Search

ABSTRACTWe describe the acquisition of flucytosine, azole, and caspofungin resistance in sequential Candida glabratabloodstream isolates collected from a bone marrow transplant patient with clinical failure. Point mutations in C. glabrata FUR1(CgFUR1) and CgFKS2and overexpression of CgCDR1and CgCDR2were observed in resistant isolates.

Twenty children with proven (n 12) or probable (n 8) invasive fungal infections received caspofungin treatment either as first-line (n 7) or as salvage (n 13) therapy and as monotherapy (n 5) or in combination (n 15). Eleven had aspergillosis, 7 had candidiasis, and 2 had Rhodotorulainfections.

ABSTRACTAspergillus ustusis an uncommon clinical species which is poorly susceptible to antifungals. We report two cases of A. ustusinfections that occurred in allogeneic stem cell transplant recipients while they were receiving either voriconazole or caspofungin. Prolonged use of these new antifungal agents may increase the risk of the emergence of resistant organisms.

Toxoplasmosis is a rare but severe complication of bone marrow transplantation. Here, we report three patients in whom toxoplasmic pneumonitis developed, leading to fatal acute respiratory distress syndrome (ARDS).

Invasive fungal infections (IFIs) remain a major clinical burden due to their morbidity and mortality, particularly in patients with acute leukemias and allogeneic HSCT which represent the main risk factors for proven/probable IFI in hematology. We conducted a study in France which enrolled 677 patients with acute myeloid leukemia (AML) receiving intensive chemotherapy from 34 ALFA centers. This study confirmed the significant lower rate of proven/probable IFI in patients who received antifungal prophylaxis (AFP), and that IFI was associated with an increased early mortality rate.

A significant challenge of functional genomics is to develop methods for genome-scale acquisition and analysis of cell biological data. Here, we present an integrated method that combines genome-wide genetic perturbation of Saccharomyces cerevisiaewith high-content screening to facilitate the genetic description of sub-cellular structures and compartment morphology. As proof of principle, we used a Rad52-GFP marker to examine DNA damage foci in ∼20 million single cells from ∼5,000 different mutant backgrounds in the context of selected genetic or chemical perturbations. Phenotypes were classified using a machine learning-based automated image analysis pipeline. 345 mutants were identified that had elevated numbers of DNA damage foci, almost half of which were identified only in sensitized backgrounds. Subsequent analysis of Vid22, a protein implicated in the DNA damage response, revealed that it acts together with the Sgs1 helicase at sites of DNA damage and preferentially binds G-quadruplex regions of the genome. This approach is extensible to numerous other cell biological markers and experimental systems.

L’utilisation du dossier pharmaceutique (DP), créé et déployé en officine depuis 2007, est en expérimentation nationale pilotée par le Conseil national de l’Ordre des pharmaciens et la direction générale de l’Offre de soins depuis 2013 dans des services d’anesthésie, de gériatrie et des urgences des hôpitaux volontaires. Le service des urgences de notre établissement participe à cette expérimentation. Après une phase de travail d’amélioration d’accessibilité au logiciel de consultation du DP, puis du positionnement du DP parmi les sources documentaires médicamenteuses pour des patients admis dans l’unité d’hospitalisation des urgences, une étude a été réalisée à l’accueil des urgences.

La prescription de scanners thoraciques à la phase précoce d’une allogreffe de cellules souches hématopoïétiques (CSH) est en augmentation alors que son apport est mal évalué.

L’aspergillose pulmonaire invasive (API) est une complication mortelle survenant chez les patients atteints d’hémopathie maligne. Depuis 2007, une prophylaxie par PZA est recommandée chez les patients à risque. Seuls quelques cas d’API survenant sous PZA (APIP) ont été rapportés. L’objectif de cette étude était de décrire l’incidence des APIP, leur présentation et leur devenir.

When an HLA-matched donor is not available for allogeneic Hematopoietic Stem Cell Transplantation (HSCT), the use of an alternative HLA-mismatched stem cell source may be considered. In Europe, HLA compatibility for HSCT is calculated for 10 alleles (HLA-A, -B, -C, -DRB1, -DQB1). The aim of this study was to retrospectively compare outcomes after transplantation from 10/10 HLA-MUD, 9/10 HLA-MMUD and UCB performed at the Hospital Saint Louis (Paris, Fr).Patients receiving a first allogeneic transplantation from a 10/10, 9/10 UD or UCB from 2000 to 2011 were included.High resolution HLA typing was performed by PCR SSO and SSP for HLA loci: A, B, C, DRB1 and DQB1. The following variables were studied as risk factors for transplant outcomes: disease, disease risk (standard/high risk), age at transplant, gender, donor/recipient sex-matching, ABO matching, donor/recipient CMV status, conditioning regimen, and use of anti-thymoglobulin (ATG).355 consecutive patients with hematologic malignancies were analyzed. One hundred and ninety-six were transplanted with MUD, 84 with MMUD (mismatches for HLA-A: 16%, -B: 16%, -C: 39%, -DRB1: 8%, -DQB1: 21%) and 75 with UCB (52% with single and 48% with two UCB unit; 87% of all UCB transplants were 4–6/6 HLA-matched). Median patient age was 31 (range: 5–55). Patient characteristics differed between the 3 groups: (i) median age at transplant: 36 in MUD, 31 in MMUD, 22 in UCB (p<0.0001), (ii) high risk disease: 37%, 51%, 68% (p<0.0001), (iii) CMV negative donor/positive recipient: 31%, 36%, 60% (p<0.0001), (iv) use of ATG: 37%, 64%, 55% (p<0.0001).Cumulative incidences of grade II-IV and grade III-IV acute GvHD disease (aGvHD) were 61% (66% for MUD, 60% for MMUD and 48% for UCB) and 17% (17%, 24% and 15%), respectively. Three-year cumulative incidence of chronic GvHD (cGvHD) was 46% (51% for MUD, 49% for MMUD and 29% for UCB). Three-year NRM was 34% (28% for MUD, 31% for MMUD and 51% for UCB). Graft failure occurred in 15% of UCB patient, 8% in MMUD group and 3% in MUD group (significant difference between UCB and MUD: OR=5.44, 95%CI 1.93–15.3, p=0.001).Multivariate analysis is summarized in table 1. It showed that MMUD tented to have a higher incidence of aGvHD III-IV than MUD and UCB. UCB had a lower incidence of cGvHD than MMUD. No significant effect of HSCT source on NRM was demonstrated.Compared to MMUD, UCB-HSCT induces less cGvHD and non significantly increased NRM. Compared to MUD, MMUD and UCB-HSCT did not result in a clear increase of NRM. UCB and 9/10 HLA-MMUD are both suitable stem cell sources for patients who cannot benefit from 10/10 HLA-MUD transplant.No relevant conflicts of interest to declare.

Abstract 1948

Over the past 20 years, allogeneic hematopoietic cell transplantation (HCT) has been increasingly performed with peripheral blood stem cells (PB) and gained benefit from better HLA-typing. Similar long-term survival has been suggested after HLA-matched related and unrelated donor HCT. Till now, the optimal strategy for donor selection is still controversial. We evaluated the impact of donor type (10/10 HLA-matched unrelated (MUD) vs. matched related (MRD)) and other donor traits on long term outcomes of patients with hematologic malignancies after PB HCT.We analyzed outcomes of 442 consecutive patients with hematologic malignancies who were transplanted with PB either from MUD (n= 164) or MRD (n=278) at our center from 01/2000 to 12/2010. Median patient age was 48 years (range 7–68). Diseases included 122 acute myelogenous leukemias, 62 non-Hodgkin lymphomas, 60 myelodysplastic syndromes, 57 multiple myelomas, 40 acute lymphoblastic leukemias, 37 myeloproliferative disorders, 29 Hodgkin diseases, 20 chronic myeloid leukemias and 15 chronic lymphocytic leukemias. Two-third of patients underwent HCT following reduced intensity conditioning. Graft-versus-host disease (GVHD) prophylaxis consisted mostly in cyclosporine plus MMF or methotrexate. ATG was used in 19% of HCT. We assessed the impact of donor factors (type, age, gender, CMV serologic status and ABO group) on chronic GVHD (cGVHD), relapse, non relapse mortality (NRM) and overall survival (OS). Concerning donor age, as the upper age limit for voluntary PB donation was usually 60 years, we completed our analysis by performing 3 groups according to donor type and age (MUD, MRD<60y and MRD≥60y) and evaluated their influence on outcomes.Median donor age was 40 years (range 18–72). Most young donors were MUD (<30y: 70%) while older were mainly MRD (≥50y: 98%). Thirty-six patients were transplanted with MRD≥60y. The proportion of female donors was 42% and 113 HCT were performed from female donor to male recipient. Half of patients were transplanted from CMV seronegative donors. Donor/recipient pairs (D/R) were CMV status mismatched in 38% of cases. D/R were ABO matched, minor and major mismatched in 57%, 19% and 24% of cases. Considering donor type, MUD and MRD HCT were balanced for patient age, disease risk and conditioning. MUD received ATG more frequently than MRD (29% MUD vs. 14% MRD [10% MRD<60y and 25% MRD≥60y], P <.0001).The median follow-up (FU) was 36 months (range 2–133) and 25% of patients had a FU of at least 60 months. The cumulative incidence (CIf) of cGVHD at 2 years was 58%. In multivariate analysis, sex mismatch (female > male) increased risk of cGVHD (HR: 1.41 [95% CI 1.05–1.88], P=.02) while MRD≥60y resulted in lower risk (HR: 0.48 [0.25–0.94], P=.031). Donor type by itself did not impact on cGVHD (58% with MRD and 59% with MUD). At 5 years, the CIf of relapse was 34% and was higher with MRD than MUD (39% vs. 24%, P=.038). Adjusted for disease risk, conditioning and infused cells count, only MRD≥60y resulted in significant higher risk of relapse than MUD (HR 2.41[1.26–4.62], P=.008) while MRD <60y had similar risk. The 5 years NRM was 26%. MUD vs. MRD was associated with higher NRM (HR: 1.84 [1.20–2.83], P=.005). Adjusted for recipient age, conditioning, and infused cells count, only MRD<60y were associated with lower risk of NRM than MUD (0.55 [0.35 to 0.86], P=.008) while MRD≥60y had similar NRM. OS was 46% at 5 years and was similar with MUD and MRD. Considering age, MRD≥60y appeared to have notable low OS at 5 years (6%, SE 6%). Adjusted for recipient age, disease risk and infused cells count, HCT from MRD≥60y was associated with higher risk of late (≥18 months) mortality (HR: 4.44 [1.53–12.9], P=.006) than MUD (Fig. 1).Donor/recipient gender parity, donor type and age appeared as significant predictive factors of long term outcomes after HLA-matched PB HCT. Nor donor CMV status nor ABO group seemed to impact on outcomes in our cohort. The selection of a sex mismatched donor (female>male) was associated with significant higher risk of cGVHD. Using PB as graft source, HLA 10/10 MUD provided higher NRM but better disease control and similar OS than MRD. Having combined donor type and age, we observed notable poor outcome (high relapse rate and low OS) for patients transplanted with MRD≥60y in our cohort. Given those results, one may question HCT with old MRD when a younger MUD is available.No relevant conflicts of interest to declare.

The new compounds [Ni(en)3]·(TiF6) (I), [PyH]2[Cu(Py)4(TiF6)2] (II), [PyH]2[Cu(Py)4(MoF6)2] (III), [H3O]2[SiF6(CuF(Py)4)2]·(F)2(IV), Cu(en)2TiF6(V), and Cu(en)2SiF6(VI) are solvothermally synthesized from mixtures of TiO2, MoO2, SiO2, CuO or NiO, HF solution, Py, en, and EtOH (microwave heating, 160 °C, autoclave, 1 h).

Six new compounds, [H4tren][Zr2F12]·H2O (I) (tren: tris‐(2‐aminoethyl)amine), α‐[H4tren][Zr2F12] (II), β‐[H4tren][Zr2F12] (III), [H3tren]4[ZrF8]3·4H2O (IV), α‐[H3tren]2[Ta3O2F16]F (V), and β‐[H3tren]2[Ta3O2F16]F (VI) are found to exist in the ZrF4(Ta2O5)—tren—HFaq.—EtOH systems at 190 °C.

Diagnosis of gastrointestinal acute graft-versus-host disease (GI-GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is based on clinical symptoms (nausea, vomiting and diarrhea quantification) and histological findings. No biomarkers are currently routinely used to predict the response to treatment whereas 30 to 50% of patients will not respond to the first line therapy. Histology can be an indicator for severity but as it's an invasive procedure, it's not available in all patients. Fecal calprotectin, alpha-1-antitrypsin (α1-AT) and elastase are noninvasive biomarkers used in the screening of intestinal inflammation, protein-losing enteropathy and exocrine pancreatic dysfunction, respectively. These markers have not been yet validated in the context of HSCT and we aim to evaluate them as diagnostic and prognostic biomarkers of GI-GVHD.From 09/2008 to 12/2010, 56 patients who developed GI symptoms for the first time after HSCT were prospectively included after inform consent in our center. Twenty patients who developed an acute GVHD without GI symptoms were also included as controls. At time of first symptoms (after a median of 2 days), fecal samples were collected to measure calprotectin, α1-AT and elastase concentrations. Data regarding GI symptoms, GVHD stage, immunosuppressive treatment, albuminemia and performance status were also collected and tested in statistical model with fecal markers. Prognostic value of markers was evaluated by their association with complete response (CR) and steroid-refractory (SR) GVHD using a multiple logistic regression. Model calibration was assessed by the calibration slope and the bootstrap bias-corrected calibration slope and model discrimination by the c-index with or without bootstrap correction for over-optimism. Cumulative incidence (CI) functions were compared using Gray's test and adjustment was performed using the Fine and Gray method.Among the 76 patients, median age was 44 years (8–66), a majority of them received a reduced intensity conditioning regimen (62%) and peripheral blood stem cells as source of stem cells (75%) from an unrelated donor (62%). Definitive diagnosis in patients with GI symptoms was GI-GVHD in 51 (histology in 43) and infection in 5 patients.Calprotectin concentration was higher in patients with GI symptoms than in controls. α1-AT concentration was higher in patients with GI-GVHD than in those with GI infections or controls. The concentration of elastase in patients with GI-GVHD was decreased but associated with high levels of calprotectin and α1-AT (76%) attesting from mucosal damage possibly not related to a pancreatic dysfunction. In patients with GI-GVHD, the concentrations of calprotectin and α1-AT increase with GI-GVHD stage but patients with stage 1 GI-GVHD have similar marker levels than patients without GI-GVHD (values in normal ranges in 87 and 83% for stage 1 vs. 92 and 88% for stage 0).Regarding CR of GI-GVHD after treatment, initial concentrations of calprotectin ≥100μg/g and α1-AT > 1.5 mg/g of dry stools decrease the probability of CR after treatment (56% vs. 86%, p=0.005; 67% vs. 90%, p=0.00007, respectively). Similarly, high level of calprotectin and α1-AT predict a 93% (vs. 33%, p=0.00001) and a 72% (vs. 21%, p=0.00009) probability of SR-GVHD.Calprotectin and α1-AT concentration were independently and exclusively associated with a lower probability of CR (HR: 0.47, [p=0.028] and HR: 0.47, [p=0.037], respectively). The model selection procedure also identified a mode with both variables together with stage > 2 GI-GVHD as best predicting SR-GVHD, although marginal testing did not yield a significant odds ratio (OR) for α1-AT (calprotectin: OR 17.1 [p=0.016]; GI stage III-IV: OR 7.11 [p=0.043]; α1-AT: OR 3.67 [p=0.11]). Interestingly, excluding GVHD stage from the model, Calprotectin and α1-AT concentration could also independently predict SR-GVHD (OR :15.8, p=0.015 & OR :4.93, p=0.038).Our results showed that fecal calprotectin and α1-AT levels are biomarkers of GI-GVHD, particularly in GI stage > I. Furthermore, an increase level of those markers predicts the response to treatment. Their use as predictors from severe GI-GVHD are very promising including in patients in whom GI-GVHD stage or histology are not available.Peffault de Latour: Alexion: Consultancy, Research Funding.

Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) from an HLA- identical sibling is the treatment of choice for young patients with acquired severe aplastic anemia (SAA). Due to increased rates of secondary solid cancer in patients with SAA who received an irradiation-based conditioning regimen, we decided 2 decades ago to use the association of Cyclophosphamide (CY) and Antithymocyte globulin (ATG). We report here the long-term follow-up of patients who underwent HSCT from an HLA-identical related donor after this conditioning regimen. Patients and Methods: 61 consecutive patients with SAA who received a first transplantation from June 1991 to February 2010 in our center were included. Patients with Fanconi anemia or other congenital bone marrow failure were excluded. The conditioning regimen consisted in CY (200mg/Kg) and ATG (2.5 mg/kg/day × 5 days). The donors were HLA-identical siblings in 60 cases and family HLA-matched in 1 case. Graft-versus -host disease (GvHD) prophylaxis associated cyclosporine and methotrexate (days 1, 3, 6 and 11). Long-term clinical outcome, immune recovery and quality of life were assessed. Results: The median age was 21 years [range: 4–43], 41 being adults. Median duration of the disease before HSCT was 93 days. Most of the patients had idiopathic aplastic anemia (n=49, 80%). Median time from diagnosis to HSCT was 3 months (range, 1 to 140). All but 2 patients received bone marrow as source of stem cells and all but 2 engrafted (primary graft failure= 3.4%) with a neutrophils count > 0.5 G/L and a platelets count >20 G/L after a median of 23 (range, 19 to 43) and 21 days (range, 10 to 177), respectively. In patients who had achieved neutrophil recovery, no secondary graft failure was observed. Cumulative incidence (CI) of acute grade II-IV GvHD was 23% (95%CI, 13 to 34) and 18 patients developed chronic GvHD (CI: 32%, 95% CI, 20 to 46). In multivariate analysis, a higher number of infused CD3 cells was associated with an increased risk of developing chronic GvHD (p=0.017). With a median follow-up of 73 months (8 to 233), the estimated 6-year overall survival was 87% (95%CI, 78 to 97). At 72 months, the CI of secondary malignancies was 9%, 10 patients developed avascular necrosis (21% CI), 12 patients were diagnosed with endocrine dysfunctions (19% CI) and 5 presented cardiovascular complications (CI of 10%). The CI of bacterial, fungal and viral infections were 25% (95% CI, 15 to 36), 8% (95% CI, 3 to 17) and 61% (95% CI, 46 to 73) at 72 months, respectively. At 2 years post HSCT, the immune reconstitution was normal for CD3, CD8 T-cells, B-cell and NK-cell but still incomplete for CD4 T-cells. A FACT-BMT questionnaire of quality of life (QOL) was sent to all survivors (n= 53) of who 26 accepted to respond to the questionnaire. There was no evidence for a change in QOL perception with time after transplantation. Our data were compared with those obtained from HSCT recipients from a Swiss transplant center (n=125 patients), mainly transplanted for hematological malignancies. The perception of QOL in patients who were transplanted for SAA was similar to the group of patients who were transplanted for other reason than SAA. Conclusions: Our results confirm that HSCT from HLA-identical sibling donors after CY-ATG conditioning regimen is a curative treatment for patients with SAA, with an excellent long-term outcome. We found an increased risk of chronic GvHD associated with the number of infused CD3 cells. Furthermore, we also found non negligible late complications as well as a similar quality of life with patients transplanted for hematological malignancies. Improving long-term health conditions must thus be a priority field for research, exploring the use of new conditioning regimen as well as new GvHD prophylaxis to improve the quality of life post HSCT of such patients.Peffault de Latour: Alexion: Consultancy, Research Funding.

Influenza (FLU, parainfluenza (PIF), respiratory syncitial (RSV) virus, Adenovirus (ADV) and less frequently Epstein Barr virus (EBV), Herpes Simplex (HSV) and Cytomegalovirus (CMV) are responsible for VRI leading to a mortality rate of 5 to 30% after HSCT. New VRI have been recently described with paradoxical conclusions concerning their pathogenicity after HSCT: rhinovirus (RV), metapneumovirus (MPV), coronarovirus (CV), Human Herpes Virus 6 (HHV6) and poliomavirus KI (KI).This study aims to describe VRI infections, outcomes and risk factors for 100-day mortality in patients who received a first HSCT in our center from 01/2007 to 10/2010. Diagnosis of VRI was performed on nasopharyngeal secretion (by nasopharyngeal aspiration (NPA)) or broncho-alveolar lavage (BAL). Viruses were detected by a multiplex PCR assay (RespiFinder19) that detects FLU, PIF, RSV, ADV, RV, MPV, CV (OC43, 229E, NL63), (and C. pneumoniae, M. pneumoniae, L. pneumophila, B. pertussis) prospectively from 09/2009 and retrospectively before this date. Real time quantitative PCR for ADV, HSV, CMV, HHV6, KI and EBV were also performed from 01/2007. Other bacterial and fungal infections were documented by usual method (sputum, BAL, aspergillus galactomannan antigenemia, radiological findings, L. pneumophila antigen and S. pneumonia urinary antigens). Factors associated with 100-day mortality were estimated using Cox proportional cause-specific Hazard models.127 patients with at least one episode of VRI were studied. Median age was 41 years (range: 8 to 66) with 38% women. The majority of patients was transplanted for hematological malignancy (87%), after a reduced intensity conditioning regimen (66%) with peripheral blood stem cells (63%) [Bone marrow 22%, cord blood 15%]. VRI was essentially diagnosed by NPA (90%) and was associated with a documented bacterial or fungal co-infection in 12% of patients. At VRI diagnosis, 143 viruses were identified in the 127 patients (concomitant viruses in some patients). The distribution of virus was: RV (32%), CV (17%), PIF (17%), ADV (11%), RSV (9%), MPV (7%), HHV6 (5%), FLU (4%), CMV (3%), PM (3%), EBV (2%), HSV (1%). After excluding patients with several virus or another co-pathogen, distribution of virus was RV (28%), CV (12%), PIF (10%), ADV (7%), RSV (6%), MPV (5%), HHV6 (2%), FLU (2%), CMV (1%), PM (2%), EBV (1%), HSV (1%). Thirty-two patients had nosocomial VRI and 36 were hospitalized during VRI evolution. At diagnosis, lower respiratory tract was involved in 52% of patients and 14% required oxygenotherapy. Four patients were transferred into intensive care unit. Seven patients died within 30 days and 14 within 3 months leading to a 3-month survival at 89%. None of them had an isolated VRI as sole cause of death: VRI was associated with active GVHD in 3 patients, active GVHD and co-infection in 3 patients, progressive malignancy in 3 patients, engraftment failure and co-infection in 2 patients, acute non-respiratory organ failure in 3 patients. Virus distribution in the 14 patients who died within 3 months was: CV (n=3), HHV6 (n=3), PIF (n=2), RV, RSV, MPV, FLU, KI, ADV (1 patient for each). Risk factors in univariate analysis for death at 3 months identified ongoing steroid therapy ≥ 1 mg/kg (HR: 4.65, P=0.004), lymphocytes count < 0.5 G/L (HR: 12.4, P=0.04), lower tract involvement (HR: 3.69, P=0.045), presence of a co-infection (HR: 3.38, P=0.043) and oxygenotherapy (HR: 4.57, P=0.008). The delay between transplantation and VRI has no evident effect on outcome. Multivariate analysis showed that lymphocyte count and steroid dose at VRI onset were associated with the 3-month survival. More precisely, patients with lymphocyte count > 0.5 G/L had the best prognosis, while those with lymphopenia had a proportionally increasing risk of death according to the steroid dose (P=0.0002), with HR at 5.75 (95%CI 2.31 to 14.3) if they received less than 1 mg/kg and 33.0 (95%CI 5.32 to 204.9) if they received 1 mg/kg or more. Importantly, the prognostic value of these factors remained true during follow-up (Figure 1).RV, MPV, CV (OC43, 229E, NL63) are frequently isolated in cases of respiratory symptoms. Early mortality attributable to all VRI is relatively low and occurred only in patients with comorbidity. Prognosis of VRI may be related to the underlying immune defect induced by GVHD and its treatment, especially on lymphocyte counts.Peffault de Latour: Alexion: Consultancy, Research Funding.

Review: 119 refs.

Voriconazole (V) treatment has been shown to improve the 12 week (W) survival rate of hematological patients (pts) with invasive aspergillosis (IA), including recipients of allogeneic hematopoietic stem cell transplants (HSCT). We investigated whether this early survival advantage could translate into a significant increase in overall survival.We retrospectively reviewed all consecutive pts who received a transplant between Sept. 1997 and Dec. 2008 at Saint-Louis Hospital and were diagnosed as having IA. The temporal origin of the study was the date of IA diagnosis for each patient. Factors associated with survival were analyzed using Cox proportional hazard models. Separate models were estimated for survival up to 12 W and for survival between 12 W and 24 months (M) in pts surviving longer than 12 W. The deaths of pts with and without IA were analyzed with a competing risk framework. Cumulative incidence curves were compared using Gray's tests.Our study examined 89 IA pts. The median follow-up was 70 M (range, 11–130 M). Two pts did not receive any antifungal treatment and were excluded from subsequent analyses. Of the 87 pts, 42 received first-line V and 45 primarily received a lipid formulation of amphotericin B (n=25), amphotericin B deoxycholate (n=10), caspofungin (n=8) or itraconazole (n=2). The primary characteristics of pts with IA and their causes of death, separated by V as first-line treatment, are shown in the table below.The median survival was 2.6 M, and the overall survival at 24 M was 19% (95% CI 12–30 M) (see figure).Overall, the survival rates of the two groups were significantly different (P= 0.010). However, the differences in survival were quite dramatic prior to 10 M, whereas both survival curves became very close after one year. At 18 M, the numbers of surviving pts were almost identical in the two groups [19% (95% CI: 11–34%) in pts who did not receive V as first-line treatment vs. 21% (95% CI 11–38%) in pts who did]. Pts who did not receive V as a first-line treatment displayed a higher probability of dying from IA than those who did (P=0.004), whereas opposite results were found for mortality in pts without IA (P=0.006). The 24-M cumulative incidence of death from IA was 47% (95% CI 31–61%) in the no V group and 19% (95% CI 9–33%) in the group treated with V. The 24-M cumulative incidence of death in pts without IA was 4% (95% CI 7–14%) in the no V group and 27% (95% CI 14–42%) in pts treated with V. The probability of death from another cause, with IA, was similar in both groups (29% vs. 36% at 24 M; P=0.46). After adjusting for donor type, conditioning regimen, progressive GVHD at diagnosis of IA and cumulated steroid dose (mg/kg) in the W preceding IA diagnosis, administration of V as first-line treatment was found to decrease the risk of death during the first 12 W by approximately 70% [HR=0.31 (95% CI 0.16–0.60); P=0.0005]. Conversely, analysis of mortality between 12 W and 24 M failed to identify any significant predictor of risk of death; however, only 24 pts died during this period.The finding that first-line treatment with V, which is associated with a tremendous improvement in IA outcome, does not translate into an increase in overall survival (even in the context of early diagnosis) is striking. Diagnosis of IA following HSCT, whatever the outcome, appears to be a strong marker for poor long-term prognosis.Bergeron: Pfizer: Speakers Bureau, none; Merck: Speakers Bureau, none; Schering: Speakers Bureau, none. Sulahian:Pfizer: Research Funding, non; Merck: Research Funding, none. Ribaud:Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau, none; Schering: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, none; Gilead: Speakers Bureau, none.