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Recently, novel strategies to control graft-versus-host disease and facilitate engraftment have allowed an increasing number of human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (haploHSCT) to be performed. A meeting was convened to review the biological rationale and the clinical results of various T-cell-depleted (TCD) and T-cell-replete (TCR) HLA-haploidentical 'transplant platforms'. The objective of the meeting was to promote discussion and consent among leading researchers in the field on three main crucial issues for haploHSCT: (i) eligibility criteria, (ii) choice of the most suitable donor, and (iii) choice of the most appropriate transplant platform. The experts in attendance agreed that a patient who is eligible for an allogeneic transplant and lacks an HLA-identical sibling or an HLA-matched unrelated donor should be considered for an alternative donor transplant. Together with the experience of the individual center, the most important decision criteria in choosing an alternative donor source should be the rapidity of transplantation so as to avoid disease relapse/progression. The choice of the mismatched donor should be driven by younger age, ABO blood group compatibility, and Cytomegalovirus status. If a TCD transplant is planned, NK-alloreactive donors and/or the mother should be preferred. Prospective comparative studies are needed to establish the relative efficacy of different transplant platforms. However, expertise in stem cell manipulation and in adoptive immunotherapy is essential if a TCD transplant platform is chosen.

We present the case of a patient with left homonymous hemianopia and chronic left neglect consequent to a stroke in the occipito-temporal regions of the right hemisphere. When the patient performed cancellation tasks with her right (dominant) hand, she had severe and persistent left neglect at retest 7 and 8 years after onset. However, her performance on line bisection was invariably within normal limits. Strikingly, performance on cancellation tests reverted to normal when the patient used her left hand. White matter tractography using spherical deconvolution demonstrated damage to the splenium of the corpus callosum, as well as a relative preservation of the right fronto-parietal network. Effector-dependent neglect may occur because splenial disconnection deprives the right fronto-parietal network from visual information processed by the left hemisphere. Consequently, spatial exploration reverts to normal when the patient uses her left hand, thus involving more directly the fronto-parietal attentional networks in the right-hemisphere.

Attention disorders after right brain damage : , Attention disorders after right brain damage : , کتابخانه دیجیتال جندی شاپور اهواز

In visual search tasks, neglect patients tend to explore and repeatedly re-cancel stimuli on the ipsilesional side, as if they did not realize that they had previously examined the rightward locations favoured by their lateral bias. The aim of this study was to explore the hypothesis that a spatial working memory deficit explains these ipsilesional re-cancellation errors in neglect patients. For the first time, we evaluated spatial working memory and re-cancellation through separate and independent tasks in a group of patients with right hemisphere damage and a diagnosis of left neglect. Results showed impaired spatial working memory in neglect patients. Compared to the control group, neglect patients cancelled fewer targets and made more re-cancellations both on the left side and on the right side. The spatial working memory deficit appears to be related to re-cancellations, but only for some neglect patients. Alternative interpretations of re-exploration of space are discussed.

Normal subjects and patients with right hemisphere lesions with or without signs of left unilateral neglect judged the length of a horizontal line presented on the left or on the right side of space. In half of the trials, the line was presented with a centrally located square or diamond, and subjects had to identify the central stimulus before performing the judgment of length. The presence of the central stimulus improved accuracy of performance in controls and in patients without neglect; neglect patients, however, produced more overestimations of left-sided lines when these was presented with a central stimulus than when the lines occurred in isolation. This finding underlines the importance of attentional factors in length estimates performed by neglect patients in their neglected space.

Objective: To assess the natural progression of cognitive impairment in Huntington’s disease (HD) and to reveal factors that may mask this progression. Background: Although numerous cross-sectional studies reported cognitive deterioration at different stages of the disease, progressive cognitive deterioration has been, up to now, difficult to demonstrate in neuropsychological longitudinal studies. Methods: The authors assessed 22 patients in early stages of HD at yearly intervals for 2 to 4 years (average, 31.2 ± 10 months), using a comprehensive neuropsychological battery based on the Core Assessment Program for Intracerebral Transplantation in Huntington’s Disease (CAPIT-HD). Results: The authors observed a significant decline in different cognitive functions over time: these involved primarily attention and executive functions but also involved language comprehension, and visuospatial immediate memory. Episodic memory impairment that was already present at the time of enrollment did not show significant decline. The authors found a significant retest effect at the second assessment in many tasks. Conclusion: Many attention and executive tasks adequately assess the progression of the disease at an early stage. For other functions, the overlapping of retest effects and disease progression may confuse the results. High interindividual and intraindividual variability seem to be hallmarks of the disease.

Left unilateral neglect is a neurological condition characterized by an impairment in orienting and responding to events occurring on the left side. To gain insight into the brain mechanisms of space processing and to provide theoretical foundations for patient rehabilitation, it is important to explore the attentional bias shown by neglect patients in the light of existing models of normal attentional orienting. Three experiments tested the hypothesis that attentional bias in neglect involves primarily exogenous, or stimulus-based, orienting of attention, with relatively preserved endogenous, or voluntary, orienting. Six patients with right hemisphere damage and left unilateral neglect and 18 age-matched participants without brain damage performed a cued reaction time (RT) task to targets which could appear in one of two lateral boxes. Cues consisted of a brief brightening of the contour of one of the boxes. The target followed the cue at 150, 550, or 1000 ms stimulus-onset asynchrony (SOA). In experiment 1, the cues were not informative about the future location of the target, and thus elicited a purely exogenous orienting of attention. Controls showed slowed RTs to the cued locations at SOAs > 150 ms, consistent with the notion of inhibition of return (IOR). Neglect patients had no evidence of IOR for right targets; they showed a disproportionate cost for left targets preceded by right (invalid) cues; this cost was maximal at the shortest SOA, consistent with the idea of a biased exogenous orienting in neglect. In experiment 2, 80% of the cues were valid (i.e., they correctly predicted the location of the impending target), thus inducing an initially exogenous, and later endogenous, attentional shift toward the cued box. Neglect patients showed again a cost for left invalidly cued targets, which this time persisted at SOAs > 150 ms, as if patients' attention had been cued to the right side not only exogenously, but also endogenously, thus rendering more difficult an endogenous reorienting toward the left. In experiment 3, only 20% of the cues were valid, so that the best response strategy was to endogenously orient attention toward the box opposite to the cued one. Controls were able to take advantage of invalid cues to rapidly respond to targets. In this condition, neglect patients were able to nullify their spatial bias; they achieved their fastest RTs to left targets, which were in the range of their RTs to right targets. However, for neglect patients fast responses to left targets occurred only at 1000 ms SOA, while controls were able to redirect their attention to the uncued box already at 550 ms SOA. Altogether, these results suggest that endogenous orienting is relatively spared, if slowed, in unilateral neglect.

Background: Combined treatment with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy regimens has remarkably contributed to improve treatment outcomes in patients with Acute Promyelocytic Leukemia (APL) patients leading to cure rates above 80%. However, information is lacking on how these patients might recover in the long-term period. Objective: The primary objective of this study was to investigate long-term health-related quality of life (HRQOL) and symptom burden in APL and to examine factors predicting better long-term HRQOL outcomes. Patients and Methods: Patients with APL treated within two large GIMEMA trials (i.e., AIDA0493 and AIDA 2000) were considered. All patients received ATRA plus Idarubicin (AIDA) for induction followed by consolidation that was risk-adapted in AIDA2000 and in most cases, maintenance for 2 years . The main inclusion criterion was having survived the initial diagnosis for more than 5 years and being in complete remission (CR) at the time of study inclusion. The SF-36 was used to assess generic HRQOL. This questionnaire consists of 36 items covering eight generic health status/QoL domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE) and mental health (MH). Mean SF-36 scores were compared between APL patients and those from general population. To minimize bias, all comparisons were performed between APL patients and corresponding propensity score-matched peers from general population, further adjusting for education, family status and geographical area using a multivariate linear mixed model. For descriptive purposes, a cut-off of 30 years was considered to distinguish between younger and older patients at the time of diagnosis and the corresponding HRQoL profiles were compared using multivariate linear regression analysis to adjust for key potential confounders. Also, M.D. Anderson Symptom Inventory (MDASI) was assessed to investigate the profile and prevalence symptom burden Results: Of the 307 patients, potentially eligible for this analysis and invited to participate in the study, 244 completed a HRQOL questionnaire (compliance 79.5%). No differences were found in the main socio-demographic and clinical characteristics between patients with or without a HRQOL evaluation. Mean age of patients was 52 years (range 20-90) and there were 47% males and 53% females. Median time from diagnosis was 14 years (range: 4-20). There were 81% of patients reporting at least 1 comorbidity at the time of HRQOL evaluation. APL long-term survivors reported a HRQOL profile broadly similar to that of their peers in the general population. However, the RP scale was statistically (P=0.016) and clinically meaningful worse in APL patients. Fatigue was the most prevalent symptom with 70% of patients reporting it with any level of concern, as well the most frequently reported moderate to severe symptom by 29 % of patients. Being distressed and problem with remembering things were the other two most prevalent symptoms reported by 65% and 62% of patients respectively. Being diagnosed at a younger age ( Conclusions APL patients successfully treated with AIDA-like regimens may expect to have broadly similar HRQOL outcomes when compared to their peers witout cancer in the general population. However, significant limitations in work or other daily activities due to physical and emotional problems still persist after many years from diagnosis in the majority of patients. Our results also show that on the long-term period, younger APL patients recover better than older ones in terms of HRQOL outcomes. Disclosures Efficace: TEVA: Consultancy, Research Funding; Seattle Genetics: Consultancy; Bristol Myers Squibb: Consultancy; Lundbeck: Research Funding. Breccia:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Ariad: Honoraria; Pfizer: Honoraria. Angelucci:Novartis oncology, celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lo Coco:Teva: Consultancy, Honoraria, Speakers Bureau; Lundbeck: Honoraria, Speakers Bureau; Novartis: Consultancy; Baxalta: Consultancy; Pfizer: Consultancy.

Newly significant advances have been made in diagnosis and treatment of multiple-myeloma (MM).Until recently,MM was defined by presence of end-organ-damage,specifically hypercalcemia, renal-failure, anemia and bone-lesions(CRAB-features). International-Myeloma-Working-Group(IMWG)revised diagnostic-criteria adding three specific-markers:clonal-bone-marrow-plasma-cells greater than 60%, serum-free-light-chain-ratio (FLC)more than 100 and at least two focal-lesions on magnetic-resonance-imaging(MRI). After this update,it's now time to change therapeutic-paradigm: new-IMWG-guidelines allow earlier intervention without waiting end-organ-damage to treat . Nevertheless there is much to learn and share about these new standards that change treatment. When is the right-time to start therapy?We have tried to answer to this dilemma in our work comparing traditional-CRAB-features with recent-myeloma-diagnostic-criteria in a group of 220 newly-diagnosed-MM followed in our Department from 1999 to 2015. The aim of our retrospective-study was to analyze development of new-IMWG-biomarkers during disease-course before CRAB-events and beginning-treatment,discussing their strengths and weaknesses as well as lights and shadows. We evaluated 110 young-patients elegible for high-dose-chemotherapy and autologous-stem-cell-transplant(ASCT)and 110 old(more than 65-year-old)treated with different-kind of therapies. We highlighted presence of IMWG-new-criteria as myeloma-defining-events(MDEs) before CRAB-markers in 44 MM-patients (20% of all): 33 of them are old (median-age of 72 years,range 53-91)and 11 are young (median-age 57,range 41-65) and treated with transplant-procedure. In details most of them presented FLC ratio >100 (30 patients as 68% of this subgroup), following by MRI-lesions(10 patients as 23%) and lastly plasma-cells-bone-marrow-involvement greater of 60%(4 patients as 9%). The majority of these patients (39 as 89%) developed CRAB-characteristics after six months (median value, range 3-15) and have evolved in myeloma-requesting-treatment in less than a year. 27 of them have IgG, 12 IgA and 5 micromolecular-MM. The largest-part (40 patients)has an antecedent MGUS and smouldering-MM.Moreover five young-patients of the whole-population analysed with MDEs and good-clinical-status weren't treated based-on our clinical-judgement and continued close-observation,saving them from both early-therapeutic-toxicity and clonal-selection. Only two patients of 220 started treatment based-on new-IMWG-biomarkers,presenting with clinical-deterioration and increase in monoclonal-component. In conclusion our paper proved that movement from symptoms to biomarkers is a huge-step-forward expecially for elderly-patients,considering both clinical-signs and biological-features. However we need more pratical-implementation of new markers that are changing philosophy of treatment: these patients should be offered appropriate clinical-trial. More caution is needed in high-risk-group expecially young to avoid an overtreating-policy,considering also counter-arguments. Physicians should continue monitoring patients using tools- now-available,while waiting for results from future-prospective-studies. Increase of monoclonal-componenent was analysed not as CRAB-classic-criterion but like disease-marker. The time-difference between new -IMWG-criteria and CRAB-events is less than one year (mean-value 6 months). Figure 1 New-IMWG-criteria-versus-traditional-CRAB. We have studied in our 44-patients with new-diagnostic-markers,time-course of hemoglobin, monoclonal-protein and creatinine-values. Figure 1. New-IMWG-criteria-versus-traditional-CRAB. We have studied in our 44-patients with new-diagnostic-markers,time-course of hemoglobin, monoclonal-protein and creatinine-values. Disclosures No relevant conflicts of interest to declare.

Introduction Primary plasma cellleukemiais a rare and aggressive disorder. While autologous stem cell transplantation has been shown to improve outcome, response durations are short and further strategies are needed. Data is needed to help guide clinicians on the best approach to manage this disease. Therefore in an era of novel agents and improved autologous and allogeneic transplantation strategies this study compared different transplantation approaches in the treatment of PCL. Material and Methods A retrospective analysis was undertaken of theEuropean Group for Bone Marrow Transplantation (EBMT) experience of patients with primary PCL undergoing hematopoietic stem cell transplantation between 1998 and 2012. Only patients who had achieved complete response, partial response or stable disease prior to transplantation were included. Patients with progressive or relapsed disease were excluded. Data was collected using MED A and MED B forms. The primary end point was overall survival and data was analysed according to the information on the planned transplant strategy reported at the time of first transplant (intent-to-treat principle). Results A total of 460 patients were identified and categorised into 4 transplant groups. 1. One patient did not proceed to Allo 2. Four patients not classified The follow up period ranged from 1 to 208 months with a median follow up of 48.9 months. Patients undergoing allo upfront were found to have the worst overall survival. Compared to single auto this was statistically significant with a Hazard Ratio (HR) 1.85 (p=0.007). Compared to auto-allo the allo up front group had an even higher risk HR 3.18 (p=0.018). The double auto versus single auto had a HR 1.39 which was not statistically significant (p=0.28). The auto-allo compared to single auto has a time varying effect with a higher mortality at the beginning and better risk afterwards. The effect on average is not significant HR 0.58 (p=0.24). When we consider time varying effects three periods were examined, 0-12, 12-36 and 36-60 months. Allo upfront is still confirmed to be inferior to single auto and also to auto-allo in the first year. Auto-allo has a trend to superiority versus single or double auto in the mid-term. However due to lack of follow up data in the auto-allo group it is difficult to assess possible benefits of auto-allo in the long term as there are few patients still at risk. Our initial analysis does suggest an advantage. Preliminary analysis suggests that the auto-allo group enjoy the best progression free survival. The superiority of auto-allo versus allo upfront may be attributed to the higher rates of non-relapse related mortality observed in allo upfront. Conclusion Our preliminary work has demonstrated that allo upfront is associated with the worst overall survival. Further data is needed to reliably assess the outcome of auto-allo group which appears to be superior. Therefore we plan to request additional information from involved centres to strengthen the power of our results. Table Table. Disclosures Foà: Ariad: Speakers Bureau; Pfizer: Speakers Bureau; BMS: Consultancy; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Janssen-Cilag: Consultancy, Speakers Bureau; Genetech: Consultancy; Roche: Consultancy, Speakers Bureau. Garderet:Takeda: Consultancy; Amgen: Consultancy; BMS: Consultancy, Honoraria; Novartis: Consultancy.

Summary Background Huntington's disease is a neurodegenerative disease of genetic origin that mainly affects the striatum. It has severe motor and cognitive consequences and, up to now, no treatment. Motor and cognitive functions can be restored in experimental animal models by means of intrastriatal transplantation of fetal striatal neuroblasts. We explored whether grafts of human fetal striatal tissue could survive and have detectable effects in five patients with mild to moderate Huntington's disease. Methods After 2 years of preoperative assessment, patients were grafted with human fetal neuroblasts into the right striatum then, after a year, the left striatum. Final results were assessed 1 year later on the basis of neurological, neuropsychological, neurophysiological, and psychiatric tests. The results obtained were compared with those of a cohort of 22 untreated patients at similar stages of the disease who were followed up in parallel. Repeated magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning with fluorine-18-labelled fluorodeoxyglucose was also done to assess metabolic activity. Findings The final PET-scan assessment showed increased metabolic activity in various subnuclei of the striatum in three of five patients, contrasting with the progressive decline recorded in the two other patients in the series, as seen in patients with untreated Huntington's disease. Small areas of even higher metabolic activity, coregistering with spherical hyposignals on MRI were also present in the same three patients, suggesting that grafts were functional. Accordingly, motor and cognitive functions were improved or maintained within the normal range, and functional benefits were seen in daily-life activities in these three patients, but not in the other two. Interpretation Fetal neural allografts could be associated with functional, motor, and cognitive improvements in patients with Huntington's disease.

Patients with lesions in the right hemisphere often show signs of unilateral neglect for the left side of space. Even in the absence of these signs, however, when exploring a visual scene these patients show an initial orientation of their attention towards the right side (Gainotti, D'Erme, & Bartolomeo, 1991). Some patients might be able to compensate for this spatial bias by actively inhibiting the rightward orientation after its occurrence; as a result, they would be capable of extending their exploration to the left part of space. However, due to conflicting demands on the same resource pool, a rightward bias in these patients is expected to reappear or be enhanced when inhibitory mechanisms are used to avoid producing prepotent but inappropriate responses. Eighteen normal controls and 40 right brain-damaged (RBD) patients (17 showing signs of left neglect, 23 without neglect) performed two reaction time tasks requiring manual motor responses to lateralised visual stimuli. In one task, trials in which a motor response was to be withheld (catch trials) were also presented. Regardless of whether they had neglect, patients responded more slowly to left-sided than to right-sided events in both tasks. The presence of catch trials further increased this rightward bias in patients without signs of neglect, but not in neglect patients, consistent with the hypothesis that RBD patients may use inhibitory processes to compensate for spatial bias.

This study describes issues related to the safety and tolerability of fetal striatal neural allografts as assessed in five patients with Huntington's disease. Huntington's disease (HD) is characterized by motor, cognitive, and behavioral disturbances. The latter include psychological disturbances and, as a consequence, we took particular care to analyze behavioral changes, in addition to the usual "safety" follow-up. We conducted multidisciplinary follow-up at least 2 years before and 1 year after grafting. Psychological care extended to close relatives. The grafting procedure itself was altogether safe and uneventful, and there were no apparent clinical deleterious effects for 1 year. The immunosuppressive treatment, however, was complicated by various problems (irregular compliance, errors of handling, side effects). Direct psychological consequences of the transplantation procedure were rare and not worrisome, although mood alteration requiring treatment was observed in one patient. Indirectly, however, the procedure required patients and relatives to accept constraints that tended to complicate familial situations already marred by aggressivity and depression. All patients and close relatives expressed major expectations, in spite of our strong and repeated cautioning. It is clearly important to be aware of these particular conditions since they may eventually translate into psychological difficulties in coping with the long-term clinical outcome of the procedure, if not beneficial. Despite an overall good tolerance, therefore, this follow-up calls for caution regarding the involvement of HD patients in experimental surgical protocols.

Whole blood coagulation analysers are widely used during percutaneous coronary interventions. The precise degree of anticoagulation in patients is important in this setting. The aim of this investigation was to compare the results obtained with ACT (Hemochron) and HMT, the Heparin Management Test (TAS) in patients undergoing percutaneous coronary interventions. Patients ( n =100) were enrolled prospectively. Each patient received 10,000 units of heparin. At the end of the procedure, the mean ACT was 284±31 seconds and the mean HMT was 292±33 seconds. The correlation between the two methods was highly significant ( r =0.64, p

Allogeneic bone marrow transplantation (BMT) is the only available curative approach for thalassemia major, although long-term morbidity and mortality are not established. The aim of this study was to assess the long-term clinical and hematological results in children and adults with thalassemia major treated with BMT. We analyzed the outcome of 115 patients (median age 9 years, range 11 months to 28 years) with thalassemia major undergoing BMT from a related donor between 1983 and 2006. All patients received the same protocol, consisting of busulfan and cyclophoshamide as conditioning therapy and cyclosporin (CSA) alone or CSA and methotrexate for graft-versus-host disease (GvHD) prophylaxis. The cumulative probability of graft rejection was 6.7%. The transplant-related mortality at 1 year was 8.7%. The 20-year Kaplan-Meier estimate of overall survival and disease-free survival was 89.2% and 85.7%, respectively. Ninety-nine patients out of 103 survivors were in excellent clinical and hematological conditions at last visit following a median follow-up of 15 years (range, 1-24 years) with the exception of two patients who had invalidating chronic GvHD. This study conducted with a large cohort of patients and covering a long period of observation time, showed BMT to be curative for the majority of patients with thalassemia major. The impact of long-term transplant-related sequelae was very limited.

AimStroke is a leading cause of long-term disability in adults. Few studies have investigated the impact of cognitive deficits on health-related quality of life (HRQOL) in patients or caregivers, notably in function of stroke laterality and of lesion volume. This research aims to a better evaluation of HRQOL with a new multi-dimensional scale based on description of the person's present state compared to the pre-stroke state.MethodsEAVQ-QdV is an auto-administered questionnaire composed of physical, cognitive, psychic and social domains. For each domain, difficulties and emotional report are evaluated. Patients’ and caregivers’ points of view are collected. Sixty-nine patients filled out the EAVQ-QdV in the chronic phase (46 right stroke, 23 left stroke). Patients also filled out SF36. MRI brain imaging was performed in all patients.ResultsPreliminary results show a significant negative correlation between EAVQ-QdV and SF36 (r=−0.54). Age, educational level, delay post-stroke or lesion volume did not correlated with the EAVQ-QdV scores. There was no difference between EAVQ-QdV scores in left-sided vs. right-sided strokes (P>0.45). However, right-brain damaged patients, but not left-brain damaged patients, underestimated their difficulties when their scores were compared to the caregivers’ (P

Normal subjects and right- and left-brain-damaged patients with and without neglect performed a task of immediate visual memory and a task of same-different judgment on visual items. In both tasks, stimull consisted in geometrical patterns, which differed either on the right or on the left side. Only right-brain-damaged patients with neglect showed an impaired performance in these tasks. They performed worse on items differing on the left side than on items differing on the right side. This impairment was more severe on the memory task than on the same-different task, suggesting that a lateralized visual memory deficit contributes to the behavioural manifestations of left hemineglect.

This chapter provides an overview of the debate concerning the lesional correlates of neglect signs, with emphasis on methodological problems in anatomo-clinical correlations. It aims at linking neglect-related deficits to the anatomy of the attention systems in the normal human brain.

In the last decades, clinicians and researches have devised many ingenious variants of the clinical tests of neglect, often in order to test a particular hypothesis concerning the functional mechanisms of neglect. This chapter is devoted to an overview of these experimental variants of neglect tests. The stress here is less on the clinical aspects than on the hypotheses advanced to explain neglect-associated deficits and on the methodological problems that researchers need to face. Thus, this chapter may be skipped by the more clinically oriented reader. On the other hand, it can provide useful information as an empirical introduction to Chap. 6, by describing some of the findings which supported or challenged theoretical models of neglect deficits.

This chapter provides an outline of several clinical conditions concerning abnormal awareness, control, or emotional reactions relative to the patient’s own body. Although links with the attention systems are less clear than for the disorders treated in the following chapters, all of these conditions are relatively specific to patients with right hemisphere damage.

This chapter provides an overview of the clinical and neuropsychological aspects of unilateral spatial neglect. Neglect is the most relevant disorder occurring after right hemisphere lesions, both from the clinical point of view, because of its frequency and of its negative prognostic value for functional recovery, and from the neuroscientific perspective, because of the severity and variety of the attention deficits which contribute to patients’ impairments.

This introductory chapter presents a brief overview of attention processes, with their putative neural bases in the human brain. The interested reader will find more material in the list of further readings at the end of the chapter. Attention is conceived as a heterogeneous set of processes, which allow us to select and act on external or internal sources of information and produce behavior which can take into account both our goals and the occurrence of unexpected events. The integrated functioning of frontoparietal networks, with specific interhemispheric differences often favoring the right hemisphere, is crucial for attention processes.

This chapter describes several unexpected instances of hemispheric asymmetries in the occurrence of deficits which neurology textbooks traditionally ascribed to basic sensory or motor forms of impairment. These deficits seem to occur much more frequently after right hemisphere damage than after left-sided lesions. This suggests that key attentional functions of the right hemisphere are important not only for “cognitive” abilities such as spatial orienting but also for more basic capacities such as visual detection or oculomotor control. Other apparently “low-level” deficits are extinction and deviations of gaze position. Extinction refers to the patient’s inability to report the contralesional stimulus of two stimuli presented simultaneously in the right and left hemispaces, whereas the same stimulus is correctly reported when presented alone in either hemispace. Right hemisphere damage may also induce tonic or phasic gaze deviations towards the right, which have a close relationship with signs of left spatial neglect (Chaps. 4, 5, 6, and 7).

Neurodegenerative diseases, such as Alzheimer’s disease and related conditions, currently represent a major public healthcare problem. Attention disorders are often present and disabling in these patients, but frequently remain undiagnosed. The present chapter focuses in particular on visual neglect and monitoring deficits.

This chapter outlines several forms of intervention devised to treat attention disorders consequent to right hemisphere damage, and particularly visual neglect, which is the most severe and common of these conditions.

Neglect behavior appears to be the complex resultant of a number of concurrent elementary deficits of different levels of severity and with different modes of interaction depending on the patient. This chapter outlines some of the putative elementary deficits of attention, motor preparation, and working memory that may contribute to neglect behavior.

International audience; The novelist Henry James shared with his brother William, the author of the Principles of Psychology, a deep interest in the ways in which personal identity is built through one's history and experiences. At the end of his life, Henry James suffered a vascular stroke in the right hemisphere and developed a striking identity delusion. He dictated in a perfectly clear and coherent manner two letters as if they were written by Napoleon Bonaparte. He also showed signs of reduplicative paramnesia. Negative symptoms resulting from right hemisphere damage may disrupt the feelings of "warmth and intimacy and immediacy" and the "resemblance among the parts of a continuum of feelings (especially bodily feelings)", which are the foundation of personal identity according to William James. On the other hand, a left hemisphere receiving inadequate input from the damaged right hemisphere may produce positive symptoms such as delusional, confabulatory narratives. Other fragments dictated during Henry James's final disease reveal some form of insight, if partial and disintegrated, into his condition. Thus, even when consciousness is impaired by brain damage, something of its deep nature may persist, as attested by the literary characteristics of the last fragments of the Master.

This chapter presents evidence from brain-damaged patients relevant to the debate concerning the neural underpinnings of visual and motor mental imagery capacities. For visual mental imagery, the domains of object shape and color, orthographic material, and spatial imagery (imaginal neglect) are examined. Concerning motor imagery, evidence is reviewed from patients with locked-in syndrome and vegetative state, Parkinson’s disease, vascular strokes, and limb amputations. Although both visual mental imagery and motor imagery have been postulated to draw on similar neural resources as the corresponding “actual” abilities (respectively, visual perception and motor acts), the available evidence from brain-damaged patients indicates that such a close correspondence only exists for motor imagery. Visual mental imagery, on the other hand, seems to rely on the activity of high-level visual processing. This possibility seems consistent with the proposed “active” character of imagery abilities, which would not necessarily require the functioning of sensory cortices devoted to the processing of external stimuli.

Inhibition of Return (IOR) refers to longer response times (RTs) when processing information from an already inspected spatial location. This effect encourages orienting towards novel locations and may be hence adaptive to efficiently explore our environment. In a previous study (Bourgeois, Chica, Valero-Cabre, & Bartolomeo, 2013), we demonstrated that repetitive Transcranial Magnetic Stimulation (rTMS) over right hemisphere parietal sites, such as the intra-parietal sulcus (IPS), or the temporo-parietal junction (TPJ), lastingly interfered with manual but not saccadic IOR, for ipsilateral right-sided targets. For contralateral left-sided targets, rTMS over the right IPS, but not over the right TPJ, impaired both manual and saccadic IOR. In the present study, we investigated hemispheric differences in the cortical control of IOR by stimulating left parietal sites with the same design. Contrary to the stimulation of the right hemisphere, rTMS over the left IPS or TPJ did not produce significant modulations of either manual or saccadic IOR. This evidence extends to IOR the validity of current models of hemispheric asymmetries in the control of visuospatial attention.

International audience; Brain damage can produce acquired deficits of color perception, or cerebral achromatopsia. In these patients, lesions tend to overlap on a restricted region in the ventral occipitotemporal cortex, close to the reported locations of the putative V4 complex and to foci of increased blood-oxygen-level-dependent (BOLD) activity related to color perception in normal participants. Unilateral lesions give rise to achromatopsia in the contralateral visual field (hemiachromatopsia). Here we present a partial English translation of the first case report of a hemiachromatopsic patient with detailed anatomical evidence (Madame R., Verrey, 1888), and discuss these results in relation to a more recent case report (Madame D., Bartolomeo et al., 1997) of a patient with two consecutive hemorrhagic lesions in the occipitotemporal regions of the two hemispheres. Strikingly, Madame D. developed full-field achromatopsia after the second lesion in the right hemisphere, without having shown any signs of hemiachromatopsia after the first lesion in the left hemisphere. Thanks to the comparison of the reconstructed lesion patterns between the two patients and with the putative location of color-related areas in the human brain, we offer a possible, if speculative, account of this puzzling pattern of anatomo-clinical correlations, based on intra- and inter-hemispheric connectivity.

International audience; Posterior cortical atrophy (PCA) is rare neurodegenerative dementia, clinically characterized by a progressive decline in higher-visual object and space processing. After a brief review of the literature on the neuroimaging in PCA, here we present a study of the brain structural connectivity in a patient with PCA and progressive isolated visual and visuo-motor signs. Clinical and cognitive data were acquired in a 58-years-old patient (woman, right-handed, disease duration 18 months). Brain structural and diffusion tensor (DT) magnetic resonance imaging (MRI) were obtained. A voxel-based morphometry (VBM) study was performed to explore the pattern of gray matter (GM) atrophy, and a fully automatic segmentation was assessed to obtain the hippocampal volumes. DT MRI-based tractography was used to assess the integrity of long-range white matter (WM) pathways in the patient and in six sex- and age-matched healthy subjects. This PCA patient had a clinical syndrome characterized by left visual neglect, optic ataxia, and left limb apraxia, as well as mild visuo-spatial episodic memory impairment. VBM study showed bilateral posterior GM atrophy with right predominance; DT MRI tractography demonstrated WM damage to the right hemisphere only, including the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus, as compared to age-matched controls. The homologous left-hemisphere tracts were spared. No difference was found between left and right hippocampal volumes. These data suggest that selective visuo-spatial deficits typical of PCA might not result from cortical damage alone, but by a right-lateralized network-level dysfunction including WM damage along the major visual pathways.

Eighty patients with high-risk hematologic malignancies underwent unmanipulated, G-CSF–primed BM transplantation from an haploidentical family donor. Patients were transplanted in first or second complete remission (CR, standard-risk: n =45) or insecond CR or active disease (high-risk: n =35). The same regimen for GVHD prophylaxis was used in all cases. The cumulative incidence (CI) of neutrophil engraftment was 93% 0.1%. The 100-day CIs for II-IV and III-IV grade of acute GVHD were 24% 0.2% and 5% 0.6%, respectively. The 2-year CI of extensive chronic GVHD was 6% 0.1%. The 1-year CI of treatment-related mortality was 36% 0.3%. After a median follow-up of 18 months, 36 of 80 (45%) patients are alive in CR. The 3-year probability of overall and disease-free survival for standard-risk and high-risk patients was 54% 8% and 33% 9% and 44% 8% and 30% 9%, respectively. In multivariate analysis, disease-free survival was significantly better for patients who had standard-risk disease and received transplantations after 2007. We conclude that unmanipulated, G-CSF–primed BM transplantation from haploidentical family donor provides very encouraging results in terms of engraftment rate, incidence of GVHD and survival and represents a feasible, valid alternative for patients with high-risk malignant hematologic diseases, lacking an HLA identical sibling and in need to be urgently transplanted.Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation. Haploidentical hematopoietic stem cell transplantation for hematologic malignancies.

International audience; The exact anatomical localization of right hemisphere lesions that lead to left spatial neglect is still debated. The effect of confounding factors such as acute diaschisis and hypoperfusion, visual field defects, and lesion size may account for conflicting results that have been reported in the literature. Here, we present a comprehensive anatomical investigation of the gray- and white matter lesion correlates of left spatial neglect, which was run in a sample 58 patients with subacute or chronic vascular strokes in the territory of the right middle cerebral artery. Standard voxel-based correlates confirmed the role played by lesions in the posterior parietal cortex (supramarginal gyrus, angular gyrus, and temporal-parietal junction), in the frontal cortex (frontal eye field, middle and inferior frontal gyrus), and in the underlying parietal-frontal white matter. Using a new diffusion tensor imaging-based atlas of the human brain, we were able to run, for the first time, a detailed analysis of the lesion involvement of subcortical white matter pathways. The results of this analysis revealed that, among the different pathways linking parietal with frontal areas, damage to the second branch of the superior longitudinal fasciculus (SLF II) was the best predictor of left spatial neglect. The group study also revealed a subsample of patients with neglect due to focal lesion in the lateral-dorsal portion of the thalamus, which connects the premotor cortex with the inferior parietal lobule. The relevance of fronto-parietal disconnection was further supported by complete in vivo tractography dissection of white matter pathways in 2 patients, one with and the other without signs of neglect. These 2 patients were studied both in the acute phase and 1 year after stroke and were perfectly matched for age, handedness, stroke onset, lesion size, and for cortical lesion involvement. Taken together, the results of the present study support the hypothesis that anatomical disconnections leading to a functional breakdown of parietal-frontal networks are an important pathophysiological factor leading to chronic left spatial neglect. Here, we propose that different loci of SLF disconnection on the rostro-caudal axis can also be associated with disconnection of short-range white matter pathways within the frontal or parietal areas. Such different local disconnection patterns can play a role in the important clinical variability of the neglect syndrome.

International audience; OBJECTIVE: To determine the neural substrates of biased spatial orienting in posterior cortical atrophy (PCA) by using a combined structural and functional neuroimaging approach. BACKGROUND: Patients with spatial neglect typically bisect horizontal long lines towards their brain lesions but the precise neural substrates of this spatial bias remain controversial and poorly explored in neurodegenerative disorders such as PCA. METHODS: 15 patients with PCA underwent brain MRI and single photon emission computed tomography (SPECT) and were required to bisect five 20 cm long lines, each centred on an A4 horizontal sheet. Direct correlations between average deviations on the bisection task and both (1) the degree of grey matter density, as estimated by voxel based morphometry and (2) regional cerebral blood flow, as assessed by SPECT, were performed. RESULTS: Seven patients (47%) had pathological bias on the bisection task, deviating consistently towards the non-neglected side for each of the five lines. Rightward bias (sign of left-sided neglect) was more frequent and severe than leftward bias (sign of right-sided neglect). Correlation analyses showed that rightward deviations correlated with atrophy and hypoperfusion exclusively in the right hemisphere, involving a large scale fronto-parietal network; cortical atrophy was prominent in the parieto-temporal cortex but extended to the frontal region; hypoperfusion was substantial both in the middle frontal gyrus and in the postcentral region. No correlations emerged from leftward deviations. CONCLUSION: The results indicate that rightward bias (sign of left-sided neglect) in PCA depends on dysfunction of a large fronto-parietal network in the right hemisphere, related to both cortical atrophy and decreased cerebral perfusion.

Molenberghs et al. (2012) contributed a clearly written meta-analysis on the debated issue of the anatomy of spatial neglect. They looked for a critical lesion site for neglect, and found several distinct regions whose damage has been associated with signs of neglect. Lesioned clusters were located in virtually the whole lateral surface of the right hemisphere (see their Figure 1), as well as in the white matter. Molenberghs et al.’s study is timely and much needed after the recent publication of new evidence concerning this debate (see, e.g., Saj et al., 2012). Despite a fairly complete covering of the literature, however, a general methodological point prevents studies such as the present one from giving adequate weight to lesions to long-range white matter pathways. As the authors acknowledge in the general discussion, while their method based on “the peak coordinates of the critical lesion site” is certainly appropriate for gray matter lesions, it seems problematic for long-range white matter bundles. At variance with gray matter lesions, where one can look for maximum overlap (Vallar and Perani, 1986) or analogous topological data (Bates et al., 2003), lesions in different sectors along a long-range white matter fascicle can produce similar effects by disconnecting the fascicle, independent of the precise location of the interruption (Catani and Mesulam, 2008). This is a general problem for studies looking for a “critical lesion site” in brain-damaged patients (Bartolomeo, 2011). Theoretically, similar behavioral deficits should be observed when a gray matter functional module is damaged as well as when white matter injury disconnects this module from the rest of the brain. Historically, neurologists have described neurological and neuropsychological deficits as disconnection syndromes (Geschwind, 1965; Catani and ffytche, 2005). However, the recent dominance of functional MRI (which identifies activation patterns in gray matter) and lesion symptom mapping based on gray matter injury (Bates et al., 2003) have led scholars to focus purely on the role of gray matter. Advances using techniques such as diffusion weighted imaging and the resulting tractography can help reveal the role of white matter (Catani, 2006). There is a clear need for methods that can integrate information from both gray and white matter injury, as these will likely provide better clinical significance and theoretical insight. At present, the only way to explore the possibility that a deficit results from disconnection of a particular fascicle is to track the relevant fascicle, draw the lesions, and see whether or not they are located along the fascicle (see, e.g., Bourgeois et al., 2012). Methods based on this idea are being developed for group studies (Rudrauf et al., 2008). Concerning meta-analyses on neglect anatomy, Bartolomeo et al. (2007) mapped the hotspots defined by a small number of previous studies on fronto-parietal white matter, and found that the maximum lesion overlaps invariably occurred on or near the right superior longitudinal fasciculus (see also Doricchi et al., 2008; Thiebaut de Schotten et al., 2008). Such a procedure, however, would be much more cumbersome in larger meta-analyses such as the present one. Despite these caveats, Molenberghs et al.’s results did reveal that “the largest region involved in the development of spatial neglect was a white matter lesion corresponding to the superior longitudinal fasciculus”, consistent with the meta-analysis of Bartolomeo et al. (2007). However, other white matter sites of damage might have been more difficult to pinpoint. For example, the possibility that a disconnection of the inferior fronto-occipital fasciculus (IFOF) may determine neglect in some patients (Urbanski et al., 2008) does not appear in the meta-analysis results. This might well depend on the relative rarity of such patients; however, it could also result from the fact that the IFOF is a particularly long white matter pathway; thus, IFOF-damaging lesions might be dispersed along its length and go undetected by methods based on lesion clustering. To conclude, Molenberghs et al. (2012) made an important attempt to clarify a complex problem such as the anatomy of neglect. Their results, however, also highlight demanding methodological issues that need to be solved in future research.

Inhibition of return (IOR) reflects a bias to preferentially attend to non-previously attended or inspected spatial locations. IOR is paramount to efficiently explore our environment, by avoiding repeated scanning of already visited locations. Patients with left visual neglect after right parietal damage or fronto-parietal disconnection demonstrated impaired manual, but not saccadic, IOR for right-sided targets (Bourgeois et al., 2012). Here we aimed at investigating in healthy participants the causal role of distinct cortical sites within the right hemisphere in manual and saccadic IOR, by evaluating the offline effects of repetitive Transcranial Magnetic Stimulation (rTMS) on the right intra-parietal sulcus (IPS) and the right temporo-parietal junction (TPJ). Our results show that rTMS over both sites lastingly interfered with manual but not saccadic IOR for right-sided targets. This behavioral pattern closely mimicked the performance of neglect patients evaluated with the same paradigm. In contrast, for left-sided targets, rTMS over the right IPS impaired both manual and saccadic IOR, while rTMS over the right TPJ produced no modulation in either task. We concluded that distinct parietal nodes of the dorsal and ventral spatial attention networks of the right hemisphere make different contributions to exogenous orienting processes implicated in IOR, and that such effects are hemifield- and task-dependent.

International audience; Visual neglect is a multi-component syndrome including prominent attentional disorders. Research on the functional mechanisms of neglect is now moving from the description of dissociations in patients' performance to the identification of the possible component deficits and of their interaction with compensatory strategies. In recent years, the dissection of attentional deficits in neglect has progressed in parallel with increasing comprehension of the anatomy and function of large-scale brain networks implicated in attentional processes. This review focuses on the anatomy and putative functions of attentional circuits in the brain, mainly subserved by fronto-parietal networks, with a peculiar although not yet completely elucidated role for the right hemisphere. Recent results are discussed concerning the influence of a non-spatial attentional function, phasic alertness, on conscious perception in normal participants and on conflict resolution in neglect patients. The rapid rate of expansion of our knowledge of these systems raises hopes for the development of effective strategies to improve the functioning of the attentional networks in brain-damaged patients.

Recent behavioral observations suggest that some forms of attentional orienting have the ability to modulate access to perceptual consciousness. However, the neural structures subserving such processes remain uncertain. We used functional magnetic resonance imaging during a visual discrimination task with near-threshold targets preceded by peripheral cues to identify the neural bases of the interactions between spatial attention and conscious visual perception. During the cue-target period critical for spatial orienting, regions within a frontoparietal network, including nodes of the dorsal attentional system, were more strongly engaged for consciously perceived targets than for nonperceived targets at attended locations. Moreover, activation increased for "unseen" targets in more ventral frontoparietal regions, known to be part of a system involved in attentional reorienting. Functional connectivity analyses revealed tighter coupling between frontoparietal nodes for valid cues leading to "seen" reports and for invalid cues leading to unseen reports. We conclude that spatial orienting to peripheral stimuli, subserved by frontoparietal attentional networks, plays a major role in determining the content of our conscious experience.

Cytogenetics play a major role in determining the prognosis of patients with acute myelogenous leukemia (AML). However, existing cytogenetics classifications were developed in chemotherapy-treated patients and might not be optimal for patients undergoing allogeneic hematopoietic cell transplantation (HCT). We studied 821 adult patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent HCT for AML in first or second complete remission between 1999 and 2004. We compared the ability of the 6 existing classifications to stratify patients by overall survival. We then defined a new scheme specifically applicable to patients undergoing HCT using this patient cohort. Under this scheme, inv(16) is favorable, a complex karyotype (4 or more abnormalities) is adverse, and all other classified abnormalities are intermediate in predicting survival after HCT (5-year overall survival, 64%, 18%, and 50%, respectively; P = .0001). This scheme stratifies patients into 3 groups with similar nonrelapse mortality, but significantly different incidences of relapse, overall and leukemia-free survival. It applies to patients regardless of disease status (first or second complete remission), donor type (matched related or unrelated), or conditioning intensity (myeloablative or reduced intensity). This transplantation-specific classification could be adopted for prognostication purposes and to stratify patients with AML and karyotypic abnormalities entering HCT clinical trials. American Society for Blood and Marrow Transplantation.

The relationships between spatial attention and conscious perception are currently the object of intense debate. Recent evidence of double dissociations between attention and consciousness cast doubt on the time-honored concept of attention as a gateway to consciousness. Here we review evidence from behavioral, neurophysiologic, neuropsychological, and neuroimaging experiments, showing that distinct sorts of spatial attention can have different effects on visual conscious perception. While endogenous, or top-down attention, has weak influence on subsequent conscious perception of near-threshold stimuli, exogenous, or bottom-up forms of spatial attention appear instead to be a necessary, although not sufficient, step in the development of reportable visual experiences. Fronto-parietal networks important for spatial attention, with peculiar inter-hemispheric differences, constitute plausible neural substrates for the interactions between exogenous spatial attention and conscious perception.

The quest for the neural correlates of consciousness has led to controversial results. When contrasting consciously seen versus unseen stimuli, some authors have proposed that consciousness is related to activity in visual areas along the ventral cortical visual stream, while others propose the implication of parietal and frontal regions ( Dehaene and Changeux 2011). When invisibility is caused by neglect or inattention, high levels of activity recorded in early visual areas ( Vuilleumier et al. 2001) suggest that further activity in fronto-parietal regions might be necessary for conscious perception. Recent functional magnetic resonance imaging evidence ( Chica, Paz-Alonso, et al. 2012) suggested a key role for the left frontal eye field (FEF) in the attentional modulation of visual consciousness. Here, we used the high temporal resolution and causal power of event-related transcranial magnetic stimulation to explore the causal contributions of the left FEF on conscious perception and to assess whether or not these effects are mediated by the orienting of spatial attention. Our results provide the first causal evidence on the contribution of the left FEF to conscious visual perception and indicate that such effects are likely to be mediated by its known role on attentional orienting.

Background Allogeneic SCT remains the only curative option in myelodysplastic syndromes (MDS). We prospectively evaluated in a multicenter phase 2 GITMO (Italian Bone Marrow Transplantation Group) trial, the feasibility of allogeneic stem cell transplantation (ASCT, primary protocol end-point) after induction treatment with azacitidine (Vidaza, Celgene). According to the protocol, patients had to perform at least 4 and up to 12 cycles of azacitidine as induction treatment before ASCT. Patients not eligible for ASCT could continue treatment until disease progression. Methods Between November 2010 and September 2014, 102 patients were enrolled by 20 Italian hematology centers. Nine patients never started treatment due to progressive disease (PD, n=2), refusal (n=3), or unknown causes (n=4). Of remaining 93 patients, 70 had with IPSS Int-2/High-risk MDS, 15 WHO-defined acute myeloid leukemia (AML) and 8 chronic myelomonocytic leukemia (CMML). There were 32 females and 61 males with median age 59 yrs (range 21-66.5 yrs). At treatment start, ECOG performance status was: 0 in 66 patients, 1 in 17 and 2 in 10 patients, while MDS HCT-index was: low (0) in 43 patients, intermediate (1-2) in 31 and high (>2) in 18 patients. All 93 patients started azacitidine s.c. at the standard dose of 75 mg/sqm/day, 7 days/month, at a median of 0.8 months (range 0-105 months) from initial MDS diagnosis. Results At response assessment after a median of 4.5 cycles (range 1-11), 25% of patients (n=19) achieved complete remission (CR), 3% marrow-CR (n=2), 14% partial remission (PR, n=11), 9% hematologic improvement (HI, n=7), 35% had stable disease (SD, n=27) and 14% PD (n=11). ASCT was performed in 48 patients (52%), after a median of 4.5 azacitidine cycles (range: 1-11). Data on ASCT are presently available for 45 patients, transplanted with bone marrow (n=10 pts) or peripheral blood stem cells (n=35 pts) from an HLA-identical donor (sibling in 11, and MUD in 34 cases). Forty-five patients did not receive ASCT due to: disease relapse or progression (n=16, 35%), adverse events (n=12, 27%), refusal (n=5, 11%), or other causes (n=12, 27%). At a median follow-up of 18.5 months (range 0.2-31.5), 43 patients are alive (25 received ASCT), and 50 patients died. Causes of death are reported in Table 1. Median overall survival (OS) for the whole patient cohort was 13.4 months (95% CI: 10.9-18.6, Figure 1). Disease status after azacitidine was predictive of significantly improved survival for patients in CR/PR/HI, compared to SD or PD (n=77 patients who completed at least 4 cycles, Figure 2). ASCT considered as time-dependent covariate was associated to a significantly longer survival (p=0.008, HR 0.4, 95% CI: 0.2-0.8). Stratification of MDS according to IPSS and karyotype was not associated to survival. Conclusions Our study shows that allogeneic transplantation following azacitidine is feasible in HR-MDS/CMML and AML, with about 50% of patients being able to undergo HSCT. These data favourably compare with previous studies in MDS on ASCT preceded by conventional chemotherapy. Disease status at the time of HSCT confirms its significant prognostic role for survival, also in the context of hypomethylating treatment, where stabilization of disease also represents a therapeutic target. Disease relapse or progression remain the major causes of death indicating the need for other strategies aimed at improving disease control in MDS. Figure 1. Overall survival (n=93 pts) Figure 1. Overall survival (n=93 pts) Figure 2. Survival according to disease status at response assessment after a median of 4.5 azacitidine cycles (n=77 evaluable pts) Figure 2. Survival according to disease status at response assessment after a median of 4.5 azacitidine cycles (n=77 evaluable pts) Disclosures Voso: Celgene: Honoraria, Research Funding. Off Label Use: Azacitidine used as induction treatment before allogeneic stem cell transplantation in MDS. Finelli:Janssen: Other: Speaker; Novartis: Other: Speaker; Celgene: Other: Speaker, Research Funding.

Multiple Myeloma (MM) is still considered an incurable disease despite a substantial global outcome improvement observed during the past decade. Despite better understanding of biological pathways, availability of sophisticated diagnostic tools and increasing number of therapeutic options almost all patients experience disease relapse. The aim of our retrospective study was to analyze global outcome in newly diagnosed MM patients eligible for high dose chemotherapy and autologous stem cell transplant (ASCT) treated in our Institution in the last 15 years. We evaluated 177 MM patients transplanted in our Institution from November 1999 to February 2015. Median age at start therapy was 58 years (range 36-71) and median follow up time (from start therapy to last follow up) was 52 months (range 7-185). Patients received different induction therapies before transplant reflecting the availability of new drugs and consequently more therapeutic choices. 65 patients received conventional chemotherapy-based induction (VAD 27, 15%, Total Therapy 2-like 37, 22%, EDAP 1 patient); 15 patients thalidomide-based (TD, 8%); 88 patients bortezomib-based (VTD 74, 43%; VCD 8, 5%; PAD 3, 1%; VD 3, 1%) and 9 patients lenalidomide-based (RD, 5%). After induction regimen 23 patients (13%) received additional therapy before transplant: 14 for Progressive Disease (PD), 9 were considered in suboptimal/unsatisfactory response (5 in Partial Response, PR and 4 in Stable Disease, SD). 71 patients received a single ASCT, 106 patients double ASCT; 11 tandem autologous and allogeneic SCT. All patients had a PR/VGPR/CR after ASCT. Treatment related mortality was 1% (3 patients: 2 of them after Allogenic ASCT, 1 for acute Graft versus Host Disease, 1 for Veno Occlusive Disease). After first line therapy 7 patients died: 3 for progressive disease, 4 for other causes (2 myocardial infarction, 1 intestinal ischemia and 1 breast cancer). 90 patients (51%) experienced MM relapse (median time from ASCT 24 months) and were treated according to different chemotherapy schedules. At last follow-up 115 patients were alive (65%), 61 of them in Complete Response, 31 in Very Good Partial Response, 8 in Partial Response, 4 in SD, 11 in PD. Median global overall survival (OS) was 109 months, median global Progression Free Survival1 (PFS1) 51 months and median global PFS2 (time from start therapy to second disease progression or death from any cause) 80 months. According to different induction therapy (chemotherapy vs bortezomib vs thalidomide vs lenalidomide-based) median OS was 117 months vs not reached (more than 96) vs 68 vs not reached (more than 60); median PFS1 was 47 months vs 60 vs 35 vs not reached (more than 60); median PFS2 was 76 months vs 92 vs 57 vs not reached (more than 60), respectively. As reported in literature the improvement of biological, diagnostic and clinical knowledge and the availability of new therapeutic tools translates in improved outcome in MM patients treated in our Center. The introduction of the proteasome inhibitor bortezomib in the induction therapy gave the best results in terms of OS, control of the disease (PFS) and response to second line therapy after relapse (PFS2). Considering the remarkable progress done in the past decade the dream of a cure is a challenge for the future. Disclosures No relevant conflicts of interest to declare.

Aims: In elderly patients with acute myeloid leukemia (AML), complete remission (CR) rate following intensive chemotherapy is approximately 45%, considerably lower than in younger patients, with a shorter duration of remission and high treatment-related mortality (30-50%). Median survival is about 12 months. Intensive chemotherapy is indicated in a small proportion of "fit" elderly patients. In a phase III, prospective, randomized, open-label, multicenter trial designed to assess the efficacy of post-remission treatment with 5-Azacitidine versus best supportive care (BSC) in patients > 60 years of age with AML in CR after conventional induction ("3+7") and consolidation chemotherapy, quality of life (QoL) was assessed from diagnosis. We present interim results of changes of QoL. Methods: Patients with newly diagnosed AML with > 30% myeloid marrow blasts, either "de novo" or evolving from myelodysplastic syndrome without contraindications for intensive chemotherapy and with an ECOG performance status < 3 are included. Induction chemotherapy consists of two courses of "3+7": Daunorubicin 40 mg/m2 daily days 1-3 and cytarabine 100 mg/m2 daily continuous IV infusion days 1-7. Patients in CR receive consolidation (cytarabine 800 mg/m2 3 hour infusion bid days 1-3) and are randomized 1:1 to receive BSC or 5-Azacitidine maintenance therapy up to 4 years and six months until AML recurrence. QoL assessment was performed using the EORTC QLQ-C30 and the QOL-E v.3 questionaires. Results: QoL results assessed at 3 time points are reported: 1) baseline; 2) at hematological recovery immediately after the first "3+7" course; and 3) after consolidation at randomization. Ninety-nine patients (male/female 50/49) of median age 70 (IQR 65-74) years have been enrolled. At diagnosis, mean hemoglobin was 9.2 (SD ± 2.4) g/dL, leukocytes were 7.9 (2.3-29.6)/µL, platelet count was 54 (IQR 29-85) Gi/L and bone marrow blasts were 70 (IQR 50-85)%. Seventy-five patients had "de novo" AML. Twenty-three patients had comorbidities. Forty-three patients had an ECOG PS 1 and 28 had ECOG PS 2. Baseline median QOL-E scores were poor (≤60) in all dimensions, except for fatigue (76, IQR 52-85). EORTC QLQ-C30 confirmed that fatigue was not prevalent at diagnosis (median 33, IQR 22-56). Median baseline EORTC QLQ-C30 scores were good in all domains except for global health status (GHS, median 50, IQR 33-67). Gender, comorbidities, bone marrow blasts and secondary AML were not related to QoL. Baseline Hb levels correlated with QOL-E functional (r=0.0216, p=0.14), fatigue (r=0.256, p=0.002) and disease-specific (r=0.247, p=0.010) scores and with EORTC QLQ-C30 GHS (r=0.270, p=0.001), physical (r=0.304, p Conclusions: Elderly patients with AML at diagnosis identified as fit for chemotherapy generally do not present fatigue, though health status is poor and is mainly correlated with Hb levels. Role function may predict response to induction chemotherapy. Patients obtaining CR perceive improvements in global health, including physical and emotional QoL and symptoms. Disclosures Oliva: Celgene: Other: Advisory Board, Speakers Bureau; Amgen: Consultancy; Novartis: Speakers Bureau.