MO315CLINICAL AND PATHOLOGICAL FEATURES OF IGA NEPHROPATHY: A REPORT FROM A SINGLE CENTER

Abstract Background and Aims IgA nephropathy (IgAN) is one of the most prevalent glomerulopathies worldwide with broad variable clinical presentation and extremely heterogeneous risk of progressive CKD and ESKD. It was recommended risk stratifying patients in order to target immunosuppressive treatment to high-risk patients. The OXFORD MEST classification and, more recently, a new international risk-prediction tool for IgAN (IgANPT) help to predict kidney outcomes and stratify patient risk, eventually aiding in treatment decision. Here, we analyzed a single center cohort of IgAN to investigate if treatment decisions were accurately accomplished using individualized risk from the IgANPT. Method A retrospective analysis of all kidney biopsies performed from January 2010 to December 2019 in a Nephrology Department was performed and adult patients with IgAN diagnosis were selected. The presence of IgA vasculitis and Henoch-Schönlein purpura as well as lack of follow-up data were exclusion criteria. Clinical, laboratorial and pathological data were collected, including treatment and kidney outcome. Risk of kidney progression decline was assessed by using the on-line web-based calculator of the IgANPT. Results A total of 33 patients met the study criteria, with median age at diagnosis of 58 (IQR 38 - 68) years-old, mostly male (84,8%, N=28) and all Caucasian. At biopsy time 60,6% (N=20) had hypertension, only 15,5% (N=5) diabetes mellitus and 57,6% (N=19) were under ACE inhibitors/ARBs. Median GFR at biopsy time was 57 (IQR 20 - 78,5) ml/min/1.73m2. More than half of the patients (57,6%, N=19) had GFR <60ml/min/1.73m2. All patients had proteinuria (UACR > 300mg/g), with 18,2% (N=6) in the nephrotic range. Hematuria was present in almost all patients. Overall MEST classification was: 51,5% (N= 17) with M1 score, 39,4% (N=13) E1, 66,7% (N=22) S1 and 45,5% (N=15) had T ≥1 score (2 patients with T2). Crescents were present in 27,3% of the biopsies (N=9). Near one-half of the patients (45,5%, N=15) presented IgA deposits on both mesangium and capillary wall. Around one-third of patients (30,3%, N=10) progressed to ESKD during follow up. According to the risk of kidney disease progression in 60-months calculated with IgANPT, patients were stratified into low/intermediate risk in 21,2% (N=7) of cases (mean predicted risk < 4,7%) and high risk in 78,8% (N=26) of cases (mean predicted risk > 4,7%). Using the chi-squared test the high-risk group was associated with progression to ESKD(p=0,019). On the contrary none of the low-risk group progressed to ESKD. The majority of patients received supportive treatment (87,9%, N= 29), mainly with ACEi/ARB (N=31) and omega (15,2%, N=5). Immunosuppressive treatment included mainly corticosteroids (51,5%, N=17), with other options being (12,1% N=4): cyclophosphamide (N=2), ciclosporin (N=1) and MMF (N=1). From the group of low/intermediate risk patients, only two (28,5%) received immunosuppressive treatment with either oral or intravenous corticosteroids. On the other hand, from the high-risk group, more than one third of patients (38,4%, N=10) did not receive immunosuppressive treatment. Conclusion A better prediction of kidney outcomes and consequent better patient selection for IS therapy may be challenging in IgA nephropathy. In spite of the existent tools, it is still difficult to determine which patients benefit from immunosuppressive treatment. In this case series we stratified our patients by using the IgANPT identifying who was at higher risk of progression to ESKD, in whom, a more aggressive treatment could have potentially benefit avoiding kidney disease progression. It was also important to stratify patients at low-risk, in whom immunosuppressive treatment could carry risk of adverse events with no additional advantage in kidney outcomes.

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Risk Stratification in Acute Promyelocytic Leukemia Based on Elevated White Cell Count and Reduced Platelet Count Does Not Identify Subsequent Relapses: A Retrospective Review of 60 Patients.

Blood ◽

10.1182/blood.v104.11.4522.4522 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4522-4522

Author(s):

Richard T. Doocey ◽

Stephen H. Nantel ◽

Michael J. Barnett ◽

Donna L. Forrest ◽

Donna E. Hogge ◽

...

Keyword(s):

High Risk ◽

Complete Remission ◽

Maintenance Therapy ◽

Risk Group ◽

White Cell Count ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

Risk Patients

Abstract Acute promyelocytic leukemia (APL) has become one of the more readily treatable subtypes of acute myeloid leukemia on the basis of its particular sensitivity to anthracyclines and the introduction of the differentiating agent all-trans retinoic acid (ATRA). Unfortunately some patients will ultimately relapse after achievement of complete remission. A PETHEMA and GIMEMA (PETH/GIM) cooperative group joint study sought to identify risk factors associated with relapse and developed a predictive model based on white cell count (WCC) and platelet count (Plt) at diagnosis. This model for relapse free survival was capable of segregating patients into low risk (WCC < 10 x 109/L / Plt > 40 x 109/L), intermediate risk (WCC < 10 x 109/L / Plt < 40 x 109/L), and high risk (WCC > 10 x 109/L). A subsequent follow up study demonstrated improved outcomes for intermediate and high risk group patients treated with an anthracycline and ATRA based risk adapted strategy. We reviewed 60 cases of adult de novo APL treated at Vancouver General Hospital from August 1995 to December 2003. Thirty five females (58%) and 25 males (42%) were treated with a standard induction and consolidation protocol consisting of 3 cycles of Daunorubicin (60 mg/m2 OD for 3 days), Cytosine arabinoside (100 mg/m2 BID for 7 days), and ATRA (45 mg/m2/day until complete remission or a maximum of 60 days). In 2000 maintenance therapy was introduced and ATRA and/or varying doses of Methotrexate and 6-Mercaptopurine were then instituted for up to 2 years duration. At the completion of induction chemotherapy complete morphological and cytogenetic remission was achieved in 55/60 patients (92%) with 4 induction failures and only 1 death during induction treatment. Subsequently during and after consolidation and maintenance therapy at a median follow up of 34 months there were a total of 10 episodes of relapse (18%) in these 55 patients. When the 55 patients in complete remission were stratified at diagnosis by the PETH/GIM risk group there were 18 low risk patients (33%), 26 intermediate risk patients (47%), and 11 high risk patients (20%). The number of relapses was 6 in the low risk group (33%), 4 in the intermediate risk group (15%) and no relapses were identified in the high risk group. In our experience the predictive model for relapse free survival developed by the PETH/GIM cooperative group does not identify those at most likelihood for subsequent relapse after achieving an initial complete remission. The greatest number of relapse was seen in the low risk group with no relapses in the high risk group. These variations may be explained in part by the different chemotherapy treatment protocols with variable maintenance therapy. Future investigation will focus on the prognostic role of immunophenotype, additional cytogenetic abnormalities and molecular isoforms in determining outcome in APL.

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Clinical Prognostic Models in Diffuse Large B-Cell Lymphoma Patients Are Still Essential in the Rituximab Era

Blood ◽

10.1182/blood.v124.21.3057.3057 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3057-3057

Author(s):

Luis Alberto de Padua Covas Lage ◽

Renata Oliveira Costa ◽

Abrahão Elias Hallack Neto ◽

Sheila Siqueira ◽

Rodrigo Santucci ◽

...

Keyword(s):

High Risk ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

High Risk Group ◽

Intermediate Risk ◽

Risk Patients ◽

Risk Categories

Abstract Introduction: To evaluate a new enhanced IPI proposed by the National Comprehensive Cancer Network (NCCN-IPI) in DLBCL patients, we compared the international prognostic index (IPI), R-IPI and NCCN-IPI in DLBCL patients treated with rituximab, cyclophosphamide, hidroxydaunorubicin, vincristine and prednisone (R-CHOP). Methods: From June 2008 to November 2011 we retrospectively evaluated 146 DLBCL patients treated with R-CHOP-21 referred for cancer treatment in a single university institution in Brazil. Patient's clinical data were assessed to calculate the IPI, R-IPI and NCCN-IPI. Results: Patient's median age was 58.9 years (range 16 – 86); 85 (57.8%) were female. According to IPI, risk categories were low (n=41, 28.1%), low-intermediate (n=43, 29.5%), high-intermediate (n=37, 25.3%) and high (n=25, 17.1%). Using R-IPI, risk categories were very good (n=19, 13%), good (n=65, 44.5%) and poor (n=62, 42.5%). According to NCCN-IPI, risk categories were low (n=12, 8.2%), low-intermediate (n=52, 35.6%), high-intermediate (n=62, 42.5%) and high (n=20, 13.7%). At 30 months (median follow up 17.7 months - range 0.6-58.2 months) the overall survival (OS) was 75.5%. The progression-free survival (PFS) at a median follow-up of 16.3 months (range 0.6-52.4) was 68.3% for all patients. Using IPI, the OS at 30 months did not differ between low and low-intermediate risk patients (96.8% vs. 82.2%; p=0.136); however, it was higher than the OS of high-intermediate risk (n=37; 96.8% vs 74.1% p=0.11) and high-risk (n=25; 96.8% vs 41% p < 0.001) patients (Figure 1). The NCCN-IPI demonstrated significant differences in OS (p < 0,001) and PFS (p<0.001) among low-intermediate, high-intermediate, and high risk groups, with the high-risk group exhibiting worse OS (32.1% in 30 months) (Figure 2). According to IPI, the OS in high-risk patients was 41%. Figure 1: OS and PFS according to International Prognostic Index (IPI) Figure 1:. OS and PFS according to International Prognostic Index (IPI) Figure 2: OS and PFS according to NCCN-IPI Figure 2:. OS and PFS according to NCCN-IPI Figure 3 Figure 3. Conclusion: In our study the NCCN-IPI, but not the IPI or R-IPI was able to discriminate a high-risk group of DLBCL patients treated with R-CHOP with worse OS. Disclosures No relevant conflicts of interest to declare.

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P3609Temporal trends of the management and outcomes of patients after myocardial infarction according to the risk for recurrent cardiovascular events

European Heart Journal ◽

10.1093/eurheartj/ehz745.0468 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T Grinberg ◽

T Bental ◽

Y Hammer ◽

A R Assali ◽

H Vaknin-Assa ◽

...

Keyword(s):

Myocardial Infarction ◽

High Risk ◽

Cardiovascular Events ◽

Risk Group ◽

Temporal Trends ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

High Risk Patients ◽

Risk Patients

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.

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Application of a Validated Predictive Model for Venous Thromboembolism in Cancer to Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.534.534 ◽

2016 ◽

Vol 128 (22) ◽

pp. 534-534

Author(s):

Natasha Catherine Edwin ◽

Jesse Keller ◽

Suhong Luo ◽

Kenneth R Carson ◽

Brian F. Gage ◽

...

Keyword(s):

High Risk ◽

Research Funding ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

Discriminative Ability ◽

Blood Institute ◽

C Statistic

Abstract Background Patients with multiple myeloma (MM) have a 9-fold increased risk of developing venous thromboembolism (VTE). Current guidelines recommend pharmacologic thromboprophylaxis in patients with MM receiving an immunomodulatory agent in the presence of additional VTE risk factors (NCCN 2015, ASCO 2014, ACCP 2012). However, putative risk factors vary across guidelines and no validated VTE risk tool exists for MM. Khorana et al. developed a VTE risk score in patients with solid organ malignancies and lymphoma (Blood, 2008). We sought to apply the Khorana et al. score in a population with MM. Methods We identified patients diagnosed with MM within the Veterans Health Administration (VHA) between September 1, 1999 and December 31, 2009 using the International Classification of Diseases (ICD)-03 code 9732/3. We followed the cohort through October 2014. To eliminate patients with monoclonal gammopathy of undetermined significance and smoldering myeloma, we excluded patients who did not receive MM-directed therapy within 6 months of diagnosis. We also excluded patients who did not have data for hemoglobin (HGB), platelet (PLT) count, white blood count (WBC), height and weight, as these are all variables included in the Khorana et al. risk model. Height and weight were assessed within one month of diagnosis and used to calculate body mass index (BMI). We measured HGB, PLT count, and WBC count prior to treatment initiation: within two months of MM diagnosis. A previously validated algorithm, using a combination of ICD-9 code for VTE plus pharmacologic treatment for VTE or IVC filter placement, identified patients with incident VTE after MM diagnosis (Thromb Res, 2015). The study was approved by the Saint Louis VHA Medical Center and Washington University School of Medicine institutional review boards. We calculated VTE risk using the Khorana et al. score: We assigned 1 point each for: PLT ≥ 350,000/μl, HGB < 10 g/dl, WBC > 11,000/μl, and BMI ≥ 35 kg/m2. Patients with 0 points were at low-risk, 1-2 points were considered intermediate-risk and ≥3 points were termed high-risk for VTE. We assessed the relationship between risk-group and development of VTE using logistic regression at 3- and 6-months. We tested model discrimination using the area under the receiver operating characteristic curve (concordance statistic, c) with a c-statistic range of 0.5 (no discriminative ability) to 1.0 (perfect discriminative ability). Results We identified 1,520 patients with MM: 16 were high-risk, 802 intermediate-risk, and 702 low-risk for VTE using the scoring system in the Khorana et al. score. At 3-months of follow-up, a total of 76 patients developed VTE: 27 in the low-risk group, 48 in the intermediate-risk group, and 1 in the high-risk group. At 6-months of follow-up there were 103 incident VTEs: 41 in the low-risk group, 61 in the intermediate-risk group, and 1 in the high-risk group. There was no significant difference between risk of VTE in the high- or intermediate-risk groups versus the low-risk group (Table 1). The c-statistic was 0.56 at 3-months and 0.53 at 6-months (Figure 1). Conclusion Previously, the Khorana score was developed and validated to predict VTE in patients with solid tumors. It was not a strong predictor of VTE risk in MM. There is a need for development of a risk prediction model in patients with MM. Figure 1. Figure 1. Disclosures Carson: American Cancer Society: Research Funding. Gage:National Heart, Lung and Blood Institute: Research Funding. Kuderer:Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Sanfilippo:National Heart, Lung and Blood Institute: Research Funding.

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SPECIFICS OF ANTIHYPERTENSION THERAPY IN HYPERTENSIVES OF VARIOUS CARDIOVASCULAR RISK (BY THE REGISTRY OF CHRONIC NON-COMMUNICABLE DISEASES IN TYUMENSKAYA OBLAST)

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2018-3-4-10 ◽

2018 ◽

Vol 17 (3) ◽

pp. 4-10

Author(s):

A. Yu. Efanov ◽

Yu. A. Vyalkina ◽

Yu. A. Petrova ◽

Z. M. Safiullina ◽

O. V. Abaturova ◽

...

Keyword(s):

Cardiovascular Risk ◽

High Risk ◽

Risk Group ◽

High Risk Group ◽

Risk Level ◽

Moderate Risk ◽

High Risk Patients ◽

Risk Patients ◽

Very High

Aim. To assess the specifics of antihypertension therapy (AHT) in hypertensives of various cardiovascular risk, in the registry of chronic non-communicable diseases in Tyumenskaya oblast.Material and methods. A random sample studied, of 1704 patients with hypertension, inhabitants of Tyumenskaya oblast (region), ascribed to dispensary follow-up. Mean age 62±7,5 y.o. Of those 31,5% (n=537) males. The prevalence and efficacy of AHT assessed according to cardiovascular risk level. The significance was evaluated with the criteria χ2.Results. AHT was characterized by the growth of the frequency of treatment approaches with cardiovascular risk consideration. Regular treatment took 33,9% patients of low and moderate risk vs 41,3% of high and very high (p<0,01). In the male group such tendency also took place. Gender specifics of AHT was characterized by that in the groups of high and very high risk females took medications significantly more commonly than males — 46,6% vs 29,1% in high risk group (p<0,01) and 47,5% vs 30% in very high risk group (p<0,01). With the increase of the risk level, there was decline of treatment efficacy — from 95% in low risk group to 32,5% in very high risk group; 53,1% of the participants were taking monotherapy, 32,9% — two drugs, 14,0% — ≥3 drugs. With the increase of risk grade there is tendency to increase of combinational AHT, however with no significant increase of efficacy. Treatment efficacy in high and very high risk patients comparing to patients with low and moderate risk was significantly lower — 33,1% vs 69,7% (p<0,01), respectively. Statins intake among the high and very high risk patients was 10,6-11,0% males and 7,8% females (p<0,05).Conclusion. AHT in hypertensives in Tymenskaya oblast, under dispensary follow-up, is characterized by insufficient usage of combinational drugs. With the raise of cardiovascular risk there is tendency to higher rate of combinational AHT. However there is no significant increase in efficacy of treatment with the increase of medications number. A very low rate of statins intake is noted. The obtained specifics witness for the necessity to optimize AHT among the high and very high risk patients — inhabitants of Tyumenskya oblast.

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A novel hyperinflammation clinical risk tool, HI5-NEWS2, predicts mortality following early dexamethasone use in an observational cohort of hospitalised COVID-19 patients.

10.1101/2021.06.16.21259011 ◽

2021 ◽

Author(s):

Michael R Ardern-Jones ◽

Hang T.T. Phan ◽

Florina Borca ◽

Matthew Stammers ◽

James Batchelor ◽

...

Keyword(s):

High Risk ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

Dexamethasone Treatment ◽

Dexamethasone Therapy ◽

Risk Patients ◽

Anti Inflammatory

Background The success of early dexamethasone therapy for hospitalised COVID-19 cases in treatment of Sars-CoV-2 infection may predominantly reflect its anti-inflammatory action against a hyperinflammation (HI) response. It is likely that there is substantial heterogeneity in HI responses in COVID-19. Methods Blood CRP, ferritin, neutrophil, lymphocyte and platelet counts were scored to assess HI (HI5) and combined with a validated measure of generalised medical deterioration (NEWS2) before day 2. Our primary outcome was 28 day mortality from early treatment with dexamethasone stratified by HI5-NEWS2 status. Findings Of 1265 patients, high risk of HI (high HI5-NEWS2) (n=367, 29.0%) conferred a strikingly increased mortality (36.0% vs 7.8%; Age adjusted hazard ratio (aHR) 5.9; 95% CI 3.6-9.8, p<0.001) compared to the low risk group (n= 455, 36.0%). An intermediate risk group (n= 443, 35.0%) also showed significantly higher mortality than the low risk group (17.6% vs 7.8%), aHR 2.2, p=0.005). Early dexamethasone treatment conferred a 50.0% reduction in mortality in the high risk group (36.0% to 18.0%, aHR 0.56, p=0.007). The intermediate risk group showed a trend to reduction in mortality (17.8% to 10.3%, aHR 0.82, p=0.46) which was not observed in the low risk group (7.8% to 9.2%, aHR 1.4, p =0.31). Interpretation The HI5-NEWS2 measured at COVID-19 diagnosis, strongly predicts mortality at 28 days. Significant reduction in mortality with early dexamethasone treatment was only observed in the high risk group. Therefore, the HI5-NEWS2 score could be utilised to stratify randomised clinical trials to test whether intensified anti-inflammatory therapy would further benefit high risk patients and whether alternative approaches would benefit low risk groups. Considering its recognised morbidity, we suggest that early dexamethasone should not be routinely prescribed for HI5-NEWS2 low risk individuals with COVID-19 and clinicians should cautiously assess the risk benefit of this intervention. Funding No external funding.

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Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group

Blood ◽

10.1182/blood-2010-03-276196 ◽

2010 ◽

Vol 116 (17) ◽

pp. 3171-3179 ◽

Cited By ~ 195

Author(s):

Francesco Lo-Coco ◽

Giuseppe Avvisati ◽

Marco Vignetti ◽

Massimo Breccia ◽

Eugenio Gallo ◽

...

Keyword(s):

High Risk ◽

Acute Promyelocytic Leukemia ◽

Risk Group ◽

High Risk Group ◽

Promyelocytic Leukemia ◽

Intermediate Risk ◽

Newly Diagnosed ◽

All Trans Retinoic Acid ◽

Risk Patients

AbstractAfter the identification of discrete relapse-risk categories in patients with acute promyelocytic leukemia (APL) receiving all-trans retinoic and idarubicin (AIDA)–like therapies, the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) designed a protocol for newly diagnosed APL (AIDA-2000) in which postremission treatment was risk-adapted. Patients with low/intermediate risk received remission at 3 anthracycline-based consolidation courses, whereas high-risk patients received the same schedule as in the previous, non–risk-adapted AIDA-0493 trial including cytarabine. In addition, all patients in the AIDA-2000 received all-trans retinoic acid (ATRA) for 15 days during each consolidation. After induction, 600 of 636 (94.3%) and 420 of 445 (94.4%) patients achieved complete remission in the AIDA-0493 and AIDA-2000, respectively. The 6-year overall survival and cumulative incidence of relapse (CIR) rates were 78.1% versus 87.4% (P = .001) and 27.7% versus 10.7% (P < .0001). Significantly lower CIR rates for patients in the AIDA-2000 were most evident in the high-risk group (49.7% vs 9.3%, respectively, P < .0001). Our data confirm that anthracycline-based consolidation is at least equally effective as cytarabine-containing regimens for low-/intermediate-risk patients and suggest that a risk-adapted strategy including ATRA for consolidation improves outcome in newly diagnosed APL. Furthermore, our results highlight the role of cytarabine coupled to anthracyclines and ATRA during consolidation in the high-risk group. This trial was registered at www.clinicaltrials.gov as #NCT 001064570.

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CFAR, An Active Frontline Regimen for High-Risk Patients with CLL, Including Those with Del 17p.

Blood ◽

10.1182/blood.v112.11.2095.2095 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2095-2095 ◽

Cited By ~ 4

Author(s):

William G Wierda ◽

Susan M O’Brien ◽

Stefan H Faderl ◽

Alessandra Ferrajoli ◽

Charles Koller ◽

...

Keyword(s):

Prognostic Factors ◽

High Risk ◽

Risk Group ◽

High Risk Group ◽

Fish Analysis ◽

Color Flow ◽

High Risk Patients ◽

Significant Difference ◽

Risk Patients

Abstract High-risk patients (pts) with CLL can be identified by prognostic factors. Traditional prognostic factors that identify high-risk pts include Rai stage, absolute lymphocyte count (ALC), rapid lymphocyte doubling time, and serum beta-2 microglobulin (β2M). Del 17p is associated with loss of the tumor suppressor gene TP53. Patients with del 17p also tend to have mutations in TP53, thereby providing a second mechanism for complete TP53 knockout. Pts with del 17p have poor response to purine analogue-based treatments. β2M greater than twice the upper limit of normal (2XULN) was an independent high-risk feature for pts treated with the frontline fludarabine (F), cyclophosphamide (C), rituximab (R) regimen (FCR). Pts younger than 70 years with β2M >2XULN treated with FCR had a complete remission (CR) rate of 60% and median time to progression (TTP) of 70 months, compared to 84% and 86 months for pts <70 yrs old with β2M <2XULN. We evaluated the CFAR regimen (F 20mg/m2 d3–5; C 200mg/m2 d3–5; R 375–500mg/ m2 d2; and Alemtuzumab 30mg d1,3,5 of each 4-wk course) as frontline treatment in a high-risk group of pts with CLL. The trial completed planned enrollment of 60 pts; 48 are currently evaluable for response and follow-up. In this high-risk group, 28% of the 48 evaluable high-risk pts had del 17p prior to treatment by FISH analysis. Overall, the CR rate for the 48 pts was 69%, 54% CR for the 13 pts with del 17p. The overall response rates were 94% and 77% for the 48 pts and 13 pts with del 17p, respectively. CFAR was associated with more myelosuppression and fewer pts could receive all 6 intended courses compared with the historic high-risk group treated with FCR. However, a higher proportion of CFAR pts had no evidence of residual disease in the bone marrow by 2-color flow cytometry evaluation at response assessment. There is currently no difference in TTP or OS, comparing CFAR and FCR in this retrospective historical analysis with a short median follow-up time of 16 months for the CFAR group. There was no significant difference in incidence of infection during treatment with CFAR compared to FCR, with the exception of CMV reactivation. The CFAR regimen is active and tolerated in the highrisk group of pts with CLL, including those with del 17p. Follow-up continues for the pts treated on this trial in order to evaluate responses in all 60 enrolled pts and to evaluate time-to-event endpoints and compare with the historic FCR experience.

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Stratified follow-up for endometrial cancer: a move to more personalized cancer care

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2021-002903 ◽

2021 ◽

pp. ijgc-2021-002903

Author(s):

Asma Sarwar ◽

Jennifer Van Griethuysen ◽

Jasmine Waterhouse ◽

Hakim-Moulay Dehbi ◽

Gemma Eminowicz ◽

...

Keyword(s):

Endometrial Cancer ◽

High Risk ◽

European Society ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

Eligibility Criteria ◽

Gynecology And Obstetrics

ObjectiveHospital based follow-up has been the standard of care for endometrial cancer. Patient initiated follow-up is a useful adjunct for lower risk cancers. The purpose of this study was to evaluate outcomes of endometrial cancer patients after stratification into risk groupings, with particular attention to salvageable relapses.MethodsAll patients treated surgically for International Federation of Gynecology and Obstetrics (FIGO) stage I–IVA endometrial cancer of all histological subtypes, from January 2009 until March 2019, were analyzed. Patient and tumor characteristics, treatment details, relapse, death, and last follow-up dates were collected. Site of relapse, presence of symptoms, and whether relapses were salvageable were also identified. The European Society of Medical Oncology–European Society of Gynecological Oncology 2020 risk stratification was assigned, and relapse free and overall survival were estimated.Results900 patients met the eligibility criteria. Median age was 66 years (range 28–96) and follow-up duration was 35 months (interquartile range 19–57). In total, 16% (n=144) of patients relapsed, 1.3% (n=12) from the low risk group, 3.9% (n=35) from the intermediate risk group, 2.2% (n=20) from the high–intermediate risk group, and 8.7% (n=77) from the high risk group. Salvageable relapses were less frequent at 2% (n=18), of which 33% (n=6) were from the low risk group, 22% (n=4) from the intermediate risk group, 11% (n=2) from the high–intermediate risk group, and 33% (n=6) from the high risk group. There were only three asymptomatic relapses in the low risk patients, accounting for 0.33% of the entire cohort.ConclusionsRelapses were infrequent and most presented with symptoms; prognosis after relapse remains favorable. Overall salvageable relapses were infrequent and cannot justify intensive hospital based follow-up. Use of patient initiated follow-up is therefore appropriate, as per the British Gynaecological Cancer Society's guidelines, for all risk groupings.

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Use of cytokeratin 18 and EAU score to predict tumor recurrence in patients with non-muscle-invasive bladder cancer following single postoperative immediate intravesical chemotherapy instillation.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.269 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 269-269

Author(s):

M. Horinaga ◽

S. Murata ◽

M. Matsushima ◽

Y. Nakahira ◽

H. Yanaihara ◽

...

Keyword(s):

High Risk ◽

Scoring System ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Nuclear Staining ◽

Intermediate Risk ◽

Ki 67 ◽

Risk Recurrence

269 Background: We examined the prognostic factors for recurrence after TURBT using molecular markers as well as the scoring system of the EAU. Methods: Eighty-eight patients with primary or recurrent bladder tumors who underwent TURBT followed by the single postoperative immediate instillation of pirarubicin and no further instillations were enrolled between 2003 and 2006; the median follow-up period was 46 months. The time to first recurrence was the primary end point of this study. Patients were divided into EAU recurrence risk groups as follows: low-risk group (total score, 0), intermediate-risk group (total score, 1-9) and high-risk group (total score, 9-17). The intermediate-risk group patients were subdivided into a total score of 1-4 and a total score of 5-9. Immunostaining using Ki-67, pHH3, CK18 and Survivin were performed on the TURBT specimens. Results: According to the risk stratification, 5, 82, and 1 were assigned to the low-, intermediate-, and high-risk recurrence groups, respectively. During the follow-up, recurrences were observed in 0% of the low-risk group, 45% (37 out of 82) in the intermediate-risk group and 100% in the high-risk group. We evaluated various predictors of a recurrence-free outcome among the 82 intermediate-risk patients. In univariate analyses, EAU score (1-4, 32.1% vs 5-9, 62.1%; p = 0.0011), high CK18 expression (negative, 31.4% vs positive 88.8%; p < 0.0001), high Ki-67 index (< 5%, 35.4% vs > 5%, 52.5%; p = 0.017) and high Survivin nuclear staining (< 5%, 35.9% vs > 5%, 62.5%; p = 0.004) were associated with recurrence. In a multivariate analysis, EAU score (HR 2.95, p = 0.003) and a high CK18 immunostaining (HR 6.70, p < 0.0001) were independent predictors of disease recurrence. Conclusions: A single immediate chemotherapy instillation is, by itself, insufficient for the treatment of patients in the intermediate- or high-risk recurrence groups defined by the EAU guidelines. Strong immunohistochemical expression of CK18 and the EAU scoring system appeared to be independent predictors of clinical outcome among patients with urothelial carcinoma of the bladder. No significant financial relationships to disclose.

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