Trends in Inpatient Chemotherapy Hospitalizations, Cost and Mortality for Patients with Hematological Malignancies: Insights from the National Inpatient Sample

INTRODUCTION: With the advent of newer treatment options for patients with acute leukemia and myeloma, therapies are increasingly safely administered on an outpatient basis. We hypothesized increasing utilization of outpatient options would result in decreased hospitalizations for chemotherapy, albeit with increased hospitalization charges. We interrogated chemotherapy utilization amongst adult inpatients with these malignancies using the National Inpatient Sample (NIS). METHODS: The NIS is a database providing information on all inpatient hospitalizations in the United States (US), including primary and secondary diagnoses, procedures, length of stay, and disposition. Approximately 20% of admissions are tracked, and weighted estimates are provided regarding the total number of hospitalizations in the US. Using the NIS, we tracked chemotherapy admissions for patients with the following hematological malignancies: acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and multiple myeloma (MM). Admissions for hematopoietic stem cell transplants were excluded from our analysis, and only patients aged 18 or greater were included in our analysis. Procedural International Classification of Disease (ICD) 9 and 10 codes were used to gain insight into trends of hospitalizations, elective versus urgent status, costs and length of stay for each indication. Time frame 2002-2017 was chosen as this was the most recent year for which NIS data is available. Inflation adjustments for charges were calculated based on US Department of Labor statistics. RESULTS: For MM, there were a total of 54,357 admissions for chemotherapy from 2002-2017. Amongst these admissions, 37,517 were elective, and 16,670 were non-elective, with the remainder lacking data on elective status. Figure 1 highlights trends in admissions for MM, with a significant decrease noted in the overall volume (7,547 in 2002 to 2,710 in 2014 (p=0.003)). Mortality rates for MM chemotherapy admissions, also highlighted in Figure 1, did not change significantly from 2002 to 2017 (p=0.15). Mean length of stay for chemotherapy hospitalizations increased from 4.67 days in 2002 to 6.47 days in 2017 (p<0.0001). Mean inflation-adjusted hospitalization charges increased from $20,865 in 2002 to $79,161 in 2017 (p<0.0001). For AML, we noted 198,288 admissions for chemotherapy from 2002-2017 of which 127,277 were considered elective, and 70,566 non-elective, with the remainder lacking data on elective status. Figure 2 highlights trends in AML admissions with a decreased volume of admissions noted from 2011 onwards after an initial increase from 2005-2008. There was a total of 14,214 admissions in 2011 compared to 10,515 in 2017 (p=0.004) There was a decrease in inpatient mortality rates from 5.5% in 2002 to 2.4% in 2017 (p<0.0001). Mean length of stay was consistent during this time period from 13.35 days in 2002 to 13.34 days in 2017 (p=0.15). Mean inflation-adjusted hospitalization charges increased from $83,904 in 2002 to $133,295 in 2017 (p<0.001). There was a total of 82,730 admissions for chemotherapy from 2002-2017 for ALL. Amongst these admissions, 54,565 were elective and 27,963 were non-elective, with the remainder lacking data on elective status. Figure 3 highlights trends in admissions, with an increase in number of admissions from 4,092 in 2002 to 5,960 in 2017 (p=0.86). There was a decrease in the inpatient mortality rate from 0.8% in 2002 to 0.4% in 2017 (p=0.0007). Mean length of stay stayed consistent at 7.70 days in 2002 to 7.62 days in 2017 (p=0.06). Mean inflation-adjusted hospitalization charges increased from $49,283 in 2002 to $94,787 in 2017 (p<0.0001). CONCLUSIONS: There has been a steady decline in the number of admissions for inpatient chemotherapy for patients with multiple myeloma and acute myeloid leukemia over time, owing to advances in therapies delivered safely and efficaciously as an outpatient. There has also been a steady decline in inpatient mortality for chemotherapy for acute myeloid and acute lymphoid leukemia, in part due to advances in supportive care. However, the inpatient mortality rate for myeloma has not decreased, likely due to sicker patients preferentially needing admission for inpatient chemotherapy. Inflation-adjusted hospitalization charges have gone up dramatically and further work is needed to elucidate factors driving these costs, and how to mitigate them. Disclosures Ganguly: Kadmon: Other: Ad Board; Settle Genetics: Speakers Bureau; KITE Pharma: Speakers Bureau. McGuirk:Astellas: Research Funding; Novartis: Research Funding; Allo Vir: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Kite Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pluristem Ltd: Research Funding; Gamida Cell: Research Funding; Bellicum Pharmaceutical: Research Funding; Fresenius Biotech: Research Funding.

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The Epidemiology and Clinical Associations of Stroke in Patients with Acute Myeloid Leukemia: A Review of 10,972 Admissions from the 2012 National Inpatient Sample

Blood ◽

10.1182/blood.v126.23.1314.1314 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1314-1314

Author(s):

Taeha Kim ◽

Joseph Shatzel ◽

Harley Friedman ◽

Frederick Lansigan

Keyword(s):

Mechanical Ventilation ◽

Renal Failure ◽

Acute Renal Failure ◽

Length Of Stay ◽

Myeloid Leukemia ◽

Hospitalized Patients ◽

National Database ◽

National Inpatient Sample ◽

Inpatient Mortality ◽

Clinical Associations

Abstract Background: Patients withacute myeloid leukemia (AML) are at increased risk for both hemorrhage and thrombosis, including in the central nervous system. There is limited data on the incidence, clinical association and mortality associated with cerebrovascular accident (CVA) in hospitalized patients with active AML. The aim of this study is to evaluate the epidemiology and mortality of hospitalized patients with AML who suffered concurrent stroke from a large national database. Methods: Using the 2012 National Inpatient Sample (NIS), admissions with an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for AML without remission and AML in relapse (205.00 and 205.02, respectively) were extracted, and correlated with age, gender, length of stay and mortality. All CVA (ICD-9-CM 434.91) data were extracted as well for comparison of mortality, length of stay (LOS). Results: Of the 7,296,968 unweighted admissions in the 2012 NIS, 9384 involved AML patients who had not yet achieved remission, and 1600 involved relapsed AML (Prevalence of 0.12% and 0.021% respectively). Of the combined group of admitted patients with active AML (N=10,984), 65 patients (0.59%) had a concomitant CVA (either hemorrhagic or ischemic, of whom 56 (0.51%) had active disease and 9 (0.08%) had relapsed disease). Compared to all other active AML patients, those who developed stroke were older (Mean age 66 y/o vs 58 y/o P=0.003), had longer LOS (20 days vs 12 days P= 0.53), were predominantly female (55% vs 45%; p=0.078) and had significantly higher inpatient mortality rates (36.9% vs 10.5%; OR 3.5; 95%CI 2.2, 5.5; P<0.0001). AML patients with CVA had significantly higher inpatient mortality then all admitted patients with stroke (36.9% vs 6.7%; OR 5.5; 95%CI 3.5, 8.8; P<0.0001). Multivariate logistic regression attempting to find significant clinical associations in AML patients who develop stroke, after controlling for confounding variables, found that acute renal failure with tubular necrosis(OR 4.47; 95%CI 1.8, 11.2; P=0.0013), hypernatremia (OR 3.85; 95%CI 1.6, 9.1; P=0.002), urinary tract infection (OR 3.28; CI95% 1.8, 6.1; P=0.0002) and secondary thrombocytopenia (OR 2.92; 95%CI 1.5, 5.7; P=0.0018) were all significantly predictive, as were mechanical ventilation >96 hours (OR 4.92; CI95% 1.02, 23.6; P=0.047) and continuous positive airway pressure ventilation (OR 3.03; CI95% 1.11, 8.26; P=0.031). Disseminated intravascular coagulation (DIC) and leukocytosis were more prevalent in AML patients with CVA compare to all AML patients, but the difference did not reach statistical significance. Conclusions: CVA in patients with active AML was strongly associated with older age and higher mortality, and appeared to be a relatively rare event, occurring in only 0.59% of patients. There was no statistically significant difference in LOS or gender distribution between those who developed CVA and those who did not amont active AML patients. As compared to all CVA patients, active AML patients with CVA had 5-fold higher risk of mortality. Significant acute renal failure, hypernatremia and thrombocytopenia appear to portend a higher risk of stroke in patients with active AML. It is unclear if UTI, and the need for mechanical ventilation is a predictor of stroke, as much as they may be a ramification of it. While more common in AML patients with CVA vs AML patients without CVA, we did not find DIC or hyperleukocytosis to be significantly predictive. Disclosures No relevant conflicts of interest to declare.

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Trends in Outcomes and Charges of Acute Myeloid Leukemia in the Elderly: A Cross-Sectional Analysis of the Nationwide Inpatient Sample from 1993 to 2001.

Blood ◽

10.1182/blood.v104.11.3142.3142 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3142-3142

Author(s):

Laura M. Katz ◽

Lee S. Stern ◽

John M. Fastenau ◽

Catherine T. Piech ◽

John J. Doyle

Keyword(s):

Acute Myeloid Leukemia ◽

Length Of Stay ◽

Myeloid Leukemia ◽

Nationwide Inpatient Sample ◽

The Elderly ◽

Inpatient Mortality ◽

Patient Death ◽

Weighted Mean ◽

Cross Sectional ◽

Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) is a malignant disorder of the blood with an incidence almost ten times greater among persons 65 years and older than among those younger than 65 years (12.2 vs. 1.3 per 100,000) (Arch Intern Med2002;162:1597–1603). Treatment includes conventional cytotoxic chemotherapy [e.g., the “7+3” regimen consisting of cytarabine and daunorubicin or idarubicin (Leukemia1996;10:389–95)], which can be associated with serious morbidity and is often not tolerated by older patients. The five-year survival rate for AML is 2% among elderly patients and has not improved appreciably in the past two decades (Arch Intern Med2002;162:1597–1603). Methods: A cross-sectional study was conducted using the Nationwide Inpatient Sample (NIS), a national all-payer inpatient database drawn from 1,000 hospitals, which is part of the Healthcare Cost and Utilization Project (HCUP). Data on AML patients aged 60 years and older from 1998 to 2001 were analyzed for descriptives (demographics and hospital characteristics), comorbidities, outcomes, resource utilization, and charges. Admission mortality, length of stay (LOS), and charges were calculated for AML patients for each year of NIS data from 1993 to 2001 and were weighted using the NIS weighting scheme to adjust for sampling differences across years. Results: Of all AML admissions from 1998 to 2001 (n=15,327), the mean age was 72.6 years (SD=7.8), and females accounted for 44.6% of admissions. Patients aged 60 to 74 accounted for 61.0% of admissions over these years, whereas patients aged 75 to 84 and 85 and older accounted for only 31.0% and 8.0% of admissions, respectively. Mean LOS per admission was 12.3 days between 1998 and 2001, with a median of 7.0 days. While the majority of these admissions (66.8%) involved discharge to home, patient death occurred in 20.2% of admissions, and the remainder resulted in discharge to other healthcare facilities. Weighted mean admission charges increased overall from 1993 to 2001; mean charges increased steadily from 1993 until 1997 (from $34,222 to $35,781, respectively), at which point they increased at a sharper rate for the remaining years (from $35,781 in 1997 to $47,786 in 2001) (Table 1). Conversely, weighted mean LOS decreased from 14.9 to 12.2 days during the same years, while mortality rates decreased from 23.9% to 20.2%. Conclusion: Hospitalization charges for elderly AML patients increased overall from 1993 to 2001, with the sharpest increase over the latter four years. This increase in charges occurred in contrast with overall decreases in LOS and mortality. Table 1: Inpatient Mortality, Length of Stay (LOS) Per Admission, and Charges Per Admission by Year Year Inpatient Mortality LOS Per Admission (Days) Charges Per Admission ($) Percent Mean SE Mean SE 1993 23.9 14.94 0.48 34,222 1,647 1994 24.7 14.28 0.45 35,243 1,840 1995 22.3 13.48 0.43 34,920 1,996 1996 22.2 13.23 0.46 36,257 1,698 1997 21.9 12.63 0.41 35,781 1,611 1998 19.8 12.55 0.36 37,176 1,452 1999 20.0 12.52 0.34 40,897 2,047 2000 20.4 12.03 0.31 45,759 2,362 2001 20.2 12.23 0.45 47,786 2,875

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Immunological and Clinical Responses in Patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Multiple Myeloma (MM) and Chronic Lymphocytic Leukemia (CLL) after RHAMM-R3 Peptide Vaccination.

Blood ◽

10.1182/blood.v110.11.1806.1806 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1806-1806 ◽

Cited By ~ 1

Author(s):

Jochen Greiner ◽

Anita Schmitt ◽

Krzysztof Giannopoulos ◽

Jinfei Chen ◽

Marlies Goetz ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Immune Responses ◽

Myeloid Leukemia ◽

Hematological Malignancies ◽

Lymphocytic Leukemia ◽

Peptide Vaccination ◽

Chromium Release ◽

Clinical Responses ◽

Acute Myeloid

Abstract We initiated a phase I/II R3 peptide vaccination for patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) overexpressing the receptor for hyaluronic acid mediated motility (RHAMM). RHAMM is a leukemia associated antigen (LAA) that is strongly expressed in several hematological malignancies and induces humoral and cellular immune responses. In this study, patients with AML, MDS, MM or CLL were included with RHAMM expression but with a limited tumor load or a minimal residual disease. To date, 25 patients were enrolled. The first 12 patients were vaccinated with 300 mcg and further patients with 1000 mcg R3 peptide emulsified with the incomplete Freund’s adjuvant. The vaccine was given four times at a biweekly interval and GM-CSF was added for five days each vaccination. Only mild drug-related adverse events were observed such as erythema and induration of the skin at the site of injection. Immunological analysis were performed using enzyme linked immunospot (ELISpot) assays for Interferon gamma and Granzyme B, tetramer staining and chromium release assays. We detected specific immune responses in 70% of patients. In most patients, we found an increase of CD8+/HLA-A2/RHAMM R3 tetramer+/CD45RA+/CCR7−/CD27−/CD28− effector T cells in flow cytometry in accordance with an increase of R3-specific CD8+ T cells in ELISpot assays. In chromium release assays, a specific lysis of RHAMM-positive leukemic blasts was shown. Moreover, we measured IL-2 and IL-10 levels in sera before and after vaccination. While IL-10 levels remained at a rather low level, we detected an increase of IL-2 in four of ten patients who showed also clinical responses. RHAMM transcripts in bone marrow and peripheral blood were quantified by real-time RT-PCR. Responding patients showed a decrease of RHAMM after vaccination. We detected positive clinical effects in several patients with myeloid disorders showing a reduction of blasts in the bone marrow. One MDS patient did not need any longer erythrocyte transfusions. Two patients with MM showed a reduction of free light chain serum levels. Taken together, RHAMM-R3 peptide vaccination induced both immunological and clinical responses. Therefore, RHAMM constitutes a promising structure for further targeted immunotherapies in patients with different hematological malignancies.

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Development of Anti-IL-1R3 Monoclonal Antibodies for Treating Cancer and IL-1 Family-Mediated Inflammation

Blood ◽

10.1182/blood.v128.22.5224.5224 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5224-5224

Author(s):

Jesper F Højen ◽

Megan K Taylor ◽

Tania Azam ◽

Stephan Fischer ◽

Daniel A Pollyea ◽

...

Keyword(s):

Colorectal Cancer ◽

Pancreatic Cancer ◽

Multiple Myeloma ◽

Overall Survival ◽

Acute Myeloid Leukemia ◽

Metastatic Colorectal Cancer ◽

Myeloid Leukemia ◽

Research Funding ◽

Advisory Board ◽

Acute Myeloid

Abstract IL-1R3 is the co-receptor required for signaling of IL-1β, IL-1α, IL-33 and IL-36α, β and γ. The naturally occurring IL-1 receptor antagonist (anakinra), is used to block IL-1β, and IL-1α and clinical trials have demonstrated a reduction in progression to multiple myeloma as well as increased overall survival in stage IV pancreatic cancer using anakinra. In addition, a monoclonal antibody that targets IL-1α increases overall survival in metastatic colorectal cancer. However, blocking IL-1R3 would reduce not only IL-1β and IL-1α but also IL-33 as well as IL-36α, β and γ. The data described below reveal the broad efficacy of anti-IL-1R3. In the present studies, monoclonal humanized anti-IL-1R3 antibodies were studied in the mixed leukocyte reaction (MLR), in peripheral mononuclear cells (PBMC) stimulated with LPS, heat-killed Candida albicans or anti-CD3/antiCD28 as well as in THP-1 cells, a cell line derived from a patient with acute myeloid leukemia (AML). In the MLR, anti-IL-1R3 at 5 µg/mL reduced IFNγ by 81% and IL-6 by 48% compared to 36% by anakinra. In LPS-stimulated PBMCs, IL-6 was reduced by 40% and 58% with anakinra and anti-IL-1R3 respectively. Using heat-killed Candida, the suppression of IL-6 production by anti-IL-1R3 was up to 70%, comparable to anakinra. Immuno-stimulation using anti-CD3/CD28 resulted in a similar inhibition capacity for anakinra (42%) and anti-IL-1R3 (45%) on IL-6 production also. Since neutralizing anti-IL-1α antibodies have increased overall survival in metastatic colorectal cancer, we also measured the effect of anti-IL-1R3 on intracellular levels of IL-1α. In PBMCs stimulated with LPS, the levels of IL-1α were reduced by 35% in cells cultured with anakinra at 10 µg/mL and by 66% in cells exposed to anti-IL-1R3 at same concentration. Activating PBMCs with anti-CD3/anti-CD28 led to a reduction in IL-1α by anakinra of 17%, whereas anti-IL-1R3 suppressed by 29%. We next examined the effect on THP-1 cells as a model for blocking IL-1 family members in AML. THP-1 were differentiated with phorbol myristate acetate (PMA) for 3 hours, washed and subsequently rested for 3 days. The cells were then stimulated with LPS for 3 hours and anti-IL-1R3 was added for 1 hour followed by inflammasome activation with ATP. The reduction in secretion of IL-1β was here 30% at 5 µg/mL of anti-IL-1R3. Collectively, these studies indicate that antibody blockade of IL-1R3 is effective in reducing cytokines from primary cells using in-vitro models of organ rejection, infection and immunostimulation. In THP-1 cells, the reduction in inflammasome-dependent IL-1β suggests that anti-IL-1R3 can be used to treat acute myeloid leukemia, or progression to multiple myeloma. Since anti-IL-1R3 inhibits the signaling through IL-1R1, both IL-1α and IL-1β are targeted by this antibody. Suggesting a future role for this antibody in not only AML, but also other cancer types dominated by IL-1 mediated inflammation, such as metastatic colorectal and pancreatic cancer. Disclosures Fischer: MAB Discovery GmbH: Employment. Pollyea:Ariad: Other: advisory board; Pfizer: Other: advisory board, Research Funding; Glycomimetics: Other: DSMB member; Alexion: Other: advisory board; Celgene: Other: advisory board, Research Funding.

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RHAMM/CD168-R3 Peptide Vaccination of HLA-A2+ Patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS) and Multiple Myeloma (MM).

Blood ◽

10.1182/blood.v106.11.2781.2781 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2781-2781 ◽

Cited By ~ 2

Author(s):

Jochen Greiner ◽

Krzysztof Giannopoulos ◽

Li Li ◽

Peter Liebisch ◽

Christiane Wendl ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

T Cells ◽

Acute Myeloid Leukemia ◽

T Cell ◽

Peripheral Blood ◽

Myeloid Leukemia ◽

Hematological Malignancies ◽

Peptide Vaccination ◽

Acute Myeloid

Abstract The receptor for hyaluronic acid mediated motility (RHAMM/CD168) has been described as a leukemia-associated antigen (LAA) eliciting both humoral and cellular immune responses in patients with hematological malignancies. RHAMM/CD168 is expressed in more than 80% of patients with acute myeloid leukemia (AML) or multiple myeloma (MM). Recently, we characterized the RHAMM/CD168-derived peptide R3 (ILSLELMKL) as a CD8+ T cell epitope. R3-primed CD8+ T lymphocytes were able to lyse autologous RHAMM/CD168+ AML blasts in a MHC class I-restricted and epitope-specific manner. Therefore, we initiated a phase I/II R3 peptide vaccination trial for patients with AML, MDS or MM overexpressing RHAMM/CD168. Patients were included with positive RHAMM/CD168 expression but with a limited tumor load. 300 mcg RHAMM R3 peptide emulsified with the incomplete Freund’s adjuvant (ISA-51, Montanide; day 3) and GM-CSF (Leukine, days 1–5) was administrated four times subcutaneously at a biweekly interval. The primary aim of the study is safety and feasibility of this peptide vaccination, secondary aims the evaluation of a specific T cell immune response to RHAMM/CD168 R3 peptide and the assessment of the influence of the R3 peptide vaccination on the remission status. Since January 2005, ten patients were enrolled in this study. The first eight patients (2 AML, 3 MDS, 3 MM) have completed the course of four vaccinations and four patients have been evaluated. The only side effects observed under R3-peptide vaccination were erythema and induration of the skin at the site of injection (CTC I°). In 2/4 patients, we found in the peripheral blood a significant increase of specific CD8+ T cells (from 0.01% to 0.8%) recognizing the R3 peptide in ELISPOT analysis and tetramer staining, one patient showed already initially a high number of HLA-A2/R3 tetramer+CCR7-CD27-CD45RA+ effector T cells and maintained this level of T cell response. Clinical responses have been assessed by the examination of peripheral blood and bone-marrow samples before and after vaccination. Patients showed a reduction of the tumor-specific expressed antigen RHAMM/CD168 in real-time RT-PCR analysis after vaccination. 2/4 patients with myeloid disorders (1 AML, 1 MDS RAEB1) showed a reduction of CD33+ cells in FACS analysis of the bone-marrow after 4 vaccinations from 10 and 7 % to 1–2 and <1%, respectively. One patient with MM showed a reduction of plasma cells in bone-marrow and a stable quantity of light chains in peripheral blood, one patient with AML showed a progressive disease. In summary, RHAMM/CD168 is a promising target antigen for immunotherapies in patients with hematological malignancies.

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SIRT6 Inhibition As a Novel Approach for Treating Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v128.22.5222.5222 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5222-5222

Author(s):

Michele Cea ◽

Antonia Cagnetta ◽

Debora Soncini ◽

Paola Minetto ◽

Davide Lovera ◽

...

Keyword(s):

Gene Expression ◽

Multiple Myeloma ◽

Dna Damage ◽

Dna Repair ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Research Funding ◽

Allogeneic Bone ◽

A Genome ◽

Acute Myeloid

Abstract Currently available therapeutics against Acute Myeloid Leukemia (AML) have improved patient outcome. However, resistance develops even to novel therapies and patient overall survival remains low, especially for patients who are not eligible for allogeneic bone marrow transplantation. Therefore, there is an urgent need to overcome the biologic mechanisms underlying drug resistance in AML, to enhance the efficacy of existing treatments and to facilitate the design of novel approaches. Recently, our group has demonstrated that SIRT6, a NAD+-dependent histone deacetylase involved in genome maintenance, is frequently up-regulated in Multiple Myeloma and its targeting induces cancer cell killing (Cea M. et al, Blood 2016). Furthermore, gene expression analyses performed by our groups show that SIRT6 is also up-regulated in AML and confers poor prognosis in a series of 200 primary AML cases from our Hematology Clinic. Thus, these data suggested a role for SIRT6 in AML biology. High SIRT6 expression was typically observed in AML cell lines characterized by constitutive DNA damage and intense replicative stress. Likewise, primary AML cases exhibiting an intermediate-to-high chromosome instability (CIN) gene expression signature were also those with the highest SIRT6 expression, and worst prognosis. Subsequent studies demonstrated that SIRT6 silencing or its chemical inhibition, as observed in Multiple Myeloma exacerbates DNA damage in response to genotoxic agents, sensitizing AML cells to cytarabine (ARA-C) and idarubicin in vitro. Overall, enhancing genotoxic stress while concomitantly blocking DNA double-strand breaks (DSBs) repair response, may represent an innovative strategy to increase chemosensitivity of AML cells. Mechanistic studies revealed that SIRT6 acts as a genome guardian in AML cells by binding DNA damage sites and activating DNA-PKcs and CtIP by deacetylation, which in turn promotes DNA repair. Overall our data suggest that genomic instability is present in all hematologic malignancies including AML. Strategies aimed to shift the balance towards high DNA damage and reduced DNA repair by SIRT6 inhibition can decrease AML growth and may benefit patients with otherwise unfavorable outcomes. Disclosures Gobbi: Gilead: Honoraria; Takeda: Consultancy; Janssen: Consultancy, Honoraria; Roche: Honoraria; Celgene: Consultancy; Mundipharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

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Sex-Based Disparities in Venous Thromboembolism Sociodemographics and Outcomes: A National Inpatient Sample (NIS)-Based Analysis

Blood ◽

10.1182/blood.v128.22.5918.5918 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5918-5918

Author(s):

Ariela L. Marshall ◽

Adam C Bartley ◽

Aneel A. Ashrani ◽

Wilson I Gonsalves ◽

Prashant Kapoor ◽

...

Keyword(s):

Length Of Stay ◽

Hospital Mortality ◽

Research Funding ◽

Mortality Rates ◽

Hospital Length ◽

Hospital Length Of Stay ◽

National Inpatient Sample ◽

Inclusion Criteria ◽

Medical Comorbidities ◽

Sociodemographic Differences

Abstract Background: Venous thromboembolism (VTE) contributes to significant morbidity, mortality, and socioeconomic burden. Though male sex is a known risk factor for recurrent VTE, there is a paucity of literature regarding sex-based sociodemographic differences as well as differences in VTE outcomes including hospital length of stay and mortality rates. Methods: We conducted a retrospective analysis from the National Inpatient Sample (NIS) database from 2012-2013. Inclusion criteria were age 18 years and older and primary discharge diagnosis of VTE Sociodemographic features and medical comorbidities were analyzed, as were hospital length of stay and in-hospital mortality rates. Results: 107,896 patients in the NIS, representing a national estimate of 539,480 patients hospitalized for VTE between 2012 and 2013, met inclusion criteria. 53% were female and 47% were male. Mean age was 63 years and on average women were older than men (65 years versus 62 years, p<0.001). There were significant differences between men and women with respect to race, primary insurance payor, and VTE location as well as medical comorbidities (Table 1). Median overall length of stay (LOS) was 4 days and in-hospital mortality rates were 2.1%. Female sex was associated with a small but significantly longer hospital LOS (RR 1.04, CI 1.03-1.05, p<0.001) which was also seen in subgroup analyses of lower extremity DVT (RR 1.05, CI 1.03-1.06, p<0.001) and pulmonary embolism (RR 1.03, CI 1.02-1.05, p<0.001) but not upper extremity (RR 1.04, CI 0.96-1.12, p=0.36). There were no significant sex-based differences in in-hospital mortality (2.2% in women versus 2.1% in men, p=0.15). In a multivariate model correcting for sociodemographic differences and medical comorbidities, there were no significant differences between women and men with respect to hospital LOS or in-hospital mortality (Table 2). Conclusion: We used data from the NIS to study a large number of patients hospitalized for VTE, and identified several sex-based disparities in sociodemographic factors and location of VTE. However, in a multivariable analysis correcting for these factors, sex was not associated with significant differences in hospital LOS or inpatient mortality rates. Disclosures Kapoor: Celgene: Research Funding; Takeda: Research Funding; Amgen: Research Funding.

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