Seattle Group Research Articles

Granny Solidarity: Understanding Age and Generational Dynamics in Climate Justice Movements

Since the 2018 Intergovernmental Panel on Climate Change (IPCC) report, a global shift in consciousness has taken place around the urgency of the Earth’s climate crisis. Amidst growing panic, teenagers are emerging as key leaders and mobilizers, demanding intergenerational justice and immediate action. They are, however, often depicted as lone revolutionaries or as pawns of adult organizations. These representations obscure the complex and important ways in which climate justice movements are operating, and particularly the ways in which dynamics of age intersect with other axes of power within solidarity efforts in specific contexts. This article explores these dynamics, building on analyses of intersectional and intergenerational solidarity practices. Specifically, it delves into detailed analysis of how the Seattle group of the Raging Grannies, a network of older activists, engaged in Seattle’s ShellNo Action Coalition, mobilizing their age, whiteness, and gender to support racialized and youth activists involved in the coalition, and thus to block Shell Oil’s rigs from travelling through the Seattle harbour en route to the Arctic. Drawing from a pivotal group discussion between Grannies and other coalition members, as well as participant observation and media analysis, it examines the Grannies’ practices of solidarity during frontline protests and well beyond. The article thus offers an analysis of solidarity that is both intergenerational and intersectional in approach, while contributing to ongoing work to extend understandings of the temporal, spatial, cognitive, and relational dimensions of solidarity praxis.

PF749 A MACHINE‐LEARNING APPROACH TO GRADE ACUTE GRAFT‐VERSUS‐HOST DISEASE

Background:Acute graft‐versus‐host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). After the presentation of the first GVHD grading score by Glucksberg et al. in 1974, revised by the Seattle group in the 1990 s, several studies have tried to further improve severity indexing (SI) of acute GVHD based on different evaluations of organ involvements. Today, the two most commonly used scoring systems are the Glucksberg grading‐ (Grades I‐IV) and the Center for International Blood and Marrow Transplant Research (CIBMTR, formerly IBMTR) grading system (Grades A‐D). Both grading systems have been prospectively validated and considered equally performing. While GVHD grading does correlate with overall survival (OS), poorly surviving patients are found among individual low‐grade GVHD patients. Despite such limitations, no superior scoring system had gained universal acceptance since. Recent GVHD severity scores involved additional concepts, such as epithelial damage in GVHD or predictive biomarkers.Aims:Machine Learning (ML) models have the potential to class and predict events in transplantation medicine. We aimed to improve GVHD grading using ML models in order to improve survival prediction within GVHD scoring.Methods:We analyzed the Glucksberg scoring system in 1354 consecutive adult patients with GVHD after HSCT from a single center between 2008 and 2018 and compared it to a ML model, based on the available GVHD organ involvement staging, transplant and OS data. We constructed a 3D discrete space (V), of which axes corresponded to the acute GVHD stage of the corresponding organ (skin, liver, intestine). Each individual patient's GVHD stages defined a point in V. A principal component analysis applied on the data and the first principal component was adopted as the new space (V ∗ ) of the SI. Then, by using the first principal component we formulated an algebraic relation to obtain a SI of each patient. The performance of the ML and Glucksberg grading systems were compared within Cox regression survival analysis.Results:The ML model revealed that GVHD grading according to the Glucksberg grading was an intact model that still insufficiently correlated with OS (Figure). We then constructed a SI with a stronger differentiation capacity with respect to OS. Cox regression survival analysis compared the proposed ML grading system to the Glucksberg grading using the SI as a risk factor and showed that the ML‐based SI offered a finer grading (125 grades, allowing to use the SI as a continuous variable). The ML model was more stable with respect to censoring period than classical grading. We observed greater variations of the Glucksberg grading, which changed over different censoring periods from a HR of 1.79 (95% Confidence interval, 1.61–1.99) to 1.56 (95%CI, 1.44–1.70), while in the ML‐grading the HR remained stable with a small CI (HR 1.55; 95%CI, 1.45–1.66). The ML‐based SI allowed to model individual patient's maximum survival expectation. Finally, the suggested ML algorithm offered a better predictive factor, because it created cohorts with more distinct hazard rates.Summary/Conclusion:A ML based scoring system using the Glucksberg organ staging categories allowed refined GVHD grading and at the same time improved OS prediction across different GVHD severity cohorts.image

Age adjusted hematopoietic stem cell transplant comorbidity index predicts survival in a T-cell depleted cohort

ObjectivesAllogeneic hematopoietic stem cell transplant (HCT) continues to evolve with the treatment in higher risk patient population. This practice mandates stringent update and validation of risk stratification prior to undergoing such a complex and potentially fatal procedure. We examined the adoption of the new comorbidity index (HCT-CI/Age) proposed by the Seattle group after the addition of age variable and compared it to the pre-transplant assessment of mortality (PAM) that already incorporates age as part of its evaluation criteria. MethodsA retrospective analysis of adult patients who underwent HCT at our institution from January 2010 through August 2014 was performed. Kaplan-Meier’s curve, log-rank tests, Cox model and Pearson correlation was used in the analysis. ResultsOf the 114 patients that underwent allogeneic transplant in our institution, 75.4% were ≥40 years old. More than 58% had a DLCO ≤80%. Although scores were positively correlated (correlation coefficient 0.43, p < 0.001), HCT-CI/Age more accurately predicted 2-year overall survival (OS) and non-relapse mortality (NRM) in patients with lower (0–4) and higher (5–7) scores (52% and 36% versus 24% and 76%, p = 0.004, 0.003 respectively). PAM score did not reach statistical significance for difference in OS nor NRM between the low (<24) and high-risk (≥24) groups (p = 0.19 for both). ConclusionsDespite our small sample population, HCT-CI/Age was more discriminative to identify patients with poor outcome that might benefit from intensified management strategies or other therapeutic approaches rather than allogeneic HCT.

Immunotherapy in lymphoma.

Immunotherapy in lymphoma.

Brachytherapy: state‐of‐the‐art radiotherapy in prostate cancer

Brachytherapy: state‐of‐the‐art radiotherapy in prostate cancer

Nutritional Delivery in Infants With CKD: Techniques to Avoid Hyperkalemia

asachelatingagentfor potassium. 3 Ithasbeenshownhistorically in the laboratory as well as in the use of this technique that by adding sodium polystyrene to liquid-based formulas one can reduce the potassium in the solution, making the clinical risk of hyperkalemia less of an issue in children. This paper points out that the younger the child, the more likely that the nutrition will be a formula that is based intheliquidform.Theyalsopointedoutthatthesechildren are polydipsic. Therefore, they take more than the usual amount of fluid for nutritional growth. Therefore, despite using a low-potassium formula (breast milk, PM 60/40), becauseof the polydipsia, theresult may ne excessive potassium intake with hyperkalemia. In older children and adults, it is easy to talk about a lowpotassium diet because the food is solid; however, in infants on liquid-based formula it is very difficult. These authors have followed through on studies that were conducted more than 2 decades ago looking at potassium-reducing techniques. They also acknowledge that there areother ways to deliver nutrition by unique formulas other than just the infant formulas. However,thebasisofthisissueishowtogiveoptimalnutritiontoaninfantwithchronicrenalfailurewhileavoiding hyperkalemia and potentially avoiding or postponing the need for dialysis. Aggressive nutrition is important for a cerebral growth, somatic growth, and an overall long-term benefit for the patient. 4 Therefore, the use of nutrition restriction may prevent hyperkalemia; however,it most likely results in negative neurologic and somatic growth in these infants, which has potential long-term implications. The Seattle group describes in clinical findings what was describedbyourgroupover2decadesago:homogenizingsodium polystyrene with formula and allowing the formula to settleout.Thisleavesaresinlayeratthebottomoftheformula, and when decanted the formula has an approximate 50% reduction in potassium. They pointed out that there is an effect on the calcium and creatinine of these patients. Whereas the creatinine has no clinical consequences, chelating out the calcium (sodium polystyrene is a nonspecific cation binder) may place the child at risk for long-term, low-calcium exposure. They further note that this will give sodium back to the patient, which in some patients may be detrimental, but in most patients with dysplasia it may be beneficial. Work by Hobbs and associates identified the use of noninfant formulas as a way to deliver low-potassium formula in infants. 5 Hobbs notes that these ‘‘adult-based formulas’’ may need to be diluted to avoid too large of an osmolal load. The Seattle group discusses that their experience with Hobbs’ approach was not always tolerated because of the formula hyperosmolality. The optimal formula, the optimal way to deliver nutrition, and the optimal amount of nutrition for infants with chronic kidney failure is still elusive. The Seattle group’s work and work by many others have identified these ongoing concerns. How can one deliver optimal nutrition and avoid the need for dialysis? For if one can have an infant grow, avoiding the risk of solute excess, then the infantmaybeabletogounder transplantationpreemptively

Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia

Royal Bournemouth Hospital, Bournemouth, 2 Royal Marsden Hospital, London, 3 Southampton General Hospital, Southampton, Cardiff and Vale NHS Trust, Cardiff Cambridge University Hospitals NHS Foundation Trust, Cambridge UK; St. James's Institute of Oncology, Leeds, Christie Hospital NHS Trust, Manchester Royal Marsden Hospital London; Heart of England NHS Foundataion Trust, Birmingham; 10 Royal Liverpool University Hospital, Liverpool; Churchill Hospital, Headington, Oxford, Norfolk and Norwich University Hospital, Norwich

Alemtuzumab Use and Survival After Reduced Intensity Allogeneic Stem Cell Transplantation in High-Risk Chronic Lymphocytic Leukemia (CLL),

Abstract 4152 BACKGROUND:Patients with biologically aggressive chronic lymphocytic leukemia (CLL) characterized by being refractory to purine nucleoside analogues and/or possessing the cytogenetic abnormality del (17p13) have poor clinical outcomes with a median survival of <3 years. Several groups have reported that nonmyeloablative allogeneic stem cell transplant (alloSCT) provides long-term disease control in a subset of high-risk CLL patients. The Seattle group also recently reported that alemtuzumab use prior to alloSCT may increase the risk of early relapse/progression (Sorror, ASH 2010). This is a potentially critical observation since alemtuzumab is one of the few active agents in patients with del(17p13) and is frequently used for pre-transplant debulking in patients with this genetic defect. METHODS:We performed retrospective analysis of 38 CLL patients who underwent nonmyeloablative alloSCT for CLL at the Mayo Clinic between 2003 and 2011. The relationship between transplant outcome and debulking regimen used immediately prior to alloSCT, disease status at the time of alloSCT, post transplant engraftment, GVHD development was explored. The degree of marrow involvement prior to alloSCT was assessed using the leukemia index calculated by multiplying the % involvement by CLL cells and the % cellularity. RESULTS:Median age at the time of alloSCT was 55.5 (range, 29–69) and 13 patients (34%) were female. The median duration from CLL diagnosis to alloSCT was 4.7 years. Thirty-two patients (84%) had received more than 3 prior therapies prior to alloSCT. Thirty-seven patients (97%) had received purine analog-based therapies, 18 (47%) patients had received alkylating agents and 25 (66%) had received alemtuzumab. 33 (87%) patients were purine analog refractory. On cytogenetic evaluation by FISH, 17 (45%) patients had del(17p13), 10 (26%) had del(11q23) and 1 (3%) had del(6q23).Nine patients were in complete remission (CR) by IWCLL 2008 criteria at the time of alloSCT and 7 patients were in complete remission with incomplete marrow recovery (CRi). Of the remaining 22 patients, 20 had either a partial remission or stable disease at the time of alloSCT and 2 had progressive disease. Two (5%) patients had bulky lymphadenopathy (≥ 5cm by CT imaging), 11 (29%) patients had splenomegaly, and 8 (21%) patients had more than 30% CLL involvement by the leukemia index.Fludarabine (F) and 200cGy total body irradiation (TBI) was used as the conditioning regimen for 35 patients (92%). 22 patients received unrelated donor grafts (15 matched, 7 mismatched), and 16 received related donor grafts (all matched). Patients received mycophenolate (MMF) and either tacrolimus (unrelated grafts) or cyclosporin (related grafts) for graft versus host disease (GVHD) prophylaxis. 31 out of 37 evaluable patients (84%) achieved initial 100% donor chimerism (22 within 100 days) and 24 (63%) developed ≥grade 2 GVHD.After median follow-up of 1 year (range = 0–5.4 years), 26 of 38 patients (68%) are alive, and the median overall survival is 47 months. To date, 13 (34%) have experienced CLL progression/relapse requiring accelerated taper of GVHD prophylaxis (n = 2), donor lymphocyte infusion (n = 5), or chemo/immunotherapies (n= 6). For the 12 deceased patients, causes of death was CLL relapse/progression (n = 5), GVHD (n = 2) and infectious or other complications without CLL relapse/progression (n = 5).Pre-transplant use of alemtuzumab (A) within 3 months of transplant was the only pre-transplant characteristics associated with overall survival (OS). Median OS of patients receiving A within 3 months of alloSCT was 1 year compared to not reached for those who did not receive A within 3 months of alloSCT (p = 0.011; Figure 1a). A trend was also observed between alemtuzumab use within 12 months of alloSCT; however, it did not reach statistical significance (p=0.069; Figure 1b). No statistically significant associations between residual marrow involvement at time of alloSCT (p = 0.93), type of graft (p = 0.65), or presence of del (17p13) (p = 0.13), number of prior treatments (p = 0.45), patient age (p = 0.80) or disease status at time of alloSCT (p = 0.21) were observed. [Display omitted] [Display omitted] CONCLUSION:In this cohort of patients with high risk CLL, alemtuzumab use prior to transplant was the greatest predictor of OS after nonmyeloablative alloSCT. Non-alemtuzumab based debulking strategies need to be developed for patients with del (17p13). Disclosures:No relevant conflicts of interest to declare.

Romiplostim (AMG531, Nplate®) for Secondary Failure of Platelet Recovery After Allogeneic Stem-Cell Transplantation

Abstract 1994Romiplostim (Rm), a protein that binds to and stimulates the thrombopoietin receptor, has been shown to increase and maintain platelet counts in splenectomised and non-splenectomised adult patients with chronic immune thrombocytopenic purpura (ITP), and few adverse events have been reported. Thrombocytopenia after allogeneic stem cell transplantation (allo-SCT) is a common complication which can sometimes be severe. All patients are thrombocytopenic until the primary recovery of platelet counts at engraftment, although some patients present with secondary failure of platelet recovery (SFPR) defined by the Seattle group as a decline of platelet counts below 20,000/μL for 7 consecutive days or requiring transfusion support after achieving sustained platelet counts ≥50,000/μL without transfusions for 7 consecutive days after allo-SCT. SFPR is associated with a greater number of complications and a worse outcome indicating that rapid correction of severe thrombocytopenia in these patients is essential.We report on seven patients treated with Rm after allo-SCT for a SFPR not due to disease relapse. The first day of the 7 consecutive days when platelet counts were <20,000/μL was considered the day of SFPR onset. Our therapeutic strategy was to start Rm at 1μg/kg and to increase dose weekly by 1μg/kg until platelet count had reached 50,000/μL. The dose was then reduced as quickly as possible until discontinuation, providing platelet counts remained >50,000/μL, to avoid unnecessary Rm exposure.Transplantations were performed between January 2009 and January 2011. The median age of the patients was 57 years (range, 25 to 60). There were 4 males and 3 females. Diseases were distributed as follow: acute myeloid leukemia (n=2), acute lymphoid leukemia (n=1), myelodysplastic syndrome (n=1), non-Hodgkin lymphoma (n=2), severe aplastic anemia (n=1). Conditioning regimes were reduced in 5 patients. Donors were siblings in 2 cases, matched unrelated in 4 cases and mismatched unrelated in 1 case (C mismatch). The sources of stem cells were peripheral blood in 4 patients and bone marrow in 3 patients. At the onset of SFPR, all patients had severe thrombocytopenia (<10,000/μL) that required transfusion support. At bone marrow aspiration, 2 patients had numerous megakaryocytes while they were rare in the other 4 patients. The median time between allo-SCT and onset of SFPR was 3 months (range, 2 to 18). The median time between onset of SFPR and start of Rm was 27 days (range, 7 to 61). Thrombocytopenia was corrected in all patients. There was a median time of 54 days (range, 24 to 84) between onset of Rm and the first day when platelet count was >50,000/μL. Median duration of treatment was 13 weeks (range, 4 to 16). Maximum dose ranged from 1 to 10μg/kg. Rm was well tolerated and no patient needed to discontinue drug treatment because of adverse events. Four patients developed SFPR within 2 months of developing acute GvHD II-IV. Another patient had an acute GvHD II-IV at 15 months before the onset of SFPR. He also had 2 episodes of CMV infection at 16 and 4 months before SFPR and 2 episodes of EBV infection at 12 and 1 month before SFPR. Moreover, the same patient developed bronchiolitis obliterans organizing pneumonia (BOOP) not due to infection at 1 month before SFPR. Another patient developed acute GvHD II-IV 6 months before SFPR. She also had 2 episodes of CMV infection at 5 and 3 months before the onset of SFPR. The last patient did not develop acute GvHD II-IV or chronic GvHD but had a CMV infection at 1 month before SFPR. Taken together, these observations underline the occurrence of SFPR shortly after episodes of acute GvHD II-IV, BOOP, EBV or CMV infections. At the last follow-up, one patient had died of a relapse of acute myeloid leukemia while others were alive and in remission without recurrence of SFPR after discontinuation of Rm.We conclude that Rm can be a therapeutic option after allo-SCT for patients with severe thrombocytopenia caused by SFPR. However, these preliminary data need to be confirmed in larger studies with a longer follow-up time to improve assessment of efficacy and safety profiles within this setting. In the meantime, if Rm is prescribed, it seems reasonable to use it at the minimally effective dose and to avoid unnecessary prolonged exposure. Disclosures:No relevant conflicts of interest to declare.

Outcomes after prostate brachytherapy are even better than predicted.

During the first 3 years after prostate cancer treatment with radiation therapy, benign prostate-specific antigen (PSA) bounces are difficult for clinicians to distinguish from a biochemical recurrence, which can result in unnecessary interventions and erroneous predictions of outcomes. The objective of this study was to evaluate a commonly used PSA failure definition in a multinational, multi-institutional study after monotherapy with prostate brachytherapy. Participants were selected from 2919 men who underwent permanent prostate brachytherapy at the University Medical Center Utrecht, Princess Margaret Hospital, or Seattle Prostate Institute between 1998 and 2006. Inclusion required not having received androgen-deprivation therapy and having at least 30 months of follow-up. Failure was defined as any post-treatment use of hormone therapy, clinical relapse, or prostogram-defined biochemical (PSA) failure. Cases in which the nomogram predicted biochemical failure were evaluated at each institution to verify biochemical status over time and the actual clinical outcome at 5 years. The median follow-up for the 1816 patients was 5.2 years. Concordance between the prostogram-predicted and actual outcomes, as measured by the Harrell c statistic, was 0.655 (95% confidence interval [CI], 0.536-0.774; P = .010) for the Princess Margaret group, 0.493 (95% CI, 0.259-0.648; P = .955) for the Seattle group, and 0.696 (95% CI, 0.648-0.744, P < .001) for the Utrecht group. The overall mean difference in biochemical recurrence-free survival at 5 years between actual outcomes and prostogram-defined outcomes was 9.2% (95% CI, 7.7%-10.6%). The total numbers of prostogram-defined and actual biochemical failures were 312 and 157, respectively (P = .001). The widely used prostogram could not adequately distinguish a benign PSA bounce from a biochemical recurrence after prostate brachytherapy and could not be used to counsel patients about their predicted outcomes after treatment. The authors conclude that, to avoid unnecessary active interventions after treatment, clinicians should monitor PSA levels for at least 3 years and provide reassurance to patients that a PSA rise during this time is common and may not indicate a treatment failure.

The Incidence of Veno-Occlusive Disease Following Allogeneic Hematopoietic Stem Cell Transplantation Has Diminished and the Outcome Improved over the Last Decade

The evolution of the incidence, morbidity, and mortality of veno-occlusive disease (VOD) was analyzed in 845 allogeneic hematopoietic stem cell transplantations (allo-HSCTs) performed over 24 years. A total of 117 patients and 73 patients developed VOD following the Seattle and the Baltimore diagnostic criteria, respectively (cumulative incidence 13.8% and 8.8%). The cumulative incidence was significantly higher in the period 1985 to 1996 than in 1997 to 2008 (11.5% vs 6.5%; P= .01). This decline was because of the low incidence of VOD among reduced-intensity conditioning-HSCT (RIC-HSCT) (2.1%) and the reduction among those receiving myeloablative-HSCT from unrelated donors (32.7% vs 10.5%, P = .001). A total of 35 patients had severe VOD (26 with multiorgan failure [MOF]), and 20 died by VOD (cumulative mortality rate 17.3%, Seattle, or 22.5%, Baltimore). The mortality declined since 1997 (from 22% to 9%; P = .06, Seattle, and from 36% to 14%; P= .04, Baltimore), with the introduction of defibrotide being the only relevant change in the management of patients. This occurred even though the severity of VOD was similar in both periods. Among those with MOF, only 2 of 8 (25%) receiving defibrotide died versus 14 of 18 (78%) receiving other treatments (P = .007). Myeloablative conditioning, previous liver disease, poor performance status, and alternative donors were the variables with higher impact on VOD development. In summary, although VOD remains a dreaded early complication of HSCT, technical and therapeutic progress in recent decades have notably reduced its incidence and improved the outcome.

Guest editorial: role of monoclonal antibodies for the prevention and treatment of graft-versus-host disease

The Japanese Society of Hematology 2011 Allogeneic hematopoietic stem cell transplantation (HSCT) has been established as an effective treatment for hematological disorders. However, graft-versus-host disease (GVHD) remains a major problem following allogeneic HSCT. The development of GVHD is strongly associated with an increased transplant-related mortality and impaired quality of life. The development of GVHD, however, may also decrease the incidence of relapse of hematological malignancies through the graft-versus-leukemia/lymphoma (GVL) effect. Nevertheless, the increased transplantedrelated mortality due to GVHD overweighs the benefit of the GVL effect in most patients, as shown in one Japanese study [1], and strategies for the prevention or treatment of GVHD remain a major issue in an effort to improve HSCT outcome. The ideal level of immunosuppression for the control of GVHD can be difficult to determine, as excessive immunosuppression may increase the incidence of disease relapse and infectious complications. In addition, each immunosuppressant has its own toxicities such as renal toxicity associated with the use of calcineurin inhibitors. The combination of cyclosporine (CSA) and methotrexate (MTX) has been established as a standard regimen for the prophylaxis against acute GVHD based on a randomized controlled trial performed by the Seattle group [2]. Subsequently, three randomized trials showed that tacrolimus (TAC) is more effective than CSA in preventing acute GVHD, although no survival benefit was observed, due to increased toxicity in the TAC group [3]. There was a

306 VALIDATION OF D'AMICO, SEATTLE, AND NCCN RISK STRATIFICATIONS FOR PROSTATE CANCER IN JAPANESE POPULATION

You have accessJournal of UrologyProstate Cancer: Staging1 Apr 2011306 VALIDATION OF D'AMICO, SEATTLE, AND NCCN RISK STRATIFICATIONS FOR PROSTATE CANCER IN JAPANESE POPULATION Takuya Koie, Noriko Tokui, Teppei Okamoto, Kengo Imanishi, Yuichiro Suzuki, Naoki Sugiyama, Tohru Yoneyama, Shingo Hatakeyama, Shigemasa Kudoh, Kazuyuki Mori, Takahiro Yoneyama, Noritaka Kamimura, and Chikara Ohyama Takuya KoieTakuya Koie Hirosaki, Japan More articles by this author , Noriko TokuiNoriko Tokui Hirosaki, Japan More articles by this author , Teppei OkamotoTeppei Okamoto Hirosaki, Japan More articles by this author , Kengo ImanishiKengo Imanishi Hirosaki, Japan More articles by this author , Yuichiro SuzukiYuichiro Suzuki Hirosaki, Japan More articles by this author , Naoki SugiyamaNaoki Sugiyama Hirosaki, Japan More articles by this author , Tohru YoneyamaTohru Yoneyama Hirosaki, Japan More articles by this author , Shingo HatakeyamaShingo Hatakeyama Hirosaki, Japan More articles by this author , Shigemasa KudohShigemasa Kudoh Hirosaki, Japan More articles by this author , Kazuyuki MoriKazuyuki Mori Hirosaki, Japan More articles by this author , Takahiro YoneyamaTakahiro Yoneyama Hirosaki, Japan More articles by this author , Noritaka KamimuraNoritaka Kamimura Hirosaki, Japan More articles by this author , and Chikara OhyamaChikara Ohyama Hirosaki, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.399AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The incidence of prostate cancer (Pca) is rapidly increasing in Asian population. A validated risk stratification for Asian people is necessary for appropriate treatment selection. AUA guideline recommends D'Amico's risk stratification for Pca. Other than D'Amico's risk stratification, Seattle group and National Comprehensive Cancer Network (NCCN) also postulate their own risk stratification. We examined whether these risk stratifications are applicable in Japanese population. METHODS From September 1993 to March 2010, 541 patients underwent radical prostatectomy for clinical stage T1c-T3 prostate cancer at our institution. The present study enrolled 370 patients who did not received neoadjuvant or adjuvant therapy. Biochemical recurrence-free survival (BRFS) rates were estimated using the Kaplan–Meier method, and the BRFS rates in the D'Amico, Seattle, and NCCN risk groups were compared using the log-rank statistic. RESULTS The mean age of the enrolled patients was 67.1 years, the median initial prostate-specific antigen (PSA) level was 7.61ng/ml, and the mean follow-up period was 44.4 months. According to D'Amico's risk stratification, 35, 280, and 60 patients were grouped into low-, intermediate-, and high-risk groups, respectively. On the basis of the Seattle risk stratification, 35, 282, and 53 patients were grouped into low-, intermediate-, and high-risk groups, respectively. According to the NCCN risk stratification, 30, 271, and 69 patients were grouped in low-, intermediate-, and high-risk groups, respectively. The BRFS rates at 44.4 months in the D'Amico low-, intermediate-, and high-risk groups were 83.1%, 79.6%, and 46.8%, respectively (P < 0.0001 at low and intermediate risk vs. high risk). The BRFS rates in the Seattle low-, intermediate-, and high-riskgroups were 79.8%, 79.8%, and 46.8%, respectively (P < 0.0001 at low and intermediate risk vs. high risk). The BRFS rates in the NCCN low-, intermediate-, and high-risk groups were 79.8%, 82.6%, and 46.8%, respectively (P < 0.0001 at low and intermediate risk vs. high risk). There was no statistically significant difference in BRFS between low-and intermediate-group in any risk stratifications. CONCLUSIONS The present risk stratification systems applied for biochemical recurrence after surgery could not discriminate Low- and Int-risk group in Japanese population. A new risk stratification is necessary for Asian population. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e124-e125 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takuya Koie Hirosaki, Japan More articles by this author Noriko Tokui Hirosaki, Japan More articles by this author Teppei Okamoto Hirosaki, Japan More articles by this author Kengo Imanishi Hirosaki, Japan More articles by this author Yuichiro Suzuki Hirosaki, Japan More articles by this author Naoki Sugiyama Hirosaki, Japan More articles by this author Tohru Yoneyama Hirosaki, Japan More articles by this author Shingo Hatakeyama Hirosaki, Japan More articles by this author Shigemasa Kudoh Hirosaki, Japan More articles by this author Kazuyuki Mori Hirosaki, Japan More articles by this author Takahiro Yoneyama Hirosaki, Japan More articles by this author Noritaka Kamimura Hirosaki, Japan More articles by this author Chikara Ohyama Hirosaki, Japan More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Association Between the Hematopoietic Cell Transplantation-Specific Comorbidity Index (CI) and Non-Relapse Mortality (NRM) After Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) for Acute Myeloid Leukemia (AML) in First Complete Remission (CR1).

Abstract 650The Seattle group previously reported that the adapted Charlson CI (Sorror-CI) was useful for predicting NRM and survival in patients undergoing allo-SCT. However, the value of this CI index is still under considerable debate, since the cohort used by Sorror et al. (Blood 2005; 106:2912-9) included a large age range, a wide variety of diseases, with both myeloablative and RIC transplants. On the other hand, toxicities and NRM prediction is most likely needed in elderly and medically infirm patients who are increasingly offered RIC allo-SCT. Therefore, the current study was designed to test the performance of this CI and its association with outcomes among a cohort of 345 patients (i) aged >50 y.; (ii) diagnosed with a single disease entity, AML in CR1, and (iii) who underwent a RIC allo-SCT reported to the EBMT registry between 1999 and 2006.In this series, the median year of allo-SCT was 2004, and the median age was 58 y. (range, 50-76). 32% of patients needed more than one induction course to achieve CR1. A fludarabine-based RIC regimen was used in 64% of patients, while 31% of patients received low-dose TBI as part of their RIC, and 6% received other non-specified RIC regimens. 76% of the patients received allo-SCT from an HLA-matched sibling donor.Based on score calculated with hazard ratios (HR) estimated on the population studied, 161 patients (47%) had a CI score of 0, 96 patients (29%) had a score of 1, and 49 (14%) had a CI score of 2. The remaining 39 patients (11%) had CI scores of 3 or more. In this cohort, 2 years overall and leukemia-free survival rates were 64±3% and 54±3% and the 2 years relapse and -NRM cumulative incidences were 32±2%, and 15±2% respectively. The 2 years NRM incidences according to comorbidities score 0, 1, 2 and 3+ were 9±2%, 15±4%, 18±5% and 31±7%, respectively. In multivariate models (adjusted for recipient age, donor type, use of TBI or not, and cytogenetics risk group) comorbidities such as moderate active liver disease, obesity, prior history of renal dysfunction, and prior history of severe liver disease were associated with the highest HRs for 2 years NRM (varying from 2.11 to 2.76) and 2 years cumulative incidences of NRM varying from 22% to 44%, whereas previous solid tumor, diabetes, rheumatologic abnormalities, moderate pulmonary diseases, cardiac abnormalities (other than arrhythmia and valve disease) were associated with the lowest HRs (varying from 0.2 to 1.0) with 2 years cumulative incidences of NRM varying from 5 to 17%.Results from this large study performed in a single disease entity and homogeneous allo-SCT setting, suggest that the hematopoietic cell transplantation-specific CI is a simple, informative and useful tool for capturing pre-transplant comorbidities, and for predicting NRM after RIC allo-SCT for AML in CR1 in patients aged >50 y. Such index may be used for clinical trials and patient counselling before RIC allo-SCT. Disclosures:No relevant conflicts of interest to declare.

Bladder Sensation Measures and Overactive Bladder

We performed a prospective multicomponent study to determine whether subjective and objective bladder sensation instruments may provide data on sensory dysfunction in patients with overactive bladder. We evaluated 70 prospectively enrolled patients with urodynamics and questionnaires on validated urgency (Urgency Perception Score), general overactive bladder (Urogenital Distress Inventory) and quality of life (Incontinence Impact Questionnaire). We first sought a correlation between sensory specific (Urgency Perception Score) and quality of life questionnaire scores. We then assessed a correlation between sensory questionnaire scores and urodynamic variables, exploring the hypothesis that certain urodynamic parameters may be bladder sensation measures. We evaluated 2 urodynamic derivatives (first sensation ratio and bladder urgency velocity) to increase sensory finding discrimination. We noted a moderate correlation between the Urgency Perception Score (0.56) and the Urogenital Distress Inventory (0.74) vs the Incontinence Impact Questionnaire (each p <0.01). A weak negative correlation was seen between Urgency Perception Score and bladder capacity (-0.25, p <0.05). No correlation was noted for the other urodynamics parameters. First sensation ratio and bladder urgency velocity statistically significantly correlated with the Urgency Perception Score despite the lesser or absent correlation associated with the individual components of these derivatives. Bladder sensation questionnaires may be valuable to identify patients with sensory dysfunction and provide additional data not obtained in generalized symptom questionnaires. Urodynamic variables correlated with bladder sensation questionnaire scores and may be an objective method to assess sensory dysfunction.

A landmark systems analysis of prion disease of the brain

A landmark systems analysis of prion disease of the brain

We Did It Our Way

We Did It Our Way

Impact of comorbidity indexes on non-relapse mortality

Comorbidity indexes (CI) have been reported to predict non-relapse mortality (NRM) and overall survival after allogeneic hematopoietic stem cell transplantation (HSCT) (Charlson's comorbidity index (CCI), hematopoietic cell transplantation CI (HCT-CI) and the pre-transplantation assessment of mortality (PAM) score). Which of these indexes best predict survival is unknown yet. We retrospectively studied 286 patients who underwent allogeneic HSCT. HCT-CI and PAM scores required grading according to pre-transplant pulmonary function tests (PFTs), which were lacking for some patients. We thus designed a reduced HCT-CI and an adjusted PAM, without results of PFTs. Using CCI, 25% of patients had indexes of 1 or more; median reduced HCT-CI score was 1; median adjusted PAM score was 24. The discriminative properties of the three CIs were rather low in our population. Comparison of patients and transplant characteristics between our and Seattle group's cohorts, however, revealed significant differences in more children, in more cord blood HSCT and in HSCT for Fanconi anemia in St Louis. Finally, multivariate analysis of scoring items revealed that age, matched unrelated or mismatched donor and hepatic disease were associated with NRM in our cohort. Translating use for patient's counseling or decision to proceed to transplant of these CIs will need prospective studies in a large independent cohort.

Rebuttal from Drs. Hughes and West

POINT-COUNTERPOINTRebuttal from Drs. Hughes and WestPublished Online:01 May 2008https://doi.org/10.1152/japplphysiol.01092.2007bMoreSectionsPDF (59 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat The areas of agreement in this debate are twofold: 1) mean pulmonary blood flow per horizontal slice [per unit volume or, more accurately, per unit density or “alveolus” (1,6)] increases in the gravity direction, independent (for the most part) of postural orientation, 2) there is considerable inhomogeneity of blood flow within a slice of minimal vertical height. Heterogeneity, whether random or ordered, is inevitable as the spatial resolution increases, just as the length of the shoreline increases indefinitely as the sample size gets smaller. Suffice to say that there are two extremes, 1) a well-expanded, vasodilated lung with low PVR and a mean Ppa level below the top of the lung, and 2) a low volume vasoconstricted lung with high PVR and a Ppa level greater than the lung's vertical height. The effects of gravity will be prominent in the former and largely obscured in the latter.The core of the debate is about the mechanisms responsible for pulmonary blood flow heterogeneity. There has been acceptance (for more than 40 yr) that mean pulmonary blood flow per horizontal slice is influenced by the relations between Ppa, Palv, and Pv (zones I, II, and III) (7), provided the lung is well expanded and PVR is normal. But what determines heterogeneity at the same horizontal level? Between acini, or larger domains, the Seattle group maintains that the architecture of the vascular tree (presumably, arterial) determines local vascular resistance and blood flow by, for example, uneven diameters of the two daughter vessels at a bifurcation. Glenny (5) maintains that this is not random, but forms part of the fractal design of the lung (4). Against this hypothesis is 1) the arterial system contributes only 40% to total PVR (2), and 2) the compliance of the arterial tree means diameters are not fixed, but respond to changes of smooth muscle tone or intra- or extravascular pressures (themselves influenced by gravity from distortion of the lung by its own weight and by other intrathoracic structures).Distal to the arterial tree, at the alveolar septal level, recruitment and distension of vessels occurs (3), independent of arteriolar domains (8), as input pressure increases and exceeds critical opening pressure (9); in the lung periphery, input pressures are a function of vertical height and gravity. So, in subtle ways, gravity may interact with compliant vascular structures to influence local PVR within as well as between horizontal lung slices.REFERENCES1 Anthonisen NR, Milic-Emili J. Distribution of pulmonary perfusion in erect man. J Appl Physiol 21: 760–766, 1966.Link | ISI | Google Scholar2 Dawson CA. Dynamics of blood flow and pressure-volume relationship. In: The Lung: Scientific Foundations, edited by Crystal RG, West JB, et al. Philadelphia: Lippincott-Raven, 1997, p. 1503–1522.Google Scholar3 Glazier JB, Hughes JMB, Maloney JE, West JB. Measurements of capillary dimensions and blood volume in rapidly frozen lungs. J Appl Physiol 26: 65–76, 1969.Link | ISI | Google Scholar4 Glenny RW, Robertson HT. Fractal modelling of pulmonary blood flow inhomogeneity. J Appl Physiol 70: 1024–1030, 1991.Link | ISI | Google Scholar5 Glenny RW. Spatial correlation of regional pulmonary perfusion. J Appl Physiol 72: 2378–2386, 1992.Link | ISI | Google Scholar6 Hughes JMB, Glazier JB, Maloney JE, West JB. Effect of lung volume on the distribution of pulmonary blood flow in man. Respir Physiol 4: 58–72, 1968.Crossref | Google Scholar7 West JB, Dollery CT, Naimark A. Distribution of blood flow in isolated lung; relation to vascular and alveolar pressures. J Appl Physiol 19: 713–724, 1964.Link | ISI | Google Scholar8 Warrell DA, Evans JW, Clarke RO, Kingaby JP, West JB. Pattern of filling in the pulmonary vascular bed. J Appl Physiol 32: 346–356, 1972.Link | ISI | Google Scholar9 West JB, Schneider AM, Mitchell MM. Recruitment in networks of pulmonary capillaries. J Appl Physiol 39: 976–984, 1975.Link | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation More from this issue > Volume 104Issue 5May 2008Pages 1535-1535 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.01092.2007bHistory Published online 1 May 2008 Published in print 1 May 2008 Metrics

Somatostatin: The beginnings, 1972

Somatostatin: The beginnings, 1972