Search for Leptonic Decays of Dark Photons at NA62.

The NA62 experiment at CERN, configured in beam-dump mode, has searched for dark photon decays in flight to electron-positron pairs using a sample of 1.4×10^{17} protons on dump collected in 2021. No evidence for a dark photon signal is observed. The combined result for dark photon searches in lepton-antilepton final states is presented and a region of the parameter space is excluded at 90% confidence level, improving on previous experimental limits for dark photon mass values between 50 and 600 MeV/c^{2} and coupling values in the range 10^{-6} to 4×10^{-5}. An interpretation of the e^{+}e^{-} search result in terms of the emission and decay of an axionlike particle is also presented.

Bloodstream infections in haematological cancer patients colonized by multidrug-resistant bacteria.

Infections by multidrug-resistant (MDR) bacteria are a worrisome phenomenon in hematological patients. Data on the incidence of MDR colonization and related bloodstream infections (BSIs) in haematological patients are scarce. A multicentric prospective observational study was planned in 18 haematological institutions during a 6-month period. All patients showing MDR rectal colonization as well as occurrence of BSI at admission were recorded. One-hundred forty-four patients with MDR colonization were observed (6.5% of 2226 admissions). Extended spectrum beta-lactamase (ESBL)-producing (ESBL-P) enterobacteria were observed in 64/144 patients, carbapenem-resistant (CR) Gram-negative bacteria in 85/144 and vancomycin-resistant enterococci (VREs) in 9/144. Overall, 37 MDR-colonized patients (25.7%) developed at least one BSI; 23 of them (62.2%, 16% of the whole series) developed BSI by the same pathogen (MDRrel BSI), with a rate of 15.6% (10/64) for ESBL-P enterobacteria, 14.1% (12/85) for CR Gram-negative bacteria and 11.1% (1/9) for VRE. In 20/23 cases, MDRrel BSI occurred during neutropenia. After a median follow-up of 80 days, 18 patients died (12.5%). The 3-month overall survival was significantly lower for patients colonized with CR Gram-negative bacteria (83.6%) and VRE (77.8%) in comparison with those colonized with ESBL-P enterobacteria (96.8%). CR-rel BSI and the presence of a urinary catheter were independent predictors of mortality. MDR rectal colonization occurs in 6.5% of haematological inpatients and predicts a 16% probability of MDRrel BSI, particularly during neutropenia, as well as a higher probability of unfavourable outcomes in CR-rel BSIs. Tailored empiric antibiotic treatment should be decided on the basis of colonization.

[Conservative management of traumatic priapism in paediatric patients]. / Manejo conservador del priapismo traumático en la edad pediátrica.

INTRODUCTION: High-flow priapism is infrequent in pediatric patients. It is mostly secondary to perineal trauma resulting in laceration of a penile artery and the formation of an arterio-cavernous fistula. It does not constitute a medical emergency in itself, and allows conservative management awaiting spontaneous resolution. CLINICAL CASE: A six-year-old boy with painless persistent erection preceded by perineal trauma. Ultrasound imaging confirmed the clinical suspicion of high flow priapism secondary to arterio-cavernous fistula. After adopting a conservative approach, the patient presented progressive detumescence, as well as ultrasound resolution one month after the episode. COMMENTS: In high-flow priapism, venous drainage of the penis is preserved. The classical approach in adults is based on therapeutic angiography, which presents greater technical complexity and the risk of iatrogenic hypoxia in pediatric patients.

INTRODUCCION: El priapismo de alto flujo es una entidad infrecuente en la edad pediátrica. Es, en su mayoría, secundario a traumatismo perineal que provoca la laceración de una arteria peneana y formación de una fístula arterio-cavernosa. No constituye una emergencia médica, permitiendo un manejo conservador a la espera de su resolución espontánea. CASO CLINICO: Niño de seis años con erección persistente e indolora tras traumatismo perineal. El diagnóstico ecográfico confirma la sospecha de priapismo de alto flujo secundario a fístula arteria-cavernosa. Tras manejo conservador, presenta detumescencia progresiva y resolución ecográfica al mes del episodio. COMENTARIOS: En el priapismo de alto flujo el drenaje venoso del pene se encuentra conservado. El manejo clásico en adultos se fundamenta en la angiografía terapéutica, de mayor complejidad técnica y riesgo de hipoxia iatrogénica en el paciente pediátrico.

The impact of comorbidity on health-related quality of life in elderly patients with chronic myeloid leukemia.

The primary objective of this study was to investigate whether the presence of comorbidities was associated with a lower health-related quality of life (HRQOL) in elderly patients with chronic myeloid leukemia (CML). A sample of 174 CML patients aged 60 years or above was analyzed. HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). A number of pre-selected sociodemographic and disease-related factors were considered as potential confounding factors for the association between comorbidity and HRQOL. Mean age of the 174 patients analyzed was 70 years (range 60-87 years) and 55 % were male. Overall, 111 patients (64 %) reported at least one comorbidity. Analysis stratified by age group category showed a greater proportion of patients with comorbidities in the older sub-group population (≥70 years) compared to younger patients (60 to 69 years). Differences in HRQOL outcomes between patients with no comorbidity at all and those with two or more comorbid conditions were at least twice the magnitude of a clinically meaningful difference in all the physical and mental health scales of the SF-36. In multivariate analysis, after adjusting for key confounding factors, the following scales were significantly lower in those with comorbidity: general health (p < 0.001), bodily pain (p < 0.001), physical functioning (p = 0.002), and vitality (p = 0.002). Assessing comorbidity in elderly patients with CML is important to facilitate identification of those most in need of HRQOL improvements.

HPV information campaigns in Italy since 2004.

BACKGROUND: Because of its high incidence, long duration and socio-economic relevance, HPV infection can be considered a social disease, which requires the intervention of the State through appropriate communication strategies. The aim of such action is to educate people to understand, choose and implement adequate methods of prevention. METHODS: This research presents a descriptive analysis of HPV public health campaigns in Italy since the first campaign in 2004 until today. The analysis focused on the distribution of the campaigns in terms of geographical distribution and time, the target audience, the style of the message, the medium used and the prevention message. RESULTS: Forty campaigns have been identified, the most numerous of these occurring in the regions of Central and Northern Italy between 2008 and 2014. The main target was women and the most used style was the informative. The most used medium was print material. However, in 92% of cases the campaign included a web portal. Primary prevention was the main message. CONCLUSIONS: The campaigns were inadequate both in terms of time and geographical distribution. Moreover, the campaigns were addressed mostly to adult female, did not include adequately teenagers and did not include teenagers and omitted the male target, adopting ineffective communication strategies. Finally, the additional factors that may increase the risk of HPV infection and related diseases were ignored.

Differences among young adults, adults and elderly chronic myeloid leukemia patients.

BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). CONCLUSIONS: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome. CLINICAL TRIAL NUMBERS: NCT00510926, NCT00514488, NCT00769327, NCT00481052.

Evaluation of interleukin-18 levels in patients affected by multiple myeloma and monoclonal gammopathy of undetermined significance: analysis and review of the literature.

OBJECTIVE: Monoclonal gammopathy of undetermined significance (MGUS) is a preneoplastic disease that often precedes multiple myeloma. The multistep evolutionary pattern of multiple myeloma is driven by genetic instability, a pro-inflammatory and immunosuppressive microenvironment, and tumor growth. Inflammation has long been recognized as a factor in both the onset and progression of cancer. PATIENTS AND METHODS: In this study, interleukin-18 plasma levels were compared in patients with multiple myeloma and monoclonal gammopathy of undetermined significance, as well as in a group of healthy controls. RESULTS: Our study shows that monoclonal gammopathy of undetermined significance patients have lower levels of interleukin-18 than healthy controls (521.657 ± 168.493 pg/ml vs. 1,266.481 ± 658.091 pg/ml for controls, p < 0.001). Thus, we discovered a significant difference in interleukin-18 levels between multiple myeloma patients and controls (418.177 ± 197.837 pg/ml; p = 0.001). CONCLUSIONS: In our work, we identified a reduction of interleukin-18 in monoclonal gammopathies. Furthermore, in this paper, we aimed to evaluate the existing literature on the potential mechanisms of action of this pro-inflammatory cytokine in the development of these diseases.

A human study model for nitric oxide research in sinonasal disease.

Sinus nitric oxide (NO) measurements present a novel and promising approach to help overcome difficulties and confounding variables associated with nasal NO measurements such as the nasal cycle, ostial patency, and individual contribution to total NO production of each sinus. Conflicting results reported on nasal NO measurements in various sinonasal diseases are presumed to originate from the variable diffusion of sinus NO into the nose where it is measured. This study presents a novel technique and research method for direct measurement of sinus NO. The authors' original technique of individual, non-destructive catheterization of the sinuses through their natural ostia is developed and refined to allow accurate measurements of NO produced in the sinuses. Our study indicates that reproducible catheterization of the sinuses through their natural ostia can be performed in the clinical research setting under local and topical anesthesia. The model can be used to test the effects of various conditions on nasal and sinus NO production in a variety of disease models and the variables affecting sinonasal gas exchange can be differentially studied. Volunteer healthy adult human subjects without nasal allergies are used. An endoscopic nasal exam with topical anesthesia followed by in vitro allergy testing is performed to determine eligibility. Sinus computerized tomography (CT) scans are used to delineate anatomic features and to calculate paranasal sinus volumes. Continuous flow sinus air sampling and NO measurement with a chemiluminescence analyzer is obtained through polyethylene tube catheters (PEC) placed endoscopically into an aerated major paranasal sinus. Catheters are introduced through natural ostia under local and topical anesthesia. Nasal and differential sinus NO measurements are performed.

Usefulness of intraoperative voiding cystourethrogram as an indicator of success in the endoscopic treatment of vesicoureteral reflux. / Utilidad de la cistouretrografía miccional intraoperatoria como indicador de éxito del tratamiento endoscópico del reflujo vesicoureteral.

OBJECTIVE: Up until now, serial voiding cystourethrogram (SVCU) has been regarded as the gold standard technique in the diagnosis of vesicoureteral reflux (VUR). The aim of intraoperative SVCU during endoscopic treatment is to detect those patients eligible to receive more biosynthetic material as a result of persistent VUR. The objective of this study was to assess the usefulness of SVCU as a predictor of treatment success. MATERIALS AND METHODS: An analytical, retrospective study of patient medical records was carried out. Patients included had undergone endoscopic VUR surgery from 2000 to 2019, and they were measured in ureteral units. VUR persistence at intraoperative SVCU following treatment was compared with SVCU results after 3 months. RESULTS: Of a total of 167 ureteral units undergoing surgery, persistent reflux immediately after surgery was observed in 17 cases (10% of the sample). Only 3 cases had other urological malformations. In the SVCU carried out after 3 months, reflux was found in 38% of the sample (64 cases). When comparing the results, intraoperative SVCU demonstrated a specificity of 92.6%, and a sensitivity of 15.6%. CONCLUSIONS: Given the low sensitivity (15.6%) of intraoperative SVCU to detect cases of persistent reflux in the mid-term, and considering the risks associated with radiation in the pediatric population - which is extremely sensitive to it -, intraoperative SVCU should be ruled out as a useful indicator of endoscopic treatment success.

OBJETIVO: La cistouretrografía miccional seriada (CUMS) ha sido hasta ahora el gold standard en el diagnóstico del reflujo vesicoureteral (RVU). La finalidad de la CUMS intraoperatoria durante el tratamiento endoscópico es detectar aquellos pacientes subsidiarios de inyectar más material biosintético por persistencia del RVU. En este estudio hemos querido evaluar la utilidad de esta prueba como predictor de éxito del tratamiento. MATERIAL Y METODOS: Estudio analítico retrospectivo mediante la revisión de historias clínicas de pacientes, medidos en unidades ureterales, intervenidos de RVU de forma endoscópica entre los años 2000 y 2019. Se comparó la persistencia de RVU en la CUMS intraoperatoria tras el tratamiento con el resultado de la CUMS a los 3 meses. RESULTADOS: De un total de 167 unidades ureterales intervenidas, se observó persistencia del reflujo inmediatamente tras la intervención en 17 casos (10% de la muestra). Solo 3 asociaban otras malformaciones urológicas. En la CUMS a los 3 meses se observó reflujo en el 38% de la muestra (64 casos). Al comparar los resultados, obtenemos para la CUMS intraoperatoria una especificidad del 92,6% y una sensibilidad del 15,6%. CONCLUSIONES: Dada la baja sensibilidad (15,6%) de la CUMS intraoperatoria para detectar los casos en los que persiste el reflujo a medio plazo y, teniendo en cuenta los riesgos asociados a la radiación que supone en una población especialmente sensible como es la pediátrica, se desestima su utilidad como indicador de éxito del tratamiento endoscópico.

How usefulness shapes neural representations during goal-directed behavior.

Value is often associated with reward, emphasizing its hedonic aspects. However, when circumstances change, value must also change (a compass outvalues gold, if you are lost). How are value representations in the brain reshaped under different behavioral goals? To answer this question, we devised a new task that decouples usefulness from its hedonic attributes, allowing us to study flexible goal-dependent mapping. Here, we show that, unlike sensory cortices, regions in the prefrontal cortex (PFC)-usually associated with value computation-remap their representation of perceptually identical items according to how useful the item has been to achieve a specific goal. Furthermore, we identify a coding scheme in the PFC that represents value regardless of the goal, thus supporting generalization across contexts. Our work questions the dominant view that equates value with reward, showing how a change in goals triggers a reorganization of the neural representation of value, enabling flexible behavior.

Melatonin Hormone Acts on Cells of Maternal Blood and Placenta From Diabetic Mothers.

Changes in glucose metabolism of diabetic mothers affect immunological components, proinflammatory factors, and placental hypervascularization that can induce cell death. The hormone melatonin has been identified as a potential modulating agent. The aim of this study was to analyze the oxidative process and the apoptosis in maternal blood and placental cells modulated by melatonin from diabetic mothers. The groups were 40 pregnant women divided into non-diabetic (ND) and type 2 diabetes mellitus (T2DM) groups. Blood and placental cells were obtained by density gradient and maintained in culture treated or not with melatonin (100 ng/mL) for 24 h (37°C, 5% CO2). Oxidative stress was evaluated by superoxide release and CuZn superoxide dismutase (SOD). Apoptosis was assessed by flow cytometry. Maternal hyperglycemia increased superoxide release and apoptosis in MN cells from maternal blood and reduced SOD level and SOD/O2- ratio. Melatonin reduced oxidative stress and apoptosis rates in MN cells in the blood of diabetic mothers. There was a reduction in SOD and SOD/O2- ratio in the placental extravillous layer, and melatonin restored the concentrations of this enzyme. There was greater superoxide release, reduced SOD/O2- ratio, and apoptosis in MN cells placental villous layer. Melatonin increased apoptosis rates in the placental villous layer from hyperglycemic mothers. These data suggest that hyperglycemia altered the processes oxidative in blood and placenta from hyperglycemic mothers. These changes reflected in the mechanisms of induction of apoptosis, especially in the vascularized layers of the placenta, and were modulated by melatonin.

The condom use among young adults and its determinants: an Italian study.

Numerous health risk behaviours have been identified as an issue in early adulthood, especially among university students, a particularly high-risk category for sexual and reproductive health. The aim of this study is to examine the condom use and its determinants among young adult in Italy. The hypothesis is that individuals' demographic characteristics (gender, faculty, to have a committed partner, to be resident) and the risk perception may play a role in condom use. The results indicate that the frequency of condom use is related to the magnitude of risk perception of certain STIs and to demographic characteristics. All the STI risks perception and the risk perception of unintended pregnancy are statistically significant associated with frequency of condom use (p<0.001). By contrast the frequency of condom use is not statistically significant associated with the following demographic characteristics: gender, faculty, to have a committed partner, to be resident. Furthermore association with age groups is observed (p=0.030). Findings suggest that universities have an opportunity to access young people's sexual health risk behaviours and at the same time to impact on sexual health promotion. University health educators and staff at student health centers could play an active role in educational campaigns.

Etiological investigation of multiple respiratory infections in cats.

In order to evaluate the relevance of multiple infections in domestic cats with Upper Respiratory Tract Disease (URTD) one hundred animals with clinical signs were investigated for detection of Feline Herpesvirus type-1 (FHV-1), Chlamydophila felis, Feline Calicivirus (FCV) and Bordetella bronchiseptica from mucosal swabs. Forty-seven cats were positive for FCV, 42 cats for FHV-1, 26 for B. bronchiseptica and 8 for C. felis. Dual or multiple infections were found in 33 of examined animals. Our results document that FCV and FHV-1 are the major recognized cause of URTD, although infections associated with other pathogens such as B. bronchiseptica or C. felis are also common in cats.

Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study.

The single-arm, phase 2 ENESTfreedom trial assessed the potential for treatment-free remission (TFR; i.e., the ability to maintain a molecular response after stopping therapy) following frontline nilotinib treatment. Patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase with MR4.5 (BCR-ABL1⩽0.0032% on the International Scale (BCR-ABL1IS)) and ⩾2 years of frontline nilotinib therapy were enrolled. Patients with sustained deep molecular response during the 1-year nilotinib consolidation phase were eligible to stop treatment and enter the TFR phase. Patients with loss of major molecular response (MMR; BCR-ABL1IS⩽0.1%) during the TFR phase reinitiated nilotinib. In total, 215 patients entered the consolidation phase, of whom 190 entered the TFR phase. The median duration of nilotinib before stopping treatment was 43.5 months. At 48 weeks after stopping nilotinib, 98 patients (51.6%; 95% confidence interval, 44.2-58.9%) remained in MMR or better (primary end point). Of the 86 patients who restarted nilotinib in the treatment reinitiation phase after loss of MMR, 98.8% and 88.4%, respectively, regained MMR and MR4.5 by the data cutoff date. Consistent with prior reports of imatinib-treated patients, musculoskeletal pain-related events were reported in 24.7% of patients in the TFR phase (consolidation phase, 16.3%).

Extramedullary involvement at relapse in acute promyelocytic leukemia patients treated or not with all-trans retinoic acid: a report by the Gruppo Italiano Malattie Ematologiche dell'Adulto.

PURPOSE: Recent reports of extramedullary disease (EMD) at recurrence in acute promyelocytic leukemia (APL) have raised increasing concern about a possible role of retinoic acid (RA) therapy. PATIENTS AND METHODS: We analyzed the risk of developing EMD localization at relapse in APL patients enrolled onto two consecutive studies of the Gruppo Italiano Malattie Ematologiche dell'Adulto. The studies investigated chemotherapy alone (LAP0389) versus RA plus chemotherapy (AIDA). RESULTS: When all relapse types were taken into account, 94 (51%) of 184 patients and 131 (18%) of 740 patients who attained hematologic remission underwent relapse in the LAP0389 and AIDA studies, respectively (P < .0001). EMD localization was documented in five (5%) of 94 and 16 (12%) of 131 patients (P = .08). Hematologic and/or molecular relapse was diagnosed concomitantly in all but two patients with EMD in the AIDA study. For patients in the LAP0389 and AIDA series, the probability of EMD localization of any type at relapse was 3% and 4.5%, respectively (P = .79), while the probability of CNS involvement was 0.6% and 2% (P = .28). No significant differences were found with regard to mean WBC count and promyelocytic leukemia/retinoic acid receptor-alpha junction type in comparisons of patients with EMD and hematologic relapse. CONCLUSION: APL patients receiving all-trans retinoic acid in addition to chemotherapy have no increased risk of developing EMD at relapse as compared with those treated with chemotherapy alone.

CD56 expression is an indicator of poor clinical outcome in patients with acute promyelocytic leukemia treated with simultaneous all-trans-retinoic acid and chemotherapy.

PURPOSE: Preliminary reports suggest that leukemic cell expression of CD56, a neural cell adhesion molecule, is associated with adverse clinical outcome in either acute myeloid leukemia with t(8;21) or acute promyelocytic leukemia (APL). We investigated the prognostic relevance of CD56 in a series of patients with APL who were treated homogeneously with all-trans-retinoic acid (ATRA) and chemotherapy. PATIENTS AND METHODS: Clinicobiologic presenting features and therapeutic results were analyzed in a series of 100 patients with genetically proven APL who were treated, according to the example of the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto multicenter trial, with ATRA plus idarubicin (AIDA) and for whom data on CD56 expression were available at diagnosis. RESULTS: Fifteen patients (15%) showed expression of CD56 in greater than or equal to 20% blasts at diagnosis and were considered as CD56(+). No differences were found regarding age, sex, WBC and platelet counts, incidence of coagulopathy, hemoglobin and fibrinogen levels, promyelocytic leukemia/retinoic acid receptor (PML/RAR) alpha fusion type, or complete remission (CR) rate in the comparison of the CD56(+) and CD56(-) populations. Conversely, compared with patients who were CD56(-), patients with CD56(+) APL had shorter CR duration (P =.04) and overall survival (P =.002). In the multivariate analysis, CD56 positivity and initial WBC count greater than 10 x 10(9) cells/L retained statistical significance in overall survival (P =.04 and P =.02, respectively). CONCLUSION: The expression of CD56 is significantly associated with inferior CR duration and survival in patients with APL who were treated with modern frontline treatment that included ATRA and simultaneous chemotherapy. Combined with other well-established prognostic factors such as WBC count, CD56 expression at diagnosis might be used to build prognostic scores for risk-adapted therapy in APL.

Diagnosis of ovine chlamydial abortions by PCR-RFLP performed on vaginal swabs.

Ovine enzootic abortion is an infectious and contagious disease clinically characterized by abortion and weak neonates, affecting sheep and goats. The etiological agent is Chlamydophila (C.) abortus, which is considered one of the most common animal pathogens of small ruminants; it has important economic implications and represents a significant zoonotic risk. Clinical diagnosis is often difficult because the clinical signs and the pathological lesions are not specific for C. abortus infection, in fact they can also be observed as a result of infections with other abortifacient agents. Moreover, the involvement of the laboratory is necessary to perform the definitive diagnosis. One hundred and seventeen vaginal swabs from sheep with clinical signs related to chlamydial infection were examined by a PCR-RFLP assay that demonstrated high specifity and sensitivity. Six samples were positive for C. abortus. Vaginal swabs are easy to handle and allow to deal with biohazardous material in safety conditions.

Mutations and long-term outcome of 217 young patients with essential thrombocythemia or early primary myelofibrosis.

We investigated the influence of molecular status on disease characteristics and clinical outcome in young patients (⩽ 40 years) with World Health Organization (WHO)-defined essential thrombocythemia (ET) or early/prefibrotic primary myelofibrosis (early-PMF). Overall, 217 patients with ET (number 197) and early-PMF (number 20) were included in the analysis. Median follow-up time was 10.2 years. The cumulative incidence of thrombosis, hemorrhages and disease evolution into myelofibrosis/acute leukemia were 16.6%, 8.6% and 3% at 15 years, respectively. No differences were detectable between ET and early-PMF patients, although the latter cohort showed a trend for worse combined-event free survival (EFS). Mutation frequency were 61% for JAK2V617F, 25% for CALR and 1% for MPLW515K, and were comparable across WHO diagnosis; however, JAK2V617F allele burden was higher in the early-PMF group. Compared with JAK2V617F-positive patients, CALR-mutated patients displayed higher platelet count and lower hemoglobin level. CALR mutations significantly correlated with lower thrombotic risk (9.1% versus 21.7%, P = 0.04), longer survival (100% versus 96%, P = 0.05) and better combined-EFS (86% versus 71%, P = 0.02). However, non-type 1/type 2 CALR mutations ('minor' mutations) and abnormal karyotype were found to correlate with increased risk of disease evolution. At last contact, six patients had died; in five cases, the causes of death were related to the hematological disease and occurred at a median age of 64 years (range: 53-68 years). Twenty-eight patients (13%) were unmutated for JAK2, CALR and MPL: no event was registered in these 'triple-negative' patients.

Long-term outcome of chronic myeloid leukemia patients treated frontline with imatinib.

For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients.