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The prognostic roles of social status and social environment in chronic lymphocytic leukemia have been highlighted in some solid tumors but remain unclear in hematological malignancies. The objective of this study was to evaluate the influence of individual social status (with socioprofessional category, SPC) and social environment (with European deprivation index, EDI) on net survival in a high-resolution population with CLL.We included CLL patients from the Regional Register of Hematological Malignancies in Normandy belonging to the French Network of Cancer Registries (Francim). The SPC variable was divided into 5 categories: farmers, craftsmen, higher employment, intermediate employment, and workers/employees. Net survival was used to estimate the excess of mortality in CLL independent of other possible causes of death using French life tables. Net survival was estimated with a nonparametric method (Pohar-Perme) and with a flexible excess mortality hazard model. Missing data were handled with multiple imputation.A total of 780 patients were included. The median follow-up was 7.9 years. The crude survival at 10 years was 50%, and the net survival at 10 years was 80%. In multivariate analysis, a higher age (EHR: 1.04 [1.01-1.07]), being a craftsman (EHRSocioprofessional category was a prognostic factor for an excess of mortality in CLL. Craftsmen and workers/employees shared a worse prognosis than workers with higher employment. The social environment was not a prognostic factor. Further work should be performed to explore causal epidemiologic or biological factors and other hematological malignancies.

Introduction Le lymphome endovasculaire (LEV) est une hemopathie severe, rare, de diagnostic difficile. Nous rapportons une observation originale revelee par un syndrome d’activation macrophagique (SAM) recidivant et des infarctus spleniques. Observation Un homme de 74 ans, tabagique, etait hospitalise en mai 2017, pour fievre a 40° depuis 1 mois, alteration d’etat general, toux, pollakiurie, resistant a de l’amoxicilline/clavulanate. L’examen clinique, pauvre, montrait un nodule indure prostatique. La biologie -anemie (8,3 g/dl), thrombopenie (110G/l), CRP 150 mg/l, ferritine 1400 μg/l, triglycerides 3,5 g/l, LDH 650U/l, gamma-GT 80 UI/l- orientait vers un SAM affirme par myelogramme. Les PSA etaient normaux. Le scanner montrait un minime epanchement pleuropericardique et une splenomegalie infraclinique (16 cm) siege de plusieurs minimes infarctus. L’AEG croissante, l’inefficacite des antibiotiques, l’installation de troubles des fonctions superieures, d’une dyspnee et desaturation, motivaient le traitement urgent du SAM par etoposide 150 mg/m2 obtenant en 48 h une evolution favorable clinique et biologique. Simultanement on cherchait l’etiologie du SAM et des infarctus spleniques. Le bilan infectieux montrait : hemocultures et ECBU steriles, echographie cardiaque TT & TO normale, negativite des recherches VIH, VHB, VHC, VZV, HSV, HHV8, PVB19, T whippeli ; positivite d’une PCR EBV (4,2log), de la serologie C pneumoniae, du test Quantiferon et de l’IDR tuberculine (22 mm) mais recherches negatives de BK (urines et tubages). Le bilan auto-immun etait negatif hormis un anticoagulant circulant transitoire, un test de Coombs positif, l’enzyme de conversion discretement elevee a 78 UI/l. Le bilan onco-hematologique, confirmait par IRM et biopsie un adenocarcinome prostatique localise de bas grade T2a Gleason3 + 3. On notait une IgG lambda monoclonale serique (4,4 g/l), une beta2microglobuline a 5,4 mg/l. Le dosage des chaines legeres libres plasmatiques et le myelogramme ecartaient un myelome. L’immunophenotypage sanguin et medullaire, le cariotype et la biopsie osteomedullaire etait normaux. Deux series de 3 biopsies en peau saine, recherchant un LEV etaient normales. Le TEP-scann montrait un hypermetabolisme modere d’une valve aortique et d’adenopathies mediastinales juxtacentimetriques. L’etat du patient autorisait son retour a domicile sans diagnostic etabli. L’evolution etait marquee par la survenue jusqu’en novembre 2018 de 6 autres episodes de SAM, identiques au 1er, etoposide-sensibles. Ni un traitement par doxycycline et antituberculeux des hypotheses d’endocardite a HC negatives ou de tuberculose, ni le traitement du cancer prostatique par analogue LH-RH et irradiation n’empechaient les poussees de SAM. On gardait l’hypothese du LEV. Un 2e immuno-phenotypage montrait une faible population lymphoide B anormale (1 %) CD19+/CD10+/CD20+/Kappa+. Trois nouvelles biopsies cutanees revenaient negatives, mais la demande de relecture permettait le diagnostic sur la presence en biopsie brachiale de grandes cellules lymphoides B CD10/CD20+ endovasculaires hypodermiques, obliterantes par endroits. Six cures de R-CHEP (rituximab-cyclophosphamide-adriamycine-etoposide-prednisone), de novembre 2018 a fevrier 2019, emaillees d’un choc cytokinique en cure 1, permettaient une remission complete clinico-biologique, encore en cours en fevrier 2021. Discussion Notre patient presentait un LEV revele par un SAM recidivant, des infarctus spleniques, une possible endocardite lymphomateuse. Le diagnostic de LEV, evoque d’emblee, n’etait affirme que 17 mois plus tard par la repetition des biopsies cutanees, evitant une splenectomie diagnostique. Le LEV est une hemopathie rare de diagnostic difficile en l’absence des signes cutanes ou neurologiques classiques. Le SAM est un mode de revelation connu, dans le variant asiatique de l’affection. Par contre nous n’avons trouve qu’un cas de LEV avec infarctus spleniques [1] , et aucun avec endocardite lymphomateuse. Le TEP scann a une place diagnostique, pouvant montrer des hypermetabolismes orientateurs. L’histologie est souvent difficile sur biopsies d’organes atteints (peau, foie, rate, SNC, surrenales..). Les biopsies systematiques de peau, idealement en peau lesee, sinon en peau saine (bras, tronc, cuisse), doivent etre profondes jusqu’a l’hypoderme. La communication avec l’anatomopathologiste et l’epuisement des blocs sont necessaires. Le pronostic redoutable est ameliore par la precocite du traitement [2] . Conclusion Le LEV constitue souvent un challenge diagnostique. Ceci a conduit des auteurs a traiter par chimiotherapie un LEV avant d’en obtenir la preuve histologique 8 ans plus tard ! [3] .

Resume Introduction La dermatose eosinophilique associee aux hemopathies (DEH), anciennement appelee reaction exageree aux piqures d’insectes, est une dermatose prurigineuse observee le plus souvent au cours de la leucemie lymphoide chronique (LLC). Nous en decrivons six observations associees a diverses hemopathies. Malades et methodes Nous avons etudie retrospectivement les dossiers des malades de notre centre atteints de DEH entre 2004 et 2009, avec relecture des lames histologiques. Resultats La moyenne d’âge au moment de l’eruption etait de 75,6 ans. Trois malades etaient porteurs d’une LLC, deux d’un lymphome du manteau (LM), un d’un lymphome de type mucosa associated lymphoid tissue (MALT). L’eruption etait tres polymorphe, faite de papules et de plaques erythemateuses, urticariennes et prurigineuses, contemporaine ou posterieure au diagnostic de l’hemopathie. Elle precedait une recidive de l’hemopathie chez trois malades. La biopsie cutanee revelait un infiltrat dermique dense constitue de lymphocytes T CD4+ et d’eosinophiles. Trois cas presentaient l’originalite d’un infiltrat lymphocytaire T dense dans l’epithelium des follicules pileux, imitant un lymphome T pilotrope. Dans la majorite des cas, la DEH disparaissait apres une chimiotherapie adaptee de l’hemopathie. Discussion Notre serie montre que la presentation clinique de la DEH est polymorphe. L’apparition d’une DEH doit faire craindre la rechute d’une hemopathie B connue, voire inciter a la rechercher. Le traitement le plus efficace de cette dermatose semble etre le traitement de l’hemopathie par une chimiotherapie adaptee. Le mecanisme pourrait etre celui d’une reaction d’hypersensibilite mediee par une population T-helper 2 (Th2) reactionnelle a l’hemopathie B, entrainant une liberation de cytokines dont l’interleukine (IL)-5, a l’origine d’une eosinophilie tissulaire.

Resume Introduction Le bortezomib est un inhibiteur du proteasome utilise dans le traitement du myelome et d’autres hemopathies. Nous rapportons deux cas de toxidermie sous ce traitement, dont l’un marque par la presence d’ulcerations muqueuses geantes. Observations Cas 1 : un homme de 62 ans etait traite par bortezomib pour un lymphome du manteau. Dix jours apres le premier cycle de traitement, on notait l’apparition d’ulcerations buccales douloureuses spontanement resolutives. Une semaine apres la fin du deuxieme cycle survenait un second episode d’ulcerations muqueuses associees a une eruption cutanee papulonodulaire. La biopsie montrait un infiltrat dermique a polynucleaires neutrophiles dans la peau et a predominance lymphocytaire sur la muqueuse. L’arret du bortezomib, associe a un traitement par colchicine, entrainait une guerison des lesions. Cas 2 : une femme de 46 ans etait traitee par bortezomib pour une leucemie a plasmocytes. Deux jours apres le premier cycle est apparue une eruption cutanee febrile, spontanement regressive. L’eruption recidivait 48 heures apres la premiere injection du deuxieme cycle, sous forme de lesions douloureuses papulonodulaires du tronc. La biopsie montrait un aspect histologique evoquant un syndrome de Sweet. Les lesions ont disparu spontanement. De la dexamethasone a ete ajoutee lors des perfusions suivantes de bortezomib et il n’y a pas eu de recidive des lesions cutanees. Discussion Les reactions cutanees induites par le bortezomib sont frequentes et ne necessitent generalement pas l’arret du traitement. Dans certaines observations publiees, le diagnostic de syndrome de Sweet induit par le medicament a ete porte, mais aucune ne mentionnait de lesion muqueuse. Chez notre patient, plusieurs hypotheses pourraient expliquer l’origine des ulcerations, mais leur rattachement a la dermatose neutrophilique induite par le bortezomib semble probable.

Resume Propos Depuis dix ans, plus de 1000 patients souffrant de maladies auto-immunes severes ont beneficie d’une autogreffe de cellules souches peripheriques. Cette therapeutique innovante a ete utilisee chez des patients souffrant de sclerodermie, de sclerose en plaque, de polyarthrite rhumatoide, d’arthrite chronique juvenile et de lupus erythemateux dissemine. Points forts L’autogreffe de cellules souches hematopoietique est devenue une alternative therapeutique dans le traitement de certaines maladies auto-immunes de mauvais pronostic. Cette revue, resume l’experience des essais de phase I et II conduits en Europe et aux Etats-Unis, en decrit les resultats et les limites. Perspectives et projets L’autogreffe de cellules souches hematopoietiques dans le traitement des maladies auto-immunes a evolue du stade de concept experimental, a la demonstration de sa faisabilite chez des patients selectionnes souffrant de formes severes de maladies auto-immunes.

La fatigue et l’anemie sont les symptomes les plus frequemment rapportes par les patients en cours de chimiotherapie. Les traitements curatifs sont souvent d’une efficacite retardee et insuffisante, et ont un cout non negligeable. Notre strategie a ete de proposer un traitement precoce de l’anemie pour tout patient en cours de chimiotherapie en utilisant des doses reduites et avec un schema simplifie. Tout patient âge de plus de 18 ans traite pour une tumeur solide ou lymphome ayant une hemoglobine inferieure ou egale a 12 g/dL recoit un traitement par erythropoietine (EPO). Le traitement est de rH-EPO 20 000 UI SC une fois par semaine. Les patients âges de plus de 70 ans recevaient de facon arbitraire darbepoietine 150 U SC une fois tous les 15 jours. L’evaluation portait sur le nombre de patients traites, transfuses, le cout global des prescriptions d’EPO. L’etude porte sur 12 mois d’octobre 2002 a octobre 2003. Le nombre de patients traites chaque mois est de 363 [317-415], soit trois fois plus qu’en 2001. Le nombre de patients transfuses a significativement baisse et est de 13 %, ce qui represente une reduction de 30 % des transfusions sur les 6 premiers mois de l’annee 2003. Le cout global des prescriptions par EPO est reste stable malgre l’augmentation du nombre de patients traites. Le traitement precocede l’anemie avec des posologies reduites et des schemas simplifies des patients traites par chimiotherapie permet de traiter un plus grand nombre de patients, de reduire les transfusions sans augmenter le cout global des traitements pour la societe.

Summary: Human herpes virus 8 (HHV8) may be sexually transmitted, but transmission via blood cells has not yet been excluded. We used a modified immunofluorescence assay to detect Ab to HHV8 latency-associated nuclear Ag in sera of 200 allogeneic BMT recipients and their related donors. In control subjects, Ab were found in 85% of patients with AIDS-related Kaposi sarcoma (n = 52), 34% of HIV-1 infected subjects without Kaposi sarcoma (n = 56) and 9.5% of blood donors (n = 42). Among BMT donors, 14.5% were HHV8 1 , while 10% of recipients were positive before, and 18% after BMT. In the 176 HHV8-negative recipients at BMT, there was no relationship between post-BMT seroconversion, which occurred in 26 cases (15%), and the donor’s serological status. Of note, 10 HHV8 1 recipients before BMT became negative post-BMT. Outcome of BMT was not influenced by prior HHV8 seropositivity, seroconversion or seroreversion of recipients. That HHV8 seropositivy among blood donors from the Paris area was comparable to that of BMT donors and recipients before BMT indicates that these patients had not been at risk of HHV8 by blood products received before BMT, although post-BMT HHV8 seroconversion probably corresponded to contamination by blood transfusions rather than by the BMT.

Although the feasibility of using HLA-mismatched unrelated donors as an alternate graft source for haematopoietic SCT (HSCT) has been shown, little is known about the safety of HLA-mismatched DLI for the treatment of relapse. We examined the outcome of 58 consecutive leukaemia patients who received escalating-dose DLI for treatment of relapse after alemtuzumab-conditioned myeloablative unrelated donor HSCT at our institution. High-resolution HLA typing on stored DNA samples revealed mismatches in 28/58 patients who were considered HLA-matched at the time of transplantation. Following DLI from HLA-matched (10/10) (n=30) or -mismatched (7-9/10) (n=28) unrelated donors, we found no significant difference in the incidence of acute GVHD (17.2% versus 23.1%, P=0.59), probability of remission at 3 years (62.1% versus 63.9%, P=0.89) or 5-year OS (89.8% versus 77.7%, P=0.22). We conclude that escalating-dose DLI can be safely given to HLA-mismatched recipients following T-depleted myeloablative HSCT.

Le lymphome T peripherique (LTP) est une pathologie heterogene avec des caracteristiques cliniques, histologiques, biologiques et pronostiques variables. La classification de l’Organisation mondiale de la sante (OMS) a divise cette pathologie en plusieurs sous-categories telles les formes leucemiques, nodales et extranodales dont l’atteinte cutanee est la plus frequente. Parmi les histologies les plus frequentes, nous distinguons les LTP non specifies (LTP-nos), les lymphomes T de type lymphadenopathies angio-immunoblastiques (LAI) et les lymphomes anaplasiques (anaplastic large- cell lymphoma: ALCL) ALK-positifs ou ALK-negatifs. Les autres sous-types de LTP sont plus rares, tels les lymphomes NK-T nasaux et extranasaux, les lymphomes T associes a l’enteropathie (EATL), les lymphomes T hepatospleniques, les lymphomes T cutanes et les panniculites [1, 2].

Objectifs Cet observatoire retrospectif mene en France en 2015 avait pour objectif d’estimer l’efficacite et la tolerance en vie reelle d’un traitement par bendamustine chez des patients atteints de LNHi ou d’un lymphome du manteau, en rechute ou refractaire au rituximab, et d’evaluer les modalites d’utilisation actuelles du produit. Methode Les donnees ont ete collectees retrospectivement jusqu’aux dernieres nouvelles des patients dans 21 centres d’hematologie. Etaient inclus les patients en rechute ou refractaires au rituximab, traites par bendamustine pour un LNHi ou un lymphome du manteau entre 2011 et 2014. Les criteres principaux de jugement etaient : le taux de reponse, le temps jusqu’au traitement suivant, la survie sans progression et la survie globale. Les survies ont ete estimees par la methode de Kaplan-Meier, avec une censure aux dernieres nouvelles, a la progression ou au deces. Resultats Un total de 260 dossiers patients (57 % d’hommes) a ete analyse. L’âge median a l’initiation de la bendamustine etait de 72 ans (33–92) ; le diagnostic etait : lymphome folliculaire (LF) (n = 119 ; 46 %), lymphome du manteau (LCM) (n = 53 ; 20 %), lymphome lymphoplasmocytaire (LLP) (n = 47 ; 18 %) et lymphome de la zone marginale (LZM) (n = 41 ; 16 %). Tous etaient en rechute ou refractaires au rituximab. Le nombre median de therapies precedant la bendamustine etait de 2 (1–7). La bendamustine etait prescrite principalement (43 %) en deuxieme ligne de traitement, a 90 mg/m2/j, 2 jours toutes les trois semaines (31 %) ou quatre semaines (69 %), en association avec du rituximab a 375 mg/m2/j (91 %). Le suivi median etait de 17 mois (0,1–52 mois). Le taux de reponse objective etait de 83 % des patients, incluant 52 % de reponse complete et 31 % de reponse partielle. A 24 mois, 64 % des patients etaient sans nouveau traitement. Pour l’ensemble de la cohorte : la duree mediane jusqu’au traitement suivant etait de 42 mois ; la survie sans progression a 24 mois etait de 65 % ; la survie globale a 24 mois etait de 77 %. Un evenement indesirable grave (EIG) lie a la bendamustine etait observe chez 62 (24 %) patients, dont une toxicite hematologique chez 17 (7 %) patients. Parmi ces EIGs les plus frequents etaient : neutropenie febrile (n = 10 ; 16 %), nausees (n = 8 ; 13 %), et thrombopenie (n = 7 ; 11 %) ; 45 patients sont decedes, d’une progression de la maladie (n = 22 ; 49 %), d’une infection (n = 6 ; 13 %), ou d’un motif autre (n = 17 ; 38 %). Conclusion Malgre les limites inherentes aux etudes retrospectives en vie reelle, la methodologie employee a permis de maitriser les biais de selection et de mesure attendus pour cet observatoire mene aupres de l’echantillon le plus important forme dans l’indication du traitement du LNHi par bendamustine. L’etude presente des resultats d’efficacite equivalents a ceux obtenus dans les essais cliniques, et montre que la bendamustine est efficace en situation de rechute ou resistance au rituximab dans une cohorte de 260 patients âges, lourdement pretraites. Bien que les effets indesirables soient moins bien decrits en pratique courante dans les dossiers medicaux que lors des essais cliniques, le profil de tolerance de la bendamustine etait globalement en accord avec le profil de securite connu du produit, dans une population plus âgee que celle des etudes cliniques.

Darbepoetin (DAR), with or without granulocyte colony-stimulating factor (G-CSF), has proved effective in treating anemia in patients with lower-risk myelodysplastic syndrome (MDS), but its effects on quality of life (QoL) and exercise functioning are less well established. In this phase II study (no. NCT00443339), lower-risk MDS patients with anemia and endogenous erythropoietin (EPO) level

One hundred and ten patients with multiple myeloma were treated with bendamustine as part of a French compassionate use program. To receive bendamustine, patients had to present with relapsed or refractory disease after prior therapies that had to include alkylators, steroids, IMiDs and bortezomib. The median number of bendamustine cycles administered was 4 (1-13). The overall response rate (≥ partial response) was 30%, including 2% complete responses. The median progression-free and overall survival for the entire cohort were 9.3 and 12.4 months, respectively. In this series of patients with advanced disease, both the response rate and the duration of response are encouraging and indicate that bendamustine presents a feasible option, which should be considered for the treatment of relapsed/refractory patients.

In B-cell acute lymphoblastic leukemia (B-ALL), testing at diagnosis for BCR/ABL1 gene rearrangements is mandatory for prognostic stratification and treatment decisions. Several diagnostic methods have been proposed using flow cytometry to identify BCR/ABL1(+) B-ALL.We evaluated expression of the myeloid antigen CD66c by flow cytometry in B-ALL. We studied 94 patients with B-ALL. The t(9;22)(q34;q11) or BCR/ABL1 rearrangement was detected by cytogenetic analysis or RT/PCR. Myeloid antigens CD66c, CD13, CD33, CD117, Myeloperoxidase, CD15 and CD65 were determined by flow cytometry.Of these 94 cases, 17 (18%) cases displayed BCR/ABL1 gene rearrangements and 38 (40%) cases were CD66c positive. CD66c was the most common myeloid antigen expressed on malignant lymphoblasts. Its expression was correlated with BCR/ABL1 rearrangements (P = 0.0001): sensitivity 82%, specificity 69%, positive predictive value 37% and negative predictive value 95%. Co-expression of CD66c(+) CD13(+) was more frequent in BCR/ABL1(+) B-ALL (29%) than BCR/ABL1(-) cases (4%) (P = 0.0044). Some BCR/ABL1(-) B-ALL cases (including hyperdiploid or cases with normal karyotype) were CD66c positive (31%).CD66c expression is correlated, but not specifically, with BCR/ABL1 rearrangement. It would seem better to interpret the absence of CD66c expression with a lack of BCR/ABL1 rearrangement. This myeloid antigen could be interesting in the detection of minimal residual disease.

Eosinophilic dermatosis of hematologic disease (EDH) or insect bite-like reaction is a pruritic dermatitis described mostly in patients with chronic lymphocytic leukaemia (CLL). We describe six patients with the disorder in association with CLL and other blood dyscrasias.We reviewed the medical records of patients with EDH seen between 2004 and 2009 in our department and re-examined histological slides.Mean age at dermatosis onset was 75.6 years and the sex ratio was 1. There were three CLL, two mantle-cell lymphomas and one MALT-type lymphoma. The dermatitis was quite polymorphic, with erythematous papules, wheals and plaques. The initial skin lesions appeared at the same time as or after the diagnosis of haematological neoplasm. Their reappearance heralded relapse of the blood disease in three cases. Histologically, all lesions had a dense dermal infiltrate of small, mostly CD4+ T-cells, with numerous eosinophils. In three patients, there was marked folliculotropism, resembling folliculotropic T-cell lymphoma. In most cases, EDH disappeared after appropriate chemotherapy for the blood disorder.Our cases show that the clinical expression of EDH is quite polymorphic. Its appearance may precede relapse of or may indicate prompt search screening for blood dyscrasia. The most efficient treatment of this dermatosis appears to be specific chemotherapy for the blood dyscrasia. There is reason to believe that a population of T-helper 2 (Th2) lymphocytes, reactive to malignant B-cells, induces tissue eosinophilia, mainly through production of interleukin (IL)-5, among other cytokines. Eosinophils appear to be the main effector cells.

Bortezomib (Velcade) is a proteasome inhibitor used in the treatment of myeloma and other blood dyscrasias. We report the cases of two patients who developed a peculiar toxic rash suggestive of Sweet's syndrome while receiving bortezomib; one patient also presented giant mucous membrane ulcerations.Case 1: bortezomib treatment was started in a 62-year-old man for mantle cell lymphoma. Ten days after the first treatment cycle, giant, painful oral ulcerations were noted but they resolved spontaneously. One week after the second cycle, further oral ulceration appeared, this time with a papulonodular skin rash. Histology showed neutrophilic dermal infiltrates in the skin with predominantly lymphocytic inflammation of the oral mucosa. Bortezomib was stopped and all lesions resolved with colchicine treatment. Case 2: a 46-year-old woman was receiving bortezomib treatment for plasma cell leukemia. A febrile skin rash appeared two days after the first treatment cycle but resolved spontaneously. After the first bortezomib injection during the next cycle, painful papules and nodules appeared on the trunk. The skin biopsy results were consistent with Sweet's syndrome. The lesions disappeared spontaneously. Dexamethasone was administered concomitantly with bortezomib in the ensuing cycles and there was no relapse of the skin lesions.Bortezomib-induced skin lesions are common and usually do not justify treatment withdrawal. Published observations of bortezomib-induced eruption occasionally show clinical and histological features of Sweet's syndrome, but there has been no mention of oral mucosal ulcerations. In our cases, these could be related to bortezomib-induced neutrophilic dermatosis.

During the past ten years, more than 1000 patients suffering from severe autoimmune disease have received an autologous haematopoietic stem cell transplant. These new therapeutic have been used in systemic sclerosis (scleroderma), multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis and systemic lupus erythematosus.Autologous haematopoietic stem cell transplantation has become a curative option for condition with very poor prognosis as severe systemic sclerosis, lupus erythematosus or other systemic diseases. This review summarizes the current experience in the phase I and II clinical trials in Europe and North America. We describe the main results and the limits of stem cell transplantation in systemic diseases.Autologous haematopoietic stem cell transplant in the treatment of autoimmune disease has evolved from a experimental concept to a clinically feasible and powerful therapy for selected patients with severe disease.

Extramedullary (EM) localizations at diagnosis or during the course of multiple myeloma (MM) are rare. We conducted a large retrospective study to more accurately describe the clinical and laboratory features of this entity, and the outcome of these manifestations. The charts of 19 eligible patients out of 432 patients with MM were retrieved from the hematology department of the Institut Paoli-Calmettes Cancer Center. Median age was 61 (range: 39-79) with a female/male sex ratio of 8/11. Ten patients were found to have EM and extraosseous tumor at the time of MM diagnosis, and nine patients developed EM tumor during the course of the disease. Neither the stage of the disease, the LDH level, or the type of immunoglobulin (Ig) was found to be associated with the development of EM disease. Patients who developed EM tumor during the course of MM had a lower serum Ig and a higher monoclonal Bence-Jones proteinuria at the diagnosis of MM than patients who presented with EM tumor at diagnosis. Multiple sites were usually involved. Resistance to chemotherapy was frequent and response to thalidomide was poor. Eight out of the 19 patients responded to high-dose chemotherapy. The remaining 11 patients progressed while on therapy. With a median follow-up of 13 months (range: 2-65), six patients are alive, four patients are in partial remission and two patients in present progressive disease. In conclusion, EM tumors are a rare manifestation of MM, with a cumulative incidence of 4.6% of MM. Multiple sites are usually involved. The response to chemotherapy is very poor with a very low response rate to thalidomide. The prognosis is very poor, especially when the diagnosis of EM tumor is concurrent with the diagnosis of MM.

Danazol has been used with success in some hematological diseases, but there is no report of this treatment in acute leukemia. We report here a case of remission of myelodysplastic syndrome with myelofibrosis in transformation after danazol therapy in a 72-yr-old man. The role of danazol in remission induction is briefly discussed.

Essential thrombocythaemia (ET) is a chronic myeloproliferative disorder (MPD) characterized by an elevated platelet count and no identifiable underlying primary cause. According to the diagnostic criteria of the Polycythemia Vera Study Group (PVSG), ET lacks features diagnostic for other MPDs, including the Philadelphia chromosome (Ph) or bcr-abl rearrangement. Recently, some authors have reported bcr-abl transcript positivity in ET patients, but these findings remain controversial. The aim of this study was to investigate whether the bcr-abl transcript could be found in ET patients and to verify the hypothesis of a new ET variant. ET patients (n = 121) with a median age at diagnosis of 55 years were enrolled. The bcr-abl transcript status was examined by multiplex reverse transcription-polymerase chain reaction. Only two cases were positive for bcr-abl, one of which had the Ph at diagnosis. The positive bcr-abl transcript was associated, in both cases, with mild basophilia at diagnosis. After a median follow-up of 43 months (0-309 months), two patients in the bcr-abl-negative group developed Ph and bcr-abl-negative acute myeloid leukaemia (AML). In contrast, one of the two patients in the bcr-abl-positive group died from AML 13 years after diagnosis. In conclusion, our data on a large group of patients shows the rarity of the bcr-abl transcript in well-established ET. However, a subset of patients with apparent ET and basophilia may express the transcript and may constitute a novel entity intermediate between chronic myeloid leukaemia (CML) and typical ET. A prospective study is warranted in order to define better the clinical and biological characteristics of bcr-abl-expressing ET.

A close association between human herpesvirus-8 (HHV-8) and Kaposi's sarcoma (KS) has been shown in transplant recipients, but donor-to-recipient transmission of HHV-8 is uncommon. Herein we report a case of a heart transplant recipient who had a fatal visceral KS in association with HHV-8 seroconversion at 18 months after transplantation with a donor having positive serology discovered after transplantation.

We report one patient with paralysis of the right upper extremity, bilateral cerebellar syndrome, and cognitive changes after treatment with interleukin-2 for metastatic renal cell carcinoma. Focal neurologic disturbances were associated with multiple images of cerebral infarcts but also with extra-neurologic signs and autoantibodies. We suggest that this is a case of cerebral vasculitis with an autoimmune mechanism triggered by interleukin-2 therapy.

e13141 Background: Sunitinib is a multitarget tyrosine kinase inhibitor with antiangiogenic and antitumoral activities and has been approved for the treatment of advanced renal cell carcinoma. Although the general tolerance is acceptable, serious complications may occur in patients treated with sunitinib. Methods: In a forty-six-year-old man with metastatic renal cell carcinoma who was receiving sunitinib for 12 months, following radiotherapy of painful vertebral metastasis between T3 and L4, a duodenal ulcer perforation resulted with acute peritonitis. Favorable outcome was obtained after surgical intervention. Since there was no therapeutic alternative and also good initial response to sunitinib, the patient continued sunitinib at a lower dose (37.5 mg/d). One year after this episode, the patient presented a fatal upper gastrointestinal bleeding. Results: Two cases of intestinal perforation in renal cancer have been reported in the literature, but no case of gastric perforation. We think that this event...