Incidence and Risk Factors for Thrombosis in Patients with Acute Promyelocytic Leukemia. Experience of the PETHEMA LPA96 and LPA99 Protocols.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1503-1503 ◽  
Author(s):  
Pau Montesinos ◽  
Javier de la Serna ◽  
Edo Vellenga ◽  
Consuelo Rayon ◽  
Juan Bergua ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Tranexamic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Univariate Analysis ◽  
Promyelocytic Leukemia ◽  
Cerebral Stroke ◽  
Flt3 Mutations ◽  
The Impact ◽  
Ischemic Events

Abstract Background: Thrombo-ischemic events can be a severe complication in patients with active acute promyelocytic leukemia (APL). In a recently published study, the incidence of thrombosis among 90 patients with APL was 9%, and it was related to CD2 surface antigen expression, FLT3 mutations and leukocytes >10×109/L. The introduction of coagulopathy prophylaxis with tranexamic acid has not shown a benefit on hemorrhagic mortality, but its impact on the incidence of thrombotic events is unclear. Objectives:Analyze the incidence and risk factors for the development of thrombosis in patients with APL undergoing induction chemotherapy.Analyze the impact of prophylaxis with tranexamic acid on development of thrombosis. Material and methods: Between 1996 and 2005 759 patients with newly diagnosed APL were registered in the multicenter PETHEMA LPA96 and LPA99 trials. Twenty-six patients (3.5%) died due to complications before start of chemotherapy (CT). Induction consisted of ATRA plus idarubicin. In the LPA99 trial prophylactic tranexamic acid 100 mg/kg/day was introduced in case of platelets <50×109/L. At the end of the LPA99 trial its use was not recommended, and overall, initiation of tranexamic acid was reported in 257 patients (35%) We performed a univariate analysis to assess clinico-biological factors associated with thrombosis. Significant variables (p<0.05) were included in a multivariate analysis. Results: 39/759 patients (5.1%) developed thrombosis. Among 26 patients who died before initiation of CT, 6 (23%) presented with thrombotic complications: 3 cerebral stroke (CNS), 2 pulmonary embolism (PE) and 1 acute myocardial infarction (AMI). Thirty-three (4.5%) of the 733 patients in whom CT was initiated experienced thrombosis: 3 at diagnosis (1 AMI, 1 CNS and 1 deep venous thrombosis (DVT)) and 30 after the start of CT (16 DVT, 6 CNS, 3 PE, 2 AMI and 2 others). Four thrombotic events were related with initiation of tranexamic acid: 2 DVT, 1 skin necrosis and 1 renal necrosis. The following factors were related to a higher incidence of thrombosis: leukocytes >10×109/L (9% vs 4%, p<0.01), M3-variant subtype (11% vs 4%, p=0.02), fibrinogen <170 mg/dl (7% vs 3%, p=0.02) and hemoglobin >10 g/dl (8% vs 4%, p=0.03). No significant relation was observed with CD2 or other surface antigens, as well as FLT3 mutations. Use of tranexamic acid showed a trend towards a higher incidence of thrombosis (6% vs 3%, p=0.08). In multivariate analysis hypofibrinogenemia and M3-v subtype remained as independent prognostic factors. Thrombosis was related with a higher induction mortality (including deaths before start of CT), 28% vs 11%, p<0.01. Conclusion: Thrombo-ischemic events are relatively frequent in active APL patients implying an elevated early mortality. Hypofibrinogenemia and M3-v are associated with a higher incidence of thrombosis. Treatment with tranexamic acid has not decreased hemorrhagic mortality and it could be related to increased thrombotic events. Therefore its prophylactic use should not be recommended.

FLT3 Mutation in Patients with Acute Promyelocytic Leukemia Has No Effect on Therapy Response.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4239-4239
Author(s):  
Meng Xing Xue ◽  
Hui Ying Qiu ◽  
Yu Feng Feng ◽  
Jin Lan Pan ◽  
Su Ning Chen ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Acute Promyelocytic Leukemia ◽  
Prognostic Significance ◽  
Therapy Response ◽  
Promyelocytic Leukemia ◽  
Genetic Changes ◽  
Prognostic Effect ◽  
Flt3 Mutations ◽  
Wbc Count ◽  
The Impact

Abstract Fms-Like tyrosine kinase 3 (FLT3) mutations are one of the most frequent genetic changes in acute myeloid leukemia (AML) and are related to poor prognosis. However, in acute promyelocytic leukemia (APL) the prognostic significance of this mutation is not firmly established. We investigated FLT3 internal tandem duplications (FLT3/ITD) or point mutation of the activation loop domain (FLT3/ALM) in initial marrow samples in 160 APL patients, also studied the impact of FLT3 mutations on disease characteristics and clinical outcome. Some of FLT3/ITD+ samples were further examined to determine the ITD allelic ratio(ITD-AR) using Genescan analysis. FLT3/ITD and FLT3/ALM were detected in 31 (19.4%) and 17(10.6%) of the patients, 2(1.25%) showed both ITD and ALM mutations. 19 of 31 FLT3-ITD+ patients were examined to determine ITD-AR, which varied from 0.11 to 1.79, with a median of 0.92. ITD-AR in 8 patients were greater than 1.0. Both mutations were associated with higher white blood cell(WBC) count at presentation(P<0.05); Among patients with WBC counts greater than 10×109/L, FLT3/ITD and FLT3/ALM rates were 49.1%(26/53) and 22.6% (12/53) respectively, were both higher than those of patients with WBC counts lower than 10×109/L (P<0.01). For clinical outcome, the complete remission(CR) of FLT3-ITD+ patients was lower than that of FLT3-ITD− patients(64.5% vs 91.5%, P<0.01), however the CR rates were not significantly different between patients with and without FLT3-LAM(84.6% vs 100%, P>0.05). Six originally FLT3-ITD+ patients were not detectable mutation after remission; so were six patients with originally FLT3-LAM+; however FLT3-LAM in one originally FLT3-LAM+ patient reappeared after relapse. In conclusion, FLT3 mutations (FLT3/ITD or FLT3/ALM) were frequently identified in patients with newly diagnosed APL, and both mutations were associated with higher WBC count at presentation. FLT3/ITD is more frequent than ALM mutation, and predicts a poorer prognosis because of the lower CR rates, while, FLT3/ALM mutation did not show the same unfavorable prognostic effect. In our study, ITD-AR were not found significantly difference between CR and no remission patients (P>0.05)

An Optimized Risk Stratification Model in Acute Promyelocytic Leukemia Identifies Patients with an Exceptionally Good Prognosis Regarding the Incidence of Relapse

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 72-72
Author(s):  
Anna Hecht ◽  
Daniel Nowak ◽  
Verena Nowak ◽  
Benjamin Hanfstein ◽  
Thomas Büchner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Factors ◽  
Multivariate Analysis ◽  
Risk Stratification ◽  
Acute Promyelocytic Leukemia ◽  
Risk Score ◽  
Risk Groups ◽  
Promyelocytic Leukemia ◽  
Expression Levels ◽  
Therapeutic Decisions

Abstract Introduction: Risk stratification in acute promyelocytic leukemia (APL) is based on the easily accessible Sanz-Score, which combines leukocyte and platelet counts at initial diagnosis. This score showed significant differences in relapse-free survival (RFS) of APL patients in various studies and is currently used to determine whether a patient can be treated with ATRA and ATO alone or needs additional chemotherapy. However, to make therapeutic decisions based on a risk stratification system derived from the endpoint RFS bears the drawback that relapses are rare in APL and most events are deaths in complete remission (CR), which can be therapy related (e.g. toxicity). The cumulative incidence of relapse (CIR) therefore seems to be a better parameter for decision making with regard to therapy intensity. In this study, we optimized a risk score combining data on gene expression of BAALC (brain and acute leukemia, cytoplasmic), ERG (ets’ related gene) and WT1 (Wilms’ tumor 1) to retrospectively predict the CIR of APL patients. Methods: Data on BAALC, ERG and WT1 expression levels of 79 patients with newly diagnosed APL were obtained from bone marrow mononuclear cells using quantitative real-time RT-PCR in preceding studies. The following gene expression levels were identified as negative risk factors: BAALC expression ≥25th percentile (BAALChigh), ERG expression >75th percentile (ERGhigh) and WT1 expression ≤25th percentile or ≥75th percentile (WT1low or high). As ERGhigh was the only independent predictor for relapse in multivariate analysis with a hazard ratio (HR) of 11.6, its predictive weight was regarded superior, respectively . Cut-off analyses were performed to determine the optimal ERG expression level cut-off for risk of relapse. Accordingly, the new cut-off for high ERG expression was set at ≥62nd percentile (optimized ERGhigh: optERGhigh; Sensitivity: 1.0, Specificity: 0.71). A combined risk score was developed as follows: For the presence of one of the mentioned risk factors, one scoring point was assigned to a respective patient, i.e. a maximum of 3 points (one point for BAALChigh, optERGhigh and WT1low or high, respectively) and a minimum of 0 points (i.e. presenting with none of the aforementioned risk factors) could be allocated to one patient. Accordingly, patients were divided into two risk groups: 34 patients scored 0-1 points and 45 patients scored 2-3 points. CIR, overall survival (OS) and RFS were calculated using the Kaplan-Meier method and a log-rank test was used to compare differences between the two risk groups (p<0.05). Results: Patients with 2-3 points had a CIR of 18% at 10 years of follow-up whereas none of the patients with 0-1 points suffered a relapse (CIR: 0%; p=0.02; Fig. 1). All relapses occurred between 8.4 months and 3.5 years after first CR. Moreover, OS and RFS also differed significantly between the two risk groups: OS was 53% for patients with 2-3 points vs. 85% for patients with 0-1 points (p=0.004); RFS was 49% vs. 93%, respectively (p<0.0001). In multivariate analysis the optimized combined risk score was the strongest independent risk factor for every endpoint. Conclusion: The combination of expression levels of BAALC, ERG and WT1 into a risk score identified a group of patients at high risk for relapse which could benefit from close monitoring resulting possibly in an early intervention when molecular relapse is detected. On the other hand, it identified a low risk group with very good outcome and no APL-related events after patients had achieved first CR. A molecular risk score focusing on relapse risk might be a promising approach to guide therapeutic decisions in the future. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Risk Factor Analysis for Infection after Medial Open Wedge High Tibial Osteotomy

2021 ◽  
Vol 10 (8) ◽  
pp. 1727
Author(s):  
Ta-Wei Liu ◽  
Chih-Hao Chiu ◽  
Alvin Chao-Yu Chen ◽  
Shih-Sheng Chang ◽  
Yi-Sheng Chan
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Multivariate Analysis ◽  
High Tibial Osteotomy ◽  
Univariate Analysis ◽  
Arthroscopic Surgery ◽  
Underlying Disease ◽  
Tibial Osteotomy ◽  
Open Wedge ◽  
Wedge High Tibial Osteotomy

Background: Medial open wedge high tibial osteotomy (MOWHTO) is a well-established treatment for osteoarthritis of the medial tibiofemoral compartment. Surgical site infection (SSI) after MOWHTO is a devastating complication that may require further surgery. In this study, we aimed to identify the risk factors for infection after MOWHTO over 1 to 4 years of follow-up. Methods: Fifty-nine patients who underwent MOWHTO combined with knee arthroscopic surgery were included in this prospective study. Artificial bone grafts were used in all cases. Possible risk factors, including sex, age, body mass index (BMI), underlying disease, hospitalization length, correction angle, and surgery time, were recorded. Both univariate and multivariate analysis were used. Results: A total of 59 patients who underwent 61 operations were included. Eleven patients (18.0%) were reported to have SSI. Univariate analysis showed that smoking and diabetes mellitus were positively associated with SSI. Multivariate analysis showed that smoking and age were positively associated with SSI. Three patients (4.9%) were reported to suffer from deep SSI, requiring surgical debridement, all of whom were male smokers. Conclusion: Smoking, diabetes mellitus, and old age were identified to be possible risk factors of SSI after MOWHTO. These findings are common risk factors of SSI after orthopedic surgery according to the literature. Patient selection should be performed cautiously, and postoperative prognosis for MOWHTO should be carefully explained to patients who smoke.

scholarly journals Prediction of Outcome for Transabdominal Cerclage in Women with Cervical Insufficiency

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Ji Eun Song ◽  
Keun Young Lee ◽  
Ga Hyun Son
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Cohort Study ◽  
Pregnancy Outcomes ◽  
Retrospective Cohort ◽  
Multivariate Analyses ◽  
Univariate Analysis ◽  
Cervical Length ◽  
Cervical Insufficiency ◽  
Prediction Of Outcome

We investigated pregnancy outcome following transabdominal cerclage (TAC) in women with cervical insufficiency (CI) and explored parameters for predicting pregnancy outcomes following TAC. In this retrospective cohort study, we included 161 women with TAC. We considered demographic, obstetric, and gynecologic histories, pre- and postoperative cervical length (CL), and CL at 20–24 weeks as parameters for predicting outcomes following TAC. Univariate and multivariate analyses were used to identify risk factors for predicting delivery before 34 weeks after TAC. 182 pregnancies occurred after TAC, and 290 pregnancies prior to TAC were identified. The rate of delivery <34 weeks significantly decreased following TAC (5% versus 82%,P<0.001). Univariate analysis demonstrated that a short CL (<25 mm) at 20–24 weeks and adenomyosis were associated with delivery at <34 weeks’ gestation following TAC (P=0.015andP=0.005, resp.). However, multivariate analysis demonstrated that only a short CL (<25 mm) at 20–24 weeks was a significant predictor (P=0.005). TAC is an efficacious procedure that prolongs pregnancy in women with CI. A short CL at 20–24 weeks may predict the delivery at <34 weeks’ gestation following TAC.

scholarly journals The Presurgical Controlling Nutritional Status (CONUT) Score is Independently Associated with Severe Peristomal Skin Disorders: A Single-center Retrospective Cohort Study

2021 ◽  
Author(s):  
Takuya Shiraishi ◽  
Hiroomi Ogawa ◽  
Chika Katayama ◽  
Katsuya Osone ◽  
Takuhisa Okada ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Nutritional Status ◽  
Laparoscopic Approach ◽  
Skin Disorders ◽  
Nutritional Interventions ◽  
Stoma Creation ◽  
Peristomal Skin ◽  
The Impact ◽  
Conut Score

Abstract Purpose: While nutritional interventions may potentially lower the risk of peristomal skin disorders (PSDs) and their exacerbation, no prior studies have evaluated the relationship between PSDs and nutritional status using the Controlling Nutritional Status (CONUT) score. Therefore, the purpose of this study was to assess the impact of preoperative nutritional status on stoma development, and determine risk factors for postoperative PSDs and their increased severity. Methods: A retrospective analysis was performed in 116 consecutive patients with rectal cancer who underwent radical surgery with stoma creation, including ileostomy and colostomy. Results: PSDs were diagnosed in 32 patients (27.6%); 10 (8.7%) cases were defined as severe based on the ABCD-stoma score. A multivariate analysis indicated that the laparoscopic approach (odds ratio [OR], 3.221; 95% confidence interval [CI], 1.001–10.362; P = 0.050) and ileostomy (OR, 3.394; 95% CI, 1.349–8.535; P = 0.009) were both independent risk factors for PSD. In a separate multivariate analysis for severe PSD, the only independent risk factor was the CONUT score (OR, 11.298; 95% CI, 1.382–92.373; P = 0.024). Conclusion: Severe PSDs are associated with preoperative nutritional disorders, as determined via the CONUT score. Furthermore, PSDs may potentially increase in severity, regardless of stoma type.

scholarly journals Risk Factors for Progression in Vestibular Schwannomas After Incomplete Resection: A Single Center Retrospective Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiuhong Li ◽  
Xueyun Deng ◽  
Daibo Ke ◽  
Jian Cheng ◽  
Si Zhang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Tumor Size ◽  
Tumor Volume ◽  
Univariate Analysis ◽  
Residual Tumor ◽  
Vestibular Schwannomas ◽  
Incomplete Resection ◽  
Cystic Component

Background and Purpose: The risk factors for progression in vestibular schwannomas (VSs) after incomplete resection (IR) remain to be elucidated. The purpose of this study was to investigate the risk factors for progression in remnant VSs after surgery.Methods: From January 2009 to January 2018, 140 consecutive patients who underwent IR of VSs via suboccipital retrosigmoid approach in our institution were retrospectively analyzed. During follow-up, if progression was detected, the patient was classified into Progressive Group (PG); if the residual tumor was stable or shrank, the patient was classified into Stable Group (SG). Univariate analysis and multivariate analysis were used to evaluate the risk factors for progression after IR of VSs.Results: After a mean follow-up of 80.4 months (range, 24–134 months), 35 (25.0%) patients (PG) had a progression, and no progression was detected in 105 (75.0%) patients (SG). The average tumor size was 36.5 ± 8.9 mm in PG and 31.0 ± 9.8 mm in SG, respectively. The residual tumor volume was 304.6 ± 443.3 mm3 in PG and 75.9 ± 60.0 mm3 in SG, respectively. Univariate analysis showed that preoperative tumor size, residual tumor volume, and irregular internal auditory canal (IAC) expansion were significantly different between the two groups, whereas gender, age, cystic component, or Ki-67 labeling index (LI) did not differ significantly between the two groups. Multivariate analysis showed residual tumor volume was the independent risk factor for progression.Conclusions: VSs that underwent IR with larger preoperative size, greater residual tumor volume, or irregular IAC expansion may have a higher progression rate. Strict follow-up with shorter interval in these patients to detect early progression is necessary.

scholarly journals Predictive factors of posttreatment fracture by definitive radiotherapy for uterine cervical cancer

2020 ◽  
Author(s):  
Kazuki Ishikawa ◽  
Tsuneo Yamashiro ◽  
Takuro Ariga ◽  
Takafumi Toita ◽  
Wataru Kudaka ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Risk Factors ◽  
Cervical Cancer ◽  
Multivariate Analysis ◽  
Radiation Therapy ◽  
Cancer Patients ◽  
Clinical Characteristics ◽  
Univariate Analysis ◽  
Uterine Cervical Cancer

Abstract Purpose Fractures are known to shorten life expectancy and worsen the quality of life. The risk of fractures after radiation therapy in cervical cancer patients is known to be multifactorial. In this study, we examined risk factors for fractures in cervical cancer patients, especially by evaluating bone densities and DVH parameters for fractured bones. Materials and Methods For 42 patients, clinical characteristics, pretreatment CT bone densities, and radiation dose were compared between patients with and without fractures. Results Posttreatment fractures occurred in 25 bones among ten patients. Pretreatment CT bone densities were significantly lower in patients with fractures (P < 0.05–0.01 across sites, except for the ilium and the ischium). Although DVH parameters were also significantly associated with fractures in univariate analysis, only CT densities were significantly associated with fractures in multivariate analysis. Conclusion Pretreatment CT densities of spinal and pelvic bones, which may reflect osteoporosis, have a significant impact on the risk for posttreatment fractures.

scholarly journals The Impact of Flt3 Gene Mutations in Acute Promyelocytic Leukemia: A Meta-Analysis

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1311 ◽  
Author(s):  
Gledson L. Picharski ◽  
Diancarlos P. Andrade ◽  
Ana Luiza M. R. Fabro ◽  
Luana Lenzi ◽  
Fernanda S. Tonin ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Meta Analysis ◽  
Gene Mutations ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Biomedical Literature ◽  
Mixed Effect ◽  
Mixed Effect Models ◽  
Wbc Count ◽  
The Impact

The association of FLT3 mutations with white blood cell (WBC) counts at diagnosis and early death was studied in patients with acute promyelocytic leukemia (APL). Publications indexed in databases of biomedical literature were analyzed. Potential publication bias was evaluated by analyzing the standard error in funnel plots using the estimated relative risk (RR). Mixed-effect models were used to obtain the consolidated RR. All analyses were conducted using the R statistical software package. We used 24 publications in the final meta-analysis. Of 1005 males and 1376 females included in these 24 publications, 645 had FLT3-ITD (internal tandem duplication) mutations. Information on FLT3-D835 mutations was available in 10 publications for 175 patients. Concurrent occurrence of the two mutations was rare. WBC count at diagnosis was ≥10 × 109/L in 351 patients. For patients with the FLT3-ITD mutation, RR was 0.59 for overall survival (OS) and 1.62 for death during induction. For those with FLT3-D835 mutations, the RR was 0.50 for OS and 1.77 for death during induction. RR for WBC count ≥10 × 109/L was 3.29 and 1.48 for patients with FLT3-ITD and FLT3-D835, respectively. APL patients with FLT3-ITD or FLT3-D835 are more likely to present with elevated WBC counts and poorer prognosis than those without these mutations.

scholarly journals Loneliness amongst Low-Socioeconomic Status Elderly Singaporeans and its Association with Perceptions of the Neighbourhood Environment

2019 ◽  
Vol 16 (6) ◽  
pp. 967 ◽  
Author(s):  
Liang Wee ◽  
Tammy Tsang ◽  
Huso Yi ◽  
Sue Toh ◽  
Geok Lee ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Public Housing ◽  
Low Socioeconomic Status ◽  
Physical Environment ◽  
Home Ownership ◽  
Univariate Analysis ◽  
Rental Housing ◽  
Neighbourhood Environment ◽  
Chi Square ◽  
The Impact

In Singapore, a densely urbanised Asian city state, more than 80% of the population stays in public housing estates and the majority (90%) own their own homes. For the needy who cannot afford home ownership, public rental flats are available. We were interested in exploring social-environmental factors that are associated with loneliness among elderly residents of public rental housing in Singapore. We surveyed residents aged ≥60 in two Singapore public housing precincts in 2016. Loneliness was measured using a three-item scale. Sociodemographic information was obtained via standardised questionnaires. We used chi-square to identify associations between loneliness and sociodemographic characteristics, as well as neighbourhood perceptions (safety, convenience and the physical environment), on univariate analysis; and logistic regression for multivariate analysis. The response rate was 62.1% (528/800). On multivariate analysis, staying in a rental flat block was independently associated with loneliness (adjusted odds ratio, aOR = 2.10, 95% confidence interval (CI) = 1.32–3.36), as was staying in a poorer physical environment (aOR = 1.92, 95% CI = 1.15–3.22). Although needy Singapore residents share the same built environment as more well-to-do neighbours, differences in the impact of loneliness do exist.

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