of acute promyelocytic leukemia (APL) by ATRA. Since its initial description, however, no large series of ATRA syndrome has been reported in detail. We analyzed cases of ATRA syndrome observed in an ongoing European trial of treatment of newly diagnosed APL. In this trial, patients 65 years of age or less with an initial white blood cell count (WBC) less than 5,000/μL were initially randomized between ATRA followed by chemotherapy (CT) (ATRA→CT group) or ATRA with CT started on day 3; patients with WBC greater than 5,000/μL received ATRA and CT from day 1; patients aged 66 to 75 received ATRA→CT. In patients with initial WBC less than 5,000/μL and allocated to ATRA→CT, CT was rapidly added if WBC was greater than 6,000, 10,000, 15,000/μL by days 5, 10, and 15 of ATRA treatment. A total of 64 (15%) of the 413 patients included in this trial experienced ATRA syndrome during induction treatment. Clinical signs developed after a median of 7 days (range, 0 to 35 days). In two of them, they were in fact present before the onset of ATRA. In 11 patients, they occurred upon recovery from the phase of aplasia due to the addition of CT. Respiratory distress (89% of the patients), fever (81%), pulmonary infiltrates (81%), weight gain (50%), pleural effusion (47%), renal failure (39%), pericardial effusion (19%), cardiac failure (17%), and hypotension (12%) were the main clinical signs, and 63 of the 64 patients had at least three of them. Thirteen patients required mechanical ventilation and two dialysis. A total of 60 patients received CT in addition to ATRA as per protocol or based on increasing WBC; 58 also received high dose dexamethasone (DXM); ATRA was stopped when clinical signs developed in 30 patients. A total of 55 patients (86%) who experienced ATRA syndrome achieved complete remission (CR), as compared with 94% of patients who had no ATRA syndrome (P= .07) and nine (14%) died of ATRA syndrome (5 cases), sepsis (2 cases), leukemic resistance (1 patient), and central nervous system (CNS) bleeding (1 patient). None of the patients who achieved CR and received ATRA for maintenance had ATRA syndrome recurrence. No significant predictive factors of ATRA syndrome, including pretreatment WBC, could be found. Kaplan Meier estimates of relapse, event-free survival (EFS), and survival at 2 years were 32% ± 10%, 63% ± 8%, and 68% ± 7% in patients who had ATRA syndrome as compared with 15% ± 3%, 77% ± 2%, and 80% ± 2% in patients who had no ATRA syndrome (P= .05, P = .003, and P = .03), respectively. In a stepwise Cox model that also included pretreatment prognostic variables, ATRA syndrome remained predictive for EFS and survival. In conclusion, in this multicenter trial where CT was rapidly added to ATRA in case of high or increasing WBC counts and DXM generally also used at the earliest clinical sign, the incidence of ATRA syndrome was 15%, but ATRA syndrome was responsible for death in only 1.2% of the total number of patients treated. However, occurrence of ATRA syndrome was associated with lower EFS and survival. © 1998 by The American Society of Hematology.

From 1960 to 1990, 557 patients with ankylosing spondylitis (428 men, 129 women) were diagnosed and indexed in the department of rheumatology. Monoclonal gammopathies were found in seven (five men, two women) patients (1.3%). With one exception, ankylosing spondylitis preceded monoclonal gammopathies by many years. The distribution of the isotypes of the mIg found in these seven patients was striking when compared either with previous reports of an association between ankylosing spondylitis and monoclonal gammopathies or with local data on the epidemiology of monoclonal gammopathies: five patients with IgG, four of them of the lambda (lambda) type, and two IgM, both of the kappa (kappa) type were found; no patients with mIgA were recorded. Two patients were HLA-B27 positive and had slight and transient monoclonal gammopathies, whereas three subjects were HLA-B27 negative and had important spikes, corresponding in two subjects to malignant diseases. This observation raises the question of whether the coexistence of HLA-B27 and ankylosing spondylitis might provide a protective action. Epidemiological studies are required to clarify such points.

ANCA positive sera, detected by the standard immunofluorescence method, derived from 37 patients with vasculitis were studied using formalin-acetone fixed chronic myelocytic leukemia cells (CML). All 37 sera were positive on CML cell smears. Furthermore formalin-actone fixation selectively impaired antinuclear antibody binding without reducing ANCA staining and thus facilitated differentiation of these autoantibodies which is often difficult with the standard immunofluorescence method. Two unequivocal and mutually exclusive ANCA binding patterns were identified using the CML smears: (1) type I with diffuse granular binding confined to the polymorphonuclear (PMN) cell lineage and preferentially staining immature cells; (2) type II with similar binding to the PMN cell lineage and, in addition, granular staining of the basophils. All type I antibodies were associated with a c-ANCA pattern suggesting that the major antigen recognized by these antibodies, recently identified as proteinase 3, is not detectable in basophils. The type II pattern was detected in both p-ANCA (84%) and c-ANCA (16%) positive sera. The type I sera remained positive on PMN cells from a myeloperoxidase (MPO) deficient subject and anti-MPO antibodies could not be detected in this group by ELISA. Conversely the type II pattern occurred in the presence of anti-MPO antibodies identified by immunofluorescence, ELISA and dot-blot with the exception of a single serum with antilactoferrin antibody. Type I binding only was observed in Wegener's granulomatosis (WG) but both patterns were found in microscopic polyarteritis (MPA) and rapidly progressive glomerulonephritis (RPGN).

The hemophagocytic syndrome is rare and sometimes associated with tuberculosis.We report the case of a 30-year-old migrant from Congo presenting with a recurrent right pleuropneumonia, cachexia and night sweat. Blood tests revealed bicytopenia with a normal myelogram. Thorax CT-scan showed large mediastinal lymph nodes and pleuritis. Mediastinal lymph node biopsy concluded to granulomatosis lymphadenopathy with necrosis and bone marrow biopsy suggested hemophagocytic syndrome. The outcome was favorable with antibiotics and corticosteroids.

Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80–11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density.

FEWER INDICATIONS AFTER SPLENECTOMY: Real therapeutic progress has been achieved over the last fifty years for patients with Hodgkin's disease known for their chronic immunodepression. Since the advent of effective chemotherapy protocols such as ABVD, and more recently intensive chemotherapy completed as needed with an autograft, splenectomy is no longer performed for therapeutic purposes but may be indicated for its contribution to diagnosis. STRATIFICATION OF RISK OF ASPLENISM: There remain however several questions concerning the infectious complications in these patients given chemotherapy and splenic radiotherapy. One of the objectives of this work was to propose a stratification of risk of asplenism as a function of treatments administered, the level of initial immunodepression, and the age of the patient.

Among neutropenic patients, diagnosis of invasive pulmonary aspergillosis is difficult. Computed tomographic scan, bronchoalveolar lavage and histology are considered invasive procedures, because they represent an infectious risk for these immunocompromised patients.We describe the clinical and noninvasive paraclinical (X-rays, serology) signs of invasive pulmonary aspergillosis, from a retrospective study of 16 cases in a haematology unit.Outside of fever and chills, cough and polypnea are the earliest signs, followed by chest pain, dyspnea, lung auscultation changes, and haemoptysis. The sensitivity of each sign is higher than 56%. Before the onset of lung auscultation changes, the chest X-ray shows mainly unilateral alveolar infiltrates. Sensitivity of serology is weak (25%), but contributed to early diagnosis in 16.6% of cases.A better knowledge of the invasive pulmonary aspergillosis clinical, radiological and serological signs could help the practician to prescribe an 'invasive' investigation (computed tomographic scan, bronchoalveolar lavage) to confirm the diagnosis of this fungal infection.

Acute promyelocytic leukemia (APL) is usually associated with the translocation t(15;17)(q22;q12-21), which disrupts the retinoic acid receptor alpha (RARA) gene on chromosome 17 and the PML gene on chromosome 15. We report a patient with typical APL without the common t(15;17). Cytogenetic studies demonstrated a normal appearance of chromosomes 15, while a small marker seemed to be an i(17q-). Molecular analysis showed RARA and PML rearrangements, suggesting that the chromosome abnormality corresponded to a variant translocation.

Objectif La LMC affecte rarement les enfants, ou les AJA. Notre objectif etait d’etudier les caracteristiques de la maladie au diagnostic, et la reponse au traitement chez les AJA. Sujets et Methodes Il s’agit d’une etude retrospective, multicentrique aupres du registre pediatrique national des LMC et aupres des centres adultes Fi-LMC sur les LMC-AJA. Resultats Sur 10 ans, 87 patients âges en mediane de 21 ans au diagnostic ont ete identifies dans 13 centres pediatriques (24 patients) et 11 centres adultes (63 patients). 9% des patients etait en phase acceleree au diagnostic. Le score de Sokal etait de risque eleve chez 34% des patients. Le traitement de premiere ligne etait un Inhibiteur de Tyrosine Kinase (Imatinib chez 87% des patients). La duree mediane de ce traitement etait de 28 mois. 48% des patients ont interrompu cette premiere ligne (pour resistance, intolerance, transformation en LAL, grossesse, ou dans le cadre du protocole STIM). Une transformation aigue (TA) a ete observee chez 6 patients. Conclusion La LMC chez les AJA apparait plus grave du fait du taux eleve de phases accelerees et de scores de Sokal eleves, avec un taux important de resistances et de TA. Ce travail permettra d’etablir de nouvelles recommandations de prise en charge adaptees a cette population.

Chronic lymphocytic leukaemia is the most frequent haematological cancer in adult patients, and its incidence raises with aging. Diagnosis needs several clinical and biological data, but hemogram together with the morphological and immunophenotypic analysis of the lymphoid cells take the major place. If the diagnosis is performed easily in about 65% of the patients, various clinicobiological entities were reported in the past few years that must be identified, at least because some are of adverse prognosis. Moreover, the other chronic lymphoid neoplasms, corresponding to the various low and intermediate grade non-Hodgkin's lymphomas (mainly of follicular type, marginal zone, mantle cell zone), may disseminate within the blood and the bone marrow. Those circulating lymphoma cells must be identified at diagnosis in order to perform the accurate diagnosis and to avoid an erroneous diagnosis of atypical chronic lymphocytic leukaemia. Up to 90% of lymphoid malignancies are B cell disorders, contrasting with only a few cases of T cell origin: some of those latter cases cannot be neglected however, as they may be observed in Western countries. Most recent classifications (REAL and WHO) defined all hematological malignancies: each entity referred to clinical, morphological, immunological, cytogenetic, and molecular findings. The basis of these classifications is pathophysiological, trying in each disorder to define a normal counterpart to the pathological clone. Reviewing main steps of the immune response in the normal patient, corresponding to those involving B cells, it is possible indeed to localize and demonstrate a function for many of the cells that expand in lymphoid malignancies.

Resume Une malade de 29 ans a presente, au jour 20 suivant la chimiotherapie (cytosine-arabinoside) pour une leucemie aigue non lymphoblastique, une violente douleur abdominale avec fievre et hepatomegalie. Les prelevements hepatiques sont restes negatifs, mais le scanner a montre de multiples abces et la serologie anti-candidosique s'est fortement positivee. De l'amphotericine B est administree par voie parenterale pendant 7 mois (3 g, 75 mg/kg), permettant une reprise de la chimiotherapie antineoplasique. A un an de l'arret de tout traitement, la patiente presente un etat hematologique et hepatique parfait.

All trans-retinoic acid (ATRA) syndrome is a life-threatening complication of uncertain pathogenesis that can occur during the treatment of acute promyelocytic leukemia (APL) by ATRA. Since its initial description, however, no large series of ATRA syndrome has been reported in detail. We analyzed cases of ATRA syndrome observed in an ongoing European trial of treatment of newly diagnosed APL. In this trial, patients 65 years of age or less with an initial white blood cell count (WBC) less than 5,000/microL were initially randomized between ATRA followed by chemotherapy (CT) (ATRA--CT group) or ATRA with CT started on day 3; patients with WBC greater than 5,000/microL received ATRA and CT from day 1; patients aged 66 to 75 received ATRA--CT. In patients with initial WBC less than 5, 000/microL and allocated to ATRA--CT, CT was rapidly added if WBC was greater than 6,000, 10,000, 15,000/microL by days 5, 10, and 15 of ATRA treatment. A total of 64 (15%) of the 413 patients included in this trial experienced ATRA syndrome during induction treatment. Clinical signs developed after a median of 7 days (range, 0 to 35 days). In two of them, they were in fact present before the onset of ATRA. In 11 patients, they occurred upon recovery from the phase of aplasia due to the addition of CT. Respiratory distress (89% of the patients), fever (81%), pulmonary infiltrates (81%), weight gain (50%), pleural effusion (47%), renal failure (39%), pericardial effusion (19%), cardiac failure (17%), and hypotension (12%) were the main clinical signs, and 63 of the 64 patients had at least three of them. Thirteen patients required mechanical ventilation and two dialysis. A total of 60 patients received CT in addition to ATRA as per protocol or based on increasing WBC; 58 also received high dose dexamethasone (DXM); ATRA was stopped when clinical signs developed in 30 patients. A total of 55 patients (86%) who experienced ATRA syndrome achieved complete remission (CR), as compared with 94% of patients who had no ATRA syndrome (P = .07) and nine (14%) died of ATRA syndrome (5 cases), sepsis (2 cases), leukemic resistance (1 patient), and central nervous system (CNS) bleeding (1 patient). None of the patients who achieved CR and received ATRA for maintenance had ATRA syndrome recurrence. No significant predictive factors of ATRA syndrome, including pretreatment WBC, could be found. Kaplan Meier estimates of relapse, event-free survival (EFS), and survival at 2 years were 32% +/- 10%, 63% +/- 8%, and 68% +/- 7% in patients who had ATRA syndrome as compared with 15% +/- 3%, 77% +/- 2%, and 80% +/- 2% in patients who had no ATRA syndrome (P = .05, P = .003, and P = .03), respectively. In a stepwise Cox model that also included pretreatment prognostic variables, ATRA syndrome remained predictive for EFS and survival. In conclusion, in this multicenter trial where CT was rapidly added to ATRA in case of high or increasing WBC counts and DXM generally also used at the earliest clinical sign, the incidence of ATRA syndrome was 15%, but ATRA syndrome was responsible for death in only 1.2% of the total number of patients treated. However, occurrence of ATRA syndrome was associated with lower EFS and survival.

We conducted a randomized multicenter study to compare the efficacy and safety of two antibiotic regimens (cefepime [2 g b.i.d.] plus amikacin or ceftazidime [2 g t.i.d.] plus amikacin) as first-line therapy for fever in patients with hematologic malignancies and neutropenia. A total of 353 patients were randomized according to a 2:1 (cefepime:ceftazidime) ratio. Two hundred-twelve patients in the cefepime group and 107 in the ceftazidime group (90% of all patients) were evaluable for efficacy. The polymorphonuclear neutrophil count was100/mm3 on enrollment for 70% of the patients. The mean duration of neutropenia was 26 days. The efficacy in both study arms was comparable, although a trend in favor of cefepime was seen in terms of therapeutic success (response rate, 27% vs. 21% for the ceftazidime group). The overall response rate after glycopeptides were added to the regimens was 60% for the cefepime group and 51% for the ceftazidime group; the bacterial eradication rates were 81% vs. 76%, respectively, and the rates of new bacterial infections were 14% vs. 18%, respectively. We conclude that the combination cefepime/amikacin is at least as effective as the reference regimen of ceftazidime/amikacin in this setting.

Erythromelalgia is a vascular disorder of the extremities and is sometimes related to myeloproliferative syndrome with thrombocythemia. We report the cutaneous histopathology in case of erythromelalgia that revealed a thrombocythemia vera. Small arteries were occluded by thrombi of different age and narrowing of the lumen occurred by intimal proliferation of smooth muscle cells. There was no involvement of venules or capillaries. These vascular changes are highly suggestive of erythromelalgia and have not to be confused with necrotizing and/or granulomatous angiitis because of absence of fibrinoid necrosis and sparse inflammatory cells.

Purpose and Methods ISOSFER is an epidemiological cross-sectional study with prospective recruitment whose objectives are to evaluate patient characteristics, quality of life (QoL), compliance and patient satisfaction with deferoxamine (DFO) therapy. Results Among 278 consecutive patients receiving regular transfusions for thalassemia major (TM), sickle cell disease (SCD) or myelodysplastic syndromes (MDS) who consulted between October 2005 and February 2006 in 24 French centers, 161 were on chelation therapy. 124 patients were treated with DFO alone for more than 1 year. Among them, 67 aged 14 years or more agreed to participate. QoL was studied using the Short Form-36 scale. Compliance was assessed with the Morisky scale and a specific questionnaire. DFO was administered via subcutaneous (sc) infusion for 70% of patients, mainly nightly and with a mean duration of 10 hours. Other ways of administering DFO included intravenous (iv) infusion (15%), sc bolus (9%) and combined sc and iv treatment (5%). Patient characteristics are summarized in the table below. In comparison with the French general population, all dimensions of QoL are impaired in all three diseases and in all dimensions (physical activities, emotional problems, social activities, bodily pain, and vitality). TM and SCD patients had a better physical activities score than MDS patients but experienced more bodily pain than MDS patients. The global physical score was significantly influenced by age, marital status and occurrence of a co-morbidity related to hemosiderosis. Good compliance scores (0 and 1 on the Morisky scale) were found in only 74%, 67% and 87% of TM, SCD, MDS patients, respectively. In addition, DFO infusion was missed at least once a week during the past month in 17%, 44% and 4% of TM, SCD, MDS patients, respectively. Compliance was influenced by age, duration and number of weekly DFO infusions. Iron chelation with DFO was generally found to be inconvenient and more than half of the patients were unsatisfied with its parenteral mode of administration. Nonetheless, patients, particularly those with TM, were convinced that DFO was an effective treatment for iron overload and a very important drug for their health. Conclusions These results suggest that QoL is severely compromised in patient on DFO and that compliance to DFO is poor. These results could help ascertain the improvement in QoL and compliance, which would result from the use of oral chelation in patients with transfusional iron overload. TM (n=24) SCD (n=17) MDS (n=26) *Cardiac, liver and endocrine diseases, lens opacities, osteoporosis Median age in years (range) 30 (15–70) 32 (14–57) 69 (45–85) Sex, M/F 11/13 6/11 14/12 Geographic origin: EU/subS; Africa/North; Africa/others 16/0/6/2 1/12/3/1 26/0/0/0 Employment/university (%) 45 27 8 Marital status + (patients >18 yrs old) 9/21 7/15 25/26 Organ dysfunction potentially related to hemosiderosis* (%) 75 47 54 Median ferritin level (μg/L) 1049 2653 2627 Nb of TF >100 (%) 100 82 42 Mean DFO frequency/week 3.7 4.5 4 Mean dose 40 17 43

From 2/90 to 6/93, 195 adult patients (pts) with HD, CS IA-IIIB without bulky tumor (nodes 2 : adriamycin 25, bleomycin (BLM) 10, vinblastin (VBL) 6, dacarbazin 375, methylprednisolone (MP) 120 = arm A, 101 pts) or EBVM-MP (Dl and D15, mg/m 2 : epirubicin 30, BLM 10, VBL 6, methotrexate 30, MP 120 = arm E, 94 pts). CT-responding pts were given (sub)total nodal and splenic RT (involved fields 40 Gy, non-involved 30 Gy). Pts characteristics: M 110, F 85; age 40 47; CS I 56, II 117, HI 22; A 152, B 43; histology: LP 21, NS 128, MC 30, LD 1, UN 15. Complete remission rates after CT and RT were 81% (A 83 pts, E 74 pts) and 95% (A 96 pts, E 90 pts) ( P = NS); 10 pts relapsed (A 1, E 9, P

To the Editor.— We describe the case of a 24-year-old woman, with a typical psoriasis that appeared 6 months after allogeneic bone marrow transplantation (BMT) from a psoriatic sibling HLA donor. Report of a Case.— In March 1986, a 24-year-old woman without psoriasis was admitted with mediastinal lymphoblastic non-Hodgkin's lymphoma. Between May and July 1986, three courses of an adriamycin-containing regimen induced complete remission. In September 1986, BMT was performed from an HLA-identical -A1, -A2, -B12, -B13, -DR7, -DRW6, negative, mixed lymphocyte culture brother with psoriasis, but no other disease. The young woman received cyclophosphamide plus fractionated total body irradiation as a conditioning regimen and graft-vs-host disease (GVHD) prophylaxis consisted of short doses of methotrexate (at days 1, 3, 6, and 11) and cyclosporine (4 mg/kg per day) intravenously, then orally twice daily. At day 62, a transient grade II acute GVHD of the skin appeared with a relapse on

Fever is a frequent complication in granulocytopenic patients. Since it can be life-threatening, it is necessary to start antibiotic therapy with a broad spectrum and rapidly acting drug. A study was performed to compare 2 dosage schedules involving cefotaxime and amikacin in immunologically compromised children. All patients were aged between 6 months and 18 years and had leucopenia and/or granulocytopenia, as well as fever (> 38OC) for at least 6 hours. Systemic antibiotic therapy within 48 hours and high suspicion of infection with Pneumocystis carinii were reasons for exclusion. Eligible patients were randomly allocated to I of 2 treatment groups: cefotaxime 200 rug/kg/day + amikacin 15 rug/kg/ day according to a twice-daily schedule; or cefotaxime 200 mg/kg/day + amikacin 15 rug/kg/day according to a 3 times daily schedule. If after 48 hours these schedules were unsuccessful, a third antibiotic was added, and amphotericin B was added on the fourth day if necessary. 30 febrile episodes in 23 patients were treated during the study, 15 episodes on each treatment schedule. There was a total of 8 positive blood cultures. The median white blood cell counts in the twiceand 3 times daily treatment groups were 0.9 and 1.2 x 109L, respectively. Apyrexia was achieved in all patients in I to 19 days (median 3 days), and there were no deaths. In the twice-daily group apyrexia was achieved within 2 days and without additional antibiotics in 11 out of 15 episodes, compared with only 3 out of 15 episodes in the 3 times daily group (p < 0.01). For a total of 23 episodes apyrexia occurred before the end of granulocytopenia. In conclusion, antibiotic therapy with cefotaxime and amikacin in neutropenic patients can provide adequate control of infection. The greater benefit achieved with a twice-daily as compared with a 3 times daily schedule is unclear, but may be connected with a more rapid bactericidal activity in the higher individual doses.

BACKGROUND Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic infections (OIs). METHODS The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs. RESULTS Among 313 patients with CVID, 28 patients (8.9%) presented with late-onset combined immune deficiency (LOCID), defined by the occurrence of an OI and/or a CD4(+) T cell count