Validation of the Meet-URO score in patients with metastatic renal cell carcinoma receiving first-line nivolumab and ipilimumab in the Italian Expanded Access Program.

BACKGROUND: The Meet-URO score allowed a more accurate prognostication than the International Metastatic RCC Database Consortium (IMDC) for patients with pre-treated metastatic renal cell carcinoma (mRCC) by adding the pre-treatment neutrophil-to-lymphocyte ratio and presence of bone metastases. MATERIALS AND METHODS: A post hoc analysis was carried out to validate the Meet-URO score on the overall survival (OS) of patients with IMDC intermediate-poor-risk mRCC treated with first-line nivolumab plus ipilimumab within the prospective Italian Expanded Access Programme (EAP). We additionally considered progression-free survival (PFS) and disease response rates. Harrell's c-index was calculated to compare the accuracy of survival prediction. RESULTS: Overall the EAP included 306 patients, with a median follow-up of 12.2 months, median OS was not reached, 1-year OS was 66.8% and median PFS was 7.9 months. By univariable analysis, both the IMDC score and the two additional variables of the Meet-URO score were associated with either OS or PFS (P < 0.001 for all comparisons). The four Meet-URO risk groups (G) had 1-year OS of 92%, 72%, 50% and 21% for G2 (29.1% of patients), G3 (28.8%), G4 (33.0%) and G5 (9.1%), respectively. OS was significantly shorter in each consecutive G (P = 0.001 for G3, P < 0.001 for both G4 and G5 compared to G2). Similarly, Meet-URO Gs 2-5 showed decreasing median PFS and response rates. The Meet-URO score showed the highest c-index for both OS (0.73) and PFS (0.67). Limitations include the post hoc nature of this analysis and the lack of a comparative arm to assess predictive value. CONCLUSION: The Meet-URO score appeared to show better prognostic classification than the IMDC alone in patients with mRCC at IMDC intermediate-poor risk treated with first-line nivolumab and ipilimumab.

Incidence, risk factors and clinical outcome of leukemia relapses with loss of the mismatched HLA after partially incompatible hematopoietic stem cell transplantation.

Genomic loss of the mismatched human leukocyte antigen (HLA) is a recently described mechanism of leukemia immune escape and relapse after allogeneic hematopoietic stem cell transplantation (HSCT). Here we first evaluated its incidence, risk factors and outcome in 233 consecutive transplants from partially HLA-mismatched related and unrelated donors (MMRD and MMUD, respectively). We documented 84 relapses, 23 of which with HLA loss. All the HLA loss relapses occurred after MMRD HSCT, and 20/23 in patients with acute myeloid leukemia. Upon MMRD HSCT, HLA loss variants accounted for 33% of the relapses (23/69), occurring later than their 'classical' counterparts (median: 307 vs 88 days, P<0.0001). Active disease at HSCT increased the risk of HLA loss (hazard ratio (HR): 10.16; confidence interval (CI): 2.65-38.92; P=0.001), whereas older patient ages had a protective role (HR: 0.16; CI: 0.05-0.46; P=0.001). A weaker association with HLA loss was observed for graft T-cell dose and occurrence of chronic graft-versus-host disease. Outcome after 'classical' and HLA loss relapses was similarly poor, and second transplantation from a different donor appeared to provide a slight advantage for survival. In conclusion, HLA loss is a frequent mechanism of evasion from T-cell alloreactivity and relapse in patients with myeloid malignancies transplanted from MMRDs, warranting routine screening in this transplantation setting.

Hepatitis B reactivation in HBsAg-negative/HBcAb-positive allogeneic haematopoietic stem cell transplant recipients: risk factors and outcome.

HBsAg-negative/HBcAb-positive haematopoietic stem cell transplant (HSCT) recipients are at high risk of hepatitis B virus (HBV) reactivation. Allogeneic HSCT recipients from years 2000 to 2010 were evaluated in order to study the impact of being HBsAg-negative/HBcAb-positive in this population. Overall, 137 of 764 patients (18%) were HBsAg-negative/HBcAb-positive before HSCT. Overall survival, non-relapse mortality (NRM), acute and chronic graft-vs.-host disease were similar in HBcAb-positive and HBcAb-negative patients. Reactivation occurred in 14 patients (10%) within a median of 19 months after HSCT (range 9-77). Cause-specific hazard for reactivation was decreased in the case of an HBV-immune/exposed donor (HRadjusted = 0.12; 95% CI, 0.02-0.96; p 0.045) and increased in patients who received rituximab treatment (HRadjusted = 2.91; 95%CI, 0.77-10.97; p 0.11). Competing risk analyses documented a protective role of an HBV-immune/exposed donor (p 0.041) and an increased probability associated with the length of treatment with cyclosporine (p <0.001) and treatment with rituximab (but not with low-dose rituximab prophylaxis, p <0.001 at each landmark point). No differences in overall survival and NRM were found between patients with and without HBV reactivation. The donor's immunity was independently and consistently associated with a decreased risk of HBV reactivation, while rituximab and cyclosporine treatments increased the probability.

Early and long-term outcomes after open or endovascular repair for abdominal aortic aneurysms in high-risk patients.

AIM: The aim of our study was to evaluate the earlier and long term survival as well the postoperative complications in high-risk patients who received endovascular aortic repair (EVAR) as first choice, or open repair when anatomical requirements for EVAR were not met. METHODS: Between January 2005 and January 2010, 593 patients underwent procedures for elective abdominal aortic aneurysm (AAA) repair; 172 of these were considered at high risk according to the American Society of Anesthesiology (ASA) score (ASA III and IV): 150 high-risk patients were males (mean age 72.7, range 53-93 years) and 22 females (mean age 72.9 years, range 60-90 years). The median AAA diameter was 64 (53-75) mm in the open repair group and 62 (55-70) mm in the EVAR group. 121 patients underwent open repair and 51 EVAR, respectively. RESULTS: The 30-day mortality rate was 0% in the EVAR group and 2.4% (3/121) in the open repair group (P=0.26). Long-term results showed: no EVAR-related mortality, no late conversion to open repair in the EVAR group was required during follow-up. No aneurysmal expansion was observed. In the open repair group, no graft-related events were observed during follow-up. The mean follow-up for survival analysis was 1542 days. Overall 5-year survival was 71.7% (SE=4.2%). Survival during follow-up was 92.2%, 86.1%, 76.2%, 65.9% and 61.8% at 12, 24,36,48,60 months respectively in EVAR Group. Open Group present long term survival of 95%, 88.9%, 83.9%, 79.7%, 76% at 12, 24, 36, 48, 60 months respectively. CONCLUSION: Our results in open repair surgery show a perioperative low mortality rate with high survival rate in long term. This result could be successfully achieved even in high-risk patients unsuitable for EVAR.

Feasibility of protein-sparing modified fast by tube (ProMoFasT) in obesity treatment: a phase II pilot trial on clinical safety and efficacy (appetite control, body composition, muscular strength, metabolic pattern, pulmonary function test).

Anecdotal data in the last few years suggest that protein-sparing modified diet (PSMF) delivered by naso-gastric tube enteral (with continuous feeding) could attain an significant weight loss and control of appetite oral feeding, but no phase II studies on safety and efficacy have been done up to now. To verify the safety and efficacy of a protein-sparing modified fast administered by naso-gastric tube (ProMoFasT) for 10 days followed by 20 days of a low-calorie diet, in patients with morbid obesity (appetite control, fat free mass maintenance, pulmonary function tests and metabolic pattern, side effects), 26 patients with a BMI ≥30 kg/m2 have been selected. The patients had to follow a protein-sparing fast by enteral nutrition (ProMoFasT) for 24 h/day, for 10 days followed by 20 days of low-calorie diet (LCD). The endpoint was represented by body weight, BMI, abdominal circumference, Haber's appetite test, body composition by body impedance assessment (BIA), handgrip strength test, metabolic pattern, pulmonary function test. Safety was assessed by evaluation of complications and side effects of PSMF and/or enteral nutrition. In this report the results on safety and efficacy are described after 10 and 30 days of treatment. After the recruiting phase, a total of 22 patients out of 26 enrolled [14 (63.6 %) females] were evaluated in this study. Globally almost all clinical parameters changed significantly during first 10 days. Total body weight significantly decreased after 10 days (∆-6.1 ± 2; p < 0.001) and this decrease is maintained in the following 20 days of LCD (∆ = -5.88 ± 1.79; p < 0.001). Also the abdominal circumference significantly decreased after 10 days [median (range): -4.5 (-30 to 0); p < 0.001] maintained then in the following 20 days of LCD [median (range) = -7 (-23.5 to -2); p < 0.001]. All BIA parameters significantly changed after 10 and 30 days from baseline. All parameters except BF had a significant change after 10 days of treatment while the difference at 30 days was lower than at 10 days for TBW, FFM and MM with no significant differences from baseline for the last two characteristics. For VAS appetite the difference was significant after 10 days and the decrease in appetite was maintained at 30 days with no significant difference (p = 0.83) between 10 and 30 days. No significant differences in the first 30 days were detected for PA and for both left and right hand grip strength. Particularly, a significant reduction of 1.82 kg in FFM after 10 days was detected, but not after 30 days. In contrast, a decrease of 3.8 kg of BF is observed after 30 days. As far as the respiratory functional tests (RFT) are concerned, a significant difference at 10 days was globally observed for functional residual capacity (p = 0.012) and expiratory reserve volume (p = 0.025). There are no reported major complications and side effects resulting from the enteral nutrition or PSMF. In particular, cardiac arrhythmias have not been reported. From the clinical point of view the PSMF with naso-gastric tube (ProMoFasT) method appears safe, it is associated with a significant weight loss related to decrease of FM and not to loss of FFM and appetite decreases. It is relevant that the RFT are significantly improved after only 10 days suggesting the efficacy of this regime in short period, too. These preliminary data underline the necessity to increase the number of RCT for this method, which could represent a possible alternative to other methodologies, such as the intragastric balloon, in particular when it is recommended to improve RFT before bariatric, gynecological, orthopedic and lymphatic surgery.

Tobacco smoking among students in an urban area in Northern Italy.

INTRODUCTION: Tobacco smoking, which usually begins in teenage, is one of the most important lifestyle risk factors for chronic diseases and a major public health problem worldwide. The aims of the study were to determine the prevalence of tobacco smoking and the mean age of initiation among adolescents in Genoa (Italy) and to identify some socio-demographic predictors that could be associated with the onset of smoking. MATERIALS AND METHODS: 2,301 randomly selected students (14-19 years old) in Genoa completed an ad hoc questionnaire. The Kaplan-Meier method was used to evaluate the instantaneous risk of experimenting with smoking. A multivariate logistic regression model was used to determine whether current or previous smoking status was associated with socio-demographic characteristics. RESULTS: 59.5% of respondents had tried smoking, while 35.6% defined themselves as current smokers. No difference in current smoking prevalence emerged between males and females (35.2% and 35.9%, respectively, p = 0.83). The mean age on initiation was 13.5 years for males and 13.9 years for females. The instantaneous probability of trying smoking changed with age, reaching a maximum at 14 years. Subjects who tried smoking before this age were more inclined to continue smoking. The probability of being a current smoker was significantly higher among students from unmarried-parent families and those attending vocational and technical secondary schools. CONCLUSIONS: There is a great need for the activation of new health promotion interventions and enforcement of those already existing, in order to raise awareness of the damage caused by smoking among adolescents, especially those belonging to high-risk groups.

Chronic GVHD is associated with lower relapse risk irrespective of stem cell source among patients receiving transplantation from unrelated donors.

Chronic GVHD (cGVHD) has been associated with reduced risk of relapse after allo-SCT for onco-hematological disease due to a graft-vs-malignancy effect. Here we retrospectively analyzed a series of 802 adult patients transplanted from unrelated donors and found that cGVHD was associated with significantly lower relapse and that the limited form was associated with a survival advantage: hazard ratio for OS=0.63 (0.46-0.87); P=0.004; this was due to combination of relapse reduction and similar non-relapse mortality with respect to patients without cGVHD. Importantly, the graft-vs-malignancy effect observed here did not differ when PBSC or BM were used as stem cell source, thus suggesting that the protective effect of limited cGVHD is similar after PBSC- or BM-based transplantation. These findings could have practical implications and suggest no qualitative difference between cGVHD occurring after transplantation performed with different stem cell sources.