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.1713 1-year OS in allografted patients (%)445621R/R AML Quizartinib monotherapy N = 57Previous exposure to midostaurin N = 27No previous exposure to midostaurin N = 30pAge (years)0 /> Median in allografted patients (months)7NR6.40 />AML status at quizartinib initiation, n (%)0. [Extracted from the article]

Posaconazole ( PSC) is currently recommended as primary prophylaxis in neutropenic patients with acute myeloid leukaemia ( AML) and in allogenic haematopoietic stem cell transplantation ( AHSCT) recipients with graft-versus-host disease ( GVHD). Studies focusing on breakthrough invasive fungal disease ( IFD) upon PSC prophylaxis show disparate results. In order to evaluate the incidence of IFD in patients on PSC prophylaxis and identify IFD risk factors, we carried out a retrospective study of all consecutive patients on PP from January 2007 to December 2010 in our hospital. Breakthrough IFDs were identified from the database of the central pharmacy and the French administrative database ( PMSI), registering final medical diagnoses of hospitalized patients. Medical data were reviewed to study proven or probable IFD, according to EORTC/ MSG definition. PSC plasma concentrations ( PPC) were also retrieved. Poisson models were used for statistical analysis. Two hundred and seventy-nine patients received PSC prophylaxis for a median duration of 1.4 months (range 0.2-17.9). Proven ( n = 6) or probable ( n = 3) IFDs were diagnosed in nine cases (3.2%). IFD incidence rate per 100 person-month was 1.65 (95% CI, 0.79-2.97). IFDs were candidaemia ( Candida glabrata, n = 2), pulmonary invasive aspergillosis ( n = 3), disseminated fusariosis ( n = 2) and pulmonary mucormycosis ( n = 2). Seven deaths were reported, directly related to IFD in three patients (33.3%). First dosage of PPC under 0.3 mg/L was the single significant risk factor for IFD ( RR, 7.77; 95% CI, 1.30-46.5; p 0.025). Breakthrough IFD in patients receiving PSC prophylaxis is rare but associated with a poor outcome. Low PSC plasma concentrations are associated with an increased risk of IFD. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukaemia (APL) accounts for approximately 8% of all acute myeloid leukemias (AML) in adults. APL is characterized by a t(15;17) chromosomal translocation, a strong tendency for bleeding at diagnosis, and a sensitivity to those agents that induce a differentiation of leukaemia blasts such as all-trans retinoic acid (ATRA) or arsenic. Combined ATRA and chemotherapy have significantly improved patient outcome, with a rate of relapse that has been reduced to approximately 15%. Today, arsenic is being used successfully to treat relapsed patients; its high efficacy allows undertaking haematopoietic stem cell transplantation and achieving second full remission. Other new agents also exhibit high efficacy in APL, which makes this type of AML, considered fearsome for long, a subset for which there are a lot of therapeutic options and satisfactory therapeutic outcome. [ABSTRACT FROM AUTHOR]

In a multicenter trial, 259 young adults (15–49 years) with newly diagnosed acute myeloid leukemia (AML) were first randomized to receive a timed-sequential induction regimen given either alone (135 patients) or concomitantly with granulocyte–macrophage colony-stimulating factor (GM-CSF) (124 patients). Patients reaching complete remission (CR) were then randomized to compare a timed-sequential consolidation to a postremission chemotherapy including four cycles of high-dose cytarabine followed by maintenance courses. In the appropriate arm, GM-CSF was given concurrently with chemotherapy during all cycles of consolidation. CR rates were significantly better in the GM-CSF arm (88 vs 78%, P<0.04), but did not differ after salvage. Patients receiving GM-CSF had a higher 3-year event-free survival (EFS) estimate (42 vs 34%), but GM-CSF did not impact on overall survival. Patients with intermediate-risk cytogenetics benefited more from GM-CSF therapy (P=0.05) in terms of EFS than patients with other cytogenetics. This was also confirmed when considering only patients following the second randomization, or subgroups defined by a prognostic index based on cytogenetics and the number of courses required for achieving CR. Priming of leukemic cells with hematopoietic growth factors is a means of enhancing the efficacy of chemotherapy in younger adults with AML.Leukemia (2007) 21, 453–461. doi:10.1038/sj.leu.2404521; published online 25 January 2007 [ABSTRACT FROM AUTHOR]

A letter to the editor is presented discussing sustained major molecular response after dasatinib treatment and autologous peripheral blood stem cell transplantation in a patient with imatinib-resistant myeloblastic-phase chronic myeloid leukaemia.

Introduction – objectifs Une prophylaxie antifongique primaire par posaconazole (PZC) est recommandée chez les patients neutropéniques traités par chimiothérapie intensive pour une leucémie aiguë (LA) et chez les patients allogreffés de moelle présentant une réaction du greffon contre l’hôte (GVH). Cette étude monocentrique rétrospective avait pour objectif d’évaluer l’incidence des infections fongiques invasives (IFI) survenant sous PZC et d’étudier l’influence des concentrations plasmatiques en PZC (CPP) sur le risque d’IFI. Matériels et méthodes Les patients d’hématologie traités depuis au moins 7 jours par PZC en prophylaxie primaire étaient inclus. Les cas d’IFI survenant sous PZC étaient identifiés grâce au fichier de prescription d’antifongiques de la pharmacie et à la base de donnée de codage des pathologies. Le premier dosage plasmatique de PZC, réalisé à partir du 5 e jour de traitement, était noté. Les dossiers étaient revus pour ne retenir que les IFI certaines et probables, selon les critères de l’EORTC/MSG. Résultats Deux cent soixante-dix-neuf patients sous prophylaxie primaire par PZC étaient inclus (durée médiane de traitement 1,4 mois, extrêmes 0,2-17,9). Neuf patients (8 LA ou aplasie médullaire, 1 GVH) ont présenté une IFI certaine (n = 6) ou probable (n = 3), parmi lesquelles 2 candidémies à Candida glabrata , 3 aspergilloses invasives, 2 fusarioses disséminées et 2 mucormycoses pulmonaires. Toutes les espèces pour lesquelles un antifongigramme était disponible (n = 5) étaient résistantes au PZC. La densité d’incidence des IFI survenues sous PZC était évaluée à 1,64 cas pour 100 personnes-mois (95 %IC 0,798-2,97). Sept patients sont décédés, trois décès étant directement liés à l’IFI. Une CPP < 0,3 μg/ ml était associée de façon statistiquement significative à un risque d’IFI (risque relatif 7,77, 95 %IC 1,30-46,5, p = 0,025). Conclusion Les IFI survenant sous PZC sont rares mais potentiellement sévères. Une CCP basse augmente le risque d’IFI sous PZC, ce qui souligne l’intérêt d’un monitoring strict de cette prophylaxie. [ABSTRACT FROM AUTHOR]

Details for diagnostic work-up, patient treatments, CT and PET/CT procedures, outcome criteria and statistical methods are outlined in the Supplementary Material. Since PET/CT has been demonstrated to be more sensitive and specific than CT for response evaluation,[7] we chose to analyse CT and PET/CT at diagnosis but only PET/CT for interim evaluation. Prognostic value of PET/CT and CT in T-cell lymphoblastic lymphoma/leukaemia patients: A retrospective cohort study of 145 patients Keywords: CT; PET/CT; T-cell acute lymphoblastic leukaemia; T-cell lymphoblastic lymphoma EN CT PET/CT T-cell acute lymphoblastic leukaemia T-cell lymphoblastic lymphoma e21 e24 4 04/20/23 20230501 NES 230501 T-cell acute lymphoblastic leukaemia (T-ALL) and lymphoma (T-LL) are malignancies arising from thymic T-cell precursors with heterogeneous tumor dissemination among bone marrow, blood and other organs. [Extracted from the article]

The article discusses the use of the 2012 European cardiovascular diseases (CVD) risk assessment model aimed at identifying high risk of cardiovascular events during nilotinib therapy in chronic myeloid leukemia (CML). It outlines the impressive performance of the European CVD risk assessment system to identify nilotinib-treated CML patients. Prevention approaches in high/very high CVD risk patients are also offered.

Objectives A relapse from Escherichia coli bloodstream infection was observed in a patient with acute leukaemia treated with ceftazidime for 7 days for febrile neutropenia. Whereas the original E. coli isolate was resistant to β-lactam/β-lactamase inhibitor combinations (EC1), the relapse E. coli isolate showed a similar phenotype but with resistance extended to ceftazidime (EC2). We investigated the molecular mechanisms of β-lactam resistance and sought if EC2 could have been selected in vivo from EC1. Methods EC1 and EC2 isolates were compared for antibiotic MICs, plasmid content, genotyping, β-lactamase genes and their environment. Both isolates were conjugated with E. coli JW4111ΔampC and MICs determined for transconjugants. In addition, ceftazidime-resistant mutants were selected in vitro from EC1. Results EC1 and EC2 showed identical patterns for genotyping and resistance plasmids. PCR sequencing of blaTEM in EC1 showed the mutations M69L and N276D corresponding to TEM-35, also called inhibitor-resistant TEM (IRT)-4. In EC2, the TEM allele showed an additional mutation, R164S, known to confer resistance to ceftazidime. The combination of these three mutations was previously reported in TEM-158, described as the complex mutant TEM (CMT)-9, associated with resistance to β-lactamase inhibitors and third-generation cephalosporins. In vitro selection of ceftazidime-resistant mutants from EC1 yielded six different CMT alleles, including TEM-158 containing the R164S mutation. Conclusions This first known report of in vivo selection of CMT from IRT, reproduced in vitro, shows how the evolution of β-lactamase enzymes is easily driven by antibiotic pressure, even during a short antibiotic therapy. [ABSTRACT FROM PUBLISHER]

Clin Microbiol Infect 2010; 16: 1191–1196 A number of agents are now available for empirical antifungal treatment (EAFT) of patients with persistent fever and neutropenia. We carried out a study of efficacy of antifungal drugs to prevent breakthrough invasive aspergillosis by reviewing the medical records of all consecutive patients who received EAFT from November 2005 to February 2006. Patients’ characteristics and the type, dose and duration of antifungal therapy were recorded. Breakthrough invasive fungal infections were documented according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definition. Fifty-six episodes of persistent fever with neutropenia requiring EAFT were recorded among 49 patients. All patients received high-dose chemotherapy for acute myeloid leukaemia (51%), acute lymphoid leukaemia (12%), lymphoma (14%) or other haematologic conditions (22%). Fourteen (29%) and five (10%) patients were allogeneic and autologous haematopoietic stem cell transplant recipients, respectively. Caspofungin was prescribed initially in 40 episodes (71%), amphotericin B (AmB) desoxycholate and liposomal AmB being prescribed in six (10%) and ten (18%) episodes, respectively. Six patients were switched from liposomal AmB to caspofungin because of adverse events. The median duration of antifungal therapy was 9 days. During follow-up, six patients (12%) were diagnosed with invasive aspergillosis after a median of 8 days (range 3–16 days) of EAFT. Invasive aspergillosis breakthrough occurred in 6/46 (13%) caspofungin recipients and in 0/16 (0%) AmB recipients (OR 3.1, p 0.32). The observed high rate of invasive aspergillosis among caspofungin recipients requires further evaluation. [ABSTRACT FROM AUTHOR]

Dasatinib is an inhibitor of BCR-ABL and SRC-family kinases for patients with imatinib-resistant or -intolerant chronic myelogenous leukemia (CML). In this international phase II trial, dasatinib was administered orally (70 mg twice daily) to patients with myeloid blast phase (MBP, n=109) or lymphoid blast phase (LBP, n=48) CML. After a minimum follow-up of 12 months (range 0.03-20.7 months), major hematologic responses were induced in 34% (MBP-CML) and 35% (LBP-CML) of patients. Major cytogenetic responses were attained in 33% (MBP-CML) and 52% (LBP-CML) of patients and complete cytogenetic responses were attained in 26 and 46%, respectively. Median progression-free survival was 6.7 (MBP-CML) and 3.0 (LBP-CML) months. Median overall survival was 11.8 (MBP-CML) and 5.3 (LBP-CML) months. Overall, dasatinib had acceptable tolerability. Fluid retention events were more frequent in the MBP-CML than the LBP-CML cohort: pleural effusion occurred in 36 and 13% (all grades) and 15 and 6% (grades 3/4), respectively. Other non-hematologic side effects were primarily grade 1/2; grade 3/4 events were recorded in

Pivotal phase II studies in acute myeloblastic leukemia (AML) patients in first relapse have used gemtuzumab ozogamicin (GO) (Mylotarg) at a dose of 9 mg/m(2) on days 1 and 14. These studies showed a 26% response rate (13% complete remission (CR) and 13% CRp (complete remission with incomplete platelet recovery)) but with high degree of hematological and liver toxicities. Based on in vitro studies showing a re-expression of CD33 antigenic sites on the cell surface of blasts cells after exposure to GO, we hypothesized that fractionated doses of GO may be efficient and better tolerated. Fifty-seven patients with AML in first relapse received GO at a dose of 3 mg/m(2) on days 1, 4 and 7 for one course. Fifteen patients (26%) achieved CR and four (7%) CRp. Remission rate correlated strongly with P-glycoprotein and MRP1 activities. The median relapse-free survival was 11 months, similar for CR or CRp patients. Median duration of neutropenia < 500/microl and thrombocytopenia < 50,000/microl were, respectively, 23 and 21 days. No grade 3 or 4 liver toxicity was observed. No veno-occlusive disease occurred after GO or after hematopoietic stem cell transplantation given after GO in seven patients. Mylotarg administered in fractionated doses demonstrated an excellent efficacy/safety profile. [ABSTRACT FROM AUTHOR]

Imatinib combined with high-dose chemotherapy is now becoming the gold standard for treatment of Philadelphia chromosome-positive acute leukemias. However, in all studies imatinib dosage was tapered to 400–600 mg per day. We decided to initiate a clinical trial to evaluate an opposite strategy based on high-dose imatinib (800 mg per day) combined with a less intensive chemotherapeutic regimen (vincristine and dexamethasone), which we called the DIV induction regimen. Thirty-one patients (18 relapsing or refractory Ph+ acute lymphoblastic leukemias and 13 lymphoid blast crisis chronic myelogenous leukemias) were enrolled. Complete remission (CR) was obtained in 28 out of 30 assessable patients. The median bcr-abl/abl ratio after the induction course was 0.1%. Median time to neutrophil recovery was 21 days. Fungus infections were observed in six patients out of 31 and possibly related to dexamethasone. Neuropathy due to vincristine was noted in 14 cases. Nine out of 19 patients under 55 years received allogenic stem cell transplantation after a median time of 78 days post-CR. Patients older than 55 years experienced a 90% CR rate without additional toxicities, suggesting the DIV regimen may also be proposed as a front line therapy in older patients.Leukemia (2006) 20, 400–403. doi:10.1038/sj.leu.2404115; published online 26 January 2006 [ABSTRACT FROM AUTHOR]

Human blood dendritic cells (DC) comprise plasmacytoid DC (PDC) and myeloid DC (MDC), which both prime antitumor T-cell responses. We prospectively monitored blood DC in 30 chronic myeloid leukemia (CML) patients before and after imatinib mesylate therapy. We found a dramatic reduction in PDC and MDC prior treatment. This reduction was associated with high plasmatic vascular endothelial growth factor (VEGF), a central regulator of angiogenesis which also participates to tumor-associated immune deficiencies. Phenotypic analysis of DC revealed in some patients a deficient expression of BDCA-4/neuropilin-1 on PDC, a molecule involved in angiogenesis and DC-T-cell interactions. High VEGF correlated to an altered Th1/Th2 balance in vivo and shifted PDC-induced T-cell polarization towards Th2 in vitro. Upon imatinib treatment, plasmatic VEGF rapidly decreased and a normal BDCA-4 expression was restored. PDC and MDC increased but did not reach the levels observed in healthy individuals. We conclude that VEGF may be a key player in blood DC deficiency in CML and we show that imatinib inhibits VEGF overproduction. Incomplete recovery of blood DC under imatinib despite VEGF normalization suggests a negative impact of this drug on dendritopoiesis in vivo and may result in a sustained defect in DC-mediated anti-CML responses. [ABSTRACT FROM AUTHOR]

Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) mutations in Myeloid Neoplams (MNs) exhibit DNA hypermethylation via 2-hydroxyglutarate (2HG) over-production. Clinical impact of azacitidine (AZA) remains inconsistent in IDH1/2-mutated MNs and the potential of serum 2HG as a suitable marker of response to AZA is unknown. To address these questions, we retrospectively analyzed 93 MNs patients (78 AML, 11 MDS, 4 CMML) with IDH1/2 mutations treated with AZA. After a median of 5 cycles of AZA, overall response rate was 28% (including 15% complete remission) and median OS was 12.3 months (significantly shorter in AML compared to MDS/CMML patients). In multivariate analysis of AML patients, DNMT3A mutation was associated with shorter OS while IDH1/2 mutation subtypes had no independent impact. No difference was observed in serum 2HG levels upon AZA treatment between responding and refractory patients suggesting that serum 2HG cannot be used as a surrogate marker of AZA response. [ABSTRACT FROM AUTHOR]

Les maladies auto-immunes et inflammatoires (MAI) sont associées à un sur-risque de survenue de néoplasies myéloprolifératives (NMP) [1]. Chez les patients présentant un syndrome myélodysplasique (SMD) ou une leucémie myélomonocytaire chronique (LMMC), les mutations des régulateurs épigénétiques TET2 et IDH1/2 étaient significativement plus fréquentes chez les patients porteurs de MAI comparativement à une cohorte témoin de patients SMD/LMMC sans MAI [2]. Dans le contexte des NMP, le phénotype des MAI associées et leur statut mutationnel ont été peu décrits. Les objectifs de notre étude étaient de décrire les caractéristiques cliniques et génétiques des patients présentant une NMP avec une MAI et d'évaluer leur impact pronostique. Dans notre centre, 1541 patients ont été diagnostiqués d'une NMP selon les critères OMS, entre janvier 2011 et janvier 2021. Des analyses moléculaires par séquençage haut débit (NGS) ciblant un panel de 36 gènes mutés dans les NMP ont été réalisées pour 998 d'entre eux, au diagnostic ou durant le suivi. Tous les cas de MAI ont été revus par un interniste et les diagnostics évalués selon les critères internationaux correspondants. Les diagnostics de MAI post-interféron ont été exclues. Notre cohorte comprenait 522 (34 %) polyglobulie de Vaquez (PV), 709 (46 %) thrombocytémie essentielle (TE) et 229 (15 %) myélofibrose primitive (MFP). Cent (6.6 %) patients présentaient une MAI associée et les 1441 patients restants ont constitué notre population témoin. L'âge médian de nos patients dans la cohorte globale était de 54 ans [IQR 40.4–63.2] et il y avait une prédominance de femmes dans le groupe avec MAI associée (66 (66 %) versus 769 (53 %), p = 0.019). Il n'y avait pas de différence significative entre les 2 groupes concernant les sous-types de NMP, les mutations « driver » (JAK2, MPL et CALR) ou encore l'hémogramme au diagnostic des NMP. L'incidence d'épisodes thrombotiques ou hémorragiques était aussi similaire dans les 2 groupes (44 (44 %) versus 564 (39 %), p = 0.356). Le diagnostic de MAI était antérieur à celui de NMP dans 34 % des cas, concomitant dans 12 % et ultérieur dans 31 %. Sur les 100 MAI, 45 était des maladies auto-immunes spécifiques d'organe, principalement des thyroïdites auto-immunes, 13 rhumatismes inflammatoires chroniques, 9 connectivites, 8 dermatoses inflammatoires, 7 vascularites et 18 inclassés. Au total, 70 % des maladies auto-immunes remplissaient leurs critères de classification. Parmi les patients ayant bénéficié d'une analyse moléculaire, 62 % avaient une mutation additionnelle à la mutation « driver ». Les mutations de TET2 étaient plus fréquemment retrouvées chez les patients avec une MAI associée (24 (34 %) versus 205 (22 %), OR = 1.84 95 %CI [1.08–3.07], p = 0.028), mais elle n'était pas associée à un sous-type de MAI particulier. Il existait une tendance à une surreprésentation des mutations IDH1/2 dans le groupe MAI (4 (6 %) versus 27 (3 %), OR = 2.02 95 %CI[0.74–5.51], p = 0.27), bien que non statistiquement significatif. Nous n'avons pas retrouvé d'autres mutations de facteurs épigénétiques, de transcription, d'épissage ou de mutation à haut risque moléculaire, associées préférentiellement au groupe NMP avec MAI associée. Après un suivi médian de 8.3 ans dans la cohorte globale, la présence d'une MAI n'avait pas d'impact défavorable sur la survie globale (p = 0.82), ni sur la survenue de myélofibrose secondaire (p = 0.98), ou la survenue de transformation en SMD/LAM (p = 0.53). Au sein de cette large cohorte rétrospective de NMP décrite sur le plan clinique et moléculaire, la prévalence de MAI est de 6.6 %, similaire à celle de la population générale. Une sur-prévalence de la mutation de TET2 a été mise en évidence dans le groupe de patients présentant une MAI associée. Nos résultats suggèrent une susceptibilité génétique commune, secondaire à la mutation de régulateur épigénétique comme TET2, potentiellement responsable des phénotypes inflammatoire et hématologique. [ABSTRACT FROM AUTHOR]

Summary Background The impact of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) bacteraemia on outcome remains controversial. Methods A retrospective analysis of the prevalence, risk factors, clinical features, and outcomes of all ESBL-EC bacteraemia in one French hospital over a 5-year period was performed. A case–control study was undertaken: cases had at least one ESBL-EC bacteraemia and controls a positive non-ESBL-EC bacteraemia. Results The prevalence of ESBL-EC bacteraemia increased from 5.2% of all positive E. coli blood cultures in 2005 to 13.5% in 2009 ( p < 0.003). CTX-M represented 70% of ESBL-EC bacteraemia strains, and strains were not clonally related. On adjusted analysis, the only significant risk factor for ESBL-EC bacteraemia was a previous ESBL-EC colonization (odds ratio 11.3, 95% confidence interval 1.2–107; p = 0.003). Initial antimicrobial therapy was less frequently adequate in the ESBL-EC group (48% vs. 85%; p = 0.003). The presence of ESBL-EC bacteraemia was not associated with a longer hospital stay ( p = 0.088). Day 30 mortality was high, but not significantly different in the two groups (30% vs. 27%; p = 0. 82). Conclusion The prevalence of ESBL-EC bacteraemia has been increasing dramatically. Previous colonization with ESBL-EC was a strong risk factor for ESBL-EC bacteraemia. More inadequate initial antimicrobial therapy was noted in the ESBL-EC group, but mortality and length of hospital stay were not significantly different from those of patients with non-ESBL-EC bacteraemia. [ABSTRACT FROM AUTHOR]

The article discusses a study of 24 myelodysplastic syndrome (MDS) patients with non-blastic skin infiltrate which were compared with 20 leukemia cutis patients. It notes that leukemia cutis has poor prognosis in MDS patients with a rapid development of acute myeloid leukemia and death. One result highlights the fact that skin lesions in myelodysplasia cutis can precede by months or years MDS diagnosis in the bone marrow underlining the value of a long follow-up especially in elderly patients.

Allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only a curative treatment in patients with higher risk myelodysplastic syndrome (MDS), although demethylating agents (DMA) have been reported to improve survival. The advantage of HSCT over other treatment comes from retrospective studies and the aim of the current study was to prospectively test this hypothesis, analyzing in particular patients from the pre-transplant period to avoid the selection bias of performing transplantation. This study was conducted to compare overall survival in MDS patients candidates to transplantation according to donor availability. The majority of patients (76%) received a treatment with DMA after registration, 69% had a human leukocyte antigen (HLA)-identical donor, 70% of whom were transplanted. Baseline patient and disease characteristics were similar according to donor availability. Four-year overall survival was significantly better in patients with an HLA matched donor (37%) compared to patients without donor (15%). There was also evidence that this overall survival advantage was because of transplantation. Mortality risk was decreased after transplantation but it became significant only after the second year post transplant, because of early transplant-related mortality. Our results appear to justify, in higher risk MDS, a transplantation approach in all potential candidates who have an HLA identical donor. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation provides the best chance of long-term survival for patients with AML, but is associated with an unpredictable risk of treatment-related mortality. From January 2000 to December 2010, we compared the outcomes for patients with AML aged 35 and over using reduced-intensity conditioning (RIC, N=60) or conventional myeloablative conditioning (MAC) regimen (N=72) transplantation. The median follow-up was 47 months (10-134). The 4-year cumulative incidence of non-relapse mortality was 21%. After adjusting for cytogenetic risk, gender donor/recipient mismatch and CD34+ cells, non-relapse mortality was significantly lower with the RIC regimen (P=0.027). The 4-year cumulative incidence of relapse was 38% and no difference was observed in the adjusted relapse rate between the two groups. The 4-year OS rate was 46%. Using both Cox regression and inverse probability-of-treatment weighted (IPTW) method, a similar OS rate was found with both regimens (adjusted hazard ratios for conventional vs reduced of 1.14 (95% CI 0.67-1.93, P=0.64) with Cox regression, and 1.14 (95% CI 0.55-2.34, P=0.73) with IPTW). Until prospective trials are completed, this study supports the use of a reduced-intensity regimen prior to transplantation for patients with AML aged 35 and over. [ABSTRACT FROM AUTHOR]

The impact of allelic HLA matching in patients with AML and myelodysplastic syndrome (MDS) who receive allogeneic PBSC after a reduced-intensity conditioning (RIC) regimen is unclear. From January 2000 to December 2010, 108 consecutive patients with AML (n=63) and MDS (n=45) received PBSC after RIC in our center, either from siblings (n=70) or from matched unrelated donors (MUD; 10/10 high resolution, n=38). Conditioning regimen was fludarabine based in 95% of patients and GvHD prophylaxis was mostly cyclosporine plus mycophenolate. Patient characteristics were similar between sibling and MUD for age (median 57 years), gender and disease distribution. Conditioning regimen (more anti-thymocyte globulin (ATG) in MUD), donor age (younger for MUD) and number of CD34+ cells infused (higher in MUD) were different. The median follow-up was 36 months (range 2-72). Engraftment, GvHD, TRM, relapse rate and OS at 3 years were comparable between sibling and MUD. After adjustment for age, cytogenetic risk, ATG and number of CD34+ cells infused, donor type still did not influence OS. In patients with AML or MDS, HSCT from MUD using PBSC after a RIC regimen led to similar outcomes than from Siblings. [ABSTRACT FROM AUTHOR]

A large proportion of lower-risk myelodysplastic syndromes (MDS) respond to erythropoiesis-stimulating agents (ESA), but most responses are transient. We updated a previously reported cohort of lower-risk MDS patients treated with ESA and analyzed outcomes after ESA failure. In 120 patients with primary resistance and 66 patients with relapse after an initial response to ESA, the 5-year cumulative incidence of acute myeloid leukemia (AML) after failure was 18.9% and 11.6%, respectively (P=0.20). Median overall survival (OS) after failure was 40.1 and 44.9 months (P=0.35), respectively. We further categorized patients as 'early failures' (including resistance and relapse after <6 months of response), or 'later failures' (that is, relapse after 6 months). The 5-year cumulative incidence of AML and median OS after failure in early and later failure were 21.6% and 9% (P=0.02) and 36.7 and 54.3 months (P=0.02), respectively. Early failure to ESA and a baseline diagnosis of refractory anemia with excess blasts (RAEB)-1 were independent prognostic factors for AML progression and, along with trisomy 8, for shorter OS. Median OS from treatment onset was 40, 90.7 and 65.8 months in early failure, later failure and no relapse, respectively (P=0.001). Lower-risk MDS with early failure to ESA have a relatively unfavorable outcome, and should be offered alternative treatments. [ABSTRACT FROM AUTHOR]

In this study, the authors sought to determine the efficacy of antifungal agents for preventing breakthrough invasive aspergillosis (IA) in a cohort of patients with persistent fever and neutropenia who received empirical antifungal therapy. Caspofungin was the most prescribed antifungal agent, followed by liposomal amphotericin B. Six of 49 patients developed possible or probable IA, all of whom were on caspofungin. These results suggest a high rate of breakthrough IA in patients receiving caspofungin. [ABSTRACT FROM AUTHOR]

Introduction et objectifs: Les candidoses hépatospléniques (CHS) sont des infections rares mais graves dont la durée de traitement et les critères de guérison sont mal définis. Matériels et méthodes: Nous décrivons des CHS diagnostiquées entre 2000 et 2007, définies par la mise en évidence de nodules hépatospléniques chez des patients (pts) à risque avec ou sans confirmation mycologique. Nous avons recherché des facteurs pronostiques de guérison et de décès. Résultats: Vingt-quatre cas de CHS ont été analysés : 6 (25 %) prouvées, 3 (13 %) probables et 15 (62 %) possibles. Le sex ratio (H/F) était de 1,2 et l’âge médian de 46 ans. Tous les pts ont présenté un épisode de neutropénie fébrile après chimiothérapie intensive, 75 % des pts avaient une colonisation digestive àCandida et 92 % avaient reçu un traitement antifongique empirique lors de la neutropénie. Le traitement curatif était dans 75 % des cas un azolé pendant 7 mois en médiane, avec une corticothérapie pour 60 % des pts. Le suivi était de 1 an en médiane ; 11 pts (46 %) sont décédés, dont 5 en échec de traitement. Au total, 19 pts (79 %) étaient en réponse complète ou partielle au moment du dernier suivi. En univariée, la neutropénie > 25 jours (RR 0,33 CI 95 % 0,11-0,98, p =0,04) et la taille des abcès > 5mm (RR 0,43, CI 95 % 0,23-0,8, p =0,01) étaient corrélés négativement à la guérison. Les facteurs prédictifs de décès étaient : l’index ECOG≥2 (alitement > 50 % du temps de veille) (RR 6,97 CI 95 % 1,48-32,83, p =0,01), la rechute hématologique (RR 11,19, CI 95 % 2,75-45,49, p =0,001) et le traitement empirique de la neutropénie par Amphotéricine B conventionnelle (RR 3,53, CI 95 % 1,07-11,61, p =0,04). Conclusion: La réponse au traitement antifongique était élevée (79 %) dans cette étude. Les principaux facteurs prédictifs de décès étaient le mauvais état général ou la rechute hématologique. [Copyright &y& Elsevier]

To illustrate methodological issues, we compared donor vs no-donor to transplant vs no-transplant comparisons in a cohort of 107 patients aged 50 years with adverse karyotype AML in first CR. Adverse karyotypes were defined as −7, del(7q), −5, del(5q), t(9;22), 11q23, 3q26 or complex abnormalities. Mantel-Byar estimations and hematopoietic SCT (HSCT) as a time-dependent variable were used to compare transplant vs no-transplant cumulative incidence of relapse (CIR), relapse-free survival (RFS) and OS. In all, 52 patients had a sibling donor, but only 35 of them were transplanted in first CR, whereas 9 patients received HSCT from alternative stem cell sources. Donor-based analysis showed lower CIR in the donor group, not translating in prolonged RFS or OS. Conversely, transplant-based analysis showed that HSCT in the first CR improved the three CIR (multivariate hazard ratio (HR), 0.31; P<0.001), RFS (multivariate HR, 0.57; P=0.047) and OS (multivariate HR, 0.54; P=0.03) endpoints. At 5 years, OS was estimated at 33% in transplanted vs 18% in non-transplanted patients. The positive effect of HSCT was more pronounced in patients aged 35 years and/or in those transplanted in the more recent years. These results confirm that HSCT is likely the best curative option in younger patients with adverse karyotype AML. [ABSTRACT FROM AUTHOR]

Gut invasive aspergillosis is an extremely rare infection in immunocompromised patients. The goal of this retrospective multicentre study is to report on cases of gut aspergillosis in haematology patients, including clinical presentation, risk factors, and outcome. Twenty-one patients from nine centres were identified. Eight had isolated gut aspergillosis, with no evidence of other infected sites, and 13 had disseminated aspergillosis. Thirteen patients had acute leukaemia. Nine were allogeneic stem cell transplant recipients. Clinical symptoms and imaging were poorly specific. The galactomannan antigenaemia test result was positive in 16/25 (64%) patients, including in four of the eight cases of isolated gut aspergillosis. Five of 21 patients had a dietary regimen rich in spices, suggesting that, in these cases, food could have been the source of gut colonization, and then of a primary gut Aspergillus lesion. The diagnosis was made postmortem in six patients. The mortality rate in the remaining patients at 12 weeks was 7/15 (47%). Gut aspergillosis is probably misdiagnosed and underestimated in haematology patients, owing to the poor specificity of symptoms and imaging. Patients with a persistently positive galactomannan antigenaemia finding that is unexplained by respiratory lesions should be suspected of having gut aspergillosis in the presence of abdominal symptoms, and be quickly investigated. In the absence of severe abdominal complications leading to surgery and resection of the lesions, the optimal treatment is not yet defined. [ABSTRACT FROM AUTHOR]

Background Cutaneous involvement has been reported in 30–40% of children with the familial form of haemophagocytic syndrome. However, few studies have focused on cutaneous manifestations in patients with reactive haemophagocytic syndrome (RHS). Objectives To describe the frequency, clinical features and prognosis of skin involvement in adult patients with RHS. Methods We conducted a retrospective study in a French university-based tertiary centre. The medical records of all adult patients with a suspected or confirmed diagnosis of RHS during a 2-year period were reviewed. Demographic, clinical, biological and histological data of patients were compared using nonparametric tests. Results The medical charts of 151 patients were reviewed, 69 of whom had a definite diagnosis of RHS (35% women; mean ± SD age 49 ± 17 years). The aetiology of RHS was mainly B-cell or T-cell lymphoma ( n = 33) or herpesvirus infection ( n = 19). Cutaneous manifestations were observed in 32 (46%) patients and were of three types: (i) specific to the underlying malignancy (Kaposi sarcoma n = 8, cutaneous lymphoma n = 4), (ii) reflecting the biological consequences of RHS (thrombopenic purpura n = 10, conjunctival jaundice n = 7), and (iii) a generalized, transient, nonpruriginous maculopapular rash ( n = 18). None presented with erythroderma, or with eczematiform, ichthyosiform, psoriasiform or bullous lesions. One patient had cytophagic histiocytic panniculitis. Histological features of maculopapular rash biopsies were usually nonspecific. The rate of in-hospital death was not significantly associated with cutaneous involvement. Conclusions A generalized, nonpruriginous, transient, maculopapular rash is frequently observed in patients with RHS. Although nonspecific, awareness of this cutaneous involvement may assist physicians in the initial diagnosis of RHS. [ABSTRACT FROM AUTHOR]

A letter to the editor in response to the article "PML-RARα ligand-binding domain deletion mutations associated with reduced disease control and outcome after first relapse of APLWilms tumor 1 (WT1) gene mutations in pediatric T-cell malignancies," published in a previous issue is presented.

Cryopreservation and thawing of haematopoietic stem cells are associated with cell loss and infusion-related toxicities. We analysed viability, total nucleated cell (TNC) and CD34+ cell recovery, and infusion-related toxicities of 952 thawed and washed products. Mean TNC and CD34+ viable cells recoveries were 55.9±18.6 and 98.0±36.5%, respectively. Mean cell viability was 68.25±18.9%. TNC recovery was correlated with viability but independent of the initial nucleated cell concentration. No difference in TNC recovery or viability was observed according to underlying diseases, except for myeloma, for which these variables were significantly lower (P<0.05). CD34+ cell recovery was not correlated with viability or CD34+ initial count and was similar for all diseases. Cryostorage duration was not associated with cell loss. Immediate adverse events occurred in 169 patients (19%) and were moderate (grade I or II) for the majority of patients. Clinical toxicity was associated with a higher infused cell number and the presence of clumps in infused bags. The washing procedure of cell products lead to a low rate of adverse events, but patients transplanted with high cell numbers or bags in which clumps were identified are predisposed to such complications.Bone Marrow Transplantation (2007) 40, 831–835; doi:10.1038/sj.bmt.1705830; published online 27 August 2007 [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) in the elderly is characterized by its ominous prognosis. On the other hand, imatinib has demonstrated remarkable, although transient, activity in relapsed and refractory Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), which prompted us to assess the use of imatinib in previously untreated elderly patients. ALL patients aged 55 years or older were given steroids during 1 week. Ph+ve cases were then offered a chemotherapy-based induction followed by a consolidation phase with imatinib and steroids during 2 months. Patients in complete response (CR) after consolidation were given 10 maintenance blocks of alternating chemotherapy, including two additional 2-month blocks of imatinib. Thirty patients were included in this study and are compared with 21 historical controls. Out of 29 assessable patients, 21 (72%, confidence interval (CI): 53–87%) were in CR after induction chemotherapy vs 6/21 (29%, CI: 11–52%) in controls (P=0.003). Five additional CRs were obtained after salvage with imatinib and four after salvage with additional chemotherapy in the control group. Overall survival (OS) is 66% at 1 year vs 43% in the control group (P=0.005). The 1-year relapse-free survival is 58 vs 11% (P=0.0003). The use of imatinib in elderly patients with Ph+ ALL is very likely to improve outcome, including OS.Leukemia (2006) 20, 1526–1532. doi:10.1038/sj.leu.2404320; published online 13 July 2006 [ABSTRACT FROM AUTHOR]

To determine the maximum-tolerated dose (MTD), dose-limiting toxicities and pharmacokinetic of semisynthetic homoharringtonine (ssHHT), given as a twice daily subcutaneous (s.c.) injections for 9 days, in patients with advanced acute leukaemia, 18 patients with advanced acute myeloid leukaemia were included in this sequential Bayesian phase I dose-finding trial. A starting dose of 0.5 mg m−2 day−1 was explored with subsequent dose escalations of 1, 3, 5 and 6 mg m−2 day−1. Myelosuppression was constant. The MTD was estimated as the dose level of 5 mg m−2 day−1 for 9 consecutive days by s.c. route. Dose-limiting toxicities were hyperglycaemia with hyperosmolar coma at 3 mg m−2, and (i) one anasarque and haematemesis, (ii) one life-threatening pulmonary aspergillosis, (iii) one skin rash and (iv) one scalp pain at dose level of 5 mg m−2 day−1. The mean half-life of ssHHT was 11.01±3.4 h, the volume of distribution at steady state was 2±1.4 l kg−1 and the plasma clearance was 11.6±10.4 l h−1. Eleven of the 12 patients with circulating leukaemic cells had blood blast clearance, two achieved complete remission and one with blast crisis of CMML returned in chronic phase. The recommended daily dose of ssHHT on the 9-day schedule is 5 mg m−2 day−1.British Journal of Cancer (2006) 95, 253–259. doi:10.1038/sj.bjc.6603265 www.bjcancer.com Published online 18 July 2006 [ABSTRACT FROM AUTHOR]

In core binding factors (CBF) acute myeloid leukemia (AML), the disruption of CBFα/β genes impairs normal hematopoietic differentiation and is supposed to cooperate with additional mutations promoting proliferation. The incidence and the prognosis of receptor tyrosine kinase (RTK) c-Kit and FLT3 mutations and Ras mutations were evaluated in 103 pediatric and adult patients with CBF-AML. c-Kit mutations were present in 17% patients. c-Kit exon 8 mutations were more frequent in inv(16) than in t(8;21) subset (20 versus 6%). Only one patient had FLT3-ITD but FLT3-D835 was as frequent as reported in AML population (7%). Ras mutations were significantly more frequent in inv(16) than in t(8;21) subset (36 versus 8%, P=0.001). RTK mutations were associated with a higher white blood cell count (WBC) (36 versus 21 G/L, P=0.05). FLT3 mutations were significantly associated with a shorter EFS and survival (P<0.0001 and P=0.0002) owing to an excess of early events. c-Kit mutations were associated with a shorter EFS and RFS (P=0.002 and P=0.003) in t(8;21) but not inv(16) patients. As previously observed, Ras mutations did not affect prognosis. Screening for RTK mutations may help to identify patients with a more adverse outcome and thus susceptible to benefit from intensified protocols or RTK inhibitors.Leukemia (2006) 20, 965–970. doi:10.1038/sj.leu.2404188; published online 6 April 2006 [ABSTRACT FROM AUTHOR]

Objective: Patients with newly diagnosed cancer responsible for organ failures may require intensive care unit (ICU) admission and immediate chemotherapy. Outcomes in this population have not been studied.Design: Prospective observational cohort study.Setting: Teaching hospital.Subjects: All patients admitted to the ICU, from January 1997 to June 2003, for organ failures due to newly diagnosed, untreated cancer and deemed necessary to receive immediate cancer chemotherapy.Interventions: None.Measurements and Main Results: For the period of 6.5 yrs, 100 patients met the study criteria: 43 had acute leukemia, 37 lymphoma, and 12 solid tumors. Median Simplified Acute Physiology Score II was 39 (30-48) points, and median Logistic Organ Dysfunction score was 5 (3-7) points. Three variables were independently associated with 30-day mortality: need for vasopressor therapy (odds ratio, 6.01; 95% confidence interval, 1.86-19.4), mechanical ventilation (odds ratio, 6.36; 95% confidence interval, 1.76-22.94); and hepatic failure (odds ratio, 7.76; 95% confidence interval, 1.25-48.27). Overall survival was 60% after 30 days and 49% after 180 days.Conclusions: Mortality was chiefly dependent on the nature and number of organ failures, not on the nature or stage of the malignancy. The 30-day and 180-day survival rates indicate that, in this selected group of patients, advanced disease at cancer diagnosis should not lead to refusal of ICU admission. Moreover, administration of chemotherapy in the intensive care unit is feasible, and although the mortality rate is high, routine ICU admission of patients with newly diagnosed cancer, specific organ failure, and the need for administration of chemotherapy in the ICU deserves evaluation. [ABSTRACT FROM AUTHOR]

Post-remission options were compared in a population of 262 relapsing and refractory acute myeloid leukemia patients achieving complete remission (CR) after the same re-induction according to etoposide?–?mitoxantrone?–?cytarabine (EMA) trials. The selection of post-remission therapy depended on trial recommendations, age, performance status, and availability of an HLA-identical sibling. One hundred and thirty patients received chemotherapy consolidation courses, 50 received autologous stem cell transplantation (SCT), and 43 underwent allogeneic bone marrow transplantation (BMT), while 39 did not receive any additional therapy. The preliminary analysis identified 3 favorable prognostic factors correlated with event-free survival (EFS): M3 subtype, previous CR duration >?1 year, and transplantation. Three year EFS was 68 vs. 23% with autologous SCT and allogeneic BMT in M3 patients and, respectively, 41 vs. 20% in non-M3 patients. Three year probabilities of treatment-related mortality were 11 and 47%, respectively. A statistical model was conceived with adjustment on prognostic factors and post-remission option. In the multivariate analysis, autologous SCT appeared significantly better than allogeneic BMT ( P <0.01) or chemotherapy ( P ?=?0.001), while allogeneic BMT was not statistically different than chemotherapy. This indicates a high treatment-related toxicity with allogeneic BMT in patients re-induced by highly intensive chemotherapy, and therefore a tendency for a better outcome with autologous SCT as post-remission treatment in those patients. [ABSTRACT FROM AUTHOR]

Internal tandem duplications (ITDs) of the FLT3 gene have been observed in about 35% of APL cases. If FLT3-ITD is associated with a worse outcome in patients with acute myeloid leukemia (AML) in general, its prognostic value in acute promyelocytic leukemia (APL) is still a matter of debate. We investigated incidence, associated clinical features, and prognostic implication of FLT3-ITD, but also FLT3-D835 point mutation and N-Ras or K-Ras mutations in 119 APL patients, all prospectively enrolled in the two consecutive APL-93 and APL-2000 trials. Mutation incidences were 38, 20, and 4%, for FLT3-ITD, FLT3-D835, and Ras, respectively. The presence of FLT3-ITD was associated with high white blood cell count, high Sanz index, M3-variant subtype, and V/S PML-RARα isoforms. Complete remission (CR), induction death, and death in CR rates were not affected by FLT3 or Ras mutations, as well as cumulative incidence of relapse. However, a trend for a shorter overall survival (P=0.09) was observed in FLT3-ITD patients, because of a very poor postrelapse survival (P=0.02). This feature, which has been also reported in patients with AML in general, is suggestive of an underlying genetic instability in FLT3-ITD patients, leading to the acquisition of additional unknown bad-prognosis gene mutations at relapse.Leukemia (2005) 19, 1153–1160. doi:10.1038/sj.leu.2403790 Published online 12 May 2005 [ABSTRACT FROM AUTHOR]

Since 1987, the GELA has initiated multicenter prospective trials for aggressive non-Hodgkin's lymphomas (NHL). Lymphoblastic lymphomas (LBL) were included in those studies until 1997, and 92 LBL patients under 61 years were identified after histological review. The protocols prescribed high-dose anthracycline regimens, four cycles given every 15 days as induction and lasted for ?6 months. A total of 23 patients underwent high-dose therapy consolidation followed by autologous stem-cell transplantation and 69 received standard chemotherapy regimens. Clinical characteristics showed a male predominance (66%) with a median age of 31 years, bone marrow (BM) involvement (22%), mediastinal involvement (66%) and elevated LDH (62%). At the end of treatment, it was seen that 71% of the patients achieved complete remission; four (4%) patients died during induction; 43 patients relapsed at a median time of 10 months. With a median follow-up of 34 months, the 5-year overall survival (OS) and event-free survival (EFS) rates were 32 and 22%, respectively. The only favorable factor significantly associated with survival was young age. These results are poorer than those obtained in other aggressive lymphomas treated with the same regimens and suggest that adult LBL patients should be treated with acute lymphoblastic leukemia protocols.Leukemia (2003) 17, 2220-2224. doi:10.1038/sj.leu.2403095 [ABSTRACT FROM AUTHOR]

FLT3 internal tandem duplications (FLT3-ITDs) are present in nearly 25% of patients with AML and have been associated with poor response to conventional therapy and poor outcome. We retrospectively evaluated the effect of reinforced courses of chemotherapy on the prognostic value of FLT3-ITDs in 159 AML patients prospectively enrolled in the ALFA-9000 trial, which randomly compared three reinforced induction regimens (standard 3+7 including high-dose daunorubicin, double induction, and timed-sequential therapy). FLT3-ITD was present in 40/159 (25%) blast samples and associated with high WBC (P = 0.002) and cytogenetics (P < 0.001) with a higher incidence (35%) in patients with a normal karyotype. There was no difference in CR rate between FLT3-wt and FLT3-1TD patients (80% vs 78%). Relapse-free survival (RFS)was similar in both groups (5-year RFS, 33% vs 32%; P = 0.41), even after adjustment for age, sex, WBC, cytogenetics, and treatment arm. A trend to a worse survival was observed in the FLT3-1TD group (estimated 5-year OS, 23% vs 37%; P = 0.09), mainly in patients with a normal karyotype. This was associated with a dramatic outcome in relapsing FLT3-ITD patients (estimated 3-year postrelapse survival, 0% vs 27%; P = 0.04). These results suggest that the bad prognosis associated with FLT3-1TDs in AML might be partly overcome using reinforced chemotherapy. Early detection of FLT3 mutations might thus be useful to intensify induction as well as post-remission therapy in FLT3-ITD patients. [ABSTRACT FROM AUTHOR]

The article analyzes the incidence and causes of early death (ED) in acute promyelocytic leukemia (APL) in French centers from December 2006 to December 2011. APL diagnosis is confirmed by the presence of t(15;17) translocation and/or promyelocytic leukemia gene-retinoic acid recepter alpha gene rearrangement. ED is caused by differentiation syndrome, myocardial infarction and multiple organ failure. The rapid admission of patients follows as all-trans retinoic acid is rapidly started.

Clin Microbiol Infect 2012; 18: E185-E187 Abstract We report a retrospective study of 24 patients with haematological malignancy and hepatosplenic candidiasis. Clinical and biological features were similar to previous reports. No patient previously received antifungal prophylaxis. Liver or spleen histological examination revealed yeasts in 6/24 patients (25%) on direct examination but all cultures were negative. After a median duration of 7 months, antifungal treatment was discontinued in 58% of the patients with no relapse. Eleven (46%) patients died during follow up. After multivariate analysis, independent factors associated with death were the duration of neutropenia (p 0.022) and relapsing haematological malignancy (p 0.015). [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses a study on the prognosis of late relapses in acute promyelocytic leukemia treated with all-trans-retinoic-acid and anthracycline-based chemotherapy.

This article presents a letter to the editor about three additional cases of chronic myeloid leukemia patients with an e802 BCR-ABL fusion transcripts treated with imatinib.

Introduction Avec 9 services d’hématologie/oncologie et une unité de brûlés, notre hôpital a eu une augmentation des diagnostics de mucormycose invasive, c’est pourquoi une étude épidémiologique de 2006 à 2016 a été entreprise avec comme objectif d’analyser les facteurs prédisposants (FDR), de faire une épidémiologie descriptive des cas et de leur évolution. Matériels et méthodes Analyse rétrospective des FDR, aspects cliniques, radiologiques, microbiologiques et de la survie de tous les patients avec un diagnostic de mucormycose invasive. Tous les cas ont été validés par un comité mutidisciplinaire. Résultats Quarante-cinq cas de mucormycose invasive diagnostiqués (10 avant 2011, et 35 après) : 11 chez des brûlés sévères, 27 en hématologie (14 leucémies aiguës, 5 lymphomes, 4 myélodysplasies, 3 aplasie médullaire,1 autre) dont 14 allogreffés, 2 avec des cancers solides, 1 transplanté rénal, 4 avec un diabète seul. Le site de l’infection était pulmonaire (19 cas, 22 %), sinusien (16 cas, 36 %), cutané (14 cas, 31 %), hépatique (3 cas, 7 %), autre (12 cas, 26 %), disséminé (4 cas, 9 %). L’examen direct montrait des filaments de type mucorales dans 35/42 (83 %) cas, avec une culture positive chez 23/40 (58 %), une PCR quantitative DNA mucorales (qPCR) sérique dans 16/18 cas (89 %) et 9/13 biopsies effectuées (69 %). Une infection concommittante était présente dans 16 (36 %) cas. Une exposition préalable aux antifongiques était notée pour 27 (60 %) patients. Une chirurgie a été effectuée dans 26 (58 %) cas, 40 (89 %) ont reçu de l’ amphotericine B liposomale (amphB), 22 (49 %) du posaconazole, 7 de la caspofongine (16 %), 1 de l’isavuconazole (2 %), et 7 (16 %) ont eu un allégement du traitement immunosuppresseur. La mortalité à 3 mois était de 50 %. Concernant les FDR, avoir reçu préalablement au diagnostic de mucormycose du voriconazole (HR : 2,4 (1,2–4,6) p : 0,008) ou du fluconazole (HR : 2,5 (1,0–6,2), p : 0,02) étaient associés à un risque accru de mortalité mais pas les autres antifongiques. En traitements curatifs, avoir reçu de l’amphB (HR : 0,4 (0,1–0,97), p : 0,04) ou du posaconazole (HR : 0,3 (0,2–0,68), p : 0,002) étaient protecteur mais l’association d’une chirurgie ( p :0,2) ou de caspofongine ( p :0,9) étaient non significatives. Conclusion Notre étude permet d’avoir une analyse épidémiologique récente des mucormycoses invasives et des challenges restant. La mortalité reste élevée chez les patients d’hématologie et les brûlés. Depuis 2 ans, des outils moléculaires par qPCR ont permis de faire des diagnostics plus rapides, les patients sévèrement brûlés sont maintenant screenés par qPCR et nous espérons voir prochainement une baisse de la mortalité. [ABSTRACT FROM AUTHOR]