Prognostic Impact of Transfusions Intensity on Survival and Development of Thrombocytopenia in Newly Diagnosed Lower-Risk MDS Patients Participating in the European Leukemianet EU-MDS Registry

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1677-1677
Author(s):  
Louise De Swart ◽  
Tom Johnston ◽  
Alexandra Smith ◽  
Pierre Fenaux ◽  
Argiris Symeonidis ◽  
...  
Keyword(s):  
Lower Risk ◽  
Research Funding ◽  
Control Group ◽  
Rapid Decline ◽  
Prognostic Impact ◽  
Platelet Counts ◽  
Risk Of Death ◽  
Increased Risk ◽  
The Impact

Abstract Background The outcome of lower-risk MDS patients with red blood cell transfusions (RBCT) dependency is inferior to that of RBCT independent patients, but whether the intensity of RBCT is important for prognosis is unknown. The EUMDS Registry is a non-interventional, observational longitudinal study enrolling patients with lower-risk MDS from 142 sites in 17 countries as described elsewhere (1). The EUMDS registry has accrued 1,902 patients as of July 21, 2015. We hypothesized that RBCT intensity is an independent prognostic factor for survival. Methods We first assessed the impact of RBCT intensity in the first year post-diagnosis (1yrPD) on progression-free survival among the 1034 patients who survived at least 1yrPD and had potential for a further year of follow-up. Secondly, we developed a longitudinal model of platelet counts throughout follow-up for 1660 patients in the registry with potential for at least one year follow-up. Results Among the 1034 patients, 323 patients had died: 67 after progression to higher-risk MDS/AML and 256 without progression. A further 41 surviving patients had progressed to AML. The overall 5-year survival was 52%. In a proportional hazards regression model (Table), the risk of death or progression increased in a non-linear fashion with age at diagnosis (p<0.001). The risk of death was increased in the intermediate IPSS-R risk group compared to low risk. Patients with RARS and 5q- syndrome had a better outcome compared to RCMD. Increased RBCT intensity in 1yrPD (Table, Figure) was strongly associated with an increased risk of death (p<0.001). In the 1660 patients no significant decline in platelet counts was observed (0.16x109 platelets/l average monthly decline, p=0.16) among patients who were not RBC transfused at any time during follow-up. However platelet counts of patients receiving RBCT declined more quickly (p<0.0001) at an average rate of 1.14x109 platelets/l/month. Among the 920 RBCT dependent patients, lower platelet counts were associated with receiving more RBCT units in the preceding six months. 185 Patients had at least 2 observations both before and after becoming RBCT dependent, defined as 1st RBCT. 50% of these patients had a decreasing trend of platelets prior to their 1st RBCT and 67% had a decreasing slope of platelets after their 1st RBCT. In the control group of RBC untransfused patients, decreasing slopes of platelets occurred in around 50% of the patients throughout the whole observation period of 4 visits. Logistic regression of the risk of having a post-1st RBCT decreasing trend in platelets showed that transfused patients were at a greater risk (OR=1.7, 95% CI: 1.1-2.7) of having a post-1st RBCT decreasing trend in platelets than untransfused patients. Conclusion These multivariate regression models including age, sex, country, IPSS and WHO classification showed that more intensive RBCT treatment is associated with poor prognosis and a more rapid decline of platelets. This indicates that the intensity of RBCT should be incorporated in the regular prognostic scoring systems and the choice of therapeutic interventions. (1): De Swart L et al. Br J Haematol 2015; 170: 372-83. Disclosures Fenaux: NOVARTIS: Honoraria, Research Funding; CELGENE: Honoraria, Research Funding; JANSSEN: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding. Hellström-Lindberg:Celgene Corporation: Research Funding. Sanz:JANSSEN CILAG: Honoraria, Research Funding, Speakers Bureau. Mittelman:Roche: Research Funding; Novartis Pharmaceuticals Corporation: Research Funding; GlaxoSmithKline: Research Funding; Johnson & Johnson: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Amgen: Research Funding. Almeida:Bristol Meyer Squibb: Speakers Bureau; Shire: Speakers Bureau; Celgene: Consultancy; Novartis: Consultancy. Park:Hospira: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Itzykson:Oncoethix: Research Funding. de Witte:Novartis: Research Funding.

scholarly journals The Impact of Clonal Hematopoiesis of Indeterminate Potential on Survival in Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4359-4359
Author(s):  
Koji Sasaki ◽  
Rashmi Kanagal-Shamanna ◽  
Guillermo Montalban-Bravo ◽  
Rita Assi ◽  
Kiran Naqvi ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Next Generation ◽  
Risk Of Death ◽  
Genetics Research ◽  
The Impact ◽  
Generation Sequencing

Abstract Introduction: Clearance of detected somatic mutations at complete response by next-generation sequencing is a prognostic marker for survival in patients with acute myeloid leukemia (AML). However, the impact of allelic burden and persistence of clonal hematopoiesis of indeterminate potential (CHIP)-associated mutations on survival remains unclear. The aim of this study is to evaluate the prognostic impact of allelic burden of CHIP mutations at diagnosis, and their persistence within 6 months of therapy. Methods: From February 1, 2012 to May 26, 2016, we reviewed 562 patients with newly diagnosed AML. Next-generation sequencing was performed on the bone marrow samples to detect the presence of CHIP-associated mutations defined as DNMT3A, TET2, ASXL1, JAK2 and TP53. Overall survival (OS) was defined as time period from the diagnosis of AML to the date of last follow-up or death. Univariate (UVA) and multivariate Cox proportional hazard regression (MVA) were performed to identify prognostic factors for OS with p value cutoff of 0.020 for the selection of variables for MVA. Landmark analysis at 6 months was performed for the evaluation of the impact of clearance of CHIP, FLT3-ITD, FLT3D835, and NPM1 mutations. Results: We identified 378 patients (74%) with AML with CHIP mutations; 134 patients (26%) with AML without CHIP mutations. The overall median follow-up of 23 months (range, 0.1-49.0). The median age at diagnosis was 70 years (range, 17-92) and 66 years (range, 20-87) in CHIP AML and non-CHIP AML, respectively (p =0.001). Of 371 patients and 127 patients evaluable for cytogenetic in CHIP AML and non-CHIP AML, 124 (33%) and 25 patients (20%) had complex karyotype, respectively (p= 0.004). Of 378 patients with CHIP AML, 183 patients (48%) had TET2 mutations; 113 (30%), TP53; 110 (29%), ASXL1; 109 (29%), DNMT3A; JAK2, 46 (12%). Of 378 patients, single CHIP mutations was observed in 225 patients (60%); double, 33 (9%); triple, 28 (7%); quadruple, 1 (0%). Concurrent FLT3-ITD mutations was detected in 47 patients (13%) and 12 patients (9%) in CHIP AML and non-CHIP AML, respectively (p= 0.287); FLT3-D835, 22 (6%) and 8 (6%), respectively (p= 0.932); NPM1 mutations, 62 (17%) and 13 (10%), respectively (p= 0.057). Of 183 patients with TET2-mutated AML, the median TET2 variant allele frequency (VAF) was 42.9% (range, 2.26-95.32); of 113 with TP53-mutated AML, the median TP53 VAF, 45.9% (range, 1.15-93.74); of 109 with ASXL1-mutated AML, the median ASXL1 VAF was 34.5% (range, 1.17-58.62); of 109 with DNMT3A-mutated AML, the median DNMT3A VAF was 41.8% (range, 1.02-91.66); of 46 with JAK2-mutated AML, the median JAK2 VAF was 54.4% (range, 1.49-98.52). Overall, the median OS was 12 months and 11 months in CHIP AML and non-CHIP AML, respectively (p= 0.564); 16 months and 5 months in TET2-mutated AML and non-TET2-mutated AML, respectively (p <0.001); 4 months and 13 months in TP53-mutated and non-TP53-mutated AML, respectively (p< 0.001); 17 months and 11 months in DNMT3A-mutated and non-DNMT3A-mutated AML, respectively (p= 0.072); 16 months and 11 months in ASXL1-mutated AML and non-ASXL1-mutated AML, respectively (p= 0.067); 11 months and 12 months in JAK2-murated and non-JAK2-mutated AML, respectively (p= 0.123). The presence and number of CHIP mutations were not a prognostic factor for OS by univariate analysis (p=0.565; hazard ratio [HR], 0.929; 95% confidence interval [CI], 0.722-1.194: p= 0.408; hazard ratio, 1.058; 95% confidence interval, 0.926-1.208, respectively). MVA Cox regression identified age (p< 0.001; HR, 1.036; 95% CI, 1.024-1.048), TP53 VAF (p= 0.007; HR, 1.009; 95% CI, 1.002-1.016), NPM1 VAF (p=0.006; HR, 0.980; 95% CI, 0.967-0.994), and complex karyotype (p<0.001; HR, 1.869; 95% CI, 1.332-2.622) as independent prognostic factors for OS. Of 33 patients with CHIP AML who were evaluated for the clearance of VAF by next generation sequencing , landmark analysis at 6 months showed median OS of not reached and 20.3 months in patients with and without CHIP-mutation clearance, respectively (p=0.310). Conclusion: The VAF of TP53 and NPM1 mutations by next generation sequencing can further stratify patients with newly diagnosed AML. Approximately, each increment of TP53 and NPM1 VAF by 1% is independently associated with 1% higher risk of death, and 2% lower risk of death, respectively. The presence of CHIP mutations except TP53 does not affect outcome. Disclosures Sasaki: Otsuka Pharmaceutical: Honoraria. Short:Takeda Oncology: Consultancy. Ravandi:Macrogenix: Honoraria, Research Funding; Seattle Genetics: Research Funding; Sunesis: Honoraria; Xencor: Research Funding; Jazz: Honoraria; Seattle Genetics: Research Funding; Abbvie: Research Funding; Macrogenix: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding; Orsenix: Honoraria; Abbvie: Research Funding; Jazz: Honoraria; Xencor: Research Funding; Orsenix: Honoraria; Sunesis: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Astellas Pharmaceuticals: Consultancy, Honoraria. Kadia:BMS: Research Funding; Abbvie: Consultancy; Takeda: Consultancy; Jazz: Consultancy, Research Funding; Takeda: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Research Funding; Novartis: Consultancy; Amgen: Consultancy, Research Funding; BMS: Research Funding; Jazz: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy; Abbvie: Consultancy; Celgene: Research Funding. DiNardo:Karyopharm: Honoraria; Agios: Consultancy; Celgene: Honoraria; Medimmune: Honoraria; Bayer: Honoraria; Abbvie: Honoraria. Cortes:Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Arog: Research Funding.

scholarly journals SURVIVAL ADVANTAGE OF APOE2

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S621-S621
Author(s):  
Sudha Seshadri
Keyword(s):  
Lower Risk ◽  
Large Population ◽  
Population Based ◽  
European Ancestry ◽  
Aggregated Data ◽  
Risk Of Death ◽  
Apoe Ε4 ◽  
Increased Risk ◽  
Ε4 Allele

Abstract Apolipoprotein E is a glycoprotein mediator and regulator of lipid transport and uptake. The APOE-ε4 allele has been associated with higher risk of Alzheimer’s disease and of mortality, but the effect of the less prevalent APOE-ε2 on survival remains elusive. We aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six large population-based cohorts to determine the association of APOE-ε2, with survival in the general population. During a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-ε3 carriers, APOE-ε2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P=1.1*10-2), whereas APOE-ε4 carriers were at increased risk (HR 1.17,1.12-1.21; P=2.8*10-16). Risk was lowest for homozygous APOE-ε2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-ε4 (HR 1.52,1.37-1.70). Results did not differ by sex. The association was unaltered after adjustment for baseline LDL or cardiovascular disease. Larger, multiethnic collaborations are ongoing.

scholarly journals The Impact of a Long-Term Rivastigmine and Donepezil Treatment on All-Cause Mortality in Patients With Alzheimer’s Disease

2018 ◽  
Vol 33 (6) ◽  
pp. 385-393 ◽  
Author(s):  
Jakub Kazmierski ◽  
Chaido Messini-Zachou ◽  
Mara Gkioka ◽  
Magda Tsolaki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cox Regression ◽  
Symptomatic Treatment ◽  
Risk Of Death ◽  
Increased Risk ◽  
Functional Assessments ◽  
The Impact

Cholinesterase inhibitors (ChEIs) are the mainstays of symptomatic treatment of Alzheimer’s disease (AD); however, their efficacy is limited, and their use was associated with deaths in some groups of patients. The aim of the current study was to assess the impact of the long-term use of ChEIs on mortality in patients with AD. This observational, longitudinal study included 1171 adult patients with a diagnosis of AD treated with donepezil or rivastigmine. Each patient was observed for 24 months or until death. The cognitive and functional assessments, the use of ChEIs, memantine, antipsychotics, antidepressants, and anxiolytics were recorded. The total number of deaths at the end of the observational period was 99 (8.45%). The patients who had received rivastigmine treatment were at an increased risk of death in the follow-up period. The higher risk of death in the rivastigmine group remained significant in multivariate Cox regression models.

24-Month Analysis of the Impact of Chelation on Clinical Outcomes in a 600 Patient Registry of Lower-Risk MDS Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2800-2800 ◽  
Author(s):  
Roger M. Lyons ◽  
Billie J. Marek ◽  
Surabhi Sharma ◽  
Carole Paley ◽  
Jason Esposito ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Lower Risk ◽  
Research Funding ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Disease Status ◽  
Cardiac Events ◽  
Leukemic Transformation ◽  
The Impact

Abstract Abstract 2800 Introduction: Many patients with MDS require regular transfusions. Several reviews have documented poorer clinical outcomes and overall survival (OS) in transfusion-dependent MDS patients. A US registry of 600 lower-risk MDS patients prospectively collected data on clinical outcomes in chelated and non-chelated transfused patients. This 24-month interim analysis reports on cardiac events, leukemic transformation and OS. Methods: This is a 5-year, non-interventional registry in MDS patients (aged ≥18 years) with lower-risk MDS (based on WHO, FAB and/or IPSS criteria) from 107 US centers. Patients had to have transfusional iron overload (serum ferritin ≥1000 μg/L and/or ≥20 packed red blood cell units and/or ongoing transfusion requirement of ≥6 units every 12 weeks). Follow-up was every 6 months for up to 60 months or death. Use of chelation therapy was not required. Chelated patients were those who had ever used iron chelation; a sub-analysis was done on patients with ≥6 months chelation. Assessments included demographics, disease status, MDS therapy, comorbidities, and causes of death. Differences between non-chelated and chelated patients are reported. Results: 600 patients enrolled; as of May 26, 2011, 249 continued in the registry. 351 patients discontinued due to: lost to follow-up (n=51, 8.5%); death (n=278, 46.3%); other (n=22, 3.7%). 263/600 patients received chelation therapy, of whom 191 received ≥6 months. Leukemic transformation and cardiac events were more common in non-chelated patients (Table 2). Time to leukemic transformation was significantly shorter in non-chelated versus chelated patients. A greater percentage of deaths occurred in non-chelated patients; time to death was significantly shorter in non-chelated versus chelated patients. The most frequent reasons for death were MDS/AML, cardiac, and infection. At baseline, non-chelated patients had a higher incidence of cardiac disorders than chelated patients (51.3% vs 35%). While on the registry, non-chelated patients had a higher incidence of comorbidities than did chelated patients, predominantly vascular, cardiac and endocrine. Lifetime use of MDS therapies (pre- and on-registry) was lower among non-chelated versus chelated patients (88.4% vs 94.3%). Conclusions: At the 24-month analysis, use of chelation was associated with lower AML transformation, fewer cardiac events, and better OS. The two patients groups had similar age, gender, and risk status breakdown (IPSS); however the non-chelated group had a higher prevalence of cardiac comorbidities. Ongoing follow-up for the 5-year duration of this registry will provide further data on differences in outcomes between chelated and non-chelated patients. Disclosures: Lyons: Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Telik: Research Funding; Alexion: Consultancy, Honoraria; Novartis: Research Funding. Sharma:Novartis: Employment. Paley:Novartis: Employment. Esposito:Novartis: Employment.

Acquisition of Cytogenetic Abnormalities (CA) Is a Very Poor Prognostic Feature in Patients (pts) with Low and Intermediate-1 (int-1) Risk Myelodysplastic Syndromes (MDS),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3802-3802
Author(s):  
Elias Jabbour ◽  
Hagop M. Kantarjian ◽  
Xuemei Wang ◽  
Lynne V. Abruzzo ◽  
A Megan Cornelison ◽  
...  
Keyword(s):  
Lower Risk ◽  
Research Funding ◽  
Regression Models ◽  
Cox Model ◽  
Time Dependent ◽  
P Value ◽  
Increased Risk ◽  
History Of ◽  
Previously Treated ◽  
The Impact

Abstract Abstract 3802 Background and Aim: The impact of the CA on prognosis and transformation into acute myeloid leukemia among pts with low and int-1 risk MDS is not known. The aims of the study were to assess the impact of CA on the natural history of pts with lower risk MDS and to identify factors associated with its development. Methods: We reviewed 721 pts clinical records of low and intermediate risk MDS pts from 2000–2010 and conducted a retrospective analysis of all pts with at least two consecutive cytogenetic analysis (365 patients, 51%). The acquisition of CA was defined by structural change or gain in at least 2 metaphases and loss in 3 metaphases, or otherwise confirmed by FISH. Cox proportional hazards regression models were fit to assess the association between transformation-free survival (TFS) or overall survival (OS) and pt characteristics. The acquisition of CA was fitted in the Cox model as a time-dependent covariate. The association between the acquisition of CA and pt characteristics was assessed through univariate and multiple logistic regression models. Results: CA was detected in 107 pts (29%) after a median follow-up of 34 months (mos). CA was observed in a median number of 4 metaphases (range, 2–30). At diagnosis, 21% and 79% of pts who acquired CA were low-and int-1risk MDS; 50% were diploid, 22% harbored chromosome 5 /7 abnormalities. At the time of acquisition of CA, the median percentage of bone marrow blasts was 4% (range, 0% to 89%), the median WBC, hemoglobin and platelets were 3.1 × 109/L, 9.5 g/dL, and 65 × 109/L, respectively; pts were low, int-1, int-2, and high-risk MDS in 3%, 42%, 26%, 29%, respectively. The median TFS and OS were 31 (95% CI: 27– 37) and 34 (95% CI: 30 – 44) mos respectively. Assessing CA as time-dependent covariate, patients with CA had a worse TFS and OS, with a median TFS and OS of 16 and 18 mos compared to 56 and 60 mos, respectively in pts without CA. Based on the multivariable Cox model and after adjusting for effects of all other covariates, pts who had acquired CA had an increased risk of transformation (HR=1.46; p-value = 0.01) or death (HR=1.50; p-value = 0.01). By multivariate analysis, female pts with prior chemotherapy had an increased risk of developing CA (OR= 5.26; p-value <0.0001). 96 pts had history of previous malignancy treated with chemotherapy +/− radiation therapy. Of those, 34 (35%) patients acquired CA. Median time from previous chemotherapy to the acquisition of CA was 61 mos (range, 11 to 180). Pts previously treated who did not acquire CA had similar outcomes to those who had never been treated and did not develop CA, while those who did develop CA whether they were previously treated or not had worse TFS and OS. Conclusion: CA occurs at a rate of 29% of pts with lower risk MDS, more common among pts with previously treated malignancy, and has a significant impact on TFS and OS, possibly reflecting genomic instability in the natural history of MDS. Disclosures: Cortes: BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding.

Difference in cardiovascular disease incidence by sociodemographic factors in adolescent and young adult (AYA) cancer survivors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6565-6565
Author(s):  
Theresa Keegan ◽  
Lawrence H. Kushi ◽  
Qian Li ◽  
Ann Brunson ◽  
Marcio H. Malogolowkin ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cancer Survivors ◽  
Sociodemographic Factors ◽  
Cancer Type ◽  
Cvd Risk ◽  
Risk Of Death ◽  
Increased Risk ◽  
Race Ethnicity ◽  
The Impact

6565 Background: AYA cancer survivors are at increased risk of developing cardiovascular disease (CVD) compared to AYAs without a history of cancer. In AYA cancer survivors, few population-based studies have focused on CVD risk and none have considered whether the occurrence of CVD differs by sociodemographic factors. Methods: Analyses focused on 64,918 patients aged 15-39 y at diagnosis for one of 14 first primary cancers during 1996-2010 and surviving > 2 years after diagnosis, with follow-up through 2013. Data were obtained from the California Cancer Registry and State hospital discharge data. CVD included coronary artery disease, heart failure, and stroke. We estimated the cumulative incidence of developing CVD, accounting for death as a competing risk, stratified by race/ethnicity, neighborhood socioeconomic status (SES) at diagnosis, health insurance status at diagnosis/initial treatment and cancer type. We examined the impact of CVD on mortality using multivariable Cox proportional hazards regression with CVD as a time-dependent covariate. Results: Overall, 2374 (3.7%) patients developed CVD, and 7690 (11.9%) died over the follow-up period. Survivors of acute myeloid leukemia (12.6%), acute lymphoid leukemia (11.1%), central nervous system cancer (9.0%) and non-Hodgkin lymphoma (6.0%) had the highest incidence of CVD at 10-years. Incidence was significantly higher among Blacks (6.7%) at 10-years than non-Hispanic Whites (3.0%), Hispanics (3.7%) and Asian/Pacific Islanders (3.7%) (p < 0.001). AYA survivors with public or no insurance (vs private) had a higher 10-year incidence of CVD (5.8% vs 2.9%; p < 0.001), as did survivors residing in low (vs high) SES neighborhoods (4.1% vs 2.7%; p < 0.001). These sociodemographic differences in CVD incidence were apparent across most cancer sites. The risk of death was increased by five-fold or higher among AYAs who developed CVD. Conclusions: AYA cancer survivors who were uninsured or publicly insured, of Black race/ethnicity, or who resided in lower SES neighborhoods are at increased risk for developing CVD and experiencing higher mortality. The proactive management of CVD risk factors in these subgroups may improve patient outcomes.

scholarly journals Patient Related Factors Have an Indepedent Impact on Overall Survival in Myelodysplastic Syndrome Patients: A Report of the MDS-Can Registry

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 165-165
Author(s):  
Rena Buckstein ◽  
Richard A. Wells ◽  
Nancy Zhu ◽  
Thomas J. Nevill ◽  
Heather A Leitch ◽  
...  
Keyword(s):  
Overall Survival ◽  
Physical Performance ◽  
Predictive Factors ◽  
Research Funding ◽  
Performance Tests ◽  
Related Factors ◽  
Risk Of Death ◽  
The Impact ◽  
Very High

Abstract Introduction: MDS is a disease of the elderly; yet, the impact of clinical frailty (an age-related vulnerability state created by a multidimensional loss of reserves) and patient-reported outcomes on overall survival (OS) are unknown. Rockwood et al. have developed a simple 9-point clinical frailty scale (CFS) that correlated highly with the risk of death, institutionalization, worsening health and hospital use (Rockwood K., CMAJ 2005). In a prospective, national MDS registry, participants have undergone annual evaluations with the following: (a) 3 geriatric physical performance tests, (b) Charlson (CCI) and Della Porta comorbidity index (DP-CCI) scores, (c) graded frailty using the Rockwood CFS, (d) disability assessments with the Lawton Brody SIADL, and (e) QOL using the EORTC QLQ C-30 and the EQ-5D. The results of these frailty assessments and the effects of these patient-related factors and reported outcomes on OS, in addition to the IPSS/revised IPSS, will be presented. Methods: Overall survival was measured from time to enrollment. Results from physical performance tests were divided into quintiles with higher scores indicating better performance. We used univariate and multivariable Cox proportional hazard model to determine significant predictive factors of overall survival (OS). The variables considered included age, IPSS, R-IPSS, ferritin, LDH, transfusion dependence, hemoglobin (hgb), ECOG, frailty, CCI and DP-CCI, grip strength, 4 M walk test, stand-sit test, modified short physical performance battery (SPPB), Lawton Brody SIADL, time from diagnosis and selected QOL domains including the EQ-5D summary score, EORTC physical functioning, dyspnea and fatigue scores. Results: 453 MDS patients (pts) have been consented and enrolled locally since January 2008 (n=231) and nationally since January 2012 (n=222). Median time from diagnosis was 5.8 mos (IQR 1.4-21). Median age was 73 y (range, 26-95 y), 65% were male and the R-IPSS scores were very low (14%), low (46%), intermediate (24%), high (10%) and very high (6%). Thirty-three % of pts were transfusion dependent at enrollment. Median CCI and DP-CCI scores were 1 (0-12) and 0 (0-6) respectively with 18% and 24% falling into the highest category scores. Median frailty scale score (n=346) was 3 (1-9) with 25% having scores indicating moderate (4-5) or severe (6-9) frailty. The CCI and DP-CCI strongly correlated (r=0.6; p< .0001) with each other, while frailty significantly but modestly correlated with them (r=0.3-0.35, p<.0001). With a median follow up (from enrollment) of 15 mos (95% CI: 13-16), 159 (35%) pts have died and 28 pts lost to follow up. Actuarial survival was 41.0 mos (range, 33.6 - 48.5 mos). When considering patient related factors - age, frailty, comorbidity (both indices), sex, ECOG, the 10 x stand sit test, the SPPB, Lawton Brody SIADL, and all QOL domains considered above were significantly predictive of OS. The multivariable model with the highest R2 included R-IPSS (p=.0004), frailty (1-3 vs 4-9, p= .004), CCI (0-1 vs >2, p=.03) and EORTC fatigue (p=.01) as summarized in Table 1 below. A frailty score > 3 predicted for worse survival (figure 1: 2 year OS 68.5% vs. 83.8%) and further refined survival within the R-IPSS categories (Figure 2). Frailty was also the single most predictive factor for OS from the start of azacitidine therapy (not shown). Conclusions: Patient-related factors such as frailty and comorbidity (that evaluate physiologic reserve and global fitness) should be considered in addition to traditional MDS prognostic indices. Abstract 165. Table. Independent Covariate Predictive factors at baseline Coefficient SE p -value HR 95% CI of HR R2 (%) Time from diagnosis (months) * 0.0335 0.1076 0.7557 1.034 0.837 1.277 17.29% R-IPSS (5 categories) <.0001 Very high vs. very low 2.5701 0.7289 0.0004 13.066 3.131 54.524 High vs. very low 2.1156 0.6437 0.0010 8.294 2.349 29.285 Intermediate vs. very low 1.0466 0.6430 0.1036 2.848 0.808 10.043 Low vs. very low 0.6346 0.6181 0.3045 1.886 0.562 6.334 Frailty (1-3 vs. 4-9) -0.8323 0.2905 0.0042 0.435 0.246 0.769 Comorbidity Charlson (0-1 vs. ³2) -0.5915 0.2749 0.0314 0.553 0.323 0.949 EORTC fatigue * 0.3671 0.1546 0.0176 1.443 1.066 1.954 natural log-transformation was applied for normalizing distribution Figure 1 Overall survival by Frailty (n=346) Figure 1. Overall survival by Frailty (n=346) Figure 2 Overall Survival by Frailty and R-IPSS Figure 2. Overall Survival by Frailty and R-IPSS Disclosures Buckstein: Celgene Canada: Research Funding. Wells:Celgene: Honoraria, Other, Research Funding; Novartis: Honoraria, Research Funding; Alexion: Honoraria, Research Funding. Leitch:Alexion: Honoraria, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Educational Grant Other, Honoraria, Research Funding. Shamy:Celgene: Honoraria, Other.

Pregnancy outcomes in women with cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6116-6116
Author(s):  
Andrea Milbourne ◽  
Charlotte C. Sun ◽  
Michelle A. Fanale ◽  
Richard L. Theriault ◽  
Sue A Rimes ◽  
...  
Keyword(s):  
Median Number ◽  
Unknown Primary ◽  
Live Births ◽  
Risk Of Death ◽  
Randomized Controlled Studies ◽  
Increased Risk ◽  
After Cancer ◽  
The Impact ◽  
Head Neck

6116 Background: Parenthood after cancer is a critical concern for many cancer patients (pts). Pregnancy (prg) during cancer is an emotional time for about 1/1000 pregnant women. No randomized controlled studies exist examining the impact of cancer treatment (tx) on the developing fetus nor on the woman with cancer. Methods: From 2002-2011, women presenting for cancer tx during prg were approached for this IRB-approved prospective database study. All pts provided written consent. Results: To date 143 pts are evaluable. The median age at diagnosis was 32.1 years and median gestational age (GA) at enrollment was 18.2 weeks. 95/143 (66.4%) are White, 19 (13.3%) are African American, 17 (11.9%) are Hispanic and 12 (8.4%) are Asian/Other. Primary cancers included breast (n=59, 41.3%), hematologic (n=29, 20.3%), melanoma (n=13, 9%), GYN (n=11, 8%), GI (n=8, 5.6%), head/neck (n=7, 6%) and other (n=16, 11%) (brain=4, GU=1, thyroid=3, head/neck=7, thoracic=1, sarcoma=6, unknown primary=1). 111/143 (77.6%) of prgs resulted in live births. Median birth weight was 6.5 lbs. Median follow-up time for pts was 32.3 months. To date, 3/19 pts who terminated prgs have died (1.6%). Most terminations occurred in the 1st trimester. To date, 79 pts (55.2%) are NED and 23 pts have died; of these 19 (1.7%) had live births. No major malformations were observed in the 74/143 (52%) of pts who received chemotherapy (CTx) during pregnancy. 57% received FAC/FEC; other regimens included ABVD (n=5), cytarabine (n=5), CHOP/R-CHOP, and platinum-based regimens. Median GA at the start of CTx was 19.7 wks. Median number of CTx cycles during prg was 4. Other pts underwent surgery (n=32), no tx (n=14), deferred tx until after delivery (n=17), radiation (2), transplant (3), other (1). Conclusions: Cancer diagnosis during prg is compatible with successful tx and prg outcome. Cancer tx during the 2nd and 3rd trimester can be safely given and in our pts did not result in adverse prg outcomes. Tx during the 1st trimester is usually not recommended. Thus cancer pts in their 1st trimester need to be extensively counseled about their disease as well as about the risks to the prg. In our pts continuation or termination of prg were not associated with an increased risk of death.

The impact of guideline treatment nonadherence on survival for colorectal cancer patients: Propensity score calibration via a validation cohort.

2016 ◽  
Vol 34 (7_suppl) ◽  
pp. 308-308
Author(s):  
Robert Brooks Hines ◽  
Sue Min Lai ◽  
Joaquina Celebre Baranda ◽  
Kimberly K. Engelman ◽  
Frank Dong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Propensity Score ◽  
Cancer Patients ◽  
Validation Cohort ◽  
Treatment Guidelines ◽  
Risk Of Death ◽  
Increased Risk ◽  
The Impact

308 Background: The quality of cancer care has been the focus of ongoing concern for cancer researchers, providers, and policy makers. The objectives of this study were: 1) to evaluate nonadherence with National Comprehensive Cancer Network treatment guidelines for colorectal cancer (CRC) patients and the impact on survival, and 2) to obtain error-corrected estimates of effect by means of propensity score calibration via a validation cohort. Methods: CRC patients identified by the Georgia Comprehensive Cancer Registry for the years 2000-07 were eligible (N = 18,388). Naïve propensity score (PSn) adjustment and PS calibration (PSC) via a validation cohort were utilized to obtain hazard ratio estimates for the impact of guideline treatment nonadherence on 5-year overall survival. The validation cohort contained additional information on comorbidity and payer status which was used to obtain error-corrected estimates of effect by PSC. Results: Treatment nonadherence conferred a large increased risk of death early in the follow-up period which declined over time (Table 1). Comparison of results from the PSn and PSC models indicated moderate to large bias due to unmeasured confounding in the PSn model (data not shown). Conclusions: PSC produced attenuated estimates and had an impact on study conclusions in the latter follow-up period. For CRC patients, health services research into the quality of care received by cancer patients is necessary to continue the improving trend in CRC-related mortality. [Table: see text]

Systematic Review and Meta-Analysis of the Association Between Transfusion Independence (TI) and Overall Survival (OS) in Patients (pts) with Myelodysplastic Syndromes (MDS)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1934-1934
Author(s):  
Sue Harnan ◽  
Shijie Ren ◽  
Tim Gomersall ◽  
Emma Everson-Hock ◽  
Anthea Sutton ◽  
...  
Keyword(s):  
Systematic Review ◽  
Random Effects ◽  
Lower Risk ◽  
Research Funding ◽  
Meta Analysis ◽  
Type A ◽  
Type B ◽  
Risk Of Death ◽  
Meta Regression ◽  
The Impact

Abstract Introduction: MDS are a diverse group of haematological disorders affecting bone marrow function and necessitating frequent blood transfusions. A number of studies, from retrospective cohort and registry analyses to randomized controlled trials (RCTs), have shown transfusion status to impact OS in MDS. While transfusion status is considered a prognostic indicator in MDS, no systematic review has been conducted to consolidate and analyze all available evidence to date. This systematic review and meta-analysis is the first to assess the association between TI and OS, and also considers patient risk and acquisition of TI post treatment. Methods: Comprehensive electronic searches were conducted in five key bibliographic databases. Relevant conference proceedings were searched electronically, experts were contacted, grey literature (national and international guidelines, unpublished and unindexed studies) was searched online, and the reference lists of relevant reviews and guidelines were checked. The protocol was published a priori on PROSPERO (ID CRD42014007264). Studies which recruited adults aged ≥ 18 years with confirmed MDS, and reported OS for TI versus transfusion-dependent (TD) pts were included. Any expression of OS and any definition of transfusion status (x transfusions per unit time) were acceptable. RCTs, cohort studies, consecutive case series ≥ 10 cases, before-after studies and case-control studies were eligible for inclusion. Where a hazard ratio (HR) was expressed for TD vs. TI, the ratio was converted by dividing 1 by the reported HR to obtain HR for TI vs. TD. A narrative synthesis and a random effects meta-analysis were conducted. The meta-analysis synthesised the multivariate HR for OS of TI compared with TD pts from non-overlapping cohorts. A random effects meta-regression assessed whether the effect of being TI on OS depends on the risk group (according to IPSS or WHO criteria) of the included pts. Results: Searches identified 1821 titles of which 89 were included, representing 60 separate analyses. Study quality (by the Quality in Prognosis Studies [QUIPS] criteria) was moderate overall, with some limitations in reporting of attrition, correction of confounders, and patient spectrum. Three types of studies were identified: a) recruited TD and TI pts and compared OS between groups (n = 45); b) recruited TD only, and compared those who became TI to those who remained TD after treatment (n = 8); c) recruited TD only, compared those with high transfusion burden to those with low (n = 7). Amongst type a studies (n = 45), TI was consistently associated with an OS benefit whether results were expressed as HRs or as other metrics such as mean survival. In a meta-analysis of all eligible type a studies (n = 11) a 57% decrease in the risk of death compared with TD pts (HR 0.43; 95% credible interval (CrI) 0.31 to 0.56) was estimated. When considering the impact of the risk category of pts through meta-regression (lower-risk and all-risk cohorts only; no higher-risk cohorts were eligible for inclusion), the coefficient of the interaction term was estimated to be HR 1.33 (95% CrI 0.6 to 2.98), which suggested that the magnitude of the benefit for pts being TI on OS was higher for all-risk groups. However, this effect was inconclusive. A meta-analysis of type b studies was not possible as study cohorts overlapped. The multivariate HR in the 3 type b studies which reported this ranged from 0.53 to 0.36, indicating a mortality reduction between 47% and 64% associated with acquisition of TI. Studies reporting other metrics also reported TI pts fared better. A meta-analysis of type c studies was neither planned nor conducted. All studies reported that pts with fewer transfusions per unit time demonstrated better OS than those with more, regardless of the high/low transfusion burden cut point used. Conclusion: A number of studies have previously suggested that MDS pts who are TI have better survival relative to those who are TD, but no meta-analysis has been conducted to date. Our findings revealed a consistent, substantial reduction in mortality among TI pts when compared with TD pts confirming the positive TI-OS association. A meta-regression analysis indicated that the impact of TI was higher in all-risk cohorts versus lower-risk cohorts, but this effect was not conclusive. A similar association was seen for those who acquired TI through treatment (Figure 1). Figure 1 Figure 1. Disclosures Harnan: Celgene Ltd: Research Funding. Ren:Celgene: Research Funding. Gomersall:Celgene Corporation: Research Funding. Everson-Hock:Celgene Ltd: Research Funding. Dhanasiri:Celgene Corp: Employment, Equity Ownership. Kulasekararaj:Celgene: Honoraria, Speakers Bureau; Alexion: Honoraria, Speakers Bureau.

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