Overall Survival In Adult Patients Research Articles

Incidence of bleeding and thromboembolism and impact on overall survival in adult patients with hemophagocytic lymphohistiocytosis: A 20‐year provincial retrospective cohort study

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by uncontrolled immune activation and high risk of death. There is scarce data on the incidence of bleeding and thromboembolism in HLH. ObjectivesTo determine the cumulative incidence of bleeding and thromboembolism and impact on survival in adults with HLH. Patients/MethodsWe conducted a multicenter retrospective cohort study of adults with HLH in Alberta, Canada (1999–2019). The cumulative incidence of bleeding and thromboembolism were calculated, accounting for competing risks. Cox proportional hazards models were used to assess the impact of bleeding and thromboembolism on overall survival (OS). ResultsWe identified 97 adults with HLH (median age 46 years). Venous thromboembolism (VTE) occurred in 11 (11%) patients at a median of 9 days from admission. ISTH major bleeding and clinically relevant non‐major bleeding occurred in 39 (40%) patients, at a median of 16 days after admission. Nadir platelet count (adjusted odds ratio [aOR] 1.8 per log decrease, 95% confidence interval [CI] 1.2–2.8) and mechanical ventilation (aOR 4.9, 95% CI 1.8–14.8) were independent predictors of bleeding on multivariable analysis. Adjusting for competing risks, the 90‐day cumulative incidences of bleeding and thromboembolism were 39% and 13%, respectively. The median OS was 18.8 months. VTE, but not bleeding, was significantly associated with adverse OS (adjusted hazard ratio 2.5, 95% CI 1.1–5.7). ConclusionsIn adults with HLH, VTE appears more common than previously described and is a predictor of mortality, although this may be due to unadjusted confounding. VTE prevention and treatment are challenging due to high bleeding rates.

Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of cytotoxic chemotherapy and other cytotoxic therapies in the management of progressive glioblastoma in adults.

These recommendations apply to adult patients diagnosed with progressive glioblastoma (pGBM). QUESTION (Q1): In adult patients with pGBM does the use of temozolomide (TMZ) with alternative dosing or the use of TMZ in combination with other cytotoxic treatments result in increased overall survival compared to other chemotherapy? Level III: Adult patients with pGBM might derive benefit in treatment with TMZ, especially those who progress after more than 5months of TMZ-treatment free interval. Combination of TMZ with other cytotoxic agents such as nitrosourea, cisplatin, electrohyperthermia, or tamoxifen is not suggested in adult patients with pGBM as a stand-alone therapy. There is insufficient data to make a recommendation about which alternative TMZ dosing provides the best benefits. QUESTION (Q2): In adult patients with pGBM does the use of systemic or in situ nitrosourea result in increased overall survival compared to other chemotherapy? Level III: In the setting of pGBM, fotemustine is suggested in elderly patients with methylated MGMT promoter status. There is insufficient evidence to compare fotemustine to other nitrosoureas. There is insufficient evidence to make a recommendation about the use of in situ nitrosourea in patients with pGBM who underwent the Stupp regimen. QUESTION (Q3): In adult patients with pGBM does the use of platinum compounds and topoisomerase result in increased survival compared to other chemotherapy? Level III: Other chemotherapy including platinum compounds and topoisomerase inhibitors are not suggested to be used in adult patients with pGBM. Other cytotoxic therapies like perillyl acohol or ketogenic diet are not suggested for use in adult patients with pGBM as a stand-alone therapy. QUESTION (Q4): In adult patients with pGBM does the use of tumor treating field (TTF) result in increased overall survival compared to chemotherapy? Level III: The use of TTF with other chemotherapy may be considered when treating adult patients with pGBM. There is insufficient evidence to recommend TTF to increase overall survival in adult patients with pGBM. QUESTION (Q5): In adult patients with pGBM does the use of oncolytic virotherapy result in increased survival compared to chemotherapy? Level III: Oncolytic virotherapy is not suggested in patients with pGBM.

Long-Term Outcomes and Prognostic Factors of Patients with Metastatic Solid Tumors Admitted to the Intensive Care Unit

Introduction: Admission of metastatic cancer patients to the intensive care unit (ICU) poses medical and ethical challenges in the absence of reliable prognostic tools to guide decision-making. Material and Methods: We retrospectively analyzed the medical charts of 129 consecutive patients with metastatic solid tumors admitted to the ICU between January and September 2014 and identified prognostic factors (PFs) using Cox models. Results: The mean patient age at ICU admission was 58.9 years (range, 25–81 years; males, 51%). Performance status (PS) was 0–1 and 2–3 in 61% and 39% of the patients, respectively. The most prevalent cancers were lung cancer (20%), sarcoma (17%), and breast cancer (16%). ICU admission was attributable to the cancer itself (53%), cancer treatment toxicity (43%), and comorbidities (37%). The median overall survival (OS) after ICU admission was 2.6 months; 15% of the patients died during the ICU stay. Poor PFs for OS were PS >1 before ICU admission (p = 0.007) and ICU admission for the cancer itself (p < 10⁻³). After ICU discharge, 58% and 42% of the patients received systemic treatment within 12 months and showed good PS recovery, respectively. Multiple organ failure and a multidisciplinary decision to limit therapeutic efforts were poor PFs for reinitiation of systemic treatment (p = 0.2 and 0.006, respectively), and the latter was also a poor PF for PS recovery (p = 0.004). Discussion: In the ICU, the OS of adult patients with solid tumors was similar to that of the noncancer population. For ICU admissions related to the cancer itself, the prognosis is poor.

Effectiveness of induction regimens on survival outcome in acute myeloid leukemia patients: a real-world data from 2001 to 2015.

Since patients with acute myeloid leukemia (AML) in the real world have a much different clinical picture than patients recruited in the clinical trials, obtaining real-world evidence of medication adoption is important for therapeutic efficiency and safety. This study used three population-based data in Taiwan, the National Health Insurance Research Database, Taiwan Cancer Registry, and National Death Registry, between 2001 and 2015, to investigate the effect of conventional chemotherapy (CCT) versus non-conventional chemotherapy (NCCT) on the overall survival (OS) of patients with AML (n = 7,763). Cox proportional hazard regression was used to estimate the hazard ratios (HR) of different treatments on the risk of mortality. To reduce the potential selection bias, we used the inverse probability of treatment weighting based on the propensity score to balance the baseline characteristics between patients receiving CCT and NCCT. The median survival time for CCT and NCCT arms was 10.2months (95% confidence interval (95% CI): 9.7-10.9) and 4.1months (95% CI: 3.8-4.5), respectively. Compared to the patients received NCCT, those receiving CCT had a lower risk of mortality (HR 0.63 (95% CI: 0.59-0.67, P < 0.001). Subgroup analysis showed that CCT did benefit patients in different gender, age, comorbidity, and socioeconomic status (SES) groups. In conclusion, the real-world population-based data exhibited CCT were more likely to be prescribed for patients with AML of younger age, fewer comorbidities, diagnosed recently (2011-2015), and higher SES. In fact, CCT had better treatment outcomes than NCCT in terms of OS for adult patients diagnosed with AML.

Factors Associated with Pulmonary Hypertension and Overall Survival in Adult Patients with Sickle Cell Disease: A Single Centre Retrospective Study

▪BackgroundPulmonary hypertension is associated with increased morbidity and mortality in the general population either related to the underlying factors predisposing to elevated pulmonary artery pressures or though the hemodynamic changes induced in the cardiopulmonary circuit. It is known that patients with Sickle cell disease have an even a greater incidence of pulmonary hypertension than the general population and presumably a similar association with poor outcome related to this.Very little data is available regarding which adult patients with sickle cell disease would be at a higher risk for Pulmonary hypertension and as such benefit from screening. Many of the more commonly suggested clinical symptoms of pulmonary hypertension may be less specific in patients with SCD. The gold standard for diagnosis of PHT is Right heart catheterization, however for practical purposes echocardiographic variables such as Tricuspid Regurgitant velocity(TRV) and right ventricular systolic pressure(RVSP) are used in the general population. Several prior studies have focused on laboratory tests or historical risk factors associated with increased hemolysis.We evaluated the association of several variables with the occurrence of PHT in a population of adult patients with SCD and assessed their association with overall survival(OS). The factors we focused on could be seen as having biological plausibility for causing PHT as they relate to factors that increase flow through the pulmonary circuit, such as occurrence of hemolysis, or affect microvascular flow such as episodes of acute chest syndrome(ACS).MethodsWe identified patients aged 18 years or older with sickle cell disease from our electronic database who had an echo performed between 2009- 2017. Primary outcome was to determine the factors associated with PHT and OS. PHT was defined as RVSP of >25 mm Hg or TRV of >250 cm/sec. Factors investigated included age, sex, sickle cell type, absolute reticulocyte count(ARC), ferritin, use of iron chelation agent, and episodes of acute chest. Chi square test was used to compare proportion of PHT among factors.ResultsWe identified 300 patients with SCD from our clinic population, of whom 243 patients had echocardiographic data available. 52.7 % were females and 47.3 % were males. Out of the 234 patients who had TRV or RVSP measured, 63 patients met our criteria for PHT. 79 patients had TRV measured. 50.6 % had TRV <250 cm/sec, 29.1% had TRV 250-300 cm/sec and 20.2 % had TRV >300 cm/sec.223 patients had data on sickle cell type. HbSS, Hb SC , HbSß⁺ Thal, HbSß°Thal occurred with a frequency of 64.3%, 17.9%,13% and 4.9 % respectively. There was no association between sickle cell type and presence of PHT or OS.243 patients with Ferritin levels documented, of which 38.7% had Ferritin levels >1000 ng/ml. There was a strong correlation between an elevated ferritin level and PHT (p value =0.001) but not with OS. ARC was not associated with PHT (p value =0.87), but interestingly a normal ARC was strongly associated with worse OS (p value = 0.03)234 patients had documentation of whether or not they had an episode of ACS. 50 patients had one or more episodes of acute chest. There was a trend towards association of acute chest episodes with PHT (p value =0.08) and OS (p value =0.11).21 patients were deceased at the time of final analysis. Median overall survival was 3.8 years after TRV was initially documented. Median TRV was 248.8 cm/sec. There was a trend towards worse overall survival with a TRV of >300 cm/sec when compared to TRV of <250 cm/sec (p value =0.08).ConclusionOur study suggests that patients with elevated ferritin and ACS episodes should undergo screening for PHT. A normal ARC in this study while not being statistically associated with PHT was very strongly associated with worse OS. These findings are as observed in a small single center study and further evaluation of these clinical and laboratory factors should be pursued using a larger database in a prospective fashion. DisclosuresNo relevant conflicts of interest to declare.

Socioeconomic Factors Associated with Overall Survival (OS) in Adults with Acute Lymphoblastic Leukemia (ALL)

Introduction:Only incremental gain in OS has been noted over the recent years for adults with ALL, when compared to the dramatic improvement in the pediatric and adolescent population. Though cytogenetics and molecular features primarily drive disease biology and OS, various socioeconomic factors influence receipt of optimal therapy and thereby OS. In this context, we utilized National Cancer Database (NCDB) to evaluate the impact of socioeconomic factors on OS in adult patients with ALL.Methods:NCDB Participant User File was used to extract patient-level data of adult patients (aged 18-80 years) diagnosed with ALL between 2003-2012. We excluded patients with unknown transplant or chemotherapy status and those who did not receive chemotherapy. Only patients treated in the reporting facility were included. Data abstracted include age, sex, race, Charlson comorbidity score, treatment facility type (academic vs. non-academic), median household income, insurance, and educational status. We performed multivariate logistic regression analysis to determine the association of these variables with OS.Results:A total of 11,871 patients were included in the study. Median OS was 23 months (95% CI 22-24). In a multivariate analysis, patients who were older than 40 years (p<0.0001), African American (p<0.03), treated at non-academic facility (p<0.001), had higher Charlson comorbidity score (p<0.0001), lower educational status (p=0.004) and Medicaid/Medicare insurance (p<0.0001) or no insurance (p=0.002) were more likely to have inferior OS. Patients with median annual household income >$68,000 had superior OS (p=0.007) [Table 1].Conclusion:Our real-world data demonstrates an association between OS and socioeconomic factors such as race, treatment facility type, insurance, educational and income status. While the likelihood of lower OS in patients with advanced age and higher comorbidities are expected, the association with socioeconomic factors may indicate a possibility of health care disparity. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Impact of decontamination therapy on gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic cell transplantation in children: Decontamination therapy in allo-HCT

Introduction: Gut colonization with antibiotic-resistant bacteria (ARB) is associated with a significantly decreased overall survival in adult patients undergoing allo-HCT because of an increased treatment-related mortality.Objective: The objective of this multicenter study was the analysis of impact of gut colonization status and the use of antibiotics on development of gastro-intestinal (GI) graft-versus-host disease (GVHD) of allo-HCT in children.Methods: All consecutive patients who underwent allo-HCT over a period of three years in all pediatric HCT centers in Poland were analyzed for the impact of gut colonization on GI GVHD, with respect to standard of care including prophylaxis of infections and supportive therapy.Results: At the time of allo-HCT, 44.2% of pediatric patients were colonized by ARB. Decontamination therapy with antibiotics was applied in 78% of children. Gut decontamination prophylactic therapy with antibiotics decreased the risk of acute GI GVHD. The use of gentamicin contributed to decreased rate of GVHD, while the use of ciprofloxacin and colistin contributed to increased incidence of GVHD after allo-HCT in children. Sepsis with ARB and non-MFD transplant contributed significantly to worse survival, while neither colonization nor gut decontamination had an impact on overall survival.Conclusions: Gut decontamination therapy contributed to lower incidence of acute GI GVHD in children undergoing allo-HCT, and the use of specific antibiotics might be responsible for this effect.

Central Nervous System (CNS) Involvement in Adult Acute Lymphoblastic Leukemia (ALL) Assessed Solely By Flow Cytometry Has an Adverse Impact on Survival

Introduction: Several studies published in recent years dealing with the detection of Central Nervous System (CNS) disease in Acute Lymphoblastic Leukemia (ALL) have demonstrated superiority in terms of sensitivity of Flow Cytometry (FCM) over standard cytology (Tawfik et al, 2018). However, whether CNS activity detected by FCM has an impact on the clinical outcome of ALL adult patients, is still a matter of debate. (Del Principe et al, 2019) Methodology: We analyzed a retrospective cohort of newly diagnosed ALL adult patients in an oncologic center in Mexico, who had a CNS analysis by FCM and conventional cytology, diagnosed between 2017 and 2019. The primary endpoint was to assess the impact on the survival of patients with CNS disease detected by FCM. We defined positive FCM (FCM+) when the patient had &amp;gt;10 phenotypically pathologic events and positive cytology (Cyt+) when the patent had confirmed CNS-2 or CNS-3 activity as defined by NCCN and ESMO; double-negative (DN) patients were considered when neither FCM nor cytology demonstrated disease as described above. Baseline characteristics were grouped in tables and summarized as medians and ranges for quantitative variables or frequencies in qualitative variables. Basal characteristics and different outcomes were compared by the chi-square test for binary variables, and the Mann-Whitney U test for quantitative variables. Overall Survival (OS) and Disease-Free Survival (DFS) analysis were made by Kaplan-Meier curves. A comparison between groups was performed using the log-rank test, with a significant P value less than 0.05 and a 95% confidence interval (CI). We performed a Cox regression model to obtain an HR with a 95% confidence interval for survival to identify risk associations. Results: Of the 92 evaluable patients, the median age was 28 years. 88% of all ALL were ALL-B. The median count of leucocytes was 11.65 x109/L (range 4.71-38.24 x109/L); median LDH was 758 UI/L (range 314-1242 UI/L). 63% of patients had an unfavorable karyotype (hypodiploidy, complex karyotype, or KMT2A). At diagnosis, 27 (28%) were positive by FCM and negative by cytology. The median of the analyzed events was 14,733 (5,025-50,000) with a viability of 38.5% (22-61.75). Only 6 patients were positive by both techniques. 45% of patients with CNS involvement had neurological symptoms (mainly headache). The most used treatment was BFM in 56.7% of patients, followed by HyperCVAD in 37.8%. Patients with documented CNS infiltration by FCM or cytology were treated with triple intrathecal chemotherapy two times per week. Three patients had no response after two weeks of treatment, one received radiotherapy without any response and the other two were dead for chemotherapy toxicity. We found gender as the only statistically significant variable associated with a higher FCM+ (77% males vs 23% females, p&amp;lt;0.01). For the entire cohort, the complete remission (CR) after induction was 84% and 63% had a negative minimal residual disease (MRD) by FCM in the bone marrow. 15% of the patients were refractory. There were no differences between CR (73% versus 88%, p= 0.16), MRD negativity (46% versus 69%, p=0.11), refractory disease (26% versus 10%, p=0.13) or relapsed disease (50% versus 43%, p=0.65) between FCM(+) and ND groups. The OS for the entire cohort was 11.3 months. Patients with FCM+ had a lower survival of 5.6 months [CI95% (0.72-10.67)] compared with 11.8 months [CI95% (0.47-11.95)] in the DN group. The median DFS for the FCM+ patients was 4.6 months [CI95% (3.42-5.92)] versus 16.4 months [CI95% (6.21-26.75)] for DN group. In the Cox regression model, the HR for survival in patients with FCM+ was 1.85 (CI95% 1.004-3.421; p=0.04). Conclusions: Despite the retrospective nature of this study, the detection of CNS involvement was increased from 6% to 28% employing FCM compared with cytology. As mentioned previously, in other studies, FCM has greater sensitivity than cytology (Ranta et al. 2014). According to our results, the presence of CNS disease, detected by FCM has an adverse impact on OS in adult patients with newly diagnosed ALL. These results dictate consideration of FCM as a routine study in the diagnosis of ALL. Prospective studies are needed to evaluate more intensive treatment in these patients. Figure Disclosures No relevant conflicts of interest to declare.

The role of radiation therapy in treatment of adults with newly diagnosed glioblastoma multiforme: a systematic review and evidence-based clinical practice guideline update.

The role of radiation therapy in treatment of adults with newly diagnosed glioblastoma multiforme: a systematic review and evidence-based clinical practice guideline update.

S1000 Is N-Acetylcysteine the Holy Grail in Non-Acetaminophen Related Acute Liver Failure: An Updated Meta-Analysis and Systematic Review

INTRODUCTION: The AASLD recommends N-acetylcysteine (NAC) may be beneficial in non-Acetaminophen related drug induced liver injury. A subsequent review and analysis however reported the current evidence to be inconclusive. Herein, we present an updated review and metanalysis assessing outcomes of NAC in adult patients with acute liver failure. AIMS: The primary outcome was to compare the overall survival in adult patients presenting with acute liver failure who received NAC vs those who did not. Secondary outcomes included difference in length of hospital stay, transplant free survival, and posttransplant free survival. METHODS: We included prospective, retrospective, and randomized controlled trials comparing outcomes in patients with acute liver failure (defined as abnormal liver enzymes along with elevated INR >1.5 with or without hepatic encephalopathy) who are ≥ 18 years of age receiving NAC vs control group. Articles were searched in Pubmed, Ovid journals, and Cochrane Database of Systematic Reviews. RESULTS: Three studies (N = 408) that met the inclusion criteria were included in this analysis. Mean age of patients in NAC group was 35.36 years while that in the control group was 37.9 years. Odds of overall survival was significantly higher in NAC group as compared to control group [odds ratio: 3.57, 95% CI: 1.99–6.41]. Transplant free survival was also higher in NAC group as compared to control group [odds ratio: 4.79, 95% CI 3.14–7.31]. Patients in control group had statistically significant odds of longer inpatient stay [MD 2.18; 95% CI: 1.83–2.53]. CONCLUSION: In patients with non-Acetaminophen related acute liver failure, NAC significantly improves overall survival and transplant free survival while decreasing overall length of hospital stay.Figure 1.: Funnel plot for Overall Survival in NAC group.

Association of ANRIL Polymorphism With Overall Survival in Adult Patients With Hematologic Malignancies After Allogeneic Hematopoietic Stem Cell Transplantation.

Genetic variations of the non-coding RNA gene, ANRIL, have been associated with human diseases including cancer, type-2 diabetes, and atherosclerosis. In the present study, we investigated the potential associations of select ANRIL single nucleotide polymorphisms (SNPs) with overall survival and other clinical outcomes in adult patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Genomic DNA was extracted from whole blood samples from 103 adult patients with hematologic malignancies who had received allo-HSCT followed by oral tacrolimus therapy. The genotypes of four select ANRIL SNPs, rs564398, rs1063192, rs2151280, and rs2157719 were determined using qRT-PCR-based genotyping assays. rs2151280 (C->T) in ANRIL was associated with worse overall survival in these patients (CT/CC vs. TT). Contrarily, rs2151280 and the other select ANRIL SNPs were not associated with death at Day-100 after transplantation, the incidence of graft-versus-host disease (GVHD), acute kidney injury (AKI), and neurotoxicity in the study cohort. rs2151280 represents a potential prognostic biomarker for overall survival in adult patients with hematologic malignancies after allo-HSCT.

A novel prognostic model for adult patients with Hemophagocytic Lymphohistiocytosis

BackgroundHemophagocytic Lymphohistiocytosis (HLH) is a type of rare disease with low survival rate. We aimed to develop a model to evaluate the six-month prognosis in adult HLH patients. The data at discharge (will be called as post-treatment) for newly diagnosed adult HLH patients was collected and independent prognostic variables were selected for inclusion in the model.ResultsThree laboratory markers were confirmed to be the independent risk factors (ferritin: hazard ratio (HR) 0.101, 95% confidence interval (CI) 0.036–0.282, P<0.001; platelets: HR 4.799, 95% CI 1.884–12.223, P = 0.001; alanine aminotransferase (ALT): HR 0.423, 95% CI 0.180–0.997, P = 0.049). These were included in the final clinical prediction model. Receiver operating characteristic (ROC) curves disclosed that this model had a better discrimination (area under the curve (AUC) = 0.842, 95% CI 0.773–0.910, P < 0.001) than each of them alone and the calibration curves aligned completely with the model predictions and actual observations. Kaplan-Meier curves revealed a significant difference in the overall survival (OS) in patients stratified by the model with higher values associated with a better OS.ConclusionThese results point out that serum ferritin, platelets and ALT levels are independent elements of OS in adult patients with HLH, and that the proposed model have a better prognostic value than any of these markers alone.

Influence of marital status on overall survival in adult patients with chordoma: a SEER-based study

BackgroundAs a rare primary bone tumor, no studies have reported the relationship between prognosis and marital status in patients with chordoma.MethodsWe classified patients with chordoma identified from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2016 into four groups: married, divorced/separated, widowed, and single groups. Kaplan-Meier curves with log-rank test and Cox regression were used to analyze the effect of marital status on overall survival (OS).ResultsA total of 1080 patients were included in the study: 700 (64.8%) were married, 88 (8.1%) were divorced/separated, 78 (7.2%) were widowed, and 214 (19.8%) were single. Among the 4 groups, the 5-year OS (45.2%), 10-year OS (12.5%), and median OS (56.0 months) were the lowest in the widowed group. After including age, sex, primary site, marital status, disease stage, tumor size, histological type, and treatment pattern, multivariate analysis showed that marital status was still an independent risk factor for patients with chordoma, and widowed patients had the lowest OS (hazard ratio [HR] 1.71; 95% confidence interval [CI] 1.25–2.33, p < 0.001) compared with married patients. Similar results were observed after stratifying the primary site and disease stage.ConclusionMarital status was an independent prognostic indicator for adult patients with chordoma, and marital status was conducive to patient survival. Compared with married patients, widowed patients have a higher risk of death.

Nomogram for Predicting the Overall Survival of Adult Patients With Primary Gastrointestinal Diffuse Large B Cell Lymphoma: A SEER- Based Study.

Background: The aim of this study was to establish a precise prognostic model, based on significant clinical parameters, for predicting the overall survival (OS) of adult patients with primary gastrointestinal diffuse large B cell lymphoma (GI DLBCL).Materials and Methods: The data of 7,121 GI DLBCL patients, diagnosed between 1997 and 2015, were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. These patients were randomly divided into two sequential cohorts: training (n = 5,697) set and validation (n = 1,424) set. ROC methodology and calibration curves were explicitly used to evaluate the predictive performance of nomogram.Results: The median OS in the training cohort was 76 months (1–239 months), and 3, 5, and 10-year OS rates were 60.3, 53.9, and 39.5%, respectively. Age at diagnosis, Ann Arbor stage, and marital status were important clinical predictors of OS. These characteristics were used to build a nomogram. The AUC of the nomogram for predicting 3, 5, and 10-year OS were 0.669, 0.692, and 0.740, respectively. All RUC and calibration curves revealed good accuracy in predicting prognosis of GI DLBCL.Conclusion: In summary, the established nomogram was validated to predict OS for adult patients with GI DLBCL. This predictive model could help clinicians identify high-risk patients to improve their prognosis.

The Hi's and Lo's of Cytarabine in Acute Myeloid Leukemia.

Cytarabine is the backbone of AML therapy, but the dose used during induction has remained controversial. Using an intermediate dose of cytarabine, compared with conventional dose, was shown to improve disease-free and overall survival in adult patients in China up to age 55, particularly in patients with intermediate cytogenetic risk.See related article by Wei et al., p. 3154.

Preoperative Statin Use and 90-Day Mortality After Noncardiac Surgery: A Hospital Registry Study.

The aim of this study was to investigate the association between preadmission statin use and 90-day mortality after planned elective noncardiac surgery in adult patients. Statin therapy is known to have pleiotropic effects, which improve the outcomes of various diseases. However, the effect of perioperative statin therapy on postoperative mortality remains controversial. This retrospective cohort study analyzed the medical records of adult patients who were admitted to a single tertiary academic hospital for elective noncardiac surgery between January 2012 and December 2018. The primary endpoint was 90-day mortality, which was defined as any mortality within 90 days after surgery. The secondary endpoint was overall survival. After propensity score matching, a total of 33,514 patients (16,757 patients in each group) were included in the analysis. The logistic regression analysis of the propensity score-matched cohort indicated that the odds ratio (OR) of 90-day mortality in the statin group was 26% lower than that of the nonstatin group [OR: 0.74; 95% confidence interval (CI): 0.59 to 0.92; P = 0.009]. The sensitivity analysis indicated that the high-dose intensity statin group had a 61% lower 90-day mortality rate than the nonstatin group (OR: 0.39; 95% CI: 0.18-0.84; P = 0.016). The overall survival time was significantly longer in the statin group than in the nonstatin group after propensity score matching (P < 0.001 by log-rank test). Preoperative statin use was associated with lower 90-day mortality and longer overall survival for adult patients who underwent elective noncardiac surgery. This association was more evident for high-intensity statin users.

Retrospective Study of Incidence and Survival for Patients with Hematologic Malignancies Residing at the U.S./Mexico Border

Introduction: Hispanics represent the largest minority group in the United States (U.S.), with 57.5 million individuals (18% of the population). Most U.S. Hispanics are of Mexican origin (63.2%), followed by Puerto Rican (9.5%), Cuban (3.9%), Salvadoran (3.8%), and Dominican (3.3%), but distribution varies by state. The majority of Hispanics in the U.S. reside in the Southwest region, and &gt;11 million live in the state of Texas. Cancer is the leading cause of death in the Hispanic population, accounting for 21% of deaths in people of all ages. Health disparities for Hispanic cancer patients have previously been linked to disproportionate poverty and other barriers to optimal healthcare, and in the case of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), Hispanics were found to be diagnosed younger and to have worse overall survival (OS) than Non-Hispanic whites (NHWs) (ACS. Cancer Facts &amp; Figures for Hispanics/Latinos 2018-2020). However, little is known about incidence and survival for Hispanic blood cancer patients residing at the U.S./Mexico border. To understand the impact of Hispanic ethnicity on outcomes for blood cancer patients diagnosed in this area, we examined OS in adult patients with hematologic malignancies throughout the state of Texas compared to Texas Health Service Region (HSR) 10, encompassing El Paso County. Methods: We retrospectively reviewed data available from the Texas Cancer Registry for hematologic malignancies diagnosed in the state of Texas between 1995 and 2016, focusing our analysis on chronic and acute leukemias (both myeloid and lymphoid), myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPNs). Survival for Hispanic and NHW groups was compared using the log-rank test, and Cox regression analyses adjusting for age and diagnosis. Differences in age at diagnosis were evaluated using t-tests and generalized linear models. Similar analyses compared Hispanic patients from HSR 10 versus Hispanic patients from the rest of Texas. Research was conducted according to a local Institutional Review Board-approved protocol in accordance with the Declaration of Helsinki. Results: Of the 69,941 cases of hematologic malignancies with available information throughout the state of Texas, 18.29% self-identified as Hispanic. Surprisingly, in unadjusted analyses, Hispanic patients had significantly better OS than NHWs diagnosed with AML (p&lt;0.0001), MDS (p&lt;0.0001), and chronic myeloid leukemia (CML, p&lt;0.0001), with no significant differences in OS for patients with ALL, MPN, acute promyelocytic leukemia (APL), or chronic lymphocytic leukemia (CLL). However, Hispanic patients were diagnosed at a significantly younger age in all diseases analyzed (Table 1), possibly explaining the improved survival. After adjusting for age, ALL (HR 1.32, p&lt;.0001), CLL (HR 1.11, p=0.002), and CML (HR 1.15, p=0.008) showed significantly worse outcomes for Hispanics, with better outcomes in MDS (HR 0.92, p=0.0004), and no significant differences for AML, APL or MPN. Running the same analyses for the entire El Paso population versus the rest of Texas, we found no significant interaction except for a suggestion of a greater ethnic disparity in CML patients from El Paso (p=0.06). We also compared Hispanic patients diagnosed in El Paso versus Hispanics from the rest of Texas. Hispanics in El Paso had a significant reduction in OS compared to Hispanics in other areas of Texas for patients with ALL (p=0.0164), AML (p&lt;0.0001), and CML (p=0.0160), but not for patients with APL, CLL, MDS, or MPN. Again the negative effects become less marked after adjustment for age, as those diagnosed in El Paso tended to be 3 years older at diagnosis than elsewhere in Texas. In analyses adjusted for age and diagnosis, there was again a suggestion that differences between El Paso and the rest of Texas were greater in Hispanics than NHW (p=0.08). Conclusions: While Hispanic patients with AML, MDS, and CML had significantly better OS compared to NHWs in Texas as a whole, this could be explained by a significant reduction in the age of diagnosis for Hispanics. However, when comparing across Texas, El Paso Hispanics with ALL, AML, and CML have a worse prognosis than in the rest of the state. There appears to be evidence that disparities in outcome by ethnicity may be different in El Paso compared with the rest of Texas. Further study is required to identify factors responsible for the disparity in OS. Disclosures No relevant conflicts of interest to declare.

58P - Functional status as a determinant prognostic factor for overall survival in adult patients with medulloblastoma treated with chemotherapy and radiotherapy

BackgroundMedulloblastomas are a rare disease in adult population. Currently the main treatment consists in surgical resection. There is a lack of prospective evidence and the adequate regimen of chemotherapy and radiotherapy is yet to be defined. MethodsWe conducted a retrospective study including adult patients with medulloblastoma treated at a tertiary referral center. The aim of this study was to estimate Overall survival (OS) and disease-free survival (DFS). ResultsWe identified a total of 58 patients. Median age was 28 years (range 16 – 62). A total of 26 patients, (44%) received at least one chemotherapy regimen. The most frequent combination was Vincristine/Cisplatin/Cyclophosphamide (VPC) (29%). 43% were treated with a concomitant chemoradiotherapy. DFS was 35.5 months, (range 4-100 months). Patients who underwent partial tumor removal presented 62-month OS. Patients with total resection surgery did not reach median OS (HR 1.98, CI 0.67 – 5.8). Those treated with chemotherapy did not reach OS. Patients without chemotherapy regimen have 62-month OS (HR 0.6 CI 0.19 – 1.8) Patients treated with VPC did not meet median overall survival, meanwhile other regimen implementations demonstrated 43-month OS (HR 2.00 CI 0.71 – 5.62) (p = 0.18). Patients who wereńt treated with chemoradiotherapy did not reach OS vs patients treated with sequential radiotherapy and chemotherapy (HR 0.65, CI 0.21 – 1.99) (P 0.45). Performance status was an important predictor of OS, patients with ECOG 3 demonstrated 12 months of OS meanwhile patients with ECOG 0 – 2 did not reach a median OS (HR 2.7, CI 1.63 – 4.55). Related to adverse events, 16% of patients treated with chemotherapy presented grade 3 and 4 toxicity. 10% of these patients manifested grade 3 or 4 neutropenia. A total of 51 pts (88%) received radiotherapy. 22 patients developed radioepithelitis (38%) and 13 pts developed radiotherapy-associated CNS toxicity. ConclusionsIn this study of 58 adult patients diagnosed with Medulloblastoma the results showed a performance status as an important OS prognostic factor. Sequential chemotherapy or concomitant therapy did not show an OS significance probably related to the size of our population. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

PF195 THE IMPACT OF COMORBIDITY ON SURVIVAL OF ADULT PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Background:Acute lymphoblastic leukemia (ALL) in adults is associated with poor outcomes with long‐term overall survival (OS) of 40%. ALL is more frequent in children, where comorbidity is infrequent. Currently, Hispanic population is characterized by an increasing adult comorbid population. The above, in addition to the high prevalence of ALL in adults, raises the need of knowing the prevalence and impact of comorbidity in adult ALL.Aims:Analyze the impact of comorbidity on OS of adult patients with ALL.Methods:Retrospective study that included &gt;18 year‐old patients with diagnosis of ALL treated and followed between January 2009 and September 2016 at our institution. To evaluate comorbidity, the hematopoietic cell transplant comorbidity index (HCT‐CI) and the Charlson comorbidity index (CCI) were used.Results:We included 176 patients. The adolescent and young adult (AYA) groups represented the 64.8% of the cohort, the additional 35.2% was represented by adults ≥40 year‐old.The most frequent comorbidities were overweight and obesity in 54.4% (AYA 45.6% vs. adults 71.0%; p = 0.001) and type 2 diabetes mellitus in 10.4% (AYA 1.8% vs. adults 25.8%; p &lt; 0.001). Regarding comorbidity scores, 29.1% had HCT‐CI ≥3 (AYA 23.7% vs. adults 39.3%; p = 0.037) and 47.4% a CCI≥1 (AYA 32.7% vs. adults 74.2%; p &lt; 0.001).The induction related mortality rate was 13.6% (AYA 10.5% vs. adults 19.4%, p = 0.113). Independent risk factors at diagnosis related to induction mortality were: total bilirubin &gt;1 g/dL (OR 3.96, 95% CI 1.19–7.37; p = 0.02) and albumin &lt;3.5 g/dL (OR 3.06, 95% CI 1.20–7.82; p = 0.02).The OS was significantly longer in the AYA group when compared to the group of adults &gt;40 years‐old with median OS of 13.8 and 8.0 months respectively (p &lt; 0.001). Patients with lower HCT‐CI scores (HCT‐CI&lt;3 vs. HCT‐CI≥3) and lower CCI (CCI&lt;1 vs. CCI≥) were significantly associated with a better OS survival (HCT‐CI OS 13.1 vs. 7.6 months; p = 0.005 and CCI OS 13.2 vs. 10.1 months, p = 0.003). Interestingly, this impact of comorbidity scores over OS, remained significant in the group of adult patients (HCT‐CI OS 10.8 vs. 4.3 months, p = 0.003 and CCI OS 11.2 vs. 6.7 months; p = 0.044) but not in the AYA group (HCT‐CI OS 14.4 vs. 12.0 months; p = 0.307 and CCI OS 13.7 vs. 14.4 months, p = 0.471). On multivariate analysis, HCT‐CI ≥3 (HR 1.59, 95% CI 1.06–2.39, p = 0.026), age &gt;40 years (HR 1.69, 95% CI 1.14–2.51, p = 0.009), and achievement of complete remission with the first induction chemotherapy regimen (HR: 0.317, 95% CI 0.217–0.462, p&gt;0.001) were independent prognostic factor for OS.Summary/Conclusion:There are no previous reports analyzing the impact of comorbidities in adults with ALL. This study shows that both HCT‐CI≥3 and CCI ≥1 are associated with poor outcomes in adults ≥ 40 years. The high prevalence of overweight/obesity and diabetes in our patients urges the need for an objective assessment of comorbidities at diagnosis.image

The Prognostic Calculator Easix Predicts Acute Gvhd, Non-Relapse Mortality and Overall Survival in Adult Patients Undergoing Reduced Intensity Conditioning Allogeneic HCT

KeywordsAllogeneic transplantation; endothelial damage; biomarkers.BackgroundEndothelial damage is associated with severe complications and increased risk of death after allogeneic hematopoietic cell transplantation (AlloHCT). The recently developed Endothelial Activation and Stress Index (EASIX) is a prognostic tool that uses clinical lab values and has been shown to predict non-relapse mortality (NRM) and overall survival (OS) at onset of acute graft versus host disease (aGVHD) in reduced intensity (RIC) alloHCT (Luft, Lancet Haematol 2017). We hypothesized that EASIX may be valuable for more broadly predicting aGVHD, NRM and OS after AlloHCT, beyond time of onset of aGVHD.DesignWe evaluated 152 adult patients who received an unmodified RIC AlloHCT from a related or unrelated donor with uniform GVHD prophylaxis of sirolimus/tacrolimus and low-dose MTX for treatment of lymphoid malignancies, between April 2008 and May 2017. The EASIX formula (LDH*Creatinine/platelet counts) was calculated at multiple timepoints (pre-HCT, day 30, day 100, onset TMA and aGVHD). For all EASIX assessments post-HCT, a landmark analysis was conducted at the given timepoint A log transformation using base 2 (log2) was applied to all EASIX variables to reduce skew. A one-unit increase in log2 EASIX is associated with a doubling (one-fold increase) of EASIX on the original scale. Kaplan-Meier, cumulative incidence, and cox modeling (cause specific for NRM and aGVHD) were used to evaluate EASIX as it relates to outcomes of interest. Relapse and death or relapse were considered competing risks for NRM and aGVHD respectively.ResultsThe median age at transplant was 54 years (range 23-78), 70% were males, a majority had non-Hodgkin lymphoma (68%), and most had sensitive disease at time of HCT (CR=56%; PR=33%). All patients, except two, received peripheral blood stem cells. Sixty-three patients had an HLA-identical related donor, while the remaining 89 had an unrelated donor transplant (HLA-matched in 75 patients, and HLA-mismatched in 14 patients). HCT-CI was 0 in 49 patients, 1-2 in 41 and ≥ 3 in 62 patients. With a median follow-up in surviving patients of 5.4 years (range, 0.8-10), the 1 and 3 years OS rate was 84.2% (95% CI, 77.3-89.1) and 67.9% (95% CI, 59.6-74.8), respectively. The NRM rate at 1 and 3 years was 7.9% (95% CI, 4.3-12.9) and 16.4% (95% CI, 10.9-22.8), respectively. The 1-year cumulative incidences of grades 1-4, 2-4 and 3-4 aGVHD were 56.6% (95% CI, 48.3-64.1), 42.1% (95% CI, 34.2-49.8) and 7.9% (95% CI, 4.3-12.9), respectively. Post-HCT thrombotic microangiopathy was only observed in 13 patients, representing too few events for EASIX analysis. As expected, HCT-CI was significantly associated with both OS and NRM. Pre-HCT EASIX was significantly associated with increased NRM (HR=1.60 [95% CI, 1.15-2.23], p=0.005) and aGVHD grade 1-4 and 2-4 (HR=1.33 [95% CI, 1.08-1.64], p=0.006 and HR=1.39 [95% CI, 1.10-1.75], p=0.005; respectively), but not OS or grade 3-4 aGVHD (Table 1). EASIX at day 30 and day 100 was significantly associated with both OS and NRM (Figures 1-4). Furthermore, confirming the results of Luft, EASIX calculated at onset of any grade aGVHD was significantly associated with OS (HR=1.34 [1.10-1.63], p=0.004) and NRM (HR=1.47 1.11-1.94], p=0.007). Finally, there was no correlation between HCT-CI and EASIX score.ConclusionsWe conclude that the EASIX formula, calculated at various timepoints pre and post AlloHCT, is significantly associated with NRM and OS. Pre-HCT EASIX also predicts risk of aGVHD, confirming prior results, EASIX at onset of acute GVHD is a predictor of NRM and OS in adult recipients RIC AlloHCT. EASIX provides an independent and easily accessible tool to predict important AlloHCT outcomes that can be used in addition to HCT-CI to better risk stratify patients. [Display omitted] DisclosuresSauter:Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy. Perales:Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Merck: Other: Personal fees; Takeda: Other: Personal fees; Abbvie: Other: Personal fees; Novartis: Other: Personal fees.