Effects of Multiple Myeloma (MM) Therapy and Type of Thromboprophylaxis On the Incidence and Timing of Venous Thromboembolism (VTE) and Factors Predictive of VTE.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2244-2244
Author(s):  
Jatin J. Shah ◽  
Aparna Hegde ◽  
Xiao Zhou ◽  
Sheeba K. Thomas ◽  
Michael Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Cancer Center ◽  
Hematopoietic Stem ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Multivariate Proportional Hazard ◽  
The Impact

Abstract Abstract 2244 Background: Patients (pts) with MM are at increased risk for VTE due to various risk factors related to the host, disease, and treatment. Immunomodulatory drugs (IMiDs) such as thalidomide and lenalidomide have further increased the risk of VTE. Several studies have shown the VTE risk can be reduced with the use of low molecular weight heparin (LMWH) or aspirin thromboprophylaxis. Based on these findings, VTE thromboprophylaxis has been recommended in pts receiving IMiDs + Dexamethasone (Dex), but the impact of these guidelines on patient outcomes in clinical practice is unclear. The objective of this observational study was to evaluate the incidence, timing and risk factors of VTE and the impact of different types of thromboprophylaxis on the incidence of VTE. Methods: This was a retrospective cohort study, and included all MM pts newly referred to the M.D. Anderson Cancer Center in 2006. Medical records of these pts were reviewed for the type and site of VTE, the incidence and timing of VTE during the five-year period from the referral date, and the risk factors, including pt demographics, co-morbidities, baseline laboratory values, types of MM and treatment, and types of thromboprophylaxis. Univariate and multivariate proportional hazard models were fitted to find the independent risk factors predictive of VTE. The stepwise selection method was employed to build a multivariate model using variables with p<0.15 in univariate analysis. Results: The cumulative incidence of VTE was 24% (38/159 pts) during the 5-year follow up period. Of the 38 pts with VTE, 25 (66%) had deep vein thrombosis (DVT), 11 (29%) had pulmonary embolus (PE), and 2 had concurrent DVT and PE. Most of the pts (32/38, 84%) had VTE within 1 year from the referral date. The incidence of recurrent VTE among these pts was 27.5% (11/38 pts), for a total of 52 episodes. Since the majority of VTEs and recurrences were within one year, we examined the risk factors for VTE during this period. Treatment with IMiDs + Dex and thromboprophylaxis with LMWH or Coumadin were independent predictive factors as shown below. The incidence of VTE was highest in pts exposed to IMiDs + Dex (30/38 pts), even after discontinuation of treatment, with most episodes (17/30) occurring during the preparation (7/30) or within 30 days (10/30) following hematopoietic stem cell transplantation (HSCT), when most (16/17) pts were not receiving anti-coagulants. Conclusions: These findings suggest that patients treated with IMiDs + Dex are at high risk for VTE, even after discontinuation of this treatment, especially, during and after the HSCT period. Future studies are needed to investigate VTE prevention strategies for this high-risk pt population. Disclosures: No relevant conflicts of interest to declare.

Polymorphisms in the CYP450 Genes Influences Regimen Related Toxicity and Outcome in Patients with Beta Thalassaemia Major Undergoing HSCT.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 869-869
Author(s):  
Poonkuzhali Balasubramanian ◽  
Salamun Desire ◽  
Vikram Mathews ◽  
Kavitha M Lakshmi ◽  
Shaji R Velayudhan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Annual Meeting ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
P Value ◽  
Thalassaemia Major ◽  
Hematopoietic Stem ◽  
Beta Thalassaemia ◽  
Variant Genotype ◽  
The Impact

Abstract Abstract 869 Polymorphisms in drug metabolizing enzymes are known to contribute to inter-individual differences in the pharmacokinetics (PK) of the two most commonly used drugs for conditioning for hematopoietic stem cell transplantation (HSCT), busulfan (Bu) and cyclophosphamide (Cy) and their metabolites in plasma. We have previously reported the impact of CYP genes on the PK of Cy, [Blood (ASH Annual Meeting Abstracts), Nov 2004; 104: 99] and the influence of Cy PK on transplant outcome [Blood (ASH Annual Meeting Abstracts), Nov 2004; 104: 1820]. We have now extended this study to evaluate a total of 19 polymorphisms in 11 genes that are known to be involved in the metabolism of Bu and Cy. 180 of the 276 patients with thalassemia major who underwent HSCT between March 1991 and Dec 2008 and for who genomic DNA was available were included in the study. The following polymorphisms were screened using PCR followed by RFLP and/ or gel electrophoresis: GSTA1*B, GSTM1 and GSTT1 deletion, GSTP1*B, CYP2B6*2, *3, *4, *5 and *6, CYP2C9*2, *3 and *4, CYP2C19*2, *3, CYP3A4*1B, CYP3A5*3, *6 and ALDH1A1*2 and ALDH3A1*2. Polymorphism frequencies were associated with regimen related toxicities, other transplant related complications using Fischer's Exact test and Cox-proportional hazard's model.. Significant associations are shown in the Table. On univariate analysis, CYP2B6*4 variant genotype was associated with incidence of hemorrhagic cystitis (HC); CYP2C9*3 variant genotype was associated with the severity of HC; CYP2C19*3 and 2C9*2 genotypes were associated with overall and even-free survival (OS and EFS) and CYP2C9*2 and CYP2C9*3 genotype was associated with transplant related mortality (TRM). Multivariate analyses performed adjusting for known clinical risk factors still showed these genotypes to be significantly associated with outcome parameters. Variant genotypes of polymorphisms that result in decreased metabolism of Cy are protective against regimen related toxicities while these polymorphisms were risk factors for EFS and OS in the present study. This is the first report on the influence of common GST, CYP and ALDH polymorphisms on outcome of HSCT in patients with thalassaemia major. Screening for these polymorphisms in patients with beta thalassaemia undergoing HSCT can help identify patients at higher risk of complications.Table:EndpointGenotypeRelative risk (95% CI)P- value HCCYP2B6*4 variant0.3 (0.13-0.889)0.028 HC grade 1 vs. HC grade 2-4CYP2C9*3 variant0.2 (0.073-0.962)0.043 TRM2C9*2 variant2.7 (1.08-6.77)0.034 2C9*3 variant2.3 (1.0-5.7)0.049 OS and EFS2C19*3 variant3.3 (1.2-9.3)0.018 2C9*2 variant1.3 (0.93-2.03)0.070 Disclosures: No relevant conflicts of interest to declare.

Abstract 78: Risk Factors Associated with Failure of Aggressive Medical Therapy in the SAMMPRIS Trial

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Michael F Waters ◽  
Brian L Hoh ◽  
Michael J Lynn ◽  
Tanya N Turan ◽  
Colin P Derdeyn ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Medical Therapy ◽  
Primary Endpoint ◽  
Univariate Analysis ◽  
Baseline Risk ◽  
Medical Group ◽  
High Risk Patients ◽  
Increased Risk ◽  
Risk Patients

Background: The SAMMPRIS trial showed that aggressive medical therapy was more effective than stenting for preventing stroke in high-risk patients with symptomatic intracranial stenosis. However, 15% of patients in the medical group still had a primary endpoint (any stroke or death within 30 days of enrollment or stroke in the territory beyond 30 days) during a median follow-up of 32.7 months. We sought to determine baseline risk factors that were associated with a primary endpoint in the medical arm of SAMMPRIS. Methods: Data on 227 patients randomized to the medical group in SAMMPRIS were analyzed. Baseline demographic features, vascular risk factors, qualifying event, brain imaging and angiographic features were analyzed. The hazard ratio and p-value from a Cox proportional hazard regression model relating time until a primary endpoint to each factor were calculated. Results: Female gender, diabetes, stroke as the qualifying event (especially non-penetrator stroke), old infarct in the territory of the stenotic artery, and > 80% stenosis were associated (p < 0.10) with a higher risk of the primary endpoint on univariate analysis (see accompanying table) (multivariate analysis will be available by the time of ISC). Variables not associated with a higher risk of a primary endpoint in the medical arm included: age, race, antithrombotic therapy at the time of a qualifying event, time from qualifying event to enrollment (< 7 days vs. > 7 days), and location of stenosis. Conclusions: Several features were associated with an increased risk of the primary endpoint in the medical group in SAMMPRIS. On univariate analysis, the most important risk factors were an old infarct in the territory of the stenotic artery and stroke (especially non-penetrator stroke) as the qualifying event. These features will be useful for identifying particularly high-risk patients who should be targeted for future clinical trials testing alternative therapies to aggressive medical management.

A Risk Model for Thrombocytopenia Requiring Platelet Transfusion After Cytotoxic Chemotherapy

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 405-410 ◽  
Author(s):  
J.Y. Blay ◽  
A. Le Cesne ◽  
C. Mermet ◽  
C. Maugard ◽  
A. Ravaud ◽  
...  
Keyword(s):  
Risk Factors ◽  
Platelet Count ◽  
High Risk ◽  
Risk Model ◽  
Univariate Analysis ◽  
Cytotoxic Chemotherapy ◽  
Phase Iii ◽  
Severe Thrombocytopenia ◽  
Increased Risk ◽  
Platelet Transfusions

Abstract Severe thrombocytopenia is a rare but life-threatening side effect of cytotoxic chemotherapy for which risk factors are not well known. Our objective was to delineate a risk model for chemotherapy-induced thrombocytopenia requiring platelet transfusions in cancer patients. Univariate and multivariate analysis of risk factors for chemotherapy-induced thrombocytopenia requiring platelet transfusions were performed on the cohort of the 1,051 patients (CLB 1996) treated with chemotherapy in the Department of Medicine of the Centre Léon Bérard (CLB) in 1996. In univariate analysis, performance status (PS) greater than 1, platelet count less than 150,000/μL at day 1 (d1) before the initiation of chemotherapy, d1 lymphocyte count ≤700/μL, d1 polymorphonuclear leukocyte count less than 1,500/μL, and the type of chemotherapy (high risk v others) were significantly associated (P &lt; .01) with an increased risk of severe thrombocytopenia requiring platelet transfusions. Using logistic regression, d1 platelet count less than 150,000/μL (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.9 to 9.6), d1 lymphocyte counts ≤700/μL (OR, 3.37; 95% CI, 1.77 to 6.4), the type of chemotherapy (OR, 3.38; 95% CI, 1.77 to 6.4), and PS greater than 1 (OR, 2.23; 95% CI, 1.22 to 4.1) were identified as independent risk factors for platelet transfusions. The observed incidences of platelet transfusions were 45%, 13%, 7%, and 1.5% for patients with ≥3, 2, 1, or 0 risk factors, respectively. This model was then tested in 3 groups of patients treated with chemotherapy used as validation samples: (1) the series of 340 patients treated in the CLB in the first 6 months of 1997, (2) the prospective multicentric cohort of 321 patients of the ELYPSE 1 study, and (3) the series of 149 patients with non-Hodgkin's lymphoma treated in the CLB within prospective phase III trials (1987 to 1995). In these 3 groups, the observed incidences of platelet transfusions in the above-defined risk groups did not differ significantly (P &gt; .1) from those calculated in the model. This risk index could be useful to identify patients at high risk for chemotherapy-induced thrombocytopenia requiring platelet transfusions.

Cytogenetic Evolution (CE) In Patients (pts) with Low and Intermediate Risk Myelodysplastic Syndromes (MDS) Is Associated with Poor Prognosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2941-2941
Author(s):  
Liunan Li ◽  
Elias Jabbour ◽  
Gautam Borthakur ◽  
Stefan Faderl ◽  
Tapan Kadia ◽  
...  
Keyword(s):  
Disease Progression ◽  
Cytogenetic Analysis ◽  
Conflicts Of Interest ◽  
Myelogenous Leukemia ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Significant Difference ◽  
The Impact ◽  
Cytogenetic Evolution

Abstract Abstract 2941 Introduction: MDS is a spectrum of abnormalities in the proliferation and differentiation of hematopoietic stem cells that result in peripheral cytopenias, bone marrow dysplasia and increased risk of transformation to acute myelogenous leukemia (AML). Cytogenetic abnormalities occur in more than 50% of patients (pts) and have an impact on survival and risk of transformation to AML. CE, or acquisition of additional clonal chromosomal abnormalities, has been reported to occur in 30 to 50% of primary MDS pts. Their impact on prognosis and transformation into AML among pts with low and intermediate risk MDS is not known. In this study, we analyzed the impact of CE on prognosis in lower risk MDS. Methods: we reviewed 722 pts clinic records of low and intermediate risk MDS pts at MD Anderson Cancer Center (MDACC) from 2000–2010 and conducted a retrospective analysis of all MDS pts with at least two consecutive cytogenetic analysis (365 patients, 50.6%) and compared the cytogenetic evolution group (CE group) with the group without cytogenetic changes (no CE group). Cytogenetic analysis was performed in the Cytogenetics Laboratory at MDACC. Results: CE was detected in 200 pts (55%). Characteristics of patients with CE are: median age 65 years (23-91), IPSS int-1 79%, diploid CG 42%, excess blasts 25%. Pts with CE were more frequently female (p=0.005), and had more frequently abnormalities of chromosome 5 and 7 (p<0.001) at baseline. There were no statistically significant difference between these two groups (p>0.05) regarding age, WBC, platelet, hgb, ANC, BM blasts percent, diagnosis (RA or RAEB), and IPSS score. There were more chr.-5/-7, insufficient metaphases, and other abnormalities, but less diploid cases in CE group compared with no CE group (p<0.001). History of malignancy (p=0.001) and prior chemotherapy exposure were also associated with CE (p=0.001), but this was not as strong for radiation exposure (p=0.066). Also, more CE patients required therapy for MDS compared to no CE patients (p=0.039). Progression free survival was significantly extended in no CE patients (p=0.02). Overall survival was a longer in no CE (34.1months), compared with CE group (26.2 months), although this was not statistically significant. Conclusion: CE is more commonly observed among pts with high-risk features, and is usually associated with disease progression and resistance. Also, prior malignancy and chemotherapy exposure were associated with CE in this study. This data indicates that genomic instability has a role in disease progression in MDS. Further analysis of CE in MDS is needed. Disclosures: No relevant conflicts of interest to declare.

Absence of High-Dose Consolidation Courses and Low Numbers of Allogeneic HSCTs Did Not Affect Overall Optimistic Results in B-Cell Precursor Ph-Negative Adult ALL Patients Treated By Non-Intensive but Non-Interruptive ALL-2009 Protocol: Data of the Russian ALL Study Group

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2497-2497
Author(s):  
Elena N. Parovichnikova ◽  
Vera V. Troitskaya ◽  
Andrey Sokolov ◽  
Galina Kliasova ◽  
Larisa A. Kuzmina ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Normal Karyotype ◽  
Risk Groups ◽  
High Dose ◽  
Late Response ◽  
Allogeneic Hsct ◽  
Blast Cells

Abstract Introduction It is postulated that the improvement in the overall treatment outcome in adult Ph-negative ALL came from the implementation of more aggressive pediatric-like protocols and higher portion of allogeneic HSCT. Here we report the results of the adult (15-55 yy) Ph-negative ALL protocol based on the opposite approaches: less intensive but non-interruptive treatment with low numbers of allo-HSCT. The study is registered on the ClinicalTrials.gov public site; NCT01193933. Patients and Methods The ALL-2009 is based on: (1) the replacement of prednisolone (Pdn) 60 mg/m2 with dexamethazone (Dexa) 10 mg/m2 if blast cells are >25% in b/m after prephase (7d); (2) de-intensified but non-interruptive 5 months induction/consolidation treatment (5 wks prd/dexa with 3 instead of 4 dauno/vncr pulses, 4 weeks of 6MP with 5 L-asp, 2 instead of 4 ARA-C blocks, 1 instead of 2 Cph injections during induction; induction-like 3 consolidations for 3wks, 2wks, 4wks-continuously without intervals), followed by (3) 2 late (at 6 mo) intensifications- with 1 day HD MTX and with 1 d HD ARA-C, both with L-asp and 3 ds dexa and (4) 2-yrs continuous 6MP/MTX maintenance with doses modification according to myelosuppression with monthly 3-days dexa/vncr/L-asp pulses (∑ L-asp = 590.000 IU/m2). The protocol was identical for all risk groups. Allo-HSCT was indicated only for extremely high-risk BCP-ALL (t(4;11),L>100). No central MRD monitoring was performed. Since Apr 2009 till June 2015 20 centers had recruited 168 BCP-Ph-negative ALL pts with a median age 28 years (15-54), 84f/84 m. Full cytogenetics was available in 67,3% (n=113), 43,4% of them (n=49) had normal karyotype (NK), 10% (n=9%) had no mitosis, 47,6% (n=54) - different abnormalities (hypoploid-1, hyperploid-12, t(11q23)/MLL-8, del11q23-2, t(1;19)-2, t(12;21)-1;others-28). 26,7% of pts (n=45) were in the standard risk (SR) group (WBC <30, EGIL BII-III, LDH < 2N; no late CR; t(4;11)-negative), 56,5% (n=95) - in the high risk (HR) group (WBC >30; EGIL BI, LDH > 2N; late CR; t(4;11)-positive), 28 patients (n=16,8%) were not qualified by the risk. The analysis was performed in June 2015. 158 pts were available for analysis. Results CR rate in 158 available for analysis pts was 87,7% (n=139), induction death occurred in 9,1% (n=14), resistance was registered in 3,2% (n=5). The majority of CR pts (87,8%) achieved it after prephase (12,2%, n=17) and the 1st phase of induction (75,6%, n=105). Late responders constituted 12,2% (n=17). Allogeneic BMT was performed only in 9 of 144 patients who survived induction (6,2%). Totally 31 pts (22,3%) had relapsed. At 60 mo OS for the whole group constituted - 50%, DFS - 51.3%. In a univariate analysis among various risk factors (age <> 30y, initial risk group, WBC, LDH, immunophenotype, late response >35d, PRD resistance) age (>30 y) became statistically significant for OS, DFS and relapse probability (RP) (pic.1), abnormal karyotype - for DFS (30% vs 68%, p=0,04) and RP (42% vs 19%, p= 0,04). In a multivariate analysis no common risk factors were significant. Conclusions Our data demonstrate that the proposed treatment approach is rather effective. We believe that constant non-interruptive treatment without intensive highly myelosuppressive consolidation courses and high portion of allogeneic HSCT may become an alternative and reproducible approach in adult Ph-negative ALL, though we have to stress that it should be very strict compliance of the pts to the protocol. All pts, mostly from the region hospitals who refused prolonged and constant treatment (~5%), relapsed. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Risk Factors for Induction Related Mortality in Adults Patients with Acute Lymphoblastic Leukemia: Report from a Hispanic Population

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5162-5162
Author(s):  
Sergio I Inclan-Alarcon ◽  
Christianne Bourlon ◽  
Oscar Manuel Fierro-Angulo ◽  
Jesus A Garcia-Ramos ◽  
Santiago Riviello-Goya ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
Adult Patients ◽  
Hispanic Population ◽  
Increased Risk ◽  
The Impact ◽  
Hispanic Adult

Abstract Introduction Acute lymphoblastic leukemia (ALL) represents 20-30% of acute leukemia in adults. Higher incidence and inferior outcomes in Hispanic population have been described. In Latin Americans induction mortality (IM) is a major cause of death representing 20-50% vs.7-11% in developed countries. Our aim was to determine risk factors (RF) related to IM in ALL Hispanic adult patients. Methods We retrospectively analyzed clinical data of ≥18yo patients with ALL diagnosed and treated at our institution within 2009 and 2016. Results A total of 170 patients were included. Median age was 29 years (16-70), 64% were AYA, 96.8% had B-cell ALL, and 62.3% received Hyper-CVAD. IM rate was 13.4%. In 64.1% IM was related to an infectious cause. The most frequent infection was pneumonia (39.8%). Gram-negative etiology was more prevalent (35.5% vs. 10.2%), however, IM rate was higher in gram-positive infections (26.3% vs .13.6%; p=.028). RF related to IM in univariate analysis were: CNS involvement (OR4.6,95%IC2.8-9.5;p=<.001), tumor lysis syndrome (TLS) (OR 5.6, 95% CI 2.2-14.1; p=<.001), need for dialysis (OR 28.9, 95% CI 5.3-157.1; p=<.001), primary hypertension (OR 3.5, 95% CI 1.0-12.7; p=.052), shock status (OR 10.3, 95% CI 3.9-27.3; p=<.001), ECOG³2 (OR 1.9, 95% IC 1.1-3.4; p=.022), T-ALL (OR 2.2, 95% IC 1.1-4.3; p=.026), Hyper-CVAD (OR 1.9, 95% IC 1.1-3.8; p=0.51), ventilation assistance (OR 7.7, 95% IC 2.8-21; p=<.001), and vasopressor use (OR 7.6, 95% IC 2.8-20.6; p=<.001). In multivariate analysis TLS, need for dialysis and shock, kept statistical significance. Conclusions To our knowledge, this is the largest study that evaluates the impact over IM of biological, social, and economic factors in Hispanic adult patients with ALL. We identified factors not previously described such as hypertension and need for dialysis. Multicenter prospective studies most be urged to asses and validate these RF, and design a bedside prognostic score that can predict an increased risk of IM at ALL diagnosis. Disclosures No relevant conflicts of interest to declare.

Incidence of venous thromboembolic disease (VTE) in a cohort of patients with colorectal cancer (CRC) according to KRAS, NRAS and BRAF status.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15136-e15136
Author(s):  
Pilar Garcia-Alfonso ◽  
Laura Ortega Morán ◽  
Iria Gallego Gallego ◽  
Gonzalo García González ◽  
Gabriela Torres Pérez-Solero ◽  
...  
Keyword(s):  
High Risk ◽  
Predictive Model ◽  
Metastatic Disease ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Low Risk ◽  
Intermediate Risk ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Cancer Associated Thrombosis

e15136 Background: A recent study has suggested that KRAS mutation could increase the risk of VTE in patients with CRC. The role of others biomarkers, such as BRAF, in this setting is unknown. The aim of this study is to analyze the incidence of cancer-associated thrombosis in a cohort of patients with CRC based on KRAS, NRAS and BRAF status. Methods: We performed a retrospective review of patients with metastatic CRC and KRAS/NRAS/BRAF status known, attended in the Medical Oncology Department of the Hospital General Universitario Gregorio Marañón (Madrid, Spain) between January 2010 and January 2018. Results: 194 patients were identified and included in the analysis. The median age was 64 years (18-86). Most were metastatic at diagnosis (58.1%). Khorana’s predictive model: low-risk 67.7%, intermediate-risk 31.0%, high-risk 2.3%. The median follow-up was 35 months (2-240). 41 patients (21.1%) experienced VTE (11 pulmonary embolism, 15 lower extremity deep-vein thrombosis, 12 visceral vein thrombosis, 2 catheter-related thrombosis, 1 unknown). Most had metastatic disease at the moment of VTE (90.2%). 40% of the events occurred at the time of diagnosis or within the first 6 months. 65% were incidental events. Khorana’s predictive model in VTE patients: low-risk 63.4%, intermediate-risk 24.5%, high-risk 7.3%. According to biomarkers, the incidence was 19.1% (13/68) in KRAS/NRAS mutated patients, 28.6% (6/21) in BRAF mutated patients and 21% (22/105) in triple-wild-type patients. 6/38 patients (15.8%) developed recurrent thrombosis. In the univariate analysis, the presence of chronic kidney disease (p = 0.022), ECOG ≥ 2 (p = 0.038) and high-risk Khorana score (p = 0.011) were significantly associated with increased risk of VTE. Metastatic disease showed a trend towards the statistical significance (p = 0.053). In the multivariate model, including this variables, age, sex and biomarkers, only ECOG ≥ 2 remained independent predictor of VTE (OR 8.73; CI 95% 1.32-57.82; p = 0.025). Conclusions: The biomarkers have not been associated with the risk of VTE. We have observed a high incidence of VTE in BRAF mutated patients that should be investigated in further studies.

Alpha-Catenin Is Dispensable for Normal Hematopoietic Stem Cell Function.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1438-1438
Author(s):  
Natallia Mikhalkevich ◽  
Michael W. Becker
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Conflicts Of Interest ◽  
Fusion Product ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
Myeloid Neoplasms ◽  
Increased Risk ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 1438 Poster Board I-461 We previously demonstrated the loss of expression of alpha-E-Catenin, the product of the CTNNA1 gene, in primary leukemic stem cells isolated from patients with advanced Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) associated with loss of all or part of the long arm of chromosome 5. To formally assess the impact of loss of Ctnna1 expression on hematopoiesis, we employed a murine model for the hematopoietic specific conditional loss of Ctnna1 expression. We demonstrate that Ctnna1 deficiency is associated with normal hematopoietic maturation and proliferation as assessed by peripheral blood examination and methycellulose colony assays. We assessed stem cell and early progenitor frequencies using both flow cytometry and functional assays. Ctnna1 deficiency was associated with equivalent frequencies of Sca1+C-Kit+CD135-Lineage- HSCs in both experimental animals and controls. Short term HSC and MPP frequencies were likewise unaltered. We assessed HSC function using transplantation studies. In competitive repopulation experiments, HSCs deficient for Ctnna1 maintained stable engraftment of recipient mice for up to 1 year. Limiting dilution analyses detected no significant difference in HSC frequency between wild type and Ctnna1 deficient mice. We examined the potential role of Ctnna1 deficient hematopoietic stem cells in two murine models for myeloid neoplasms 1.) exposure to mutagen ENU and 2.) a model for murine AML driven by the HoxA9-Nup98 fusion product. Following exposure of HSCs to ENU, loss of Ctnna1 was not associated with an increased risk of development of a myeloid neoplasm. Expression of the HoxA9-Nup98 fusion product by retroviral infection of Ctnna1 deficient and wild type Sca1+C-Kit+Lineage- cells resulted in no difference in time to development of the previously characterized myeloproliferative disorder or acute leukemia. Taken together, these data demonstrate that in the absence of specific genetic abnormalities, loss of Ctnna1 expression in primary murine HSCs is not associated with aberrant HSC function or the development of myeloid neoplasms. Further studies are necessary to define a role for of loss of Ctnna1 expression in human myeloid malignancies. Disclosures No relevant conflicts of interest to declare.

scholarly journals Identification of a Predictive Pre-Chemotherapy Score for Febrile Neutropenia - the Fnipi INDEX

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Marco Sanna ◽  
Giovanni Caocci ◽  
Antonio Ledda ◽  
Elisabetta Belardinelli ◽  
Pietro Garau ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Febrile Neutropenia ◽  
Univariate Analysis ◽  
Central Line ◽  
Assessment Tools ◽  
Predictive Score ◽  
Chronic Obstructive Pulmonary Disorder ◽  
Increased Risk ◽  
Active Disease

Introduction Febrile neutropenia (FN) is a leading cause of morbidity and mortality in hematology; typically, patients considered at high risk of FN are those who experience chemotherapy-induced neutropenia longer than 7 days. Other potential risk factors have been reported to impact on mortality but evidence is scarce. Also, clinicians still lack valid prediction model to identify patients at increased risk of FN. Methods We retrospectively analyzed a cohort of 100 consecutive patients who underwent intensive chemotherapy cycles (ICC) for several hematologic malignancies from October 2019 to February 2020, for a total of 368 chemotherapy courses. All patients were evaluated for age, sex, diagnosis, central line catheter, disease status, chemotherapy regimen, number of previous ICC administered, antibiotic prophylaxis, antimycotic prophylaxis, antiviral prophylaxis, anti-hepatitis B reactivation prophylaxis, G-CSF therapy, pegylated (PEG)-G-CSF therapy, previous appendectomy, diabetes, chronic obstructive pulmonary disorder (COPD), previous FN. A binary logistic regression was used to evaluate the association between independent variables and FN; statistically significant variables were included in a FN predictive score. Results In univariate analysis, an higher incidence of FN was found in patients with active disease (p&lt;0.001, HR=3.98, 95%CI= 2.07-7,66), AML diagnosis (p&lt;0.001, HR=6,6, 95%CI= 2.82-15.6), previous appendectomy (p&lt;0.001, HR=3.45, 95%CI=1.65-7.2), diabetes (p&lt;0.001, HR=4.23, 95%CI= 1.77-10.1), central line catheter in comparison with peripherally inserted central catheter (PICC) or no central line catheter (p&lt;0.001, HR=2.66, 95%CI=1.36-5.1), CHOP like chemotherapy (p&lt;0.001, HR=0.39, 95%CI=1.28-5.3), ICC&lt;3, (p=0.006, HR=2,6, 95%CI=1,28-5,3). In multivariate analysis only 4 variables remained significantly associated with FN incidence: AML diagnosis (p=0.007, HR=4.28, 95%CI=1.48-12.38), active disease (p=0.002, HR=3.11, 95%CI=1.5-6.45), previous appendectomy (p=0.007, HR=3.19, 95%CI=1.36-7.47) and diabetes (p=0.01, HR=3.6, 95%CI=1.34-9.67) (Figure 1). The 4 significant variables were considered in a new score called Febrile Neutropenia Incidence Prognostic Index (FNIPI). A single point was assigned to each variable, for a maximum of 4 points. The incidence of FN was found significantly higher in cycles showing a FNIPI score of 2-4 in comparison with 0-1 (p&lt;0.001, HR=10.1, 95%CI 4.77-21.3). Conclusions We identified several pre-treatment risk factors associated with chemotherapy-induced FN risk. Here we propose a novel score, the FNIPI, based on 4 factors (AML diagnosis, active disease, previous appendicectomy, diabetes) that discriminates patients at risk of FN after ICC. Risk assessment tools could represent a useful instrument for clinicians, to develop adequate strategies in patients at high risk of FN. To note, this observation requires larger prospective cohorts to be confirmed. Disclosures No relevant conflicts of interest to declare.

Risk Factor of Hepatic Veno-Occlusive Disease: Analysis of Clinical Data of 5024 Patients Extracted from the Database of the Japan Marrow Donor Program.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2970-2970
Author(s):  
Miwa Sakai ◽  
Kazuteru Ohashi ◽  
Takuya Yamashita ◽  
Hideki Akiyama ◽  
Hisashi Sakamaki
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Clinical Data ◽  
Univariate Analysis ◽  
Disease Status ◽  
Occlusive Disease ◽  
Blood Type ◽  
Hematopoietic Stem ◽  
Increased Risk

Abstract Hepatic veno-occlusive disease (VOD) is one of the most serious complication of hematopoietic stem cell transplantation (HSCT). Various factors have been identified as increasing the risk of hepatic VOD, but few of them have been associated with a significantly increased risk. We retrospectively analyzed the clinical data of 5024 transplant recipients (median age28, range 0–68) which extracted from the Japan Marrow Donar Program. The diagnosis of VOD was made according to the McDonald’s criteria, and 324 out of 4833 patients (6.7%) were eventually diagnosed with VOD. The possible risk factors based on the previous studies were counted on an initial univariate analysis, and cumulated significant factors were further analyzed for their potential value for VOD development in multivariate analysis. Variables correlated with an increased risk of VOD were: time of transplant >2 times (relative risk (RR) 2.7; p=0.006), pretransplant disease status (RR 2.3; p=0.000), prior liver disease (RR 2.1; p=0.017), ABO blood type mismatch (RR1.7; p=0.000). In patients receiving either busulfan or melphalan for conditioning increased VOD risk (RR 1.5 and 1.8; p=0.007 and 0.002, respectively). In our multivariate analysis, stem cell source, and prophylactic use of heparin and Ursodiol had no significant effect on VOD development. This analysis might contribute to revise the previously reported risk factors for VOD and the data could be used to know which patients might be suitable subjects for new trials for VOD prevention.

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