scholarly journals Integrated Mutational and Cytogenetic Analysis Identifies New Prognostic Subgroups in Chronic Lymphocytic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 712-712
Author(s):  
Davide Rossi ◽  
Silvia Rasi ◽  
Valeria Spina ◽  
Alessio Bruscaggin ◽  
Sara Monti ◽  
...  
Keyword(s):  
High Risk ◽  
General Population ◽  
Life Expectancy ◽  
Clonal Evolution ◽  
Lymphocytic Leukemia ◽  
Low Risk ◽  
Risk Category ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
Risk Patients

Abstract Abstract 712 The identification of NOTCH1, SF3B1, MYD88 and BIRC3 genetic lesions in chronic lymphocytic leukemia (CLL) prompts a comprehensive and dynamic prognostic algorithm including gene mutations, chromosomal abnormalities, and their changes during clonal evolution. The study utilized both time-fixed (637 newly diagnosed CLL) and time-dependent (257 CLL provided with 524 sequential samples) approaches. Each sample was investigated for TP53, NOTCH1, SF3B1, MYD88, and BIRC3 mutations by Sanger sequencing and for 17p13, 11q22-q23, 13q14 and BIRC3 deletions and +12 by FISH. Del13q14 and +12 distributed in a mutually exclusive fashion (p<0.0001), and identified three main genetic subgroups: cases harboring del13q14, cases harboring +12 and cases lacking both del13q14 and +12. With the sole exception of the expected association between NOTCH1 mutations and +12 CLL (p=0.0014), the prevalence of the other genetic lesions did not differ among molecular subgroups. FISH abnormalities segregated patients in distinct prognostic groups according to Döhner (Fig 1A). Among new genetic lesions, survival analysis confirmed the independent prognostic value of NOTCH1, SF3B1 and BIRC3 lesions in this study cohort. MYD88 mutations had no prognostic effect (p=0.1728). Recursive partitioning analysis followed by random survival forest validation established the hierarchical order of relevance of the genetic lesions, and created an integrated mutational and cytogenetic (MUCY) model that classified newly diagnosed CLL into four prognostic subgroups (Fig 1B). High risk patients harbored TP53 disruption and/or BIRC3 disruption independent of co-occurring lesions (10-year survival: 29.1%). When the demographic effects of age, sex and year of diagnosis were compensated, the 10-year life expectancy of high risk patients was only 37.7% of that expected in the matched general population (p<0.0001). Intermediate risk patients harbored NOTCH1 and/or SF3B1 mutations and/or del11q22-q23 in the absence of TP53 and BIRC3 abnormalities (10-year OS: 37.1%). The 10-year life expectancy of intermediate risk patients was reduced to 48.5% compared to the matched general population (p<0.0001). The low risk category comprised both patients harboring +12 and patients wild type for all genetic lesions (i.e. normal) (10-year OS: 57.3%), with a 10-year life expectancy of 70.7% compared to the matched general population (p<0.0001). Very low risk patients harbored del13q14 as the sole genetic lesion (10-year OS: 69.3%), with a 10-year life expectancy only slightly (84.2%) and not significantly (p=0.1455) lower than that expected in the matched general population. Multivariate analysis selected the MUCY model as one of the most important independent risk factor of CLL OS (HR: 1.38; 95% CI: 1.18–1.60; p<0.0001; 99% bootstrap selection), along with age (HR: 1.06; 95% CI: 1.04–1.07; p<0.0001; 100% bootstrap selection), Rai stage (HR: 1.36; 95% CI: 1.23-1-51; p<0.0001; 100% bootstrap selection) and unmutated IGHV genes (HR: 1.63; 95% CI: 1.17–2.26; p=0.0039; 92% bootstrap selection). Overall, 21.5% (105/488) low risk patients according to the FISH model (del13q14, normal and +12) were reclassified into high risk genetic subgroups by the MUCY model because of the co-occurrence of NOTCH1 (64/488, 13.1%), SF3B1 (35/488, 7.1%), and TP53 (17/488, 3.4%) mutations or BIRC3 disruption (14/488, 2.8%). Consistently, the inclusion of NOTCH1, SF3B1 and BIRC3 lesions in addition to FISH abnormalities significantly improved the model accuracy of OS prediction (c-index: 0.617 vs c-index: 0.642 p<0.0001). At 10 years from diagnosis, 24.5% CLL of the very low and low risk genetic subgroups developed new TP53, NOTCH1, SF3B1, BIRC3 or del11q22-q23 lesions due to clonal evolution, and therefore switched to a higher risk category of the MUCY model. By time-dependent and landmark analysis, the MUCY model retained a statistically significant impact on CLL OS (HR: 1.52; 95% CI: 1.21–1.90; p=0.0003) at any time from diagnosis and independent of its dynamic changes due to clonal evolution. The MUCY model classifies CLL patients into more precise subgroups, advances our understanding of CLL biology, and improves current prognostic algorithms. These findings have relevant implications for the design of clinical trials aimed at assessing the use of mutational profiling to inform therapeutic decisions based on risk stratification. Disclosures: No relevant conflicts of interest to declare.

Assessing a prognostic model for predicting VTE occurrence in cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1577-1577
Author(s):  
Deesha Sarma ◽  
So Yeon Kim ◽  
David H. Henry
Keyword(s):  
High Risk ◽  
Cancer Patients ◽  
Risk Group ◽  
Low Risk ◽  
Risk Category ◽  
Valuable Insight ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Prophylactic Measures ◽  
Risk Patients

1577 Background: Venous thromboembolism (VTE) poses a significant health risk to cancer patients and is one of the leading causes of death among this population. The most effective way to prevent VTE and reduce its prominence as a public health burden is by identifying high-risk patients and administering prophylactic measures. In 2008, Khorana et al. developed a model that classified patients by risk based on clinical factors. Methods: We conducted a retrospective study to test this model’s efficacy, on 150 patients with cancer receiving chemotherapy at an outpatient oncology clinic between January 1 and August 1, 2011. We aggregated data and assigned points based on the five factors in the Khorana model: site of cancer with 2 points for very high-risk site and 1 point for high-risk site, 1 point each for leukocyte counts more than 11 x 109/L, platelet counts greater than 350 X 109/L, hemoglobin levels less than 100 g/L and/or the use of erythropoiesis-stimulating agents, and BMI greater than 35 kg/m2 (Khorana et al., Blood 2008). Based on this scoring system, patients with 0 points were grouped into the low-risk category, those with 1-2 points were considered intermediate-risk, and those with 3-4 points were classified as high-risk. Results: As shown in the table, VTE incidence for the low-risk group was 1.9%, intermediate-risk group was 3.9%, and high-risk group was 9.1%. Conclusions: High-risk patients were about 4.5 times more likely to develop a VTE than low risk patients. These results provide valuable insight in determining which patients might benefit from prophylaxis and in motivating the design of prospective clinical trials that assess the VTE predictive model in various ambulatory cancer settings. [Table: see text]

scholarly journals Long-term colorectal cancer incidence after adenoma removal and the effects of surveillance on incidence: a multicentre, retrospective, cohort study

Gut ◽  
2020 ◽  
Vol 69 (9) ◽  
pp. 1645-1658 ◽  
Author(s):  
Amanda J Cross ◽  
Emma C Robbins ◽  
Kevin Pack ◽  
Iain Stenson ◽  
Paula L Kirby ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
General Population ◽  
Cox Regression ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Hazard Ratios ◽  
Risk Patients ◽  
Time Varying Covariates

ObjectivePostpolypectomy colonoscopy surveillance aims to prevent colorectal cancer (CRC). The 2002 UK surveillance guidelines define low-risk, intermediate-risk and high-risk groups, recommending different strategies for each. Evidence supporting the guidelines is limited. We examined CRC incidence and effects of surveillance on incidence among each risk group.DesignRetrospective study of 33 011 patients who underwent colonoscopy with adenoma removal at 17 UK hospitals, mostly (87%) from 2000 to 2010. Patients were followed up through 2016. Cox regression with time-varying covariates was used to estimate effects of surveillance on CRC incidence adjusted for patient, procedural and polyp characteristics. Standardised incidence ratios (SIRs) compared incidence with that in the general population.ResultsAfter exclusions, 28 972 patients were available for analysis; 14 401 (50%) were classed as low-risk, 11 852 (41%) as intermediate-risk and 2719 (9%) as high-risk. Median follow-up was 9.3 years. In the low-risk, intermediate-risk and high-risk groups, CRC incidence per 100 000 person-years was 140 (95% CI 122 to 162), 221 (195 to 251) and 366 (295 to 453), respectively. CRC incidence was 40%–50% lower with a single surveillance visit than with none: hazard ratios (HRs) were 0.56 (95% CI 0.39 to 0.80), 0.59 (0.43 to 0.81) and 0.49 (0.29 to 0.82) in the low-risk, intermediate-risk and high-risk groups, respectively. Compared with the general population, CRC incidence without surveillance was similar among low-risk (SIR 0.86, 95% CI 0.73 to 1.02) and intermediate-risk (1.16, 0.97 to 1.37) patients, but higher among high-risk patients (1.91, 1.39 to 2.56).ConclusionPostpolypectomy surveillance reduces CRC risk. However, even without surveillance, CRC risk in some low-risk and intermediate-risk patients is no higher than in the general population. These patients could be managed by screening rather than surveillance.

Prognostic significance of free-floating right heart thromboemboli in acute pulmonary embolism

2014 ◽  
Vol 111 (01) ◽  
pp. 53-57 ◽  
Author(s):  
Cecilia Becattini ◽  
Emanuele Guglielmelli ◽  
Irene Floriani ◽  
Vincenzo Morrone ◽  
Carla Caponi ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Low Risk ◽  
Risk Category ◽  
Intermediate Risk ◽  
Right Heart ◽  
Risk Of Death ◽  
Risk Patients

SummaryThe exact prevalence of mobile right heart thromboemboli (RHTh) in patients with pulmonary embolism (PE) is unknown, depending upon PE severity and the use of early echocardiography. Similarly, the mortality rate is variable, though RHTh detection appears to substantially increase the risk of death in patients with PE. The aim of this study was to assess the prevalence of RHTh in different risk categories in a wide series of patients with PE, and to analyse the effect of RHTh on in-hospital mortality. Among 1,716 patients enrolled in the Italian Pulmonary Embolism Registry, 1,275 (13.3% at high risk, 59.3% at intermediate risk and 27.4% at low risk) had echocardiography within 48 hours from hospital admission and entered the study. Overall, RHTh were detected in 57 patients (4.5%, at admission echocardiography in 88%): in 27/169 (16%) high-risk, in 29/756 (3.8%) intermediate-risk and 1/350 (0.3%) low-risk patients, respectively. At multivariate analysis, only advanced age (odds ratio [OR] 1.61, 95% confidence [CI] 1.27–2.03, p<0.0001), high-risk category (OR vs low-risk category 37.82, 95% CI 11.26–127.06, p<0.0001) and recurrent PE (OR 45.92, 95%CI 15.19–139.96, p<0.0001) showed a statistically significant effect on mortality. The presence of RHTh significantly increased the risk of dying (OR 3.89, 95%CI 1.98–7.67, p=0.0001) at univariate analysis, but this result was not mantained in the multivariate model (OR 1.64, 95%CI 0.75–3.60, p=0.216). In conclusion, though patients with RHTh had a more severe presentation of PE, this study did not detect an association between RHTh and prognosis.

A Molecular Model to Predict Durable Remission after First Line Fludarabine-Cyclophosphamide-Rituximab Treatment in Chronic Lymphocytic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3300-3300
Author(s):  
Davide Rossi ◽  
Lodovico Terzi di Bergamo ◽  
Annalisa Chiarenza ◽  
Pietro Bulian ◽  
Carlo Visco ◽  
...  
Keyword(s):  
High Risk ◽  
General Population ◽  
Lymphocytic Leukemia ◽  
Low Risk ◽  
First Line ◽  
Mutation Status ◽  
Risk Patients ◽  
11Q Deletion ◽  
Durable Remission

Abstract Background. Fludarabine, cyclophosphamide, and rituximab (FCR) has represented a significant advancement in the treatment of patients with chronic lymphocytic leukemia (CLL) and has the potential of inducing durable remissions of the disease. In the new scenario of targeted agents for CLL, there is an increasing interest in identifying patients who may gain the maximum benefit in terms of disease control by a single shot of FCR chemo-immunotherapy. Purpose. Here we aimed at identifying predictors of durable remission after first line FCR treatment. Methods. The study was based on 405 progressive and previously untreated CLL patients who consecutively received standard FCR (up to 6 cycles) as first line therapy in 19 hematologic centers between 2001 and 2010. According to an intention to treat approach, all patients who received at least one FCR cycle were registered in the study. This series was representative of a FCR treated CLL cohort with respect to baseline characteristics, including age (median: 61 years; >65 years in 33% of patients), gender (male in 68% of patients), stage (progressive Binet A in 11% of patients; Binet B in 59%; Binet C in 30%) and number of FCR courses (median: 6; <6 in 42% of patients). Most patients were evaluable for IGHV mutation status (unmutated in 192/296, 65%) and genomic aberrations at treatment requirement (17p deletion in 30/306, 9.8%; 11q deletion in 56/300, 19%; +12 in 70/298, 23%; 13q deletion in 108/301, 36%). Results. After a median follow-up of five years, 159 patients have progressed and 72 have died, accounting for a 5-year progression free survival (PFS) according to the IWCLL criteria of 47% (median: 58 months) and for a 5-year overall survival (OS) of 81% (median: not reached). When the demographic effects of age, gender and year of treatment were compensated, the 5-year and 10-year survival of the whole CLL cohort were 85% and 68%, respectively, of those expected in the matched normal general population (p<0.001). By multivariate analysis, unmutated IGHV genes, 11q deletion and 17p deletion maintained independent association with both PFS and OS, thus providing the rationale to utilize them in the development of a model to predict remission duration after FCR. By recursive partitioning analysis, 17p deletion was the most important variable in predicting PFS after FCR, followed by 11q deletion and IGHV mutation status (Fig. 1A). Based on the application of an amalgamation algorithm, cases harboring unmutated IGHV genes and 11q deletion were grouped into a single category because they showed an identical drop of the PFS curve (Fig. 1A). By this approach, three CLL subgroups were hierarchically classified. Clinical features and treatment indication were superimposable across the three risk groups. The low risk category comprised patients harboring mutated IGHV genes but neither 11q or 17p deletion, and accounted for 26% of all cases. Most of the low risk patients (67%) remained free of progression after FCR (Fig. 1B), and their hazard of relapse dropped to zero after 5 years of follow-up. Consistently, the PFS curve of low risk patients plateaued after 5-years from FCR (Fig 1B). The life expectancy of low risk patients (91% at 5 year) was superimposable to that observed in the matched normal general population (Fig. 1D), indicating that neither the disease, nor complications of its treatment affected survival in this favorable group of CLL. Conversely, patients belonging to the intermediate risk (IGHV unmutated and/or 11q deleted) and high risk (17p deleted) categories showed a constant increase of the hazard of progression over time and almost all were projected to relapse after FCR, although at a different rate: 10% per year of follow-up in the intermediate risk group and 17% per year of follow-up in the high risk group (Fig. 1B-C). The 5-year life expectancy of intermediate and high-risk patients was significantly impaired compared to that observed in the matched general population (85% and 60%, respectively) (Fig. 1D), indicating an excess of deaths related to the disease or treatment complications in these unfavorable groups of CLL. Conclusions. The combination of three biomarkers that are routinely tested at treatment allows to segregate a subgroup of CLL (IGHV mutated without 17p or 11q deletion) that may achieve a durable remission after first line FCR treatment and experience an expected survival similar to that of the general population. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Remission in Patients with Acute Promyelocytic Leukemia Treated with Arsenic Trioxide (varitrinox) As the First Line in Colombia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-3
Author(s):  
Gustavo Milone ◽  
Samuel Sarmiento Doncel ◽  
Carol Agudelo Rico ◽  
Fabiola Vizcarra Reyes ◽  
Gina Alejandra Diaz Mosquera ◽  
...  
Keyword(s):  
High Risk ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Conflicts Of Interest ◽  
Promyelocytic Leukemia ◽  
Remission Induction ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
First Line ◽  
Risk Patients

Acute promyelocytic leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML) in which a chromosomal translocation t (15; 17) (q22; q12) is generated by fusing produces a hybrid PML / RARα gene, generating an altered signal . The combination of transretinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of newly diagnosed standard risk patients with acute promyelocytic leukemia (APL) in several countries. The objective of the present study is to describe the frequency of remission in patients with acute promyelocytic leukemia who were administered as a first line Arsenic Trioxide (varitrinox) during the period from November 2017 to June 2020 in Colombian patients. Methods: Retrospective observational and descriptive study of 12 patients diagnosed with acute promyelocytic leukemia treated with ATO Arsenic trioxide (Varitrinox) as first line, the source of information was provided by the treating hematologists (medical records) by filling out the technical concept format. Active pharmacovigilance scientist in Colombia, this format keeps the identification information of the patient anonymized and the confidentiality of the data is guaranteed as well as compliance with the rules of good clinical practice. Results: Twelve patients with age range between 22 and 69 years with a median age of 34.0 were analyzed. It was found in the analysis that 100% had induction hematologic remission with a median of 45 days. 75% of patients received ATO + ATRA and were at low and intermediate risk, the remaining 25% received ATRA + ATO + Chemotherapy and were at high risk, and intermediate risk. 91.7% of molecular remission in consolidation was obtained and it was measured in cycle 3 by means of PCR (undetectable), 8.3% (n = 1) was positive 3% and is finishing consolidation. Regarding the most frequent adverse events, intravascular coagulation (n = 9), neutropenia (n = 6) and thrombocytopenia (n = 6) were observed. 75% of patients are disease-free, 16.7% are on maintenance (they received ATO + ATRA + Induction chemotherapy) and 8.3% are on consolidation. So far, none of the patients under study have died. Conclusions: Our results support the use of ATO (Varitrinox) in newly diagnosed APL patients (as first line), as a care strategy for low, intermediate and high risk patients. The role of ATRA-ATO is guaranteed in other studies where they manage patients of different risks. Key words: Arsenic trioxide, leukemia promyelocytic acute, leukemia myeloid acute, remission induction, tretinoin. Disclosures No relevant conflicts of interest to declare.

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

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.

Identifying patients at risk of futile resuscitation: palliative care indicators in out-of-hospital cardiac arrest

2019 ◽  
pp. bmjspcare-2019-001828
Author(s):  
Mia Cokljat ◽  
Adam Lloyd ◽  
Scott Clarke ◽  
Anna Crawford ◽  
Gareth Clegg
Keyword(s):  
At Risk ◽  
Palliative Care ◽  
Cardiac Arrest ◽  
High Risk ◽  
Low Risk ◽  
Intermediate Risk ◽  
Patients At Risk ◽  
Risk Patients ◽  
Record Review ◽  
Hospital Cardiac Arrest

ObjectivesPatients with indicators for palliative care, such as those with advanced life-limiting conditions, are at risk of futile cardiopulmonary resuscitation (CPR) if they suffer out-of-hospital cardiac arrest (OHCA). Patients at risk of futile CPR could benefit from anticipatory care planning (ACP); however, the proportion of OHCA patients with indicators for palliative care is unknown. This study quantifies the extent of palliative care indicators and risk of CPR futility in OHCA patients.MethodsA retrospective medical record review was performed on all OHCA patients presenting to an emergency department (ED) in Edinburgh, Scotland in 2015. The risk of CPR futility was stratified using the Supportive and Palliative Care Indicators Tool. Patients with 0–2 indicators had a ‘low risk’ of futile CPR; 3–4 indicators had an ‘intermediate risk’; 5+ indicators had a ‘high risk’.ResultsOf the 283 OHCA patients, 12.4% (35) had a high risk of futile CPR, while 16.3% (46) had an intermediate risk and 71.4% (202) had a low risk. 84.0% (68) of intermediate-to-high risk patients were pronounced dead in the ED or ED step-down ward; only 2.5% (2) of these patients survived to discharge.ConclusionsUp to 30% of OHCA patients are being subjected to advanced resuscitation despite having at least three indicators for palliative care. More than 80% of patients with an intermediate-to-high risk of CPR futility are dying soon after conveyance to hospital, suggesting that ACP can benefit some OHCA patients. This study recommends optimising emergency treatment planning to help reduce inappropriate CPR attempts.

Independent Validation of the 2008 World Health Organization (WHO) Reclassification of Myelodysplastic Syndromes (MDS) Associated with Ring Sideroblasts

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2686-2686 ◽  
Author(s):  
David P. Steensma ◽  
Curtis A Hanson ◽  
Ayalew Tefferi
Keyword(s):  
High Risk ◽  
Median Survival ◽  
Scoring System ◽  
Who Classification ◽  
Risk Group ◽  
Low Risk ◽  
Risk Category ◽  
Intermediate Risk ◽  
Multilineage Dysplasia ◽  
Ring Sideroblasts

Abstract Background: The 2001 WHO classification of myeloid neoplasms distinguished 2 forms of MDS associated with &gt;=15% ring sideroblasts and &lt;5% marrow blasts: refractory cytopenia with multilineage dysplasia and with ring sideroblasts (RCMD-RS) vs. refractory anemia with ring siderblasts (RARS, erythroid-restricted dysplasia). However, the real prognostic value of separating RCMD-RS from RCMD with &lt;15% ring sideroblasts and from RARS is uncertain, and the WHO has proposed merging RCMD-RS and RCMD in the 2008 classification revision. Furthermore, the WHO-based Prognostic Scoring System (WPSS), proposed by Malcovati and colleagues in 2005 as a dynamic system that overcomes some of the limitations of the 1997 International Prognostic Scoring System (IPSS), has undergone limited independent external validation to date and its applicability to sideroblastic MDS in particular is unclear. We assessed the validity of the 2008 WHO reclassification and the WPSS for MDS cases associated with &gt;=15% ring sideroblasts and a normal blast proportion. Methods: We reviewed WPSS and IPSS component parameters at diagnosis and the clinical outcomes of 465 patients (68% males, median age 72) evaluated at our institution over a 13-year period: 140 with RARS, 114 with RCMD-RS, and 211 with RCMD. Patients were assigned a WPSS score and risk category (very low-risk group=0 points; low=1; intermediate=2, high=3 or 4) by summing 3 subscores: 2001 WHO classification (0 for RARS, 1 point for RCMD or RCMD-RS), IPSS cytogenetic risk group (0=good, 1=indeterminate, 2=poor), and red cell transfusion dependence (0=no, 1=yes). Survival was assessed by Kaplan-Meier estimates, and prognostic factors examined by proportional hazards analysis. Results: The median time until death or last followup was 26 months, and 70% of patients were known to have died. The median survival by WHO MDS subtype was 75 months for RARS, 25 months for RCMD-RS, and 26 months for RCMD (Log-Rank p&lt;0.0001 for RARS vs. either RCMD-RS or RCMD; p=0.60 for RCMD vs. RCMD-RS ). Both the WPSS and IPSS predicted overall survival in patients with ring sideroblasts. Median survival for the patients grouped by WPSS risk category was 89 months for very low risk (n=95), 41 for low risk (n=198), 31 for intermediate risk (n=82), and 11 for high risk (n=91) (p&lt;0.0001, except for low risk vs. intermediate risk, p=0.31). (Very high risk WPSS scores cannot be achieved without excess marrow blasts, and such patients were excluded from this analysis.) Median survival by IPSS was 73 months for low-risk, 33 months for intermediate-1, and 8 months for intermediate 2 (p&lt;0.0001). The IPSS’ predictive power was unchanged if patients with secondary MDS were included or excluded (the IPSS was based on a review of 816 patients with apparently de novo MDS). Conclusions: These data support the WHO’s proposal to merge RCMD and RCMD-RS, and suggest that the adverse prognostic significance of multilineage dysplasia renders the presence of ring sideroblasts unimportant. The WPSS is a valid prognostic tool in patients with MDS associated with ring sideroblasts, but in this subgroup both the WPSS and IPSS stratify patients into 3 risk groups, and the WPSS does not offer additional value over the IPSS. Figure Figure

Disease-Attributable Mortality in the Myelodysplastic Syndromes (MDS): A Study from the Spanish MDS Cooperative Group (GESMD)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1672-1672
Author(s):  
Meritxell Nomdedeu ◽  
Xavier Calvo ◽  
Dolors Costa ◽  
Montserrat Arnan ◽  
Helena Pomares ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Mortality Rates ◽  
Low Risk ◽  
Attributable Mortality ◽  
Risk Category ◽  
Intermediate Risk ◽  
Advisory Committees ◽  
Very High ◽  
Risk Categories

Abstract Introduction: The MDS are a group of clonal hematopoietic disorders characterized by blood cytopenias and increased risk of transformation into acute myeloid leukemia (AML). The MDS predominate in old people (median age at diagnosis > 70 years) so that a fraction of the observed mortality would be driven by age-related factors shared with the general population rather than the MDS. Distinguishing between the MDS-related and unrelated mortality rates will help better assessment of the population health impact of the MDS and more accurate prognostication. This study was aimed at quantifying the MDS-attributable mortality and its relationship with the IPSSR risk categories. Methods: The database of the GESMD was queried for patients diagnosed with primary MDS after 1980 according to the WHO 2001 classification. Patients with CMML, younger than 16 years or who lacked the basic demographic or follow-up data were excluded. Relative survival and MDS-attributable mortality were calculated by the cohort method and statistically compared by Poisson multivariate regression as described by Dickman (Stat Med 2004; 23: 51). Three main parameters were calculated: the observed (all-cause) mortality, the MDS-attributable mortality (both as percentage of the initial cohort), and the fraction of the observed mortality attributed to the MDS. Results: In total, 7408 patients met the inclusion criteria and constitute the basis for this study. Among these patients, 5307 had enough data to be classified according to the IPSSR. Median age was 74 (IQR: 16-99) years and 58 % were males. The most frequent WHO categories were RAEB, type I or II (29% of cases), RCMD (28%), and RA with ring sideroblasts (16%). Most patients (72%) were classified within the very low and low risk categories of the IPSSR. At the study closing date (December 2014), 1022 patients had progressed to AML, 3198 had died (974 after AML) and 3210 were censored alive. The median actuarial survival for the whole series was 4.8 (95% CI: 4.6-5.1) years and 30% of patients are projected to survive longer than 10 years. The overall MDS-attributable mortality at 5 years from diagnosis was 39%, which accounted for three-quarters of the observed mortality (51%, figure). The corresponding figures at 10 years for the MDS-attributable and observed mortality were 55% and 71%, respectively. According to the IPSSR, the 5-year MDS-attributable mortality rates was 19% for the very low risk category, 39% (low risk), 70% (intermediate risk), 78% (high risk), and 92% (very high risk). On average, the incidence rate ratio for the MDS-attributable mortality increased 1.9 times (95% CI: 1.7-2.3, p<0.001) as the IPSSR worsened from one to the next risk category. The fraction of the observed mortality attributed to the MDS was 0.55 for the very low risk category, 0.79 (low risk), 0.93 (intermediate risk), 0.96 (high risk), and 0.99 (very high risk). After distinguishing between AML-related and unrelated mortality, the 5-year MDS-attributable mortality not related to AML was 10% for the very low risk category, 20% (low risk), 33% (intermediate risk), 42% (high risk), and 44% (very high risk). By comparing these figures with the above ones, we could estimate that about 50% of the MDS-attributable mortality was AML-unrelated and that such fraction kept nearly constant across the five IPSSR categories. Conclusions: About three-quarters of the mortality observed in patients with MDS is caused by the disease, the remaining one-quarter being due to MDS-independent factors shared with the general population. The MDS-attributable mortality increases with the IPSSR risk category, from half the observed mortality in the very low risk to nearly all the mortality observed in the high and very high risk groups. Half the MDS-attributable mortality is driven by factors unrelated to leukemic transformation, a proportion that keeps constant across the five IPSSR risk categories. Disclosures Valcarcel: AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NOVARTIS: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELGENE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ramos:AMGEN: Consultancy, Honoraria; NOVARTIS: Consultancy, Honoraria; JANSSEN: Honoraria, Membership on an entity's Board of Directors or advisory committees; CELGENE: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Esteve:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria.

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