scholarly journals The predictive value of absolute lymphocyte counts on tumor progression and pseudoprogression in patients with glioblastoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Xi ◽  
Bilal Hassan ◽  
Ruth G. N. Katumba ◽  
Karam Khaddour ◽  
Akshay Govindan ◽  
...  

Abstract Background Differentiating true glioblastoma multiforme (GBM) from pseudoprogression (PsP) remains a challenge with current standard magnetic resonance imaging (MRI). The objective of this study was to explore whether patients’ absolute lymphocyte count (ALC) levels can be utilized to predict true tumor progression and PsP. Methods Patients were considered eligible for the study if they had 1) GBM diagnosis, 2) a series of blood cell counts and clinical follow-ups, and 3) tumor progression documented by both MRI and pathology. Data analysis results include descriptive statistics, median (IQR) for continuous variables and count (%) for categorical variables, p values from Wilcoxon rank sum test or Fisher’s exact test for comparison, respectively, and Kaplan-Meier analysis for overall survival (OS). OS was defined as the time from patients’ second surgery to their time of death or last follow up if patients were still alive. Results 78 patients were included in this study. The median age was 56 years. Median ALC dropped 34.5% from baseline 1400 cells/mm3 to 917 cells/mm3 after completion of radiation therapy (RT) and temozolomide (TMZ). All study patients had undergone surgical biopsy upon MRI-documented progression. 37 had true tumor progression (47.44%) and 41 had pseudoprogression (52.56%). ALC before RT/TMZ, post RT/TMZ and at the time of MRI-documented progression did not show significant difference between patients with true progression and PsP. Although not statistically significant, this study found that patients with true progression had worse OS compared to those with PsP (Hazard Ratio [HR] 1.44, 95% CI 0.86–2.43, P = 0.178). This study also found that patients with high ALC (dichotomized by median) post-radiation had longer OS. Conclusion Our results indicate that ALC level in GBM patients before or after treatment does not have predictive value for true disease progression or pseudoprogression. Patients with true progression had worse OS compared to those who had pseudoprogression. A larger sample size that includes CD4 cell counts may be needed to evaluate the PsP predictive value of peripheral blood biomarkers.

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S162-S163
Author(s):  
Jennifer B Radics-Johnson ◽  
Daniel W Chacon ◽  
Li Zhang

Abstract Introduction Burn camps provide a unique environment and activities for children that have experienced a burn-injury. Positive outcomes from attending burn camp include increased self-esteem, decreased feelings of isolation and a greater sense of self-confidence. In a 3-year retrospective review of camper evaluations from one of the largest and longest running week-long burn camps in the nation for ages 5–17, we aimed to assess if a child’s gender, age, TBSA or ethnicity affected the impact that burn camp had on a child. Methods A 3-year retrospective review of a Burn Camp’s camper evaluation forms was conducted for campers that attended burn camp between 2017–2019. Camp rosters were reviewed to determine the camper gender, age, TBSA and ethnicity. Camper self-evaluation forms completed at the end of each camp session were reviewed to record camper responses to questions regarding their opinions on the impact camp had on them as well as how camp will impact their lives once they return home. Categorical variables were summarized as frequency and percentage, and continuous variables were described as median and range. To check the relationship between two categorical variables, Chi-square test was used. To compare the continuous variable among groups, Kruskal-Wallis ANOVA was used. Statistical significance was declared based on a p value< 0.5. Results Within 2017–2019, there were 413 camper records. Participants’ demographic characteristics are summarized in Table 1. There were 208 males (50.3%) and 205 females (49.6%). The median age of campers were 11.86, 12.44 and 12.45 for 2017–2019, with the range from 5.16 years to 17.96 years. The median TBSA were 20, 20 and 18 for 2017–2019, with the range from 0.08 to 90. Collectively there were 47.7% Hispanic (n= 197); 24.2% Whites (n=100); 13.1% Black (n= 54); 4.6% Asian (n=19) and 7.7% Other (n=32). There were 395 camper self-evaluation forms submitted. Results of three questions there we were interested in are summarized collectively in Table 2. 57% of campers responded, “Yes, Definitely” to the question “After going to this event, will you feel more comfortable being around your classmates or friends?” 54% responded, “ Yes, Definitely” to the question “Do you feel more confidents in sharing your burn story with others when returning home?” and 51% responded “Yes, Definitely” to “Did you learn anything that will help you when you return home?” Conclusions In analyzing the camper responses, there was no statistically significant difference in responses comparing gender, age, TBSA or ethnicity.


2020 ◽  
Vol 10 (4) ◽  
pp. 296-300
Author(s):  
Ameet Jesrani ◽  
Pari Gul ◽  
Nida Khan ◽  
Seema Nayab ◽  
Fahmida Naheed

Objective: To assess different pathological breast lesions in ultra sound in a subgroup of population. Study design and setting: It was a cross sectional study conducted at Bolan Medical Complex Hospital Quetta, Pakistan from June 2018 to January 2019. Methodology: Total 103 patients with breast swelling, pain and discharge were targeted. Gray scale and Doppler Ultrasound of breast followed by FNAC/biopsy of breast lesion was performed. Data presented as mean ± standard deviation for continuous variables and frequency with percentages for categorical variables. Results: Out of 48 clinically palpable lumps US detected all of 48 lumps and additionally 12 clinically non palpable masses were detected on US examination. Thus, overall sensitivity of ultrasound in detecting breast lumps was 100%. Fibroadenoma of the breast was diagnosed accurately in 80.3% of women. Ultrasound reliably differentiated cystic from solid breast masses (100%). The sensitivity of ultrasound for detecting breast carcinoma was 63.4% with a positive predictive value of 87.5%, a negative predictive value of 99.5% and accuracy of 58.33%. US findings most suggestive of benign lesions were oval or round shape in 88.3%, well defined margin in 84%, absent lobulation in 86.04% and wider than taller ratio in 90.69% of the cases.US findings of most predictive for malignancy were of irregular shape in 81.8%, ill-defined margin in 90.9% and length to height ratio in 63.6% of cases. Conclusion: Ultrasound is simple, cheap, safe and relatively accessible imaging modality for evaluation of breast pathologies. Due to its high sensitivity in diagnosing benign breast lesions particularly cystic lesions and fibroadenoma unnecessary interventions can be avoided


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Thomas M Hemmen ◽  
Rema Raman ◽  
Karin Ernstrom ◽  
Debra Paulson ◽  
Valerie Lake ◽  
...  

Background: Dysphagia is common after stroke and is associated with an increased risk for pulmonary complications and mortality. Current standards mandate screening for dysphagia before oral intake in all acute stroke patients. We aimed to show if this early screening affects long-term outcomes after stroke. Methods: We included all UCSD Medical Center discharges with diagnosis AIS, ICH and SAH between July 1 2008 and June 30 2011; and evaluated baseline demographics, admission diagnosis (AIS, ICH, SAH), admission source (ED or transfer) length of hospital stay (LOS), ICU-LOS, aspiration pneumonia, in-hospital, 30-day and 6-month mortality by public death records for all patients. Patients were grouped as: 1) no dysphagia screening performed, 2) Nil per os (NPO) until discharge, 3) dysphagia screening performed. Adjustments for stroke severity and CMI were not possible. Statistical comparisons were done with the Kruskal-Wallis test (continuous variables) or Fisher-Freeman-Halton test (categorical variables). For pairwise comparisons we used the Wilcoxon tests (continuous variables) or Fisher’s Exact test (categorical variables), with Holm’s adjusted p-values. Results: A total of 476 patients were included, Group 1: 47, Group 2: 119, Group 3: 310. There was no significant difference in age, gender, race/ethnicity, and diagnosis of HTN, DM, afib, prior stroke and admission source. More patients with SAH and ICH were in Group 2. Overall, LOS and ICU LOS, aspiration pneumonia, in-hospital, 30-day and 6-month mortality were found to be different among groups (p<0.0001). Pair-wise comparisons showed that all outcomes were significantly higher in Group 2, but similar between Groups 1 and 3 (NS). Conclusion: We found no difference in outcomes between patients who received dysphagia screening versus not (Group 1 vs 3). Excluding patients who were left NPO and are more likely to suffer from ICH, SAH with increased morbidity and mortality, it remains uncertain if a targeted early dysphagia screening can reduce morbidity and mortality after stroke. Further studies are needed to find the appropriate population that most benefits from dysphagia screening.


2019 ◽  
Vol 143 (3) ◽  
pp. 272-278
Author(s):  
Tareq Abu Assab ◽  
David Raveh-Brawer ◽  
Julia Abramowitz ◽  
Mira Naamad ◽  
Chezi Ganzel

Introduction: The objective of this prospective study was to examine whether thromboelastogram (TEG) can predict the presence of venous thromboembolism (VTE) in patients who arrive at the emergency room with signs/symptoms that raise the suspicion of acute VTE. Methods: Every patient was tested for D-dimer and all TEG parameters, including: reaction time, clot time formation, alpha-angle, maximal amplitude, clot viscoelasticity, coagulation index, and clot lysis at 30 min. For categorical variables, χ2 or the Fisher exact test were used, and for continuous variables the t test or other non-parametric tests were used. Results: During 2016, a total of 109 patients were enrolled with a median age of 55.7 (21–89) years. Eighteen patients were diagnosed with VTE. Analyzing the different TEG parameters, both as continuous and categorical variables, did not reveal a statistically significant difference between VTE-positive and VTE-negative patients. Combining different TEG parameters or dividing the cohort according to gender, clinical suspicion of VTE (Well’s criteria), or different levels of D-dimer did not change the results of the analysis. Conclusion: The current study could not demonstrate a significant value of any TEG parameter as a predictor of VTE among patients who came to the emergency room with signs/symptoms that raise the suspicion of VTE.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O Maniuc ◽  
T Salinger ◽  
F Anders ◽  
J Muentze ◽  
D Liu ◽  
...  

Abstract Background and purpose From the various mechanical cardiac assist devices and indications available, use of the percutaneous intraventricular Impella CP pump is usually restricted to acute ischemic shock or prophylactic indications in high-risk interventions. In the present study, we investigated clinical usefulness of the Impella CP device in patients with non-ischemic cardiogenic shock as compared to acute ischemia. Methods In this retrospective single-center analysis, patients who received an Impella CP between 2013 and 2017 due to non-ischemic cardiogenic shock were age-matched 2:1 with patients receiving the device due to ischemic cardiogenic shock. Inclusion criteria were therapy refractory hemodynamic instability with severe left ventricular systolic dysfunction and serum lactate >2.0 mmol/l at implantation. Basic clinical data, indications for mechanical ventricular support, and outcome were obtained in all patients with non-ischemic as well as ischemic shock and compared between both groups. Continuous variables are expressed as mean ± standard deviation or median (quartiles). Categorical variables are presented as count and percent. Results 25 patients had cardiogenic shock due to non-ischemic reasons, and were compared to 50 patients with cardiogenic shock due to acute myocardial infarction. Resuscitation rates before implantation of Impella CP were high (32 vs 42%; P=0.402). At implantation, patients with non-ischemic cardiogenic shock had lower levels of HsTNT (110.65 [57.87–322.1] vs 1610 [450.8–3861.5] pg/ml; P=0.001) and LDH (377 [279–608] vs 616 [371.3–1109] U/I; P=0.007), while age (59±16 vs 61.7±11; P=0.401), GFR (43.5 [33.2–59.7] vs 48 [35.75–69] ml/min; P=0.290), CRP (5.17 [3.27–10.26] vs 10.97 [3.23–17.2] mg/dl; P=0.195), catecholamine-index (30.6 [10.6–116.9] vs 47.6 [11.7–90] μg/kg/min; P=0.663), and serum lactate (2.6 [2.2–5.8] vs 2.9 [1.3–6.6] mg/dl; P=0.424) were comparable between both groups. There was a trend for longer duration of Impella support in the non-ischemic groups (5 [2–7.5] vs 3 [2–5.25] days, P=0.211). Rates of hemodialysis (52 vs 47%; P=0.680) and transition to ECMO (13.6 vs 22.2%; P=0.521) were comparable. No significant difference was found regarding both 30-days survival (48 vs 30%; P=0.126, Figure 1) as well in-hospital mortality (66.7 vs 74%; P=0.512) although there was a trend for better survival in the non-ischemic group. 30-days survival Conclusions The current results position short-time use of the Impella CP as an alternative in the treatment of patients with cardiogenic shock due to underlying non-ischemic cardiomyopathy and/or complicating additional factors. However, additional studies are needed to test whether these findings can be confirmed in larger patient populations and which subgroups might benefit most from Impella therapy.


2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0017
Author(s):  
Jon-Michael Caldwell ◽  
Harry Lightsey ◽  
Hasani Swindell ◽  
Justin Greisberg ◽  
J. Turner Vosseller

Category: Sports Introduction/Purpose: Achilles tendon ruptures are increasingly common injuries. There are several known risk factors for Achilles tendon rupture, although little is reported on the seasonal variation of the incidence of these injuries. Of the few studies in the literature touching on this question, the results have been varied. We sought to determine if there is any seasonal pattern of Achilles tendon ruptures. Knowledge of such a seasonal pattern could be advantageous for patient education, risk assessment, and ultimately prevention of these injuries. Methods: We queried billing records for CPT codes 27650, 27652, and 27654 as well as ICD diagnosis codes 727.67, 845.09, and S86.01x pertaining to Achilles tendon injury, repair, and reconstruction. Charts were screened and included if the patient suffered an acute Achilles tendon rupture on a known date. Charts were excluded if the patient had a chronic Achilles tear or underwent reconstruction or debridement for tendonitis, Haglunds deformity, tendon laceration, or any other indication aside from acute rupture. Data was analyzed using a chi-squared test for categorical variables, binomial tests for dichotomous variables and Mann-Whitney-U or Welch t-test for continuous variables. Significance was set at p < 0.05. Results: Our search yielded 499 cases with 245 meeting inclusion criteria. Sixty-six percent (66%) of injuries were identified as sports-related while 34% were non-sports related. When stratified by month, significant peaks occurred in April and July (p = .036, .011 respectively) with significantly fewer injuries occurring in October through December (p = 0.049). The highest rate of injury was seen in Spring (p = .015) and the lowest was seen in Fall (p < .001). There was no significant difference between seasons when only the non-sports related injuries were considered. Basketball was the most common sport involved (n=78) accounting for 51% of injuries (p < .001), followed by soccer and tennis. There was no significant variation between seasons in any particular sport. Conclusion: There was significant seasonal variation in the incidence of Achilles tendon ruptures. Both sports and non-sports-related injuries followed a similar pattern, with most injuries occurring during the Spring and Summer and fewer during Fall and Winter. This increase corresponds to the increase in activity in the recreational athlete population in the region which is often preceded by a time of relative inactivity. Our study confirms that the deconditioned athlete is at particularly elevated risk for Achilles tendon rupture during the Spring season when abrupt increases in sporting activity are common. Targeted education and prevention efforts could help mitigate this risk.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 461-461 ◽  
Author(s):  
Fabiola Traina ◽  
Anna M Jankowska ◽  
Valeria Visconte ◽  
Yuka Sugimoto ◽  
Hadrian Szpurka ◽  
...  

Abstract Abstract 461 Aberrant DNA methylation is a hallmark of myelodysplastic syndromes (MDS), MDS/myeloproliferative neoplasms (MDS/MPN) and secondary acute myeloid leukemia (sAML). It provides a rationale for treating these malignancies with hypomethylating agents like 5-azacitidine (AZA) and decitabine (DAC). However, treatment outcomes remain limited and heavily weighed on morphologic/cytogenetic results. The discovery of novel mutations has provided important insight into the pathogenesis of MDS and related disorders. Genes implicated in epigenetic regulation, including DNMT3A, TET2, IDH1/IDH2, EZH2, ASXL1 and UTX have been found mutated in MDS, while others have also been implicated in MDS pathogenesis. There is limited data on the predictive value of these genetic defects for treatment response and disease outcome. We hypothesized that these defects are important biomarkers predictive of response to hypomethylating agents. We studied 88 patients with MDS (RCUD=2, RARS=6, RCMD=11, MDS-U=3, RAEB-1/2=29, CMML1/2=16, MDS/MPN-U=5, RARS-T=5, AML from MDS=11) who received hypomethylating agents (AZA=53, DAC=24, both=11). The median number of cycles was 7 [range 1–35], median age was 69 years (range 42–82) and median follow-up was 18 months (range 0–76). Responses were scored according to IWG criteria. DNMT3A, TET2, IDH1/2, EZH2, ASXL1, UTX, KRAS, NRAS, CBL, RUNX1, TP53 and SF3B1 were sequenced using standard techniques. Categorical variables were analyzed using Chi-square statistics. Overall survival (OS) was analyzed using Kaplan-Meier; p-values ≤ 0.05 were considered statistically significant. Mutated patients were older than wild type (WT) cases (72 vs. 68 years, p=.01) but were well matched for marrow blast %, cytogenetic risk group and cycles of hypomethylating agents received. We found mutations in 40/88 (45%) patients. Mutations were most frequent in SF3B1 (6/11; 55%), ASXL1 (13/50; 26%), TET2 (18/88; 20%), KRAS (3/34; 9%), and DNMT3A (7/88; 8%). Less common were mutations in EZH2 (2/43; 5%), TP53 (1/23; 4%), IDH1 (4/88; 5%), IDH2 (3/88; 3%), and UTX (1/36;3%). No mutations were found in CBL, NRAS or RUNX1. Based on single mutations, overall response rate (ORR) was higher in mutated vs WT patients for DNMT3A (6/7 [86%] vs 33/81 [41%]; p=.02), ASXL1 (11/13 [85%] vs 14/37 [38%]; p=.003), and TET2 (12/18 [67%] vs. 27/70 [39%]; p=.03). All heterozygous DNMT3A mutants responded to hypomethylating agents. Differences remained significant when stratified to AZA treatment alone for DNMT3A (6/7 [86%] vs 21/56 [38%]; p=.01) and ASXL1 (9/11 [82%] vs 12/29 [41%]; p=.02) but not TET2 (6/10 [60%] vs 21/53 [40%]; p=0.22). The predictive value of combined mutations were analyzed for DNMT3A, TET2 and/or IDH1/2, showing better response to hypomethylating therapy in patients who had a mutation; ORR (mutated: 18/28 (64%) vs WT: 21/60 (35%); p=.01). This difference remained significant in patients receiving only AZA (n=53); ORR was 11/18 (61%) in mutant and 11/35 (31%) in WT patients (p=.03). No differences in ORR were noted for KRAS, EZH2 and IDH1/2 mutant and WT patients. No SF3B1 mutants responded to treatment while both patients with UTX and TP53 mutations responded. The frequency of AML evolution was also analyzed and showed no difference between mutant and WT cases for TET2 (7/18 [39%] vs 22/70 [31%];p=.52), ASXL1 (4/10 [40%] vs 11/35 [31%]; p=.61), and DNMT3A (3/7 [43%] vs 26/81 [32%];p=.56). No differences in OS and progression free survival (PFS) were noted between responders and non-responders to hypomethylating therapy (28 vs 17 mos, p=.25; 16 vs 8 mos, p=.54). Comparison of survival outcomes for mutant and WT patients showed no significant difference for DNMT3A (OS: 30 vs 21 mos, p=0.43; PFS: 20 vs 11, p=.53), ASXL1 (OS: 28 vs 22, p=.68; PFS: 16 vs 10, p=.88), and TET2 (OS: 30 vs 20 mos, p=.30). PFS was better in TET2 mutants compared to WT (19 vs 9, p=.03). No survival differences were noted between mutant and WT cases who responded to hypomethylating agents for DNMT3A (OS: 25 vs 28,p=.84; PFS: 14 vs 16, p=.78), ASXL1 (OS: 10 vs 18, p=.48; PFS: 10 vs 6, p=.76) TET2 (OS: 27 vs 16, p=.79; PFS: 18 vs10, p=.19). In conclusion, DNMT3A, ASXL1 and TET2 mutations were independently associated with a better response to hypomethylating drugs. Moreover, combined mutations in DNMT3A/TET2/IDH1/IDH2 may influence the response to hypomethylating agents, especially AZA supporting its role as a predictive biomarker in MDS treatment. Disclosures: Maciejewski: Celgene and Eisai, NIH, AA&MDS Foundation: Research Funding. Tiu:MDS Foundation Young Investigator Award: Research Funding.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 267-267
Author(s):  
Ashwin Reddy Sama ◽  
Aakanksha Asija ◽  
James Casey ◽  
Jocelyn Andrel-Sendecki ◽  
Nancy Lewis ◽  
...  

267 Background: PNETs are rare tumors with multiple classification systems. We compared the WHO 2004 and 2010 classification systems for predicting mortality and metastasis. Variables associated with mortality were explored. Methods: Descriptive statistics were calculated for characteristics of 50 PNET patients. The relationship between the WHO 2004 and 2010 system was investigated using an exact Chi squared test. WHO grade categorization was explored by vital status, by the exact method, in order to determine if there was a difference in survivorship and metastasis by grading system. Associations between death and categorical variables were tested using exact methods and between death and continuous variables by the Wilcoxon test. Survival was explored using Cox Proportional Hazards regression (COX). Results: 62 % of patients were female and the median age was 60 years. Both grading systems were strongly associated with predicting mortality (table 1); all cases of mortality were in the higher grades. The 2010 grades do slightly better in predicting metastasis as metastases occur only in high grades (G2 and G3). Patients with lymphovascular or perineural invasion had significantly higher mortality. Mitotic Index was significantly different with a median of 0 in live patients versus 15 in deceased, p <0.001. This was similarly borne out in the survival analysis using COX, where for every one unit increase in Mitotic Index, there was about a one third increase in the hazard of death (p = 0.001). There was no significant difference in survival by tumor size, comorbidities, or margins. Conclusions: The WHO 2010 grading system is strongly associated with predicting mortality and performs better in predicting metastasis than the 2004 grading system. [Table: see text]


Objective: Our research article aimed to determine if six-month mortality amongst hepatitis B and C patients undergoing cardiac surgery varied according to gender, post-operatively. Secondarily, we highlighted the significant differences among the two genders in their pre-operative, operative, and post-operative characteristics and deduced significant predictors of mortality. Methods: We obtained approval from the International Review Board of the Dow University of Health Sciences, and conducted a retrospective study targeting hepatitis B and C patients who had undergone cardiac surgery between January 2013 to October 2018 at the Ruth Pfau Civil Hospital, Karachi, Pakistan. The data was analysed using the Statistical Package for Social Sciences (Version 20.0). The population was divided into two groups, based on gender. Chi-squared test was used to compare categorical variables and odd ratios with 95% confidence interval were also computed. Differences in continuous variables were assessed using independent T-test or Mann-Whitney U test. Results: There was no significant difference in six-month mortality between the genders, with a 22.5% mortality in males and 20.0% mortality in females. Post-operatively, males had higher creatinine (p=0.003) levels but females tended to have a longer ward stay (p=0.032). On multivariate logistic regression, duration of intubation (aOR=1.131, 95% CI: 1.002-1.275), cardiopulmonary bypass time (aOR=1.030, 95% CI: 1.002-1.059) and duration of ward stay (aOR=1.100, 95% CI: 1.031-1.175) were found to be significant predictors of mortality. Conclusion: There is no association between six-month mortality and gender among hepatitis B and C patients undergoing cardiac surgery. Additionally, duration of intubation, cardiopulmonary bypass time and duration of ward stay are significant predictors of six-month mortality.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3466-3466
Author(s):  
Steven M. Johnson ◽  
Lori Ramkissoon ◽  
James Haberberger ◽  
Naomi L Ferguson ◽  
Jonathan Galeotti ◽  
...  

Abstract Introduction: ASXL1 mutations are frequently seen across the clinical spectrum of myeloid neoplasia. The most commonly identified ASXL1 mutation represents a single base duplication within an 8-guanine repeat at nucleotide position 1934 (c.1934dupG). Due to technical limitations of sequencing homopolymer regions, the ASXL1 c.1934dupG variant has been identified as potential artifact in some sequencing assays, though modern next generation sequencing assays and bioinformatics pipelines can generally accurately detect this mutation. However, a comprehensive comparison of ASXL1 c.1934dupG mutations versus non-c.1934dupG ASXL1 mutations have not been performed to date. Thus, we sought to explore a large dataset to determine if any biologic differences existed between these two groups. Methods: Comprehensive genomic profiling by FoundationOne ®Heme testing was performed on patient samples with known or suspected myeloid neoplasms (MN). All MN patients ≥18 years old with 1 or more mutation were identified by internal database query. Patients were categorized as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), non-chronic myeloid leukemia myeloproliferative neoplasms (MPN), or MDS/MPN overlap based on mutation and outside clinical and pathology data. Mutations with variant allele fractions (VAF) &gt;1% were included for analysis, except for the ASXL1 c.1934dupG variant, which was only reported if the VAF was ≥15%. Fisher's exact tests were used to evaluate proportional differences between categorical variables, and Mann-Whitney U tests were used for comparisons of continuous variables. Results: Truncating ASXL1 mutations were identified in 1,414 included patients, occurring in 18% of AML and 26% of chronic myeloid neoplasms. Twenty-eight (2%) patients had multiple ASXL1 mutations, and ASXL1 was the sole mutated gene in 52 patients (4%). The most common ASXL1 mutation was c.1934dupG (Figure 1A), and this was the sole or dominant ASXL1 mutation in 520 cases (37%). The remaining 894 patients (63%) had one or more mutations at other sites in the ASXL1 gene (ASXL1other), with p.E635Rfs, p.R693*, and codon 591 mutations being the most common. There were no significant differences in age, sex, or ancestry signatures between ASXL1c.1934dupG and ASXL1other. We noted slightly fewer ASXL1c.1934dupG mutations in patients with MDS (ASXL1c.1934dupG: ASXL1other 0.48:1) compared to AML (0.65:1, p = 0.03) and MPN (0.60:1, p = 0.01) and those in whom ASXL1 was the sole mutation (Figure 1B). However, these trends may have been due to VAF-based reporting thresholds, as ASXL1 VAFs were lower in singly mutated patients and those with an MDS diagnosis classification. Comparison of co-mutated genes with VAFs ≥15% between ASXL1c.1934dupG and ASXL1other revealed no significant difference in median non-ASXL1 mutations (each median 4, IQR 2-5, p = 0.74). When individual genes were assessed, co-mutation rates of STAG2 (p = 0.01) and KMT2A (p = 0.02) were higher in ASXL1c.1934dupG MNs, while SETBP1 (p = 0.01) mutations were more common with ASXL1other. In all MNs, the absolute differences in the frequency of mutations in ASXL1c.1934dupG versus ASXL1other were small. However, some differences emerged within phenotypic subgroups (Figure 1C). For instance, KMT2A rearrangements and STAG2 mutations were strongly associated with ASXL1c.1934dupG in MDS/MPN and MPN, with ASXL1c.1934dupG: ASXL1other ratios of 5:1 (p = 0.03) and 9:1 (p &lt; 0.001), respectively. In contrast, AML patients with TP53 or SETBP1 mutations had a significantly higher mutation rate in ASXL1other (TP53: 11% vs. 3% in ASXL1c.1934dupG, p &lt; 0.01; SETBP1: 14% vs. 7%, p=0.04). We further identified that other specific ASXL1 mutations were more commonly co-mutated in AML with TP53 (ASXL1 p.R693*, p &lt; 0.001) or SETBP1 (ASXL1 p.R404*, p &lt; 0.001). Conclusion: Our results confirm the ASXL1 c.1934dupG variant occurs in a similar patient population to other ASXL1 mutations, and further supports its pathogenicity in myeloid neoplasia. Subset analysis suggests that ASXL1c.1934dupG and ASXL1other may be associated with certain phenotypic and co-mutational tendencies. Thus, ASXL1 mutation site may be an important variable in some patients and should be considered in future mechanistic and clinical studies. Further study is warranted to determine whether clinical outcomes are affected by different ASXL1 mutations. Figure 1 Figure 1. Disclosures Haberberger: Foundation Medicine, Inc.: Current Employment. Ferguson: Foundation Medicine Inc: Current Employment, Other: ownership.


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