High IPSS Score Research Articles

Long term outcomes from uncorrected hypospadias: a scoping review

IntroductionThe goal of hypospadias repair is to optimize urinary and sexual function, improve cosmesis and minimise the psychosocial effects associated with a penile anomaly. However, a lack of clarity exists regarding the role of surgery in milder hypospadias where the anomaly is inconspicuous and there is no anticipated impact on function. The aim of this study was to review the long term functional, cosmetic and psychosocial outcomes in men with uncorrected hypospadias. This information may be helpful for parents who are burdened with deciding the correct treatment for their child's hypospadias. MethodsA scoping review of PubMed, EMBASE, and CINAHL + databases was performed in adherence with PRISMA guidelines. Eight studies were identified for inclusion in the review. ResultsMen with mild uncorrected hypospadias have similar functional outcomes to those without hypospadias, preferring to void standing and reporting similar IPSS scores. However, those with severe untreated hypospadias experience significant urinary difficulties, higher IPSS scores, and are more likely to sit when voiding. They reported worse SHIM scores, more ventral curvature, and greater difficulty with intercourse. Most men with incidentally identified hypospadias are unaware of their condition and are satisfied with their penile appearance. There was no difference in the attainment of psychosocial milestones between men with uncorrected hypospadias versus no hypospadias. ConclusionThere is a lack of research regarding the experiences of adult men with uncorrected hypospadias. However, there is some evidence to support the non-operative management of mild hypospadias. Therefore, the decision to defer surgery in infancy should balance parental wishes and physician guidance, particularly in cases where the risk of functional impairment is low.

Resultados a largo plazo de hipospadias no intervenidos: una revisión exploratoria

IntroductionThe goal of hypospadias repair is to optimize urinary and sexual function, improve cosmesis and minimise the psychosocial effects associated with a penile anomaly. However, a lack of clarity exists regarding the role of surgery in milder hypospadias where the anomaly is inconspicuous and there is no anticipated impact on function. The aim of this study was to review the long term functional, cosmetic and psychosocial outcomes in men with uncorrected hypospadias. This information may be helpful for parents who are burdened with deciding the correct treatment for their child's hypospadias. MethodsA scoping review of PubMed, EMBASE, and CINAHL+ databases was performed in adherence with PRISMA guidelines. Eight studies were identified for inclusion in the review. ResultsMen with mild uncorrected hypospadias have similar functional outcomes to those without hypospadias, preferring to void standing and reporting similar IPSS scores. However, those with severe untreated hypospadias experience significant urinary difficulties, higher IPSS scores, and are more likely to sit when voiding. They reported worse SHIM scores, more ventral curvature, and greater difficulty with intercourse. Most men with incidentally identified hypospadias are unaware of their condition and are satisfied with their penile appearance. There was no difference in the attainment of psychosocial milestones between men with uncorrected hypospadias versus no hypospadias. ConclusionThere is a lack of research regarding the experiences of adult men with uncorrected hypospadias. However, there is some evidence to support the non-operative management of mild hypospadias. Therefore, the decision to defer surgery in infancy should balance parental wishes and physician guidance, particularly in cases where the risk of functional impairment is low.

Higher Prevalence of Chronic Kidney Disease in Myelodysplastic Syndromes Patients Compared to Age- Adjusted General Population - Results from the Polish Adult Leukemia Group (PALG) Registry

Introduction Chronic comorbidities that are common in the elderly population can have a significant impact on the clinical course, the choice of treatment, and survival of myelodysplastic syndromes (MDS) patients. No studies have focused on the coexistence of two diseases that are common in the elderly population, chronic kidney disease (CKD) and MDS, so the epidemiological data and clinical implications of both diseases occurring together are unknown. Aims Primary objective: to assess the prevalence of CKD in patients with MDS in comparison to the age-adjusted general population. Secondary objective: to evaluate the impact of CKD on clinical course in MDS patients. Methods This was a prospective analysis using clinical and laboratory data from MDS patients who were registered in the Polish Adult Leukemia Group (PALG) Registry from 2010 to 2023. Data have been provided by 28 hematologic centers. CKD was defined as an eGFR < 60 mL/min/1.73m², disregarding albuminuria since urinalysis results were not recorded in the database. The stages of CKD were classified based on eGFR according to the NKF KDOQI National Kidney Foundation Kidney Disease Outcome Quality Initiative guidelines, and eGFR was calculated using CKD-EPI equation. For comparison of the prevalence of CKD in MDS subjects aged ≥60 years to the general population, we used data from the PolSenior 2 study (covering the years 2018-2019). Data were age and sex standardized using demographic tables from Statistics Poland (https:// demografia.stat.gov.pl/bazademografia/Tables.aspx). Median survival time was calculated using Kaplan-Meier estimator. Multivariate analysis was performed using Cox regression. Results Overall, data (including eGFR) were available for 1813 MDS patients. Median age at diagnosis was 71 years [IQR 64 - 78]. and 55.3% patients were male. Sixty percent of the patients were diagnosed as IPPS lower risk. At the time of MDS diagnosis, CKD was detected in 479 patients (26.4%). Among patients aged ≥ 60, the crude rate of CKD was 30.3%. The standardized rate of CKD in the general population aged ≥ 60 years was significantly lower than in the similarly aged MDS group, with rates of 13.2% [CI 12.3-14.1] and 25.5% [CI 22.9-28.4]; p<0.001, respectively. (Figure 1) Patients with CKD were significantly older (median 78 yo) than those without CKD (median 68 yo; p<0.001), and more likely to have diabetes (33.2% vs 19.7%; p<0.001), and to have coincidence of another malignancy (21.6%) than those without CKD (14.9%; p=0.001). Median hemoglobin concentration was significantly lower in the CKD group (8.9 g/dL) than in the non-CKD group (9.4 g/dL; p < 0.05). Subjects with decreased eGFR were more likely to be dependent on RBC transfusion (56.5%) than subjects with eGFR ≥ 60 ml/min per 1.73m 2 (48.9%; p=0.0008). Median survival of patients with eGFR ≥ 60 ml/min per 1.73m 2 was 2.5 y [CI 1.0-6.1] vs 1.4 y [CI 0.6-4.2] for CKD. In multivariate analysis we found that CKD stage, age ≥ 65, higher IPSS score, high-risk IPSS cytogenetics and ECOG >1 were independent predictors of shorter survival. (Figure 2). Conclusions Myelodysplastic syndrome (MDS) subjects are more likely to have chronic kidney disease (CKD) than the general population. The presence of CKD in MDS patients is associated with worse overall survival and higher RBC transfusion requirement.

Variation of inflammatory indexes in patients with chronic abacterial prostatitis treated with an herbal compound/extract.

Inflammation is a highly prevalent finding in the prostate. Men with inflammation have higher IPSS score and increased prostate size. For men with prostatic inflammation, there is a significantly increased risk of developing acute urinary retention and the need of a surgical approach to the disease. Some laboratory tests (i.e. fibrinogen, C-reactive protein), can play a role in identifying patients at greatest risk of complications and adverse outcomes after surgery. There have been several experiences exploring the role of nutraceutical approach to the prostate inflammation. Aim of our study were to describe the variation in symptoms and inflammatory indexes in men affected by chronic abacterial prostatitis, treated with an herbal extract containing Curcuma Longa 500 mg, Boswellia 300 mg, Urtica dioica 240 mg, Pinus pinaster 200 mg and glycine max 70 mg. A prospective multicenter study was conducted from February 2021 and March 2022. One hundred patients, with a diagnosis of Chronic Prostatitis were enrolled in a multicentric phase III observational study. They were treated with the herbal extract, one capsule per day, for 60 days. No placebo arm was included. In each patient, inflammatory indexes, PSA, prostate volume, IIEF-5, PUF, uroflowmetry (Qmax), IPSS-QoL, NIH-CPPS were registered and statistically compared at baseline and at the follow up visit. The variation obtained on the inflammation indexes showed a global improvement after treatment, including the PSA reduction. We also recorded a significant improvement on IPSS-QoL, NIH-CPPS, PUF and Qmax scores. The herbal extract considered in our study may represent a promising and safe therapeutic agent leading to a reduction of inflammation markers, and could be used in the treatment of prostatitis and benign prostatic hyperplasia.

Prostate Volume Influence on Postoperative Outcomes for Patients Undergoing RARP: A Monocentric Serial Analysis of 500 Cases.

A total of 500 consecutive patients who underwent RARP between April 2019 and August 2022 were included. Patients were dichotomized into two groups using a prostate volume cut-off of 50 mL (small and normal prostate (SNP) n = 314, 62.8%; large prostate n = 186, 37.2%). Demographic, baseline, and perioperative data were analyzed. The postoperative complications and readmission rates within 90 days after RARP were compared between groups. A univariate linear analysis was performed to investigate the association between prostate volume and other relevant outcomes. Patients with larger prostates had a higher IPSS score, and therefore, more relevant LUTS at the baseline. They had higher ASA scores (p = 0.015). They also had more catheter days (mean 6.6 days for SNP vs. 7.5 days for LP) (p = 0.041). All oncological outcomes were similar between the groups. Although statistical analysis showed no significant difference between the groups (p = 0.062), a trend for minor complications in patients with larger prostates, n = 37/186 (19.8%) for the LP group vs. n = 37/314 (11.7%) in the SNP group, was observed. Namely, acute urinary retention and secondary anastomosis insufficiency. Major complications with an SNP (4.4%) and LP (3.7%) (p = 0.708) and readmissions with an SNP (6.25%) and LP (4.2%) (p = 0.814) were infrequent and distributed equally between the groups. In univariate analysis, prostate volume could solely predict a longer console time (p = 0.005). A higher prostate volume appears to have minimal influence on the perioperative course after RARP. It can prolong catheter days and increase the incidence of minor complications such as acute urinary retention. However, it might predict minor changes in operating time. Yet, prostate volume has less influence on major complications, readmissions, or oncological results.

The Interaction between IPSS Score and JAK2 Mutation Identifies Patients at Different Vascular Risk in Primary Myelofibrosis

The Interaction between IPSS Score and JAK2 Mutation Identifies Patients at Different Vascular Risk in Primary Myelofibrosis

The predictive factors of nocturia in young Asian adult males: an online survey

The present study investigated the association between severity of depressive mood and nocturia in young Asian adult men. Participants were 3127 adult male Facebook users aged 20–40 years who could read and write traditional Chinese. Participants completed online questionnaires on demographic characteristics, frequency of waking to urinate during the night (International Prostate Symptoms Score [IPSS]), and frequency of depressive symptoms (Taiwanese Depression Questionnaire [TDQ]). Those who awoke to pass urine during the main sleep period were considered to have nocturia. Student’s t test and Pearson’s chi square test were used to compare participants with and without nocturia. Univariate and multivariate logistic regression were used to evaluate predictive factors for nocturia. One thousand four hundred thirty (45.7%) participants had nocturia, and 21.9% were suspected to have depression. Age over 30 years, body mass index over 25 kg/m2, and higher IPSS score (except times of nocturnal voiding) were factors predictive of nocturia. Higher TDQ somatic subscores, rather than affective/cognitive subscores, were also predictive of nocturia. Associations were found between normal-high TDQ scores and nocturia. Young men with nocturia at risk of developing depression should be identified with a culturally relevant questionnaire. Early referral for psychiatric assessment and intervention may be warranted.

Circulating Platelet Vs Megakaryocyte-Derived Microparticles Identify Myelofibrosis Patients with JAK2V617F Mutation, High Disease Burden and Ruxolitinib Response

Myelofibrosis (MF) is a clonal neoplasia of the hematopoietic stem/progenitor cells characterized by distinctive abnormalities in megakaryocyte (MK) development and platelet (PLT) activation. Therapy with Ruxolitinib (RUX), a JAK1/2 inhibitor, suppresses both clonal myeloproliferation and release of proinflammatory cytokines, reducing splenomegaly and constitutional symptoms in around half of patients (pts). However, a deeply understanding of the activated inflammatory pathways and the biological effects of RUX is still lacking. Microparticles (MPs) produced by cells may occur as a key cellular communication process in homeostasis, which may increase under inflammatory stimuli and neoplastic diseases. Most of circulating MPs are of PLT and MK origin. Their role and modulation in the inflammatory microenvironment of MF are elusive.We evaluated whether circulating MK and PLT-derived MPs are dysregulated in MF and how the inflammatory microenvironment may drive their pattern. Also, we investigated whether circulating MK and PLT-derived MPs may be considered as a novel biomarker of response to RUX.EDTA-anticoagulated peripheral blood (PB) was collected from 42 MF pts, 13 Polycythemia Vera (PV)/Essential Thrombocythemia (ET) pts and 10 age/sex-matched healthy donors (HD). Samples from MF, ET/PV pts were obtained at diagnosis or out of cytotoxic treatment for at least 3 months; 14 MF pts were studied also after 6 months of RUX therapy. Spleen response (SR) was evaluated according to the 2013 IWG-MRT criteria. PLT (CD61+CD62P+) and MK (CD61+CD62P-)-derived MPs were analysed in PLT poor plasma samples by flow cytometry (CytoFLEX, Beckman Coulter, MPs ranging 0.5-0.9 μm).MF pts were JAK2V617F (n=24), CALR (n=9) and MPL (n=4) mutated; 5 pts were TN . The mean percentage of PLT-derived MPs of JAK2V617F mutated pts was significantly increased as compared with HD (p<0.05; Fig. 1A). On the contrary, as a sort of compensatory mechanism, the mean percentages of MK-derived MPs were significantly decreased in JAK2V617Fand TN pts as compared to HD (p<0.05, respectively; Fig. 1B). Interestingly, among MPNs, PLT-derived MPs were significantly increased in ET pts only as compared with HD (p<0.05).MF pts were at low/intm-1 (n=16), or at intm-2/high IPSS score (n=26). Higher-risk (HR)- JAK2V617F pts only showed a significantly increase of PLT-derived MPs along with a significant decrease in the percentage of MK-derived MPs as compared to lower risk (LR)- JAK2V617F and HD (p<0,0001, respectively; Fig. 1C-D).Remarkably, at baseline, contrary to pts with no response (NR; n=7), pts achieving a SR (R; n=7) showed a low PLT-/MK-derived MPs ratio (Fig. E, baseline), as result of the reduction of MK-derived MPs in NR pts (p<0,05) (Fig. 1G). Accordingly, it may prompt to consider this ratio as potential predictive marker to RUX response. After 6 months of RUX, the PLT-/MK-derived MPs ratio of R pts was significantly decreased as compared with that of NR pts (p<0,01) (Fig. 1E, 6-months post-RUX); this is mainly due to the strong reduction of PLT-derived MPs in R pts (p<0,001) (Fig. 1F).To evaluate whether inflammatory status may play as a key regulator of MPs, we correlated the level of crucial inflammatory factors (Interferon (IFN)-γ, Interleukin (IL)-1β, IL-6, IL-8, Tumor Necrosis factor (TNF)-α, Thrombopoietin (TPO)) to circulating MPs. Surprisingly, we reported a highly inverse relationship between levels of IFN-γ (r=-0,5534; p<0,01), IL-1β (r=-0,4648; p<0,01), TNF-α (r=-0,4444; p<0,05) and MK-derived MPs percentages, highlighting an impaired response to inflammation. Concomitantly, we observed a positive correlation between IL8 with MK-derived MPs hinted at its implication in MK dysregulation. The percentages of PLT-derived MPs were positively correlated with only TPO plasma levels (r=0.4299; p<0.05), that may influence PLT/MK-derived MPs ratio by activating PLT.Overall our results demonstrate that in MF pts the inflammatory status may contribute to drive MK and PLT-derived MPs dysregulation. We also show that the mutation status impacts the proportion of circulating MK-and PLT-derived MPs, suggesting a role of mutated JAK2 in MPs biogenesis/clearance and, ultimately, in cell (MK, PLT) to cell communication. Interestingly, MK vs PLT-derived MPs pattern may be a biomarker of disease identifying JAK2V617F -mutated pts at high IPSS risk and RUX responsive.DF, MB, FR and FP, LC equally contributed [Display omitted] DisclosuresMartinelli:Ariad/Incyte: Consultancy; Pfizer: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Johnson&Johnson: Consultancy; Roche: Consultancy.

Favorable Impact of Allogeneic Stem Cell Transplantation in Patients with Therapy-Related Myelodysplasia Regardless of TP53 Mutational Status

Background: Therapy-related myelodysplastic syndrome (t-MDS), a long-term complication of cancer survivors who received cytotoxic therapy, is characterized by high-risk genetics and poor outcome. Allogeneic hematopoietic cell transplantation (alloHCT) represents the only potentially curative modality for t-MDS, but the prognostic impact of pre-transplant genetics and clinical features has not been fully characterized.Methods: In this retrospective IRB-approved study, a total of 266 consecutive patients with diagnosis of t-MDS (n=67) or de novo MDS (N=199) who received allogeneic HCT from matched sibling (n=111) or unrelated donors (n=155) at the City of Hope between January 2000 and October 2014 were analyzed. t-MDS was defined solely based on past history of exposure to any cytotoxic chemotherapy and/or radiotherapy administered for prior malignant or non-malignant conditions. Patient's DNA was extracted from whole blood samples before HCT. All patients had ≥ 20% circulating myeloid lineage cells at the time of the sample collection. A next generation sequencing (NGS)-based 72 gene panel was used to detect somatic mutations and cytogenomic microarray (CMA) was performed using the Affymetrix CytoScan HD platform.Results: As compared to de novo MDS cohort, t-MDS cases were less frequently categorized by WHO classifications as RAEB-1/2 (39.1% vs 47.0%; p=0.004) and had higher risk cytogenetics (p=0.00003), lower blasts% at the time of HCT (p=0.03), higher IPSS score at diagnosis (p=0.03) and more frequently received reduced intensity conditioning (mostly fludarabine+melphalan) HCT (94.0% vs 70.4%; p=0.00003).After a median follow-up of 4.8 years (range, 0.5-15.8) for surviving patients, the 5-year overall survival (OS) for the entire cohort was 52.8% (95% CI: 46.2-59.4%). There were no differences in the 5-year OS (49.9% vs. 53.9%, p=0.61), relapse-free survival (RFS) (47.2% vs. 49.5%, p=0.68), non-relapse mortality (NRM) (30.2% vs. 26.8%, p=0.48) and relapse (22.6% vs. 23.7%, p=0.81) rates between t-MDS and de novo patients (Figure 1a). In a multivariate model, prior cytotoxic therapy before t-MDS diagnosis did not impact survival (p=0.7) in the whole cohort. For t-MDS (n=67),older age was associated with trend toward lower OS (HR: 1.04 for each year, p=0.06) and lower RFS (HR: 1.04, p=0.05). More recent HCT era was associated with superior OS (HR: 0.27, p=0.02 for 2005-2009 and HR: 0.21, p=0.002 for 2010-2014). Karyotypes, IPSS score and percentage of marrow blasts before alloHCT were not independently associated with OS or RFS.Of the 67 t-MDS patients, 60 had available pre-HCT DNA samples; 43 (72%) of them had at least one detectable gene mutation. Among patients with detectable mutations, the median number of mutations per case was 2 (range: 1-6). The most common mutated gene was TP53, which was present in 18 (30%) cases. Of 18 cases with somatic mutations involving TP53 gene, 5 (28%) had multiple distinct TP53 mutations (two mutations: n=4, three mutations: n=1). Other more common mutations (observed in ≥ 4 cases) were RUNX1 (12%), TET2 (8%), U2AF1 (8%), ASXL1 (8%), DNMT3A (7%) and SETBP1 (7%). Additional non- TP53 mutations (U2AF1, RUNX1, ASXL1, TET2, and STAG2) were observed in 33% TP53 -mutated cases. TP53 -mutations were more frequently associated with complex and/or monosomal karyotype compared to TP53 -wild cases (38% vs. 78%, p=0.02).Contrary to previous reports, presence of mutations in TP53 or mutations in any other of the high-risk genes (EZH2, ETV6, RUNX1, ASXL1 : n=29, 48%) did not significantly impact either OS (Figure 1b) or RFS. In 3 cases of MDS, TP53 alterations were found only by CMA but not by NGS. Re-classifying these additional del17p cases onto the TP53 mutated group still showed similar OS between TP53 mutated and TP53 unmutated groupsConclusion: AlloHCT is a curable treatment for patients with t-MDS with similar long-term survival to de novo MDS despite higher-risk features. While TP53 alteration was the most common mutation in t-MDS, the finding was not detrimental in our case-series. [Display omitted] DisclosuresKhaled:City of Hope: Research Funding; Daiichi Sankyo, Inc: Other: Travel Support. Salhotra:Kadmon: Consultancy. Stein:Stemline: Consultancy; Amgen: Consultancy, Speakers Bureau. Pillai:Trillium Therapeutics: Research Funding.

Patient-reported fatigue refines prognosis in higher-risk myelodysplastic syndromes (MDS): a MDS-CAN study.

The incorporation of patient-reported outcomes with traditional disease risk classification was found to strengthen survival prediction in patients with myelodysplastic syndromes (MDS). In the present Canadian MDS registry analysis, we validate a recently reported prognostic model, the Fatigue-International Prognostic Scoring System among higher-risk patients [FA-IPSS(h)], which incorporates patients' reported fatigue, assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30), with a threshold of ≥45points, in higher IPSS score, stratifying them into distinct subgroups with different survival outcomes. We further validated this concept, using the Revised IPSS >3·5 as cut-off for the definition of higher-risk MDS, and patients' reported fatigue according to Edmonton Symptom Self-Assessment Scale (ESAS) Global Fatigue Scale (GFS), a single-item fatigue rating scale, which is easier to deploy. This emphasises the power of self-reported fatigue at refining overall survival predictions in higher-risk MDS and further bolsters the importance of considering patient-related outcomes in global assessments.

Patients presenting with lower urinary tract symptoms who most deserve to be investigated for primary bladder neck obstruction

We aimed to investigate clinical features potentially useful in primary bladder neck obstruction (PBNO) diagnosis in men presenting with lower urinary tract symptoms (LUTS). Data from 1229 men presenting for LUTS as their primary complaint at a single centre were retrospectively analysed. All patients underwent a comprehensive medical and physical assessment, and completed the International Prostate Symptoms Score. All patients were investigated with uroflowmetry, and trans-rectal ultrasound imaging to define prostate volume. Urodynamic evaluation was performed when the diagnosis of benign prostatic enlargement was not confirmed and the patient presented a significant chance of detrusor overactivity or underactivity. As per our internal protocol, patients < 60 years old with bothersome LUTS and > 60 years with a prostate volume (PV) < 40 mL were also investigated with urethrocystoscopy to rule out urethral stricture. Logistic regression analysis tested clinical predictors of possible PBNO. Of 1229 patients, 136 (11%) featured a clinical profile which was consistent with PBNO. Overall, these patients were younger (p < 0.0001), had lower BMI (p < 0.0001), less comorbidities (p = 0.004) and lower PSA values (p < 0.0001), but worse IPSS scores (p = 0.01) and lower PV values (p < 0.0001) compared to patients with other-aetiology LUTS. At multivariable analysis, younger age (OR 0.90; p = 0.003) and higher IPSS scores (OR 1.12; p = 0.01) were more likely to be associated with this subset of patients, after accounting for other clinical variables. One out of ten young/middle-aged men presenting for LUTS may be affected from PBNO. Younger patients with more severe LUTS systematically deserve an extensive assessment to rule out PBNO, thus including urethrocystoscopy and urodynamics with voiding-cysto-urethrogram.

Characteristics and Outcome of Myelofibrosis Patients on Long-Term Ruxolitinib Therapy (≥3 years)

Characteristics and Outcome of Myelofibrosis Patients on Long-Term Ruxolitinib Therapy (≥3 years)

Stereotactic Body Radiation Therapy (SBRT) for Prostate Cancer in Men With a High Baseline International Prostate Symptom Score (IPSS ≥ 15).

Background: Patients with a high pretreatment IPSS may have higher rates of late urinary morbidity after radiation therapy for prostate cancer (1). Stereotactic body radiation therapy (SBRT) delivers fewer high-dose fractions of radiation, which may be radiobiologically favorable to the conventional low-dose external beam fractions. The urinary toxicity associated with SBRT, however, remains unclear in patients with a high IPSS (1). We report our experience using SBRT for localized prostate cancer in patients with pretreatment IPSS ≥ 15.Methods: Localized prostate cancer patients with a pre-treatment IPSS ≥ 15 treated with SBRT at Georgetown University Hospital from 2009 to 2016 were included in this retrospective review of prospectively collected data. These patients were treated to 35–36.25 Gy in five fractions delivered via CyberKnife (Accuray Inc., Sunnyvale, CA). Urinary toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4). Urinary quality of life was assessed using validated questionnaires (IPSS and EPIC-26).Results: 53 patients at a median age of 71 years (range 57–89 years) received SBRT with a minimum follow up of 3 years. The median prostate size was 37 cm3 (range 12–100 cm3) and 30.2% patients received ADT. The 3-years incidence rate of Grade 3 urinary toxicity was 7.5% with median time to toxicity of 2.9 years. There were no Grade 4 or 5 toxicities. A mean baseline IPSS score of 19.8 significantly decreased to 12.9 at 3 months post-SBRT (p = 0.002) and remained stable at 36 months (13.7). A mean baseline EPIC-26 obstructive/irritative score of 64.1 significantly improved to 80.2 at 3 months (p = 0.002). This improvement was maintained to 36 months. There was no significant change from the mean baseline EPIC-26 urinary incontinence score at any point during follow up.Conclusions: SBRT for clinically localized prostate cancer was well-tolerated in men with baseline IPSS ≥ 15 (1). Grade 3 toxicities occurred but resolved with time. Our data suggest that poor baseline urinary function does not worsen following SBRT and may even improve. High baseline IPSS score should not be considered a contraindication to SBRT.

Allogeneic Hematopoietic Stem Cell Transplantation for Therapy-Related Myelodysplastic Syndromes and Acute Myeloid Leukemia

Patients who develop therapy-related myelodysplastic syndromes (t-MDSs) or acute myeloid leukemia (t-AML) following prior chemotherapy or an autologous hematopoietic cell transplant (HCT), have a poor prognosis. An earlier analysis of allogeneic HCT (n=868, 1990-2004) showed 5-year overall survival (OS) and disease free survival (DFS) were 22% and 21% (reference). Furthermore, older age, graft source other than a HLA-matched sibling or HLA well matched unrelated donor (URD), t-AML not in remission or advanced t-MDS, and poor risk cytogenetics were associated with worse outcomes. Modern supportive care and conditioning regimens including reduced intensity (RIC) regimens may have improved outcomes. Therefore we analyzed 1531 HCT for t-AML (n = 772) or t-MDS (n = 759) performed from 2000 to 2014. The median age at transplant was 52 (18-77) for t-AML and 59 (18-74) for t-MDS. Eleven percent of patient with t-AML and 24% of patient with t-MDS had a prior autologous transplant. A myeloablative regimen was used for conditioning in 61% of patients with t-AML and 49% of patients with t-MDS (Table 1). For t-AML, the 5-year non-relapse mortality (NRM) and relapse rates (RR) were 33% (95% confidence interval [CI], 30-36) and 43% (40-47), respectively. For t-MDS, the 5 year TRM and RR were 32% (29-36) and 46% (43-50), respectively. Five year DFS and OS were 24% (21-27) and 25% (22-28), respectively, for patients with t-AML. Five year DFS and OS were 21% (18-24) and 27% (23-31), respectively, for patients with t-MDS. In multivariate analysis, t-AML OS and DFS was worse for: previous autologous transplant, relapsed disease at HCT, intermediate or adverse cytogenetics, partially matched and cord blood grafts, and RIC. For t-MDS: age greater than 60, previous autologous transplant, very high IPSS score, and use of HLA-partially matched unrelated grafts. A significant minority of patients with t-AML and t-MDS can achieve long-term remission with allogeneic HCT, yet risks of both NRM and relapse are still excessive. Relapse is the major cause of treatment failure. Disclosures Metheny: Takeda: Speakers Bureau; Incyte: Speakers Bureau. Weisdorf:Incyte: Research Funding; Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy. Kebriaei:Jazz: Consultancy; Amgen: Research Funding; Pfizer: Honoraria; Kite: Honoraria.

Ixazomib, Rituximab and Dexamethasone (IRD) in Patients with Relapsed or Progressive Waldenstrom's Macroblobulinemia: Results of the Prospective Phase I/II HOVON 124/Ecwm-R2 Trial

Ixazomib, Rituximab and Dexamethasone (IRD) in Patients with Relapsed or Progressive Waldenstrom's Macroblobulinemia: Results of the Prospective Phase I/II HOVON 124/Ecwm-R2 Trial

Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms: What Is the Role and Significance of Inflammation?

The purpose of this review is to summarize the role and significance of inflammation as a putative additional factor contributing to lower urinary tract symptoms and the progression of benign prostatic hyperplasia. We review (1) the histologic definition of prostatic inflammation and its prevalence, (2) the effects inflammation in the prostate including on risk of acute urinary retention, and (3) the effects of systemic inflammation on the prostate and on voiding. Inflammation is a highly prevalent finding in the prostate, both on a histological and biochemical level. Men with inflammation have higher IPSS scores and increased prostate size; however, these differences appear to be imperceptibly small. Men with inflammation do experience a significantly increased risk of developing acute urinary retention, an event that is associated with significant morbidity. Recently, attempts have been made to identify more specific biochemical markers of local inflammation, and to identify regional patterns of inflamed tissue within the prostate which may be associated with higher IPSS scores, accelerated progression, and AUR. The effects of systemic inflammatory states, most notably MetS, and their role in LUTS have also been examined. Inflammation is a common finding in prostates of aging men, but its contribution to lower urinary tract symptoms and benign prostatic hyperplasia progression appears to be small when considered as a clinically relevant entity. Advances in the understanding of different forms of inflammation, and their impact when experienced in different locations within the prostate, may refine this knowledge. Systemic inflammation affects voiding, including in the absence of a prostate, but again significant effects of systemic inflammation on the prostate itself are also difficult to demonstrate. Prostatic inflammation is associated with a significantly increased risk of acute urinary retention.

Prognostic and Predictive Impact of Small PNH Clones in a Large Cohort of Patients with Myelodysplastic Syndromes and Aplastic Anemia: A Single-Center Experience

▪Background: the use of high sensitive FLAER in the last 10 years improved the detection of very small PNH clones (<1%) in various hematologic conditions, including aplastic anemia (AA)/myelodysplastic syndromes (MDS). Although generally considered unremarkable, the recent observation of asymptomatic end-organ damage due to undiagnosed thrombosis even in patients without overt hemolysis questions the assertion that small PNH clones are of subclinical value.Aim: To evaluate the prevalence of PNH clones ≥0.01% in AA/MDS patients tested at a single tertiary center, and to assess their impact on disease prognosis (leukemic evolution, death), occurrence of thrombosis, and response to current therapies.Methods: We retrospectively collected clinical (diagnosis, stage, therapy, complications and outcome) and laboratory features (complete blood counts, LDH, PNH clone size) of 869 MDS and 531 AA patients tested from March 1998 till October 2017.Results: Figure 1 shows clinical and laboratory characteristics of MDS and AA patients, divided according to the presence/absence of PNH clones. A PNH clone was less frequently found in MDS cases versus AA (20.3% vs 61%). Focusing on MDS, PNH+ cases were significantly more hypoplastic, mainly displayed IPSS low/int-1 score, and showed deeper cytopenias (significantly for Hb and PLT) and higher LDH levels. Dividing patients according to clone size (negative, 0.01-1%, 1.01-10%,10.01-50%, and >50% on granulocytes), we observed a significant worsening of cytopenia and raise of LDH along with clone size increase. Likewise, lower IPSS risk patients more frequently displayed a greater clone size. As regards therapy, PNH+MDS showed significantly higher response rates to immunosuppressive therapies (ATG and CyA, 84% vs 44.7%, p=0.01) and to HSCT (71% vs 56.6%, p=0.09) compared to PNH-, and the cumulative probability of response to any treatment significantly improved along with clone size increase (from 52 to 100%, p=0.03). In addition, PNH+MDS showed lower rate of progression and AML evolution, and a longer OS [mean 11.9+0.7 years (10.5-13.3) vs 7.3+0.3 (6.6-7.9), p<0.0001] compared to PNH- ones. Interestingly, we observed a significant reduction of death frequency along with clone size increase (56% in PNH- vs 24% in PNH+ with clone size 0.01-1%, p<0.0001). However, PNH+MDS had a higher incidence of thrombotic events, with greater frequency along with clone size increase (from 5% in PNH- to 50% in PNH+ with clone size >50%, p<0.0001). As expected, worse OS also significantly correlated with older age, male gender, transfusion dependence, MDS progression/AML evolution, higher IPSS score, and non-response to therapy.Regarding AA, together with a higher frequency of PNH clones, we also found a higher frequency of large clones (>10%) compared to MDS (p=0.04, bars chart). PNH+AA showed deeper thrombocytopenia, higher reticulocyte counts and LDH values. As observed for MDS, we found a significant worsening of cytopenia and raise of LDH along with clone size increase. In addition, PNH+ AA showed higher response rates compared to PNH- (97 vs 77% for HSCT, p=0.01; 78 vs 50% for IST, p<0.0001; and 88% vs 65% considering any treatment, p<0.0001). PNH+AA also showed lower rate of MDS progression and death (p=0.01 and p<0.0001), and longer OS [mean 15.8+0.43 years (14.9-16.7) vs 6.5+0.35 (5.8-7.21), p<0.0001]. Also in AA, we observed a significant reduction of death frequency along with clone size increase (32.1% in PNH- vs 9.2% in PNH+ with clone size 0.01-1%, p<0.0001). Worse OS also correlated with older age, male gender, presence of cytopenia, and non-response to therapy.Conclusions: Prevalence of PNH clones of any size is high in patients with MDS and AA. We firstly show a positive impact of PNH clone positivity on response to IST and HSCT in MDS. The presence of a PNH clone also correlated with lower disease progression and better OS. Furthermore, we confirm the known favourable prognostic and predictive value of PNH clones in a large AA cohort. Clone size analysis suggests that even small clones (0.01-1%) have a clinical and prognostic significance. [Display omitted] DisclosuresKassam:AbbVie: Equity Ownership. Yallop:Pfizer: Consultancy; Servier: Other: Travel funding. Mufti:Celgene: Research Funding. Kulasekararaj:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Other: Travel Support .

Risk factors analysis of persistent frequency after transurethral resection of the prostate

Objective To discuss the risk of factors influencing persistent frequency after transurethral resection of the prostate (TURP). Methods The clinical data of 119 post-TURP patients treated from January 2014 to June 2015 was retrospectively analyzed. The age was (72.1±2.3)years old. There were 15 cases with hypertension, 23 cases with diabetes and 6 cases with heart disease. The preoperative IPSS score of 119 cases was (22.1±5.9) points, with (10.2±1.8) points in urinary storage period and (11.8±4.7) points in urination period. Urination frequency was (10.8±2.6) times per day and there were (3.8±0.8) times of nocturnal urination. B-ultrasound: residual urine volume was (38.1±9.1) ml and prostate volume was (34.1±4.2) ml. Preoperative maximum urine flow rate was (8.8±3.9) ml/s. The detrusor pressure at maximum urinary flow rate was (43.9±14.1) cm H2O (1 cmH2O = 0.098 kPa), maximum detrusor pressure was (99.7±12.2) cmH2O and effective bladder volume was (217.5±14.8) ml. Contraction of bladder weakened in 40 cases (33.6%) and 36 cases (30.2%) had detrusor overactivity. According to whether continuous urinary frequency was developed, the patients were divided into frequency-positive group and frequency-negative group. The differences between the patients in two groups were compared and univariate analysis was performed. A multivariate logistic regression was performed on statistically significant indicators. Results Among the 119 patients, 21 were frequency-positive and 98 were frequency-negative. Univariate analysis showed that age, IPSS score, preoperative urinary storage score, detrusor pressure at maximum urinary flow rate, maximum detrusor pressure, effective bladder volume, contraction decrease of bladder, preoperative detrusor activity were important indicators affecting the condition of postoperative urinary frequency (all P<0.05). Multivariate analysis showed that old age (OR=3.842, P=0.021), high total IPSS score (OR=5.109, P=0.011), low maximum detrusor pressure (OR=3.477, P=0.039), low effective volume of bladder (OR=4.051, P=0.017) and detrusor overactivity (OR=3.662, P=0.025) were independent risk factors for urinary frequency after TURP. Conclusions The age, the high IPSS score before operation, low maximal detrusor pressure, low effective bladder capacity and the bladder detrusor activity could be independent predictive factors of persistent frequency after TURP. Key words: Transurethral resection of prostate; Persistent frequency; Risk factors

Phase 2 study of ruxolitinib in combination with 5-azacitidine in patients with myelofibrosis.

7063 Background: Ruxolitinib (RUX) is effective in controlling symptoms and organomegaly in patients with myelofibrosis (MF). Combination with azacitidine (AZA) may further improve its efficacy. Methods: RUX 15 or 20 mg orally twice daily was given continuously since cycle 1. AZA 25 to 75 mg/m2 on days 1-5 of each 28-day cycle was added starting cycle 4. Responses were assessed per International Working Group for Myelofibrosis Research and Treatment 2013 criteria (IWG-MRT). Results: Among 44 pts enrolled between 03/2013 and 06/2016, 39 patients (89%) were evaluable for response. After median (med) follow-up of 20.4+ months (range, 0.5-37+); 24 pts (54%) are on study with a med overall survival of 39+ months. Med age was 66 years (range, 48-87), 36 pts (82%) had int-2/high IPSS score, 29 (66%) had spleen ≥5cm, and 24 (55%) were JAK2 V617F positive. Twenty five pts (57%) were previously treated. Twenty eight (72%) pts had objective response regardless of previous therapy (Table). Med time to response was 1.0 months. 7 (25%) responses occurred after the addition of AZA with med time to response of 4.2 months. In total, 23 pts (79%) had palpable spleen reduction by &gt; 50%, which occurred after AZA was added in 6 (28%) of them. JAK2V617Fallele reduction was noted in 13 (87%) evaluable pts, including &gt; 50% reduction in 3 pts (13%). A reduction in bone marrow fibrosis grade was observed in 12 (31%) responders, including ≥2 and 1 grade reduction in 2 and 9 pts, respectively. Grade 3/4 non-hematological and hematological toxicities occurred in 4 and 16 pts, respectively. The most common reasons for therapy discontinuation (n=17) were stem cell transplantation (n=6), lack of response (n=3) and progression to AML (n=2). Conclusions: Concomitant RUX with AZA was feasible with overall IWG-MRT response rate of 72%, including &gt;50% spleen reduction in 79% of patients, which compares favorably to single RUX. Clinical trial information: NCT01787487. [Table: see text]

Epigenetic dysregulation of ID4 predicts disease progression and treatment outcome in myeloid malignancies.

Promoter hypermethylation‐mediated inactivation of ID4 plays a crucial role in the development of solid tumours. This study aimed to investigate ID4 methylation and its clinical relevance in myeloid malignancies. ID4 hypermethylation was associated with higher IPSS scores, but was not an independent prognostic biomarker affecting overall survival (OS) in myelodysplastic syndrome (MDS). However, ID4 hypermethylation correlated with shorter OS and leukaemia‐free survival (LFS) time and acted as an independent risk factor affecting OS in acute myeloid leukaemia (AML). Moreover, ID4 methylation was significantly decreased in the follow‐up paired AML patients who achieved complete remission (CR) after induction therapy. Importantly, ID4 methylation was increased during MDS progression to AML and chronic phase (CP) progression to blast crisis (BC) in chronic myeloid leukaemia (CML). Epigenetic studies showed that ID4 methylation might be one of the mechanisms silencing ID4 expression in myeloid leukaemia. Functional studies in vitro showed that restoration of ID4 expression could inhibit cell proliferation and promote apoptosis in both K562 and HL60 cells. These findings indicate that ID4 acts as a tumour suppressor in myeloid malignancies, and ID4 methylation is a potential biomarker in predicting disease progression and treatment outcome.