Considering Bone Marrow Blasts from Nonerythroid Cellularity Improves the Prognostic Evaluation of MDS in the Context of IPSS-R and Permits a Better Risk Assessment of MDS Patients Classified into the Intermediate Risk Category

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3185-3185
Author(s):  
Xavier Calvo ◽  
Leonor Arenillas ◽  
Elisa Luño ◽  
Leonor Senent ◽  
Esther Alonso ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lower Risk ◽  
Risk Group ◽  
Intermediate Risk ◽  
Leukemic Transformation ◽  
Prognostic Evaluation ◽  
Prognostic Assessment ◽  
Risk Patients ◽  
Very High ◽  
Risk Categories

Abstract Introduction: Proportion of bone marrow (BM) blasts is a major prognostic factor for outcome in patients with myelodysplastic syndromes (MDS) and is included in the most applied prognostic scoring systems: IPSS and IPSS-R. IPSS-R stratifies patients in five risk categories: very low (VL), low (L), intermediate (I), high (H) and very high (VH). Some concerns exist about the real prognostic significance of intermediate risk group, as these patients showed around 30 months of median overall survival (OS) in different studies. The Spanish Group of myelodysplastic syndromes considers as high-risk patients those with an expected median OS inferior to 30 months. As showed in a recent study of our group, considering BM blasts from nonerythroid cellularity improves the prognostic evaluation of MDS (Arenillas et al, J Clin Oncol 2016) when applying IPSS and WHO classification. Aims: 1) To assess OS and leukemia-free survival (LFS) prediction by IPSS-R by counting BM blast percentage from nonerythroid cells (NECs). 2) To evaluate whether considering BM blasts from NECs rather than from total nucleated cells (TNCs) improves the prognostic assessment of patients classified into the intermediate risk group. 3) To establish which of these methods present the best prediction capacity for survival and leukemic transformation. Methods: We retrospectively analyzed 3,924 denovo MDS diagnosed according to WHO 2008 from the MDS spanish registry. Percentage of BM blasts from NECs was calculated as follows: [%BM blasts from TNCs/(100 - %BM erythroblasts) x 100]. Survival curves were constructed by using the Kaplan-Meier (K-M) method and compared using the log-rank test. C-index was implemented to assess the method with the best predictive value for survival and leukemic transformation. Results: Median age at diagnosis was 75y (16-101y) and 59% were males. Estimated median follow-up, as calculated by reverse K-M method, was 46.5 months (95% CI, 43.9-49) and median OS was 56.97 months. We assessed OS predicted by IPSS-R by considering BM blasts from TNCs and from NECs (recoded IPSS-R) Fig 1A and 1B. As depicted, five groups with significant differences in OS were observed by using both methods. Interestingly, median OS of intermediate risk group patients changed from 32.3 to 40.4 months by considering blasts from NECs instead of TNCs, whereas patients classified in high and very high risk categories showed almost the same survival even though the higher-risk categories were increased in 25.7%. Of 3,285 patients, 164 (5%) classified in the lower-risk IPSS-R categories (VL, L, I) were reclassified into higher-risk categories (H, VH) when BM blasts were enumerated from NECs. OS and LFS of these upgraded patients was significantly shorter to those observed in patients who remained in the initial categories (median OS, 28.2 vs 71.7 months, P<0.001; median LFS, 63 vs N.R. months, P<0.001) Fig 2A and 2B. In the same way, 24% of patients classified into the intermediate IPSS-R risk group were reclassified into higher-risk categories and showed a significantly shorter OS and LFS (median OS, 24 vs 34.3 months, P=0.012; median LFS, 56.8 vs 164.7 months, P=0.005). Thus, by counting BM blasts from NECs we were able to detect a group of patients labeled at present as having lower-risk disease but who presented an outcome much closer to that of higher-risk patients. The worse outcome observed in these reclassified patients was mainly influenced by the difference in the weight of blasts when assessed from NECs, as other prognostic factors that could explain this difference in outcome, as cytogenetics and degree of cytopenias, were adjusted by using the IPSS-R. Finally, C-index was calculated at 2 and 5 years and the recoded IPSS-R showed a slightly higher value for the prediction of survival and leukemic transformation [(survival, recoded IPSS-R vs IPSS-R: 2y, 0.731 vs 0.728; 5y, 0.696 vs 0.695) (leukemic transformation, recoded IPSS-R vs IPSS-R: 2y, 0.731 vs 0.730; 5y, 0.719 vs 0.716)]. Conclusions: calculating the percentage of BM blasts from NECs improves prognostic assessment of MDS in the context of IPSS-R. By using this method, a more comprehensive distribution of patients was observed, as patients now included in the intermediate risk group presented an outcome much closer to that expected in lower-risk patients. This approach could help clinicians in risk-adapted therapeutic decisions by allowing a better definition of this controversial group. Figure Figure. Figure Figure. Disclosures No relevant conflicts of interest to declare.

Considering Bone Marrow Blasts From Nonerythroid Cellularity Improves the Prognostic Evaluation of Myelodysplastic Syndromes

2016 ◽  
Vol 34 (27) ◽  
pp. 3284-3292 ◽  
Author(s):  
Leonor Arenillas ◽  
Xavier Calvo ◽  
Elisa Luño ◽  
Leonor Senent ◽  
Esther Alonso ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Who Classification ◽  
Refractory Anemia ◽  
International Prognostic Scoring System ◽  
Prognostic Assessment ◽  
Erythroid Hyperplasia ◽  
Risk Patients ◽  
Risk Categories

Purpose WHO classification of myeloid malignancies is based mainly on the percentage of bone marrow (BM) blasts. This is considered from total nucleated cells (TNCs), unless there is erythroid-hyperplasia (erythroblasts ≥ 50%), calculated from nonerythroid cells (NECs). In these instances, when BM blasts are ≥ 20%, the disorder is classified as erythroleukemia, and when BM blasts are < 20%, as myelodysplastic syndrome (MDS). In the latter, the percentage of blasts is considered from TNCs. Patients and Methods We assessed the percentage of BM blasts from TNCs and NECs in 3,692 patients with MDS from the Grupo Español de Síndromes Mielodisplásicos, 465 patients with erythroid hyperplasia (MDS-E) and 3,227 patients without erythroid hyperplasia. We evaluated the relevance of both quantifications on classification and prognostication. Results By enumerating blasts systematically from NECs, 22% of patients with MDS-E and 12% with MDS from the whole series diagnosed within WHO categories with < 5% BM blasts, were reclassified into higher-risk categories and showed a poorer overall survival than did those who remained in initial categories (P = .006 and P = .001, respectively). Following WHO recommendations, refractory anemia with excess blasts (RAEB)-2 diagnosis is not possible in MDS-E, as patients with 10% to < 20% BM blasts from TNCs fulfill erythroleukemia criteria; however, by considering blasts from NECs, 72 patients were recoded as RAEB-2 and showed an inferior overall survival than did patients with RAEB-1 without erythroid hyperplasia. Recalculating the International Prognostic Scoring System by enumerating blasts from NECs in MDS-E and in the overall MDS population reclassified approximately 9% of lower-risk patients into higher-risk categories, which indicated the survival expected for higher-risk patients. Conclusion Regardless of the presence of erythroid hyperplasia, calculating the percentage of BM blasts from NECs improves prognostic assessment of MDS. This fact should be considered in future WHO classification reviews.

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

Blood ◽  
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.

scholarly journals MIPSS70+ v2.0 predicts long-term survival in myelofibrosis after allogeneic HCT with the Flu/Mel conditioning regimen

2019 ◽  
Vol 3 (1) ◽  
pp. 83-95 ◽  
Author(s):  
Haris Ali ◽  
Ibrahim Aldoss ◽  
Dongyun Yang ◽  
Sally Mokhtari ◽  
Samer Khaled ◽  
...  
Keyword(s):  
Molecular Markers ◽  
High Risk ◽  
Scoring System ◽  
Conditioning Regimen ◽  
International Prognostic Scoring System ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Risk Patients ◽  
Transplantation Outcomes ◽  
Very High

Abstract Although allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for myelofibrosis (MF), data are limited on how molecular markers predict transplantation outcomes. We retrospectively evaluated transplantation outcomes of 110 consecutive MF patients who underwent allo-HCT with a fludarabine/melphalan (Flu/Mel) conditioning regimen at our center and assessed the impact of molecular markers on outcomes based on a 72-gene next-generation sequencing panel and Mutation-Enhanced International Prognostic Scoring System 70+ v2.0 (MIPSS70+ v2.0). With a median follow-up of 63.7 months, the 5-year overall survival (OS) rate was 65% and the nonrelapse mortality (NRM) rate was 17%. In mutational analysis, JAK2 V617F and ASXL1 mutations were the most common. By univariable analysis, higher Dynamic International Prognostic Scoring System scores, unrelated donor type, and very-high-risk cytogenetics were significantly associated with lower OS. Only CBL mutations were significantly associated with lower OS (hazard ratio [HR], 2.64; P = .032) and increased NRM (HR, 3.68; P = .004) after allo-HCT, but CALR, ASXL1, and IDH mutations did not have an impact on transplantation outcomes. Patient classification per MIPSS70 showed worse OS for high-risk (HR, 0.49; P = .039) compared with intermediate-risk patients. Classification per MIPSS70+ v2.0 demonstrated better OS when intermediate-risk patients were compared with high-risk patients (HR, 0.291) and much lower OS when very-high-risk patients were compared with high-risk patients (HR, 5.05; P ≤ .001). In summary, we present one of the largest single-center experiences of Flu/Mel-based allo-HCT, demonstrating that revised cytogenetic changes and MIPSS70+ v2.0 score predict transplantation outcomes, and thus can better inform physicians and patients in making decisions about allo-HCT.

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.

Statin dose titration patterns and subsequent major cardiovascular events in very high-risk patients: estimates from Swedish population-based registry data

2020 ◽  
Vol 6 (4) ◽  
pp. 323-331
Author(s):  
Jonas Banefelt ◽  
Maria Lindh ◽  
Maria K Svensson ◽  
Björn Eliasson ◽  
Ming-Hui Tai
Keyword(s):  
High Risk ◽  
Statin Therapy ◽  
High Intensity ◽  
Lower Risk ◽  
Cardiovascular Events ◽  
Population Based ◽  
Moderate Intensity ◽  
Risk Patients ◽  
Population Based Registry ◽  
Very High

Abstract Aims Clinical studies have demonstrated the efficacy of intensive statin therapy in lowering low-density lipoprotein cholesterol and cardiovascular (CV) events. Our objective was to examine statin titration patterns and the association between titration patterns and subsequent CV events in very high-risk patients. Methods and results Using Swedish national population-based registry data, we identified 192 435 patients with very high risk of atherosclerotic CV disease initiated on moderate-intensity statin therapy between 2006 and 2013. Outcomes of interest were titration to high-intensity therapy and the major adverse cardiovascular events (MACE) composite (myocardial infarction, ischaemic stroke, and CV death) outcome. Cumulative incidence of MACE was assessed by titration status 1-year post-treatment initiation in patients adherent to treatment during the first year, using a 12-week cut-off from initiation to define early, delayed and no up-titration to high-intensity statins. Cox regression analysis was used to estimate adjusted hazard ratios (HRs). In 144 498 eligible patients, early titration was associated with significantly lower risk of MACE in the subsequent 2 years compared to no up-titration (HR 0.76, P &lt; 0.01]. Delayed up-titration was associated with a smaller reduction (HR 0.88, P = 0.08). The majority of patients did not up-titrate. Conclusion Early up-titration to high-intensity statins was independently associated with lower risk of subsequent CV events compared to no up-titration. Delayed up-titration was not associated with the same benefit. Despite the higher risk associated with no up-titration, few patients at very high CV risk who started treatment on moderate-intensity up-titrated to high intensity, indicating a potential need for more aggressive lipid management of these patients in clinical practice.

Patients with FLT3 Negative Acute Myeloid Leukemia and Normal Cytogenetic who Have the Combination Mutations (NPM1-/CEBPA-) Have Better Survival Than Patients Who Have the Combination Mutations (NPM1+/CEBPA+)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4874-4874
Author(s):  
Shamail Butt ◽  
Pascal Akl ◽  
Himanshu Bhardwaj ◽  
Samer A Srour ◽  
Terry Dunn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Mutation Analysis ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Intermediate Risk ◽  
Cebpa Mutations ◽  
Normal Cytogenetics ◽  
Acute Myeloid

Abstract Abstract 4874 Introduction: Acute Myeloid Leukemia (AML) is the most common type of acute leukemia in adults. About 50% of patients with AML have normal karyotype, and are categorized as intermediate risk group. However, the clinical behavior and response to treatment in this group is heterogeneous. As a result, there is strong interest in characterizing molecular genetic features in the intermediate-risk AML patients that might rectify their stratification risk. In this group, FLT3-ITD (Internal Tandem Duplication) and FLT3-TKD (Tyrosine Kinase Domain) mutations are known to confer unfavorable risk whereas NPM1 and CEBPA mutations are known to be favorable risk markers. The purpose of this study is to analyze the combination of NPM1 and CEBPA mutations in presence or absence of FLT3 mutations on prognosis of AML patients referred to the State's largest tertiary care center over a period of 10 years for the treatment of leukemia. Patients and Method: We performed a retrospective chart review of all patients with AML evaluated at University of Oklahoma Health Sciences Center between January 2000 and December 2010. Patient's age, gender, race, laboratory and clinical data as well as bone marrow biopsy and aspirate findings were reported. PCR and Fragment Analysis were conducted on all available DNA preserved bone marrow materials to test the FLT3, NPM1 and CEBPA mutations. For statistical analysis, Kaplan-Meyer curve was used. Results: A total of 239 patients were evaluated. Male to female ratio was 2/1. Median age at diagnosis was 46y. 21 out of the 239 patients were less than 18 year old. DNA samples were present on 132 patients and mutation analysis for FLT3, CEBPA and NPM1 was performed. Correlation between mutations and AML prognosis was determined. 67/132 (50.8 %) patients were categorized into intermediate risk group (majority of patients had normal cytogenetics). 14/67 (20.9%) pts were FLT3+ (FLT3-ITD or FLT3-TKD mutation). 17/67 (23.9%) were NPM1+. 7/67 (10.4%) were CEBPA +. Kaplan-Meier curve was used to identify cumulative proportion surviving over time. FLT3 presence or absence itself was not identified to be statistically significant (p 0.416) in terms of overall survival. Interestingly, presence or absence of combined NPM1/CEBPA mutation in FLT3 negative patients, among intermediate risk group, was found to be statistically significant (p<0.05) in determining overall survival. In this subgroup, presence of NPM1/CEBPA combination (NPM1+/CEBPA+) was associated with poor prognosis (figure 2, lower curve), while absence of NPM1/CEBPA combination (NPM1-/CEBPA-) carries a better prognosis (figure 2, upper curve). Conclusion: Results of our study highlight the importance of performing combinations of mutation analysis in evaluation of overall prognosis in AML patients. FLT3-/NPM1+ profile in patients with normal cytogenetics is thought to confer a favorable prognosis. We demonstrated in this study that using combination mutation analysis in patients with FLT3- can change the risk stratification in patients with intermediate risk group and might affect therapeutic interventions in this patient population. Larger prospective studies are needed in the future for further validation of our findings. Disclosures: No relevant conflicts of interest to declare.

Reduced Intensity Transplant May Improve Survival in Patients Over the Age of 40, Especially If a Sibling Donor Is Used: Pooled Analysis of 2454 Patients and 407 Transplants in the UK NCRI AML15 and AML16 Trials

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 231-231
Author(s):  
Nigel H Russell ◽  
Robert K. Hills ◽  
Lars Kjeldsen ◽  
John L Yin ◽  
Charles Craddock ◽  
...  
Keyword(s):  
Older Patients ◽  
Risk Group ◽  
Pooled Analysis ◽  
Cell Transplant ◽  
Intermediate Risk ◽  
Sibling Donor ◽  
Risk Patients ◽  
The Uk ◽  
The Impact ◽  
Reduced Intensity

Abstract Abstract 231 Reduced Intensity conditioning (RIC) offers a feasible option for older patients to an allogeneic stem cell transplant and to potentially benefit from a graft vs leukaemia effect. However the relative clinical benefit in AML is less clear. Since our previous experience did not show an overall survival advantage from myeloablative transplant in patients >40 years we have examined the impact of RIC allograft in 1st CR on the outcome of patients aged 40–70 years treated within the UK NCRI AML15 (2002–2009) and AML16 (2006–2012) trials compared to chemotherapy. Methods: Both trials offered the option of RIC transplant in CR1 for patients who were not good risk. A total of 2454 patients between 40 to 70 years entered CR (AML15: 1580 and AML16: 874) of whom 407 received a RIC (292/1580 in AML15 and 115/874 in AML16). Matched sibling transplants were given in 229, and MUDs in 178. The cytogenetic risk groups were 258 intermediate, 59 adverse, 90 not known. Follow-up is complete to 1st January 2012. Comparisons of transplant versus not are carried out using Mantel-Byar analysis to allow for time to transplant, with patients censored at the time of non-RIC allo transplant. Data from the two trials were pooled and split by age. Results: The OS for the 255 patients <60 yrs. was significantly superior to no transplant (53% vs 41%, HR 0.79(0.66–0.96), p=0.02). There was clear benefit in the 164 intermediate risk group patients (59% vs 44%, HR 0.67 (0.53–0.86) p=0.0008) with less evidence for the 40 who had adverse risk (16% vs 10%, HR 0.89 (0.58–1.35) p=0.6). In 152 patients 60+ yrs. the overall benefit was not significantly superior (37% vs 24%, HR 0.85 (0.68–1.06), p=0.2), there was a non-significant trend for benefit in the 94 intermediate risk group patients (43% vs 26%, HR 0.73 (0.49–1.09), p=0.3), and clearer benefit in the 19 patients in the adverse group (16% vs 3%, HR 0.57 (0.36–0.91), p=0.01). Considering the types of transplant, in the <60 group the survival benefit was restricted to sibling RIC (Sibling 61%: MUD 35%: no transplant 41%), and in the 60+ group a similar trend of borderline significance was seen (Sibling 49%:MUD 28%: no transplant 24%). In analysis by cytogenetic group, with the exception of patients over 60 yrs with adverse karyotype, sibling allograft gave consistently better survival. Conclusion: This pooled analysis shows that RIC allo SCT in AML 1st CR improves the survival of older patients with AML aged <60 but possibly only if a sibling donor is used. There was less benefit (sibling or MUD) for adverse risk patients. For patients aged >60 years overall benefit was less clear but there was a similar trend for benefit in intermediate risk patients. However, given the lack of statistical heterogeneity, our data does not exclude a benefit for patients with adverse risk cytogenetics or for those undergoing SCT from an unrelated donor. This observation runs counter to what we observe in patients <40 yrs, where the benefit is limited to adverse risk patients. Disclosures: No relevant conflicts of interest to declare.

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.

Disease Response Guiding Therapy in Acute Lymphocytic Leukemia: Pivotal Role of Minimal Residual Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. SCI-34-SCI-34
Author(s):  
Michael A. Pulsipher
Keyword(s):  
Flow Cytometry ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Lower Risk ◽  
Residual Disease ◽  
Response To Therapy ◽  
Risk Patients ◽  
Very High ◽  
Minimal Residual ◽  
Risk Of Relapse

In spite of an explosion of data regarding mutations associated with childhood ALL, to date these key genetic changes rarely have been the driver of therapy. Clinical parameters at presentation (WBC, age, T- vs. B-lineage, etc.) have dictated initial risk stratification and induction approaches, followed by risk-adapted therapy based upon leukemic response measured by minimal residual disease (MRD, either PCR- or flow cytometry-based). With minor variations, rapid disappearance of peripheral MRD, followed by significant clearance from the marrow after induction, and most importantly, the level of MRD after consolidation have allowed clear distinctions in outcomes that have driven intensification or de-intensification of therapy resulting in improved outcomes. Although specific gene mutations have been associated with risk, MRD has further identified better risk patients within genetic subgroups. For patients noted to be very high risk who are candidates for hematopoietic cell transplantation (HCT), the presence of MRD both pre- and post-transplant has been associated with increased risk of relapse; the risk being modified by level of MRD, whether or not GVHD occurs after HCT, and timing after HCT when MRD is measured. In lower risk patients being treated with chemotherapy and higher risk patients eligible for HCT, more sensitive approaches to flow cytometry and PCR, as well as next-generation sequencing (NGS) MRD approaches (sensitive to 1/10^7 cells) are currently being tested. It is not clear yet whether NGS-MRD offers substantial improvements in patients treated with chemotherapy, as broad-based testing is underway; the latest comparative outcomes will be presented. There is evidence of a striking improvement in our ability to define patients who will do very will after transplant (not relapse), and preliminary evidence that post-HCT NGS MRD testing is more sensitive that other methodologies in defining risk of relapse after transplant. As the latest information about the ability of different approaches to MRD is shown in this session, we will also present how response to therapy based upon MRD interacts with various genetic subtypes (Ph+ ALL, extreme hypodiploidy, etc.). Even in subclasses that are considered very high risk based solely upon genetics, measurement of MRD can define higher and lower risk groups. Going forward, as more and different types of patients are subcategorized and treated with targeted agents based upon specific mutations, it is likely MRD response will continue to be important in mapping intensity of approach and defining children at highest risk of relapse who might benefit from HCT or other cellular therapeutic approaches. Disclosures Pulsipher: Novartis: Membership on an entity's Board of Directors or advisory committees.

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]

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