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Infertility has been characterized as a disease by the World Health Organization (WHO) and reportedly affects about 10-12% of couples worldwide, while the incidence is even higher in Italy, at about 15%. The issue of iatrogenic infertility arising from treatments that can compromise an individual's reproductive capacity, it is necessary to inform patients of the possible damage on their future fertility and on the possibilities to preserve it. The complexities inherent in the various techniques and approaches aimed at preserving fertility should be expounded upon thoroughly to the patients, who should also receive proper psychological assistance and counseling, which ought to take into account the ethical distinctive challenges and the possible misgivings that may be caused in patients. Ovarian Tissue Cryopreservation (OTC) and ovarian tissue transplantation (OTT) can constitute a valuable part of the clinical armamentarium for preserving fertility, although the data are still inconclusive, particularly in over-36 patients. The multidisciplinary nature of the healthcare teams involved in such interventions is of paramount importance to optimize results.

The Event Horizon Telescope (EHT) is a very-long-baseline interferometry (VLBI) experiment that aims to observe supermassive black holes with an angular resolution that is comparable to the event horizon scale. The South Pole occupies an important position in the array, greatly increasing its north-south extent and therefore its resolution. The South Pole Telescope (SPT) is a 10-meter diameter, millimeter-wavelength telescope equipped for bolometric observations of the cosmic microwave background. To enable VLBI observations with the SPT we have constructed a coherent signal chain suitable for the South Pole environment. The dual-frequency receiver incorporates state-of-the-art SIS mixers and is installed in the SPT receiver cabin. The VLBI signal chain also includes a recording system and reference frequency generator tied to a hydrogen maser. Here we describe the SPT VLBI system design in detail and present both the lab measurements and on-sky results.

As the Atacama Large Millimeter/submillimeter Array (ALMA) nears completion, 73 dual-polarization receivers have been delivered for each of Bands 3 (84-116 GHz) and 6 (211-275 GHz). The receivers use sideband-separating superconducting Nb/Al-AlOx/Nb tunnel-junction (SIS) mixers, developed for ALMA to suppress atmospheric noise in the image band. The mixers were designed taking into account dynamic range, input return loss, and signal-to-image conversion (which can be significant in SIS mixers). Typical SSB receiver noise temperatures in Bands 3 and 6 are 30 and 60 K, respectively, and the image rejection is typically 15 dB.

180-degree IF hybrids are potentially useful for balanced superconductor-insulator-superconductor (SIS) mixers. We have developed a compact Nb-based 180-degree hybrid for 4-12 GHz which addresses concerns of element size, ohmic loss, and IF bandwidth. The fabrication scheme developed for these elements will be discussed, including the use of a thin overlayer Au process for via contacts, RF diode sputtered SiOx in lieu of sublimated SiOx films in order to improve the wafer yield, and diagnostic Nb capacitors to evaluate these SiOx films. Experimental results will be presented and compared with simulations of these lumped element transmission line "rat-race" hybrids. It should be noted that the hybrids can be used in cryogenic balanced mixers for any RF band.

From April 2008 to August 2010 the Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS (IDEFICS) intervention aimed to encourage healthier diets, higher physical activity levels and lower stress levels among European children and their families. While the intervention was intended to improve children's health, we also wished to assess whether there were unwelcome aspects or negative side-effects. Therefore all parents of children who participated in the IDEFICS intervention were asked for their views on different aspects of the intervention.A total of 10,016 parents of children who participated in the IDEFICS survey and who were involved in the intervention were invited to complete a questionnaire on positive and negative impacts of the intervention. Responses to each of the statements were coded on a four point Likert-type scale. Demographic data were collected as part of the baseline (T0 ) and first follow-up (T1 ) surveys; intervention exposure data was also collected in the T1 follow-up survey. Anthropometric data was collected in the same surveys, and child's weight status was assessed according to Cole and Lobstein. After initial review of the univariate statistics multilevel logistic regression was conducted to analyse the influence of socio-economic factors, child's weight status and intervention exposure on parental responses.In total 4,997 responses were received. Approval rates were high, and few parents reported negative effects. Parents who reported higher levels of exposure to the intervention were more likely to approve of it and were also no more likely to notice negative aspects. Less-educated and lower income parents were more likely to report that the intervention would make a lasting positive difference, but also more likely to report that the intervention had had negative effects. Parents of overweight and obese children were more likely to report negative effects - above all, that 'the intervention had made their child feel as if he/she was "fat" or "overweight." 'While the results represent a broad endorsement of the IDEFICS intervention, they also suggest the importance of vigilance concerning the psychological effects of obesity interventions on overweight and obese children.

INTRODUCTION: From April 2008 to August 2010 the Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS (IDEFICS) intervention aimed to encourage healthier diets, higher physical activity levels and lower stress levels among European children and their families. While the intervention was intended to improve children's health, we also wished to assess whether there were unwelcome aspects or negative side-effects. Therefore all parents of children who participated in the IDEFICS intervention were asked for their views on different aspects of the intervention. METHODS: A total of 10,016 parents of children who participated in the IDEFICS survey and who were involved in the intervention were invited to complete a questionnaire on positive and negative impacts of the intervention. Responses to each of the statements were coded on a four point Likert-type scale. Demographic data were collected as part of the baseline (T0 ) and first follow-up (T1 ) surveys; intervention exposure data was also collected in the T1 follow-up survey. Anthropometric data was collected in the same surveys, and child's weight status was assessed according to Cole and Lobstein. After initial review of the univariate statistics multilevel logistic regression was conducted to analyse the influence of socio-economic factors, child's weight status and intervention exposure on parental responses. RESULTS: In total 4,997 responses were received. Approval rates were high, and few parents reported negative effects. Parents who reported higher levels of exposure to the intervention were more likely to approve of it and were also no more likely to notice negative aspects. Less-educated and lower income parents were more likely to report that the intervention would make a lasting positive difference, but also more likely to report that the intervention had had negative effects. Parents of overweight and obese children were more likely to report negative effects - above all, that 'the intervention had made their child feel as if he/she was "fat" or "overweight." ' CONCLUSION: While the results represent a broad endorsement of the IDEFICS intervention, they also suggest the importance of vigilance concerning the psychological effects of obesity interventions on overweight and obese children.

Background: Azacitidine (AZA) at a dose of 75 mg/mq/day subcutaneously for 7 days, every 28 days, induces high hematologic response rates and prolongation of survival in high-risk MDS patients (pts) (Fenaux, 2009). However few data are hitherto available concerning the efficacy and safety of Aza in lower risk MDS. A lower dose regimen, AZA 5 (75 mg/mq daily, subcutaneously, for 5 consecutive days every 4 weeks) have shown to induce response rates consistent with the currently approved schedule (Lyons, 2009), however in this study pts were not classified according to IPSS risk. Aim: In our phase II, prospective, multicentric trial, AZA 5 regimen was administered to IPSS low-or-intermediate-1 risk pts, for a total of 8 courses, in order to evaluate its efficacy and safety. Furthermore pharmacogenomic studies (GEP, SNP) cytokine network and PI-PLCbeta1 methylation and gene expression, before and at the end of 4th and 8th course of Aza treatment, were planned to identify new biological markers to predict the response. Methods: From September 2008 to February 2010, 34 low-risk MDS patients with a median age of 71 (56–84) yrs were enrolled into the study. Results: At present time 30/34 pts are evaluable: 26/30 pts (87%) completed the treatment plan (8 courses). According to the 2006 International Working Group criteria, overall response rate (ORR) was 58% (15/26 pts): 5 pts (19%) achieved complete remission (CR), while 10 pts (39%) showed an hematologic improvement (HI). 11/26 pts (42%) maintained a stable disease (SD). Generally the drug was very well tolerated. The most commonly reported hematologic toxicities were neutropenia (55%) and thrombocytopenia (20%). 4/30 pts (13%) died during treatment. The median duration of response was 5 months (range 1–14 months). Surprisingly, 3/15 patients (2 CR and 1 HI erythroid) showed a long duration of response (11, 13 and 14 months, respectively), still ongoing, after discontinuation of AZA. Preliminary data on the lipid signalling pathways suggested a direct correlation between the demethylating effect on PI-PLC-beta1 and responsiveness to treatment. Conclusion: Our study shows that AZA low-dose schedule may be a feasible and effective treatment for low-risk MDS pts and may induce durable responses. Despite AZA safety, extreme caution is needed in pts with age-related comorbidities and/or with severe neutropenia or thrombocytopenia, especially in low-risk MDS. Furthermore, PIPLC-b1 demethylation and gene expression could represent a new biological marker to predict the clinical response to AZA

The Arizona Radio Observatory (ARO) operates two radio telescopes in the millimeter and sub-millimeter wavelength region. Recently, one of these instruemnts, the aging, former NRAO 12 meter telescope on Kitt Peak, was replaced with one of the 12 m ALMA prototype antennas. The high performance design of this new instrument, including its 20 microns surface and sub-arcsecond pointing, will expand observational capabilites at the ARO. New receivers and backends are also in development at ARO. A dual polarization sideband separating SIS mixer covering the 0.7 mm atmospheric windw, ranging from 385 GHz to 500 GHz, has been installed as a facility instrument on the Sub-Millimeter Telescope (SMT) on Mount Graham. A prototype Band 2 receiever, based on HEMT amplifier technology, has been built and tested on the sky. These new additions and other developments will be presented.

Objective: To determine the predictive value and define threshold levels for basal antral follicle number and mean ovarian diameter in patients undergoing ART cycles. Design: Retrospective. Setting: Tertiary care center. Patients: Two hundred seventy-eight patients who had ovarian measurements performed on cycle day 3 before beginning treatment with gonadotropins. Intervention: Pretreatment ovarian ultrasound measurements. Main Outcome Measure: Number of oocytes retrieved, hormone levels, and cycle outcomes. Results: A direct linear correlation was observed between mean ovarian diameter and basal follicle number. Both measures demonstrated a positive linear correlation with recovered oocytes, basal E 2 , and peak E 2 . Both demonstrated a negative linear correlation with ampules of gonadotropins administered, days of stimulation, patient age, cycle day 3 FSH, and FSH:LH ratio. An antral follicle count of ≤10 or a mean ovarian diameter of Conclusions: Ovarian diameter and basal antral follicle number identify patients who may respond poorly to ART stimulation. These ovarian measures correlate well with ART screening and stimulation parameters. This knowledge allows physicians to evaluate and counsel patients immediately before an ART stimulation and to optimize stimulation protocols.

The methods of Krishnamoorthy et al. [Krishnamoorthy, U., Sniffen, C.J., Stern, M.D., Van Soest, P.J., 1983. Evaluation of a mathematical model of rumen digestion and an in vitro simulation of rumen proteolysis to estimate the rumen undegraded nitrogen content of feedstuffs. Br. J. Nutr. 50, 555–568] and Roe et al. [Roe, M.B., Sniffen, C.J., Chase, L.E., 1990. Proc. Cornell Nutrition Conference, Dept. of Animal Science, Cornell University, Ithaca, NY, pp. 81–88], and a new one presented in this paper have been compared, and a revised procedure is proposed using a fixed ratio of enzyme to true protein (TP) determined by tungstic acid precipitation. A comparison of the three methods shows that they are statistically different. The ratio of enzyme has also significant effect ( p >0.01) on the estimate of degradable nitrogen when compared to the fixed concentration of enzyme in the original method. The effect of buffer pH (6.7 vs. 8) on degradation of protein sources was also statistically significant ( p >0.05) with somewhat higher degradation at pH 8.

As the Atacama Large Millimeter/submillimeter Array (ALMA) nears completion, 73 dual-polarization receivers have been delivered for each of Bands 3 (84-116 GHz) and 6 (211-275 GHz). The receivers use sideband-separating superconducting Nb/Al-AlOx/Nb tunnel-junction (SIS) mixers, developed for ALMA to suppress atmospheric noise in the image band. The mixers were designed taking into account dynamic range, input return loss, and signal-to-image conversion (which can be significant in SIS mixers). Typical SSB receiver noise temperatures in Bands 3 and 6 are 30 K and 60 K, resp., and the image rejection is typically 15 dB., Submitted to IEEE Trans. Microwave Theory Tech., June 2013. 10 pages, 21 figures

HAEMATHOLOGICA, VOL 86 (SUPPL) N.RO 10

A large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72, a gene located on chromosome 9p21, has been recently reported to be responsible for 40% of familial amyotrophic lateral sclerosis cases of European ancestry. The aim of the current article was to describe the phenotype of amyotrophic lateral sclerosis cases carrying the expansion by providing a detailed clinical description of affected cases from representative multi-generational kindreds, and by analysing the age of onset, gender ratio and survival in a large cohort of patients with familial amyotrophic lateral sclerosis. We collected DNA and analysed phenotype data for 141 index Italian familial amyotrophic lateral sclerosis cases (21 of Sardinian ancestry) and 41 German index familial amyotrophic lateral sclerosis cases. Pathogenic repeat expansions were detected in 45 (37.5%) patients from mainland Italy, 12 (57.1%) patients of Sardinian ancestry and nine (22.0%) of the 41 German index familial amyotrophic lateral sclerosis cases. The disease was maternally transmitted in 27 (49.1%) pedigrees and paternally transmitted in 28 (50.9%) pedigrees (P = non-significant). On average, children developed disease 7.0 years earlier than their parents [children: 55.8 years (standard deviation 7.9), parents: 62.8 (standard deviation 10.9); P = 0.003]. Parental phenotype influenced the type of clinical symptoms manifested by the child: of the 13 cases where the affected parent had an amyotrophic lateral sclerosis-frontotemporal dementia or frontotemporal dementia, the affected child also developed amyotrophic lateral sclerosis-frontotemporal dementia in nine cases. When compared with patients carrying mutations of other amyotrophic lateral sclerosis-related genes, those with C9ORF72 expansion had commonly a bulbar onset (42.2% compared with 25.0% among non-C9ORF72 expansion cases, P = 0.03) and cognitive impairment (46.7% compared with 9.1% among non-C9ORF72 expansion cases, P = 0.0001). Median survival from symptom onset among cases carrying C9ORF72 repeat expansion was 3.2 years lower than that of patients carrying TARDBP mutations (5.0 years; 95% confidence interval: 3.6-7.2) and longer than those with FUS mutations (1.9 years; 95% confidence interval: 1.7-2.1). We conclude that C9ORF72 hexanucleotide repeat expansions were the most frequent mutation in our large cohort of patients with familial amyotrophic lateral sclerosis of Italian, Sardinian and German ancestry. Together with mutation of SOD1, TARDBP and FUS, mutations of C9ORF72 account for 60% of familial amyotrophic lateral sclerosis in Italy. Patients with C9ORF72 hexanucleotide repeat expansions present some phenotypic differences compared with patients with mutations of other genes or with unknown mutations, namely a high incidence of bulbar-onset disease and comorbidity with frontotemporal dementia. Their pedigrees typically display a high frequency of cases with pure frontotemporal dementia, widening the concept of familial amyotrophic lateral sclerosis.

Purpose In 1987 the Italian Cooperative Group for the Study of hairy cell leukemia (HCL) started a prospective trial with the following three major aims: 1) to confirm the effectiveness of alpha-IFN as first-line treatment; 2) to assess the usefulness of splenectomy as consolidation treatment in patients achieving a satisfactory partial remission (PR) with alpha-IFN, and 3) to explore whether splenectomy in patients achieving complete remission (CR) with alpha-IFN can reduce the risk of relapse after discontinuation of the drug. Patients and methods One-hundred seventy-seven patients with histologically-confirmed HCL were registered in the HCL88-A trial between December 1987 and January 1992. Inclusion criteria included no previous treatment and age less than 66 years. All patients received total doses of 3 MU of alpha-IFN daily for 12 months except for those who achieved early CR and would stop treatment after 6 or 9 months. Patients could be treated with different alpha-IFNs. At the time of the present analysis, 166 patients (93.8%) were fully evaluable. Results Treatment of HCL patients with alpha-IFN at the onset of the disease resulted in 28 CR (16.9%), 103 PR (62.0%), and 27 Minor Remissions (MR) (16.3%). Patients treated with different alpha-IFNs achieved similar results: the overall response rate (CR + PR + MR) was 92.7%, 97.2%, and 95.3% for patients treated with r-alpha-2a, r-alpha 2b, and alpha-N1, respectively. The presence of a leukemic phase and a poor performance status were associated with a statistically significant lower response rate. Patients who were randomly assigned and underwent splenectomy after achieving a PR had a better but not significant 4-year progression-free survival than cases randomized for observation (53% vs. 22%, p = 0.116). Overall, 5 patients died after study entry, with an actuarial 5-year survival rate of 96% for the entire group of 166 patients. After a mean follow-up time of 38 months, only one second malignancy has been recorded. Conclusions Initial therapy with alpha-IFN, regardless of the type of alpha-IFN used, induces satisfactory responses in the majority of patients with HCL, but in most instances discontinuation of treatment results in recurrence of disease. In most cases alpha-IFN improves the performance status of patients and favors a satisfactory bone marrow recovery and thus could still play a role in the initial management of the disease. Although splenectomy following alpha-IFN could prolong the progression free survival, its use should be restricted to selected cases.

Astronomical observations in the millimeter and sub-millimeter regions are performed at the two facilities of the Arizona Radio Observatory (ARO). The Sub-Millimeter Telescope (SMT) located on Mount Graham utilizes 3 heterodyne SIS receivers to cover 3 of the 4 atmospheric windows from 210 to 720 GHz and soon a new receiver will cover the remaining window. The 12-Meter telescope located on Kitt Peak use 3 heterodyne SIS receivers to the cover the 2 windows from 68 to 180 GHz. All receivers now employ orthogonal polarization optics and soon 4 will utilize wideband dual channel sideband separating mixer technology. Presented here are new instrumentation developments and recent scientific results from the ARO.

In this paper a Boolean neural networks which is able to learn and to control temporal sequences of simple behaviors (called primitive) is prsented. This ability is based on a specific organization of subnetworks called assemblies. We discuss here a novel model of assembly.

Here, we discuss a Boolean neural networks which is able to learn and to control temporal sequences of simple behaviors (called primitive). This property is achieved by imposing a specific neural network organization. In particular, in this paper we underline that by this specific organization a Boolean neural network can be considered as ruled based system learning new rules by examples.

To train a Boolean neural network to comment on the progress of the task it is controlling, we have implemented in the network an Hebbian rule with the help of the node assemblies. Actually, our network can comment also on its communications with us without any danger to enter in a loop-like endeless activity

– The authors present their experience with bilateral renal cell carcinoma, as well as an assessment of the tumour for possible conservative surgery with partial mono or bilateral nephrectomy.

Ninety ET patients diagnosed according to the PVSG criteria entered a phase II study designed to identify a treatment with PEG Interferon α-2b (PEG Intron, Schering-Plough Corp) safe and able to obtain and to maintain for a long time the Hematological Response (HR, PLTs < 500x 109/L). The patients, 30 Males and 60 Females, median age 45 years (18–72), judged at risk and in the majority of cases pre-treated with cytoreductive drugs (60%), at study entry showed a mean PLT count of 1093 ± 357 x 109/L (>1000 in 49% of cases). During the first year (part 1 of the study) the PEG Intron starting dose of 25 μg/week was gradually increased if necessary at week 13, 26 and 39 till a maximum of 100 μg/week to reach the HR. The HR at the end of the 1st year (primary endpoint) was registered in 64 patients who represented the 71% of the 90 enrolled subjects (analysis on Intent-to-Treat, ITT) and the 79% of the 81 patients still receiving PEG Intron. The PEG Intron effective dose had a mean value of 50 ± 22 μg/week resulting very low (25μg/week) in 33% of cases. The primary endpoint was reached independently by sex, age, cytoreductive pre-treatment and baseline PLT count. Nevertheless, the HR was more frequent in the patients with true ET respect those with false ET (WHO criteria, HR 93% vs. 68%). In the 64 responder patients admitted to the part 2 of the study according to the protocol, the HR at the end of the 2nd year was registered in 75% of cases on ITT and in 87% of the 55 patients still on treatment, with a PEG Intron maintenance dose gradually reduced to a mean level of 27 μg/week. No thrombotic or hemorrhagic events occurred during the study and, moreover, a decrease of splenomegaly (from 22% to 6%) and of disease related symptoms (from 42% to 2%) was registered. The unmaintained HR, in 29 valuable patients who discontinued the PEG Intron treatment after two years, had a median duration of 11 weeks (4–52). Eighteen patients discontinued PEG Intron treatment (9 during the 1st year and 9 during the 2nd year) as consequence of PEG Intron toxicity and side effects (n 7), loss of compliance (n 5) and drug unrelated reasons (n 6). Toxicity and side effects (WHO grading) were never of grade 4, in very few cases of grade 3 and in the majority of patients of grade 1 or 2 (mainly flu-like syndrome, leukopenia, hypertransaminasemia). The ECOG Performance status (PS) was of grade 0 in all but few patients who showed a transitory grade 1 PS. In conclusion, PEG Intron treatment performed at relatively low dose seems safe and able to induce and to maintain the HR for a long time in the majority of at risk ET patients.

Recent studies suggest that extracorporeal photochemotherapy (ECP) may be beneficial in patients with steroid-refractory chronic graft-versus-host disease (cGvHD). However, it is not yet clear whether certain conditions, such as age, mode of onset of cGvHD etc., influence clinical response and whether certain affected organs are more sensitive to ECP than others. We analysed the main clinical and laboratory parameters related to evolution of the disease in 32 steroid-refractory cGvHD patients, to identify any useful response predictors to ECP. ECP affected the course of the disease positively in 78% (25/32) of our cases.

Major questions are whether mothers infected with the Human Immunodeficiency Virus type 1 (HIV-1) transmit the virus through breast milk and the magnitude of the additional transmission risk. The demonstration of a dose-response effect is an epidemiological method to demonstrate causality. Thus, a study was carried out by the Italian Register for HIV Infection in Children on 961 children of known infection status. Duration of breast-feeding was considered as the level of exposure in 168 ever breast-fed children. Results showed that duration of practice significantly increased the risk of transmission. The adjusted infection odds ratio for one day of breast- versus exclusive formula-feeding was 1.19 with narrow confidence limits (1.10-1.28). In a second study by the Register on 556 children of known infection status and derived prospectively, an infection odds ratio of 2.55 (confidence interval: 1.03-6.37) was calculated in breast- versus exclusively formula-fed children. Several lines of evidence, including the above-mentioned data from the Italian Register for HIV Infection in Children, showed a contribution of breast-feeding to mother-to-child HIV-1 transmission. Thus, this practice is now discouraged in HIV-1 infected mothers living in industrialized societies where formula feeding is practical and attainable. Mode of feeding was known in 2183 children enrolled in the Register and born to HIV-1 infected mothers since 1981. It could be observed that feeding habits of at-risk infants changed in Italy in the middle 1980s, when a large majority of subjects was identified at birth.(ABSTRACT TRUNCATED AT 250 WORDS)

YNK01 (Starasid) is a prodrug that is adsorbed in the gut and is transformed in the liver in arabinosyl cytosine (AC). Low-dose AC (LDAC) is useful for the treatment of Philadelphia positive (Ph+) chronic myeloid leukemia (CML), especially in combination with alpha-interferon (alphaIFN). The use of YNK01 can avoid the daily s.c. injection of conventional AC. To assess the safety and the efficacy of alphaIFN and YNK01, we enrolled 86 consecutive previously untreated chronic phase Ph+ CML patients in a phase II study of alphaIFN (Intron-A) 5 MIU/m(2) daily and YNK01 600 mg daily 14 days a month. The 6-month complete hematologic response and the 12-month major cytogenetic response rates were 78 and 28%, respectively. In a prior study of alphaIFN and conventional LDAC, they were 62 and 22%, respectively. However, the compliance to the treatment was poor, with 25% of cases discontinuing the treatment within the first year. This was not because of the severity of the side effects but because of the frequency, duration and repetition of the side effects, for an overall frequency of 13.17 adverse events, mostly grade 1 and 2, per patient per year. Therefore, the study of this effective combination is being pursued, testing lower doses of alphaIFN and YNK01.

A 200-300 GHz SIS mixer-preamplifier with an IF bandwidth of 8 GHz Is described. The mixer uses Nb/Al-oxide/Nb tunnel junctions in a circuit with low IF capacitance and inductance. The mixer block is designed to mount directly on the body of the 4-12 GHz InP HFET preamplifier and mixer bias is provided through the input circuit of the preamplifier. At a LO frequency of 230 GHz, the mixer-preamp gain is 30-35 dB, and the DSB receiver noise temperature is 45-57 K across the whole IF band. This is the largest instantaneous bandwidth reported to date for an SIS receiver.

Progress in treatment of acute myeloid leukemia (AML) is slow and treatment intensification alone has limited effects, particularly in poor-risk cases. Poor-risk cases, that are identified mainly by prior history, leukemic cell mass and cytogenetic abnormalities, share multiple mechanisms of drug resistance that are responsible for treatment failure. Since Pgp-mediated resistance to anthracycline can be reduced with Idarubicin (IDA) and resistance to arabinosyl cytosine (AC) can be reduced with Fludarabine (FLUDA), we tested a combination of high dose AC (2000 mg/sqm, 5 doses), FLUDA (30 mg/sqm, 5 doses) and IDA (12 mg/sqm, 3 doses) for remission induction and consolidation in 45 consecutive cases of poor-risk AML. The complete remission (CR) rate was 71% after the first course and 82% overall, with a projected 2-year survival and relapse-free survival of 44% and 50% respectively. Non-hematologic toxicity was very mild, that is very important in elderly patients, but hemopoietic toxicity was substantial, with a time to hematologic recovery of 3 to 4 weeks and two cases of death in CR. Peripheral blood stem cells (PBSC) could be mobilized and collected successfully only in 11 cases. This three-drug combination is effective and has a limited non-hematologic toxicity, but FLUDA may increase the difficulty of obtaining PBSC early after remission induction.