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BACKGROUND: Patients with lung cancer are known to be at increased risk for venous thromboembolism (VTE). However, there have been few studies of risk factors for VTE in lung cancer patients undergoing systemic chemotherapy. METHODS: CANTARISK was a prospective, non-interventional, global cohort study including patients with lung cancer initiating a new chemotherapy regimen. Clinical data were collected at baseline and at 2, 4 and 6 months follow-up. The impact of patient-, disease- and treatment-related factors on the occurrence of VTE in the first 6 months was evaluated in univariable and multivariable Cox regression analyses. RESULTS: A total of 1,980 patients with lung cancer were enrolled from 2011-12 of which 84% were diagnosed with non-small cell lung cancer (NSCLC). Median age was 63 years (range, 25-91) and 63% were male while 82% were active or former smokers. Race was white (70%), Asian (22%), or black (4%) with similar numbers from North America, Europe, and other regions including Asia. Metastatic disease was reported in 70% and ECOG PS was ≥2 in 13%. During the first six months, 121 patients developed a VTE (6.1%), of which 47.1% had pulmonary embolism (PE), 45.5% deep venous thrombosis (DVT), 3.3% catheter-associated thrombosis, and 4.1% visceral thrombosis. Among significant factors in univariable analysis, independent predictors for VTE in multivariable Cox regression analysis included female gender, US geographic region, leg immobilization, and presence of a central venous catheter (Table) with a trend toward greater risk for higher grade histology. Although predictive of early all-cause mortality in this study population (Kuderer et al ASCO 2016), the previously validated risk score for VTE in ambulatory cancer patients (Khorana et al: Blood 2008) was not significantly associated with VTE in either univariable or multivariable analysis. CONCLUSIONS: Several demographic, geographic, and clinical factors are significantly associated with an increased risk of VTE in patients with lung cancer receiving systemic chemotherapy. Future analysis will attempt to assess how novel targeted treatment options might impact the Khorana score's predictive ability across all lung cancer patients. Disclosures Kuderer: Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Lyman:Amgen: Research Funding. Khorana:Bayer: Consultancy, Honoraria; Leo: Consultancy, Honoraria, Research Funding; Halozyme: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding.

Background: Venous thromboembolism (VTE) represents a leading cause of morbidity and mortality among hospitalized patients with cancer. Methods: Hospitalization data reported on adult cancer patients at US academic medical centers and affiliated hospitals between 1995 and 2012 were analyzed. Cancer diagnosis, presence of VTE, comorbidities and complications were based on ICD-9-CM codes. Major comorbidities considered were diabetes, and cerebrovascular, peripheral-vascular, heart, liver, and lung renal disease. In patients with multiple hospitalizations during the time period, a randomly selected hospitalization was utilized in the analysis. Hospitalization cost estimates were inflation adjusted to 2015 US dollars. Results: Nearly 6 million hospitalizations of 3,146,388 individual patients with cancer from more than 200 institutions were evaluated. VTE was reported in 8.4% of patients when all admissions are considered during the time period. When a single selected hospitalization is considered for each patient, VTE was reported in 166,547 (5.3%) of individual patients including 56,125 (1.8%) with pulmonary embolism (PE). The annual rate of VTE increased progressively from 3.5% in 1995 to over 6.5% in 2012 with the rate of PE nearly tripling from 0.8% in 1995 to 2.3% in 2012. For hospitalized patients receiving cancer chemotherapy, the annual rate of VTE more than doubled from 3.6% in 1995 to 8.3% in 2012. VTE was reported in 5.2%, 5.8% and 5.4% of patients with solid tumors, lymphoma, and leukemia, respectively (Table). Rates of VTE were greatest among patients with pancreatic (10.2%), gastric (7.1%) or other abdominal malignancies except colorectal cancer (9.2%) as well as those with ovarian (7.1%), lung (6.8%) and esophageal cancers (6.3%). The risk of VTE increased progressively from 2.3% in those with no comorbidities to over 11% for patients with 4 or more comorbid conditions. The strongest risk factors for VTE were infectious complications including sepsis (14%), invasive candidiasis (16%), pneumonia (11%) and IV line infections (14%).During this same time period, imaging related to VTE actually decreased with significantly lower rates of CT, vascular ultrasound and ventilation perfusion lung scans reported. In-hospital mortality was reported in 5.5% of cancer patients without VTE and in 15.0% of those with VTE including 19.4% of those with pulmonary embolism. In-hospital mortality during this time period decreased by approximately one-third in cancer patients both with and without VTE. While reported rates of VTE increased, the length of hospital stay shortened for patients with as well as without VTE during this period. Average costs per hospitalization adjusted to 2015 dollars for patients with and without VTE were $37,352 and $19,994, respectively. The estimated average inflation adjusted daily cost of hospitalization for patients with cancer and VTE increased nearly 50% between 1995 ($2,256) and 2012 ($3,297). Conclusions: VTE reported among hospitalized patients with cancer has increased significantly during the period of observation along with the cost of hospitalization while in-hospital mortality and imaging rates have decreased. However, patients with additional major medical comorbidities are at exceptionally high risk of serious complications including in-hospital mortality. Disclosures Lyman: Amgen: Research Funding. Kuderer:Janssen Scientific Affairs, LLC: Consultancy, Honoraria.

Risk of venous thromboembolism (VTE) is elevated in cancer, but individual risk factors cannot identify a sufficiently high-risk group of outpatients for thromboprophylaxis. We developed a simple model for predicting chemotherapy-associated VTE using baseline clinical and laboratory variables. The association of VTE with multiple variables was characterized in a derivation cohort of 2701 cancer outpatients from a prospective observational study. A risk model was derived and validated in an independent cohort of 1365 patients from the same study. Five predictive variables were identified in a multivariate model: site of cancer (2 points for very high-risk site, 1 point for high-risk site), platelet count of 350 × 109/L or more, hemoglobin less than 100 g/L (10 g/dL) and/or use of erythropoiesis-stimulating agents, leukocyte count more than 11 × 109/L, and body mass index of 35 kg/m2 or more (1 point each). Rates of VTE in the derivation and validation cohorts, respectively, were 0.8% and 0.3% in low-risk (score = 0), 1.8% and 2% in intermediate-risk (score = 1-2), and 7.1% and 6.7% in high-risk (score ≥ 3) category over a median of 2.5 months (C-statistic = 0.7 for both cohorts). This model can identify patients with a nearly 7% short-term risk of symptomatic VTE and may be used to select cancer outpatients for studies of thromboprophylaxis.

BACKGROUND: The survival expectations of adults with AML have significantly improved over the last 4 decades, partly due to supportive care advancements that have enabled the delivery of increasingly intensive treatment modalities. Even today, however, mortality is high and long-term sequelae are substantial for adults with AML if ICU support becomes necessary. Thus far, information on risk factors for ICU admission and subsequent outcomes in these patients largely stems from small, single-institution studies. Additionally, existing studies have not focused on resource utilization or cost. We therefore utilized the University HealthSystem Consortium (UHC) database to examine risk factors, length of stay (LOS), mortality, and cost associated with ICU admission for adults with AML hospitalized in centers across the United States (U.S.) over a 9-year period. METHODS: A longitudinal discharge database derived from 239 U.S. UHC participating hospitals was used to retrospectively study adults with AML hospitalized between 2004 and 2012. Clinical data from discharge summaries from each hospital was extracted by certified coders and cost data from all payers was analyzed. This data was then merged to create the central UHC database. To identify the patient population of interest, we developed inclusion criteria based on ICD-9 CM code information. To be included, patient claims had to contain a diagnosis of active AML. Patients were excluded if their disease was in remission or if they had undergone a hematopoietic stem cell transplant. For those with >1 admission during the observation period, one hospitalization was selected randomly for analysis. Primary outcomes included total hospitalization duration, ICU admission and LOS, mortality, and cost (adjusted to 2014 dollars). Independent variables included age, gender, race, year of hospitalization, geographic location, hospital size, comorbidities (e.g. cardiac disease, thrombosis), and types of infectious complications. For binary outcomes, risk categories were compared using unadjusted odds ratios (ORs). Data are presented as means, proportions, or ORs followed by their 95% confidence intervals. RESULTS: 43,334 hospitalized adult patients with AML were identified. The mean age was 59 years and 41.3% were age ≥65. 54.9% were male, 73.0% Caucasian, 9.6% Black, 4.9% Hispanic, 2.6% Asian, and 9.9% other/unknown. Overall, 26.0% of patients were admitted to the ICU during their hospitalization with a mean ICU LOS of 9.3 days (9.1-9.6). Risk factors for ICU admission included black race (OR=1.2 [1.12-1.29]), hospitalization in the South (OR=1.58 [1.50-1.66]), ≥1 comorbidity (OR=3.61 [3.37-3.86]), and diagnosis of invasive fungal infection (OR=2.35 [2.14-2.59]; p CONCLUSION: ICU admission for adults with AML is associated with high mortality and cost that both increase proportionally with the number of comorbidities.Factors associated with ICU admission and mortality in AML patients include both non-modifiable demographic factors (age, race, and geographic location), and medical characteristics (number of comorbidities and underlying infections). These factors may be useful in identifying patients at increased risk for ICU admission early and provide an opportunity for the testing of primary prevention and intervention strategies. Disclosures Walter: Amgen, Inc.: Research Funding; Pfizer, Inc.: Consultancy; AstraZeneca, Inc.: Consultancy; Covagen AG: Consultancy; Seattle Genetics, Inc.: Research Funding; Amphivena Therapeutics, Inc.: Consultancy, Research Funding. Lyman:Amgen: Research Funding.

Background: Febrile neutropenia (FN) remains a serious complication of cancer chemotherapy often leading to hospitalization and an increased risk of mortality and cost. Methods: Data on hospitalizations between 2004 and 2012 at US academic medical centers and their affiliated hospitals reporting to the University Health Consortium were utilized. The analysis included admissions of adult patients (age ≥18 years) with lymphoma or solid tumors and neutropenia. For patients with multiple admissions, the first hospitalization during the time period studied was selected. Cancer diagnosis, presence of neutropenia, comorbidities, and infectious complications were based on ICD-9-CM codes. The primary outcome of the analysis was total cost of hospitalization. All cost estimates were adjusted for inflation and converted to 2014 US dollars. Length of stay (LOS) and mortality were studied as secondary outcomes. A multivariable linear regression model was used to evaluate the association of demographic and clinical factors with the total cost. Both total cost and LOS were log-transformed in the model. Results: Among 3.3 million hospitalizations of adult patients with solid tumors or lymphoma from 239 medical institutions, there were 108,807 admissions with neutropenia in 86,611 individual patients including 29% with lymphoma, 13% gastrointestinal cancer, 13% lung cancer, 10% breast cancer, and 35% with other solid tumors. Nearly one-quarter (24%) were between 50-59 years of age and an additional 27% of patients were 60-69 years old. Major comorbid diseases were present in 70% of patients with 25,923 (30%), 19,636 (23%), and 15,005 (17%) having 1, 2, or ≥3 major medical comorbidities, respectively. Median (mean) LOS was 5 (8.6) days with a quarter of patients hospitalized >10 days and 17% requiring the intensive care unit (ICU) stay. Average cost per day and total cost of hospitalization were $2,556 and $22,126, respectively. For patients who required ICU care, considerably higher total cost (mean: $51,745 vs. $15,953), cost per day (mean: $3,598 vs. $2,075), and length of hospitalization (mean: 15.8 vs. 7.1 days) were observed compared to patients without ICU stay. Hospitalization costs were greater in patients with lymphoma (mean=$29,853) compared to solid tumors (mean=$18,883) where the mean cost ranged from $11,337 in patients with breast cancer to $28,581 in those with brain tumors. Hospitalization costs increased in patients with major comorbidities with the highest mean costs for venous thromboembolism ($43,660), cerebrovascular disease ($43,273) and hepatic disease ($42,441) with mean lengths of stay of 15.6, 14.8, and 13.2 days, respectively. Regardless of tumor type, presence of multiple comorbidities further increased cost. Infectious complications associated with greatest mean costs were sepsis ($45,861), IV line infection ($45,021), pneumonia ($40,438), and fungal infections ($36,203). While changes in average LOS over time were small (mean 8.3 and 8.6 days in 2004 and 2012, respectively), the average cost of hospitalization, adjusted for inflation, rose from $18,815 in 2004 to $23,352 in 2012. In-hospital mortality was observed in 6.9% of patients overall with annual mortality rates varying between a minimum of 6.4% and maximum of 7.5% remaining relatively stable over time (6.8% in 2004, 6.4% in 2012). After adjusting for age, ethnicity, cancer type and LOS in the multivariable model, multiple comorbidities, infection, and year of hospitalization remained significantly associated with increased total cost. Conclusions: FN represents an oncologic emergency often requiring hospitalization and is associated with considerable mortality and costs. Major drivers of hospitalization costs include type of malignancy, number of major comorbidities and infectious complications. While lengths of stay and mortality rates have remained relatively constant, costs of hospitalization with cancer and neutropenia have risen over the past decade, considerably outpacing the rate of inflation. Disclosures Lyman: Amgen: Research Funding. Crawford:Aggenix: Consultancy; Amgen: Consultancy, Research Funding; Bayer: Consultancy; Boehringer Ingelheim: Consultancy; Eli Lilly: Consultancy; Gilead: Consultancy; Hospira: Consultancy; Ono Pharmaceutical: Consultancy; Astra Zeneca: Research Funding; GTx: Research Funding; Med Immune: Research Funding; Morphotek: Research Funding. Dale:Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Background: Venous thromboembolism (VTE) occurs commonly in patients with cancer and is associated with considerable morbidity and mortality. While the risk of VTE is greater in hospitalized patients and those undergoing active treatment, less is known about factors associated with increased risk of mortality and costs in this setting. The study presented here evaluates the risk of mortality among hospitalized cancer patients with VTE and the association of patient comorbidities and infectious complications on duration of hospitalization, in-hospital mortality and costs. Methods: Data on hospitalization of adult patients (age≥18) with cancer between 2004 and 2012 from 239 US academic medical centers reporting to the University Health Consortium were analyzed. For patients with multiple hospitalizations, the first admission during the time period studied was utilized. Primary outcomes consisted of length of stay, in-hospital mortality and estimated cost of hospitalization. Stratified analyses were performed based on patient characteristics, year of hospitalization, cancer type, major comorbidities and infectious complications. Costs were adjusted to 2014 dollars. Results: Among more than 3.8 million admissions of adult patients with cancer, 246,653 included a diagnostic code for VTE representing 198,173 individual patients with both cancer and VTE. Overall, 41% of patients with cancer and VTE were hospitalized for 10 days or longer with an in-hospital mortality rate of 11.3% and estimated average costs per hospitalization of $37,039. While length of stay and mortality rates remained relatively stable over the 9 years of observation, 2014-adjusted costs per day hospitalization increased from $2,600 in 2004 to $3,200 in 2012. In-hospital mortality was greatest in patients with lung (15.8%) and gastric (14.1%) cancers and leukemia (14.2%). Medical comorbidities associated with the highest rates of mortality included congestive heart failure (19.8%), cerebrovascular disease (20.4%), and major disorders of the lung (20.6%), liver (20.0%), and kidney (21.4%) with mortality increasing in direct proportion to the number of comorbidities. Likewise, comorbidities associated with the greatest average costs per hospitalization included congestive heart failure ($51,885), cerebrovascular disease ($55,815), and major disorders of the lung ($53,899), liver ($51,332), and kidney ($55,774) with estimated costs increasing from $22,622 with no medical comorbidity to over $70,000 with four or more. Alternatively, infectious complications associated with the highest rates of mortality and greatest average costs were sepsis (38.1%; $90,529) and pneumonia (26.0%; $69,024). Conclusions: Hospitalized patients with cancer and VTE are at considerable risk for prolonged hospitalization and in-patient mortality accompanied by considerable hospital costs. Patients with additional major comorbidities and infectious complications are at even greater risk of in-hospital mortality and substantially greater costs. Additional efforts to identify cancer patients at greater risk for VTE and its complications including prolonged hospitalization and in-hospital mortality are needed as well as better strategies and agents for reducing the risk and consequences of VTE. Disclosures Lyman: Amgen: Research Funding.

Background: Hematologic toxicities are common side effects of cancer chemotherapy. Despite advances in supportive care, febrile neutropenia (FN) continues to represent a serious adverse event often requiring hospitalization and is associated with an increased risk of mortality. The purpose of this analysis was to investigate the impact of comorbidities and infectious complications on in-patient length of stay (LOS) and mortality in hospitalized patients with cancer and neutropenia over the past decade. Methods: Hospitalization data from the University Health Consortium database inclusive of the years 2004-2012 from 239 US medical centers were analyzed. Cancer type, presence of neutropenia, comorbidities, and infection type were based on ICD-9-CM codes recorded during hospitalization. This analysis includes adult patients with malignant disease and neutropenia. Patients undergoing bone marrow or stem cell transplantation were excluded. For patients with multiple hospitalizations, the first admission during the time period studied was utilized. Primary study outcomes included hospital length of stay (LOS≥10 days) and in-hospital mortality. Multivariate logistic regression analysis was utilized to study the impact of major comorbidities on the primary outcomes. Major comorbidities under consideration included heart, liver, lung, renal, cerebrovascular, peripheral-vascular disease, diabetes and venous thromboembolism. Results: Among 135,309 patients with cancer hospitalized with neutropenic events, one-third were age 65 years or older and 51% were male. Approximately one-quarter (24.5%) of patients experienced more than one admission with FN. The mean (median) length of stay increased progressively from 11.1 (6) days in 2004 to 12.8 (7) days in 2012. Patients with leukemia, lymphoma and central nervous system (CNS) malignancies experienced the longest mean LOS (21.4, 10.5, 10.2 days, respectively). Overall, 50,846 (37.6%) had a LOS≥10 days and 10,261 (7.6%) patients died during the hospitalization with no difference seen over the time period of observation. (P=.30). Greater rates of mortality were observed in patients with lung (11.2%) or CNS (9.3%) malignancies, and leukemia (9.3%). Infectious complications were documented in 59.5% of patients and their presence was associated with greater LOS≥10 days (48.2% vs. 22.0%) and higher mortality (11.2% vs. 2.3%). Greater LOS≥10 days (51.6% vs. 37.1%) and increased mortality (9.8% vs. 7.5%) were also observed among obese patients with cancer. Likewise, patients with multiple comorbid conditions had more prolonged hospitalizations and a greater risk of in-hospital mortality. (Table) | | Solid tumors | Lymphoma | Leukemia | | ---------------------------- | ----------------------- | -------------- | ---------------------------------- | ----------------------- | | No. of comorbidities | No. of patients | % died | % with LOS≥10 days | No. of patients | % died | % with LOS≥10 days | No. of patients | % died | % with LOS≥10 days | | | 17,858 | 0.9 | 11.2 | 8,189 | 0.6 | 17.0 | 10,395 | 0.8 | 53.5 | | 1 | 18,172 | 3.4 | 17.9 | 7,751 | 2.6 | 26.6 | 11,380 | 3.4 | 63.2 | | 2 | 14,250 | 8.9 | 27.2 | 5,386 | 8.1 | 41.0 | 8,603 | 9.7 | 69.9 | | 3 | 7,499 | 18.0 | 38.4 | 2,861 | 18.4 | 55.2 | 5,040 | 22.8 | 77.7 | | 4 | 2,705 | 25.1 | 51.4 | 1,060 | 33.6 | 70.5 | 2,004 | 38.1 | 83.1 | | ≥ 5 | 602 | 35.2 | 62.3 | 278 | 39.9 | 80.6 | 577 | 49.0 | 87.0 | | All patients* | 61,086 | 7.0 | 22.6 | 25,525 | 6.6 | 32.2 | 37,999 | 9.2 | 65.4 | Abstract 2601. Table LOS – length of stay; * 10,699 patients with other type or multiple tumors not included in the table The trend toward longer LOS and greater mortality with increased number of comorbidities persisted in multivariate analyses after adjusting for cancer type, age, gender, ethnicity and type of infection (odds ratio (OR) per +1 comorbidity increase: [mortality: OR =1.89; 95% CI: 1.85-1.92; P

Abstract 1022 Background: Neutropenic complications represent important dose-limiting toxicities of cancer chemotherapy. We recently developed and validated a risk model for neutropenic complications in patients with solid tumors or lymphoma receiving cancer chemotherapy (Lyman et al. Cancer 2011). While practice guidelines recommend primary colony-stimulating factor (CSF) prophylaxis for patients at >20% risk of febrile neutropenia (FN), many patients receive chemotherapy regimens associated with an intermediate risk (10–20%) of FN. For these patients, the decision to give or withhold primary CSF prophylaxis is based on clinical judgment. We report here the ability of the risk model to identify patients with individual characteristics placing them at high risk for neutropenic complications among patients receiving intermediate risk chemotherapy regimens. Methods: A prospective cohort study was conducted of consenting patients initiating a new chemotherapy regimen at 115 randomly selected US oncology practices between 2002–2006. The risk of cycle 1 severe or febrile neutropenia was estimated [95% CI] utilizing logistic regression analysis adjusting for key clinical factors including: planned chemotherapy, prior chemotherapy, age, abnormal hepatic or renal function, low pretreatment white blood count, and immunosuppressive medications. The cumulative incidence of severe neutropenia and FN across 4 cycles was estimated by the product limit method of Kaplan and Meier. Results: Among 3,760 patients with cancers of breast, lung, ovary, colon, or lymphoma, 2,270 received an intermediate risk chemotherapy regimen based on NCCN guidelines. Overall, in the subpopulation receiving intermediate risk regimens, severe or febrile neutropenia occurred in cycle 1 in 21.4% while FN over 4 cycles was observed in 11%, and primary CSF prophylaxis was utilized in 16.4%. The performance of the risk model was good in this subgroup with a c-statistic of 0.82 [0.80–0.84]. Among the half of patients classified as high risk based on the model despite receiving an intermediate risk chemotherapy regimen, cycle 1 severe or febrile neutropenia occurred in 38% [35%–41%] compared to 5% [4%–6%] of patients classified as low risk based on the model receiving such regimens. Model sensitivity and specificity were 89% and 61%, respectively. The cumulative risk of FN over 4 cycles of chemotherapy was 20% in predicted high risk group versus 5% in the low risk group (Figure). The majority of severe or febrile neutropenia events (67%) and FN events (55%) were observed in cycle 1. One-half of high risk patients who did not receive primary CSF prophylaxis in cycle 1 received CSF during subsequent cycles following a neutropenic event. Conclusions: Our model for predicting neutropenic complications can identify patients at high individual risk for severe neutropenia in cycle 1 or FN in the first 4 cycles of chemotherapy when receiving intermediate risk chemotherapy. This analysis emphasizes the potential value of determining an individual patient's risk of chemotherapy complications based on a validated risk model. Disclosures: Lyman: Amgen: Research Funding. Crawford:Amgen: Consultancy, Honoraria, Research Funding. Dale:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kuderer:Amgen: Research Funding.

Abstract 1502 Background Randomized controlled trials (RCTs) have shown that granulocyte colony-stimulating factor (G-CSF) can reduce the risk of neutropenic complications as well as early mortality (Kuderer et al. JCO 2007). The impact of G-CSF support of chemotherapy on overall survival in patients with lymphoma is assessed here in a systematic review of RCTs of chemotherapy with versus without G-CSF in studies with at least 2 years of follow up. Methods A systematic review of RCTs of patients with malignant lymphoma receiving chemotherapy with versus without primary G-CSF support and reporting overall mortality by study arm identified 16 eligible studies. Data extraction was conducted by two independent reviewers. Heterogeneity was evaluated using Cochran's Q-statistic and the Inconsistency Index (I2). Weighted summary estimates of relative risk (RR) and absolute risk (AR) were based on the method of Mantel and Haenszel. Chemotherapy relative dose intensity (RDI) with G-CSF support compared to control was meta-regressed on the logarithm of RR for mortality. Egger's regression intercept was utilized to assess publication bias. Results Sixteen (16) eligible RCTs of patients receiving chemotherapy with (n=2,731) versus without (n=2,757) primary G-CSF support were identified. Deaths were reported in 927 patients randomized to receive primary G-CSF and in 1,064 controls. No significant heterogeneity was observed (Q=12.50, P=.641; I2=0%). Overall RR for mortality with versus without G-CSF support of chemotherapy was 0.876 [95% CI: 0.822 – 0.935; P Conclusions A highly significant reduction in overall mortality was associated with G-CSF support compared to control in 16 RCTs of lymphoma patients receiving chemotherapy. Patients receiving greater RDI with G-CSF support, especially those receiving dose dense regimens, experienced the greatest reduction in mortality. Disclosures: Lyman: Amgen: Research Funding. Crawford:Amgen: Consultancy. Dale:Amgen: Consultancy, Research Funding.

Abstract 3100 Poster Board III-37 Background The risk of acute myeloid leukemia and myelodysplastic syndromes (AML/MDS) is increased following prior exposure to cytotoxic cancer chemotherapy and radiation therapy. A few retrospective studies have suggested a potential risk for AML/MDS in cancer patients also receiving granulocyte colony-stimulating factor (G-CSF). A systematic review and meta-analysis of randomized controlled clinical trials (RCTs) in patients receiving cancer chemotherapy ± initial G-CSF support was conducted to evaluate the risk of AML/MDS and impact on all-cause mortality. Methods Electronic databases including Medline, EMBASE, Cochrane Library and meeting proceedings were searched. Eligible studies included RCTs of solid tumor or lymphoma patients receiving chemotherapy ± initial G-CSF and ≥2 years follow-up reporting AML/MDS or second malignancies. Dual blinded data extraction was performed. After evaluating for heterogeneity, relative risk (RR) and absolute risk (AR) difference [95% confidence limits] were estimated by the method of Mantel and Haenszel. Results In the 25 eligible RCTs, 6,058 patients were randomized to receive chemotherapy with and 6,746 without G-CSF support. Mean and median follow-up in all studies were 60 and 53 months, respectively. Among 23 RCTs reporting AML/MDS, 22 cases (0.36%) were reported in control- and 43 (0.79%) in G-CSF-treated patients. The RR and AR increase for AML/MDS in G-CSF-supported patients was 1.92 [1.19, 3.07; P=.007] and 0.41% [0.10%, 0.72%; P=.009], respectively. A trend suggesting publication bias was observed for AML/MDS consistent with an underreporting of small negative studies based on funnel plot asymmetry [Egger's regression intercept, P=.039]. No significant difference in reported AML/MDS was found based on source of study funding with RR for AML/MDS for industry and non-industry funded studies of 2.57 and 1.71, respectively. Trends toward greater risk of AML/MDS with higher cumulative chemotherapy dose were observed but none reached statistical significance. Mortality was reported in all 25 trials occurring in 1,845 patients randomized to receive G-CSF and in 2,099 controls. The RR and AR decrease for mortality in G-CSF-supported patients were 0.897 [0.857, 0.938; P Conclusions Risk of AML/MDS is increased while all-cause mortality is decreased in patients receiving G-CSF-supported chemotherapy. Greater reductions in risk for all cause mortality were observed in larger studies and with greater planned and delivered chemotherapy dose intensity. Disclosures Lyman: Amgen: Research Funding, Speakers Bureau. Crawford:Amgen: Consultancy. Kuderer:Amgen: Husband receives research support. Dale:Amgen Inc.: Consultancy, Honoraria, Research Funding, Speaker.

Background: Retrospective studies have reported inconsistent results concerning risk of acute myeloid leukemia or myelodysplastic syndrome (t-ML) in cancer patients receiving granulocyte colony-stimulating factor (G-CSF) along with systemic chemotherapy. In order to further evaluate any potential impact of chemotherapy with G-CSF support on overall survival (OS) and risk of t-ML in malignant lymphoma, a systematic review and subsequent meta-analysis of prospective, randomized controlled clinical trials were conducted. Methods: Electronic databases including Medline, EMBASE, BIOSIS and the Cochrane Library were searched through August 2008 identifying 5885 articles for initial screening. Eligibility criteria included studies of adult patients with non-myeloid malignancies receiving chemotherapy (CT) with or without G-CSF with at least 2 years of follow-up. Of the 136 potentially eligible publications identified, 8 were from prospective, randomized, controlled trials (RCTs) in adult patients with non-Hodgkin’s lymphoma (7) or Hodgkin’s disease (1). Excluded reports consisted of retrospective studies, duplicate reports, studies with no control group or studies involving stem cell transplantation. Study outcomes included all secondary malignancies, t-ML, OS and delivered chemotherapy dose intensity. Meta-analyses were based on the method of Mantel and Haenszel with summary estimates and 95% CIs for both relative risk (RR) and absolute risk difference (ARD;%). Results: In 8 RCTs, a total of 4089 patients were randomized to receive CT with G-CSF support (n=2032) versus no G-CSF (n=2057). In 5 of the 8 trials, dose intensified or dose dense CT was given in the G-CSF arms compared to standard CT without initial G-CSF. Initial CT dose and schedule were the same in the remaining 3 trials although each reported significantly greater overall delivered dose intensity in the G-CSF arm. No signficant heterogeneity was observed for the primary outcomes. Among 6 reporting RCTs, secondary malignancies occurred in 36 patients in the G-CSF arms versus 35 patients in control arms. T-ML was reported in 15 patients randomized to G-CSF compared to 6 in control patients [RR=2.30; 0.95–5.58; ARD = 0.6%; −0.1%–1.3%; p=.06]. In all 8 studies, patients receiving G-CSF received significantly greater chemotherapy dose intensity compared to controls. Among patients randomized to G-CSF support, a statistically significant increase in OS [RR=0.87; 0.81–0.94; ARD = −5.0%; −7.7%–−2.3%; p Conclusions: A meta-analysis based on an extensive search of the literature demonstrated that intensified chemotherapy with G-CSF support in malignant lymphoma resulted in a significant improvement in OS despite a non-significant trend toward an increase in t-ML. There were insufficient data to definitively examine the independent roles of G-CSF versus dose intensified chemotherapy on risk of t-ML.

Background: Venous Thromboembolism (VTE) is a common complication of cancer and is strongly associated with early all-cause mortality during the course of cancer chemotherapy (Kuderer et al. ASCO 2008). A clinical model for predicting the risk of VTE in cancer patients initiating chemotherapy has been recently developed and validated (Khorana et al. Blood 2008). Risk of VTE in low (group I), intermediate (group II) and high risk patients (group III) was 0.8%, 1.8% and 7.1%, respectively. The aim of current study is to evaluate the ability of the VTE risk model to predict disease progression and early all-cause mortality. Methods: A prospective study of 4,458 adult cancer patients with solid tumors or malignant lymphoma initiating a new chemotherapy regimen was conducted between 2002 and 2006 at 115 randomly selected practice sites throughout the USA. Demographic, clinical and treatment-related information was captured prospectively at baseline and during the first four cycles of chemotherapy, including rates of documented VTE, disease recurrence and deaths from all causes. Progression-free survival (PFS) and overall survival (OS) within 4 months of starting chemotherapy were estimated by the method of Kaplan-Meier and adjusted hazard ratios (HR ± 95% CI) were estimated by a Cox regression model, incorporating VTE as a time-dependent covariate. Results: Patient age ranged from 18–97 with a mean of 60 years. VTE occurred in 3% of patients by 4 months with a median of 38 days following initiation of chemotherapy. The HR for VTE occurrence among risk score groups II and III, compared to group I, were 3.07 [1.39–6.77] and 11.73 [5.22–16.37], (P Conclusions: VTE is strongly associated with increased early all-cause mortality during the course of cancer chemotherapy. A recently validated risk score is not only predictive of VTE occurrence, but also of progression-free and overall survival demonstrating a strong association with prognostic factors for disease progression and mortality.

Introduction: Neutropenic complications including severe neutropenia (SN) and febrile neutropenia (FN) represent major dose-limiting toxicities of cancer chemotherapy. A prospective study was undertaken to develop and validate a predictive model for neutropenic events in patients receiving cancer chemotherapy. The final risk model based on mature data is presented. Methods: Between 2002 and 2006, 4458 consenting patients starting a new chemotherapy regimen at 115 randomly selected community oncology practices throughout the United States were enrolled including 3760 with cancers of breast, lung, colorectum, ovary and malignant lymphoma receiving at least one cycle of treatment. Using a 2:1 random split sample methodlogy, a risk model for first-cycle SN or FN was derived and validated based on multivariate logistic regression analysis incorporating pretreatment variable information. The cumulative risk of events over the initial 120 days of treatment was estimated by the method of Kaplan and Meier. High and low risk groups were defined on the basis of the median predicted risk and model test performance characteristics were estimated. Results: Following adjustment for cancer type, important predictive factors included: older age, prior chemotherapy, abnormal hepatic or renal function, low pretreatment white blood count, immunosuppressive medications and planned relative dose intensity >85% as well as use of several specific chemotherapeutic agents including anthracyclines, taxanes, alkylating agents, topoisomerase inhibitors, gemcitabine or vinorelbine. Lower risk of neutropenic complications were associated with primary prophylaxis with a colony-stimulating factor (CSF). Individual risk estimates based on the model ranged from 0–89% with mean and median of 19.2% and 10.1%, respectively. The model was associated with an R2 of 0.34 and demonstrated excellent discrimination with a c-statistic of 0.833 [95% CI: 0.813–0.852, P Discussion: Based on excellent test performance characteristics, the risk model identified patients with a cumulative incidence of FN of at least 20% who are candidates for targeted prophylaxis with a CSF. Further validation of this model in actual clinical practice is currently underway.

Anemia represents the most common hematological toxicity in cancer patients receiving systemic chemotherapy and is associated with considerable morbidity and cost. Current guidelines for chemotherapy-induced anemia call for intervention at a hemoglobin Methods: 3640 patients with solid tumors or malignant lymphoma initiating a new regimen have been prospectively registered at 110 randomly selected U.S. practice sites. A logistic regression risk model for hemoglobin Results: Over a median of 3 cycles of chemotherapy, hemoglobin 1 g/dL (OR=4.48; P100000/mm3 (OR=1.54;P Discussion: This conditional risk model based on both pretreatment characteristics and first cycle events identified cancer patients receiving chemotherapy at substantial risk for clinically significant anemia. The use of ESAs early in the course of treatment based on individual risk assessment must consider both the potential benefit and risks and careful monitoring is essential.

Anemia represents the most common hematological toxicity in cancer patients receiving chemotherapy and is associated with considerable morbidity and cost. ASH/ASCO guidelines call for intervention at a hemoglobin (hgb)1 (1.70); CHF (1.54); history of vascular disease (2.66); ulcer disease (2.58); COPD (1.29); connective tissue disease (1.84); advanced cancer stage (1.19); cancer type and chemotherapy based on anthracyclines (2.15), carboplatin (2.40), gemcitabine (2.48), cyclophosphamide (1.60), etoposide (2.84), topotecan (4.21), or trastuzumab (1.43), planned cycle length >1 week (2.0), while normal baseline hemoglobin, platelet count and GFR were associated with a reduced risk. Model fit was good (P

Background: Anemia represents the most common hematological toxicity in cancer patients receiving systemic chemotherapy and is associated with considerable morbidity and cost (Lyman‚ Value in Health 2005). Current ASH/ASCO guidelines call for intervention at a hemoglobin (Hgb) Methods: More than 3‚000 patients with cancer of the breast‚ lung‚ colon and ovary or malignant lymphoma initiating a new chemotherapy regimen have been prospectively registered at 115 randomly selected U.S. practice sites. Data on at least one cycle of chemotherapy were available on 2‚842 patients. A logistic regression model for Hgb Results: Over a median of three cycles of chemotherapy, Hgb Conclusions: This risk model identified cancer patients initiating chemotherapy who are at risk for clinically significant anemia using common clinical parameters. Validation of the model in a separate population of patients is in progress.

Background: Myelosuppression including severe and febrile neutropenia continues to represent a major cause of dose-limiting toxicity of cancer chemotherapy. Neutropenic complications in cycle 1 have been shown to frequently lead to reduced dose intensity or addition of a myeloid growth factor. A prospective, nationwide study was undertaken to develop and validate risk models for first cycle neutropenic events associated with cancer chemotherapy. Methods: Patients with malignant lymphoma initiating a new chemotherapy regimen have been prospectively registered at 115 randomly selected practice sites. Data on at least one cycle of chemotherapy were available on 357 patients including 56 with Hodgkin’s disease and 301 with non-Hodgkin’s lymphoma. A logistic regression model for first cycle neutropenic events based on pretreatment characteristics was developed and predictive test performance characteristics examined. Results: Severe or febrile neutropenia occurred in 81 (22.7%) of patients in cycle 1. Two-thirds of patients with one or more neutropenic events experienced their initial event in cycle 1. Significant independent pretreatment predictive factors for first cycle neutropenic complications were: history of renal disease (OR=33.15, P=.011) or recent infection (OR=12.41, P=.035), Caucasian (OR=4.13, P=.053), use of an anthracycline-based chemotherapy regimen (OR=6.9, P Discussion: The risk model identified lymphoma patients at increased risk for first cycle neutropenic complications using common clinical parameters. Validation of the model in a separate population of patients is in progress.

Background: Venous thromboembolism (VTE) is a significant complication of cancer and particularly of newer anti-cancer therapies. The risk of VTE is estimated to be 0.04%/month (0.5%/year) in cancer patients. We conducted a prospective analysis to determine the frequency and risk factors for symptomatic VTE in cancer patients actively receiving chemotherapy. Methods: The Awareness of Neutropenia in Cancer (ANC) Study Group is currently enrolling patients with breast, lung, colon, ovary and other cancers, at 137 sites nationwide, with an accrual goal of 4,500 patients. Patients are registered at the time of initiation of a new chemotherapy regimen, and followed for the duration of 4 cycles. The association of VTE with clinical variables was studied in univariate analysis and in a multiple logistic regression model. No significant first-order interactions were observed between the variables in this model. A risk score for VTE was estimated for each subject from the weighted sum of model predictor variables from the multivariate model. Results: A total of 2,151 patients treated with at least one cycle of chemotherapy were available for analysis. Pulmonary embolism occurred in 11, and deep venous thrombosis in 35, for a VTE incidence of 2.14 % over median follow-up of 2.5 months (0.85%/month). Incidence of first VTE event was greatest in cycles 1 (0.93%/cycle) and 2 (0.88%/cycle), and declined in cycle 3 (0.53%/cycle). Incidence varied significantly by site of disease (p=0.01) with highest rates in patients with upper gastrointestinal (2.4%/month) and lung cancers (1.2%/month), and lymphomas (1.2%/month). Other clinical variables associated with development of VTE in univariate analysis included baseline platelet count ≥350,000, an ECOG PS ≥ 2, and baseline use of erythropoietin or colony-stimulating factors. Patients with VTE reported a chemotherapy delay of ≥ 7 days in 40% compared to 23.6% in patients without VTE (OR 2.15, p=0.01). Based on the results of the multivariate model (c statistic=0.73[.65,.81]) the population was divided into low, intermediate and high-risk based on tertiles of risk scores. Patients deemed high-risk had a VTE risk of 1.5%/month, which was a six-fold increase compared to those deemed low-risk (see Table). Conclusion: Symptomatic VTE is much more frequent in cancer patients on chemotherapy than previously estimated, even in patients with hematologic malignancies. VTE is associated with a nearly two-fold risk of significant delay in chemotherapy, which could impact on cancer outcomes. This is the first prospectively generated predictive model for chemotherapy-associated thrombosis, and can be used to define a high-risk study population for trials of thromboprophylaxis. Incidence of Chemotherapy-Associated VTE By Risk Categories Risk Score N VTE events Observed VTE Incidence(%) Predicted VTE Incidence(%) Low 648 4 0.62(0.24/month) 0.58(0.23/month) Intermediate 702 10 1.42(0.56/month) 1.48(0.59/month) High 799 30 3.75(1.5/month) 3.73(1.49/month)

Background: Chemotherapy-induced neutropenia is frequently associated with neutropenic complications resulting in reduced relative dose intensity (RDI) potentially compromising clinical outcomes. Retrospective analyses have identified several factors but are limited by variable reporting and missing data. Methods: Results from an ongoing prospective study of cancer chemotherapy patients based at more than 100 randomly selected US centers are reported. Demographic, clinical and treatment-related variables were obtained on 345 patients with malignant lymphoma (ML). Data are presented on the first 265 patients completing at least one cycle of chemotherapy. Planned and unplanned reductions in relative dose intensity (RDI) were estimated along with the risk of neutropenia and febrile neutropenia (FN) over the first four cycles of treatment are presented. Results: Patients with Hodgkin’s disease (HD; N=43) received five different regimens including ABVD (84%) while patients with Non-Hodgkin’s lymphoma (NHL; N=222) received 33 different regimens the most common of which was CHOP (53%). Neutrophil nadirs Conclusions: This prospective study confirms previous retrospective surveys that showed a substantial proportion of patients with ML receive reduced RDI potentially compromising clinical outcomes. Predictive models based on the risk factors identified should enable clinicians to target supportive care efforts in a more cost-effective manner.

Introduction: Myelosuppression represents the major dose-limiting toxicity of cancer chemotherapy. This prospective, nationwide study was undertaken to better define risk of neutropenia and its complications and to develop risk models for selecting patients for appropriate supportive care. Methods: More than 3,500 patients initiating a new chemotherapy regimen have been prospectively registered at 137 randomly selected practice sites. Major disease sites include breast, lung, colorectal, ovary and lymphoma. Primary outcomes include severe neutropenia (SN; absolute neutrophil count nadir Results: This analysis is based on the first 2,361 patients treated to date including 924 (39%) age ≥65. Severe neutropenia was documented in 28% and FN in 16% across all cancer categories. The proportion of patients with ANC Neutropenic Events By Cycle (% Patients) Primary Outcome Cycle 1 (N=2361) Cycle 2 (N=2032) Cycle 3 (N=1724) Cycle 4 (N=1246) Total (N=2361) Any SN 16 11 10 11 48 1st Cycle SN 16 6 4 2 28 Any FN 8 6 5 1 20 1st Cycle FN 8 4 3 1 16 The proportion of initial episodes of severe neutropenia that occur in cycle 1 include: colorectal (67%); lung (59%); ovary (44%); lymphoma (62%) and breast (70%). Likewise, the proportion of initial episodes of FN occurring in cycle 1 include: colorectal (53%); lung (60%); ovary (57%); lymphoma (56%) and breast (58%). Conclusions: Rates of severe and febrile neutropenia vary with tumor type. The initial episode of severe or febrile neutropenia is most likely to occur during the first cycle of chemotherapy across all major cancer types.

Background: Venous thromboembolism (VTE) is a frequent and significant complication of cancer and of chemotherapy, with an estimated risk of 0.04%/month (0.5%/year). Patients with thrombocytopenia are widely perceived to be at low-risk for VTE. Conversely, thrombocytosis may contribute to risk of VTE, but this has not been well-studied. We conducted a prospective analysis to determine the association of platelet counts with the incidence of symptomatic VTE in cancer patients receiving chemotherapy. Methods: The Awareness of Neutropenia in Cancer (ANC) Study Group is currently enrolling patients with breast, lung, colon, ovary and other cancers, at 137 sites nationwide, with an accrual goal of 4,500 patients. Patients are registered at the time of initiation of a new chemotherapy regimen, and followed for 4 cycles. The association of VTE with platelet counts and other clinical variables was studied in univariate analysis and in a multiple logistic regression model. Results: A total of 2,151 patients treated with at least one cycle of chemotherapy were available for analysis. Of these, 18.1% had platelet counts Conclusion: This is the first report describing an independent association of platelet counts with symptomatic VTE in cancer patients receiving chemotherapy. Patients with platelet counts of ≥ 350,000 prior to initiation of chemotherapy are at a three-fold greater risk for developing VTE. The role of platelets in the pathogenesis of chemotherapy-associated thrombosis warrants further study. Platelet counts should be taken into account when defining high-risk patients for thromboprophylaxis. Figure Figure

Background: Thromboembolism (TE) is a common complication of hospitalized non-transplant cancer patients. To date, the extent and impact of TE in stem cell transplant patients is unknown, in part because it is considered a low risk group given the high prevalence of thrombocytopenia. The purpose of this study is to evaluate the incidence of and risk factors for TE in cancer patients undergoing stem cell transplantation. Methods: We conducted a retrospective analysis of all discharge summaries from the 115 US academic health centers reporting to the University HealthSystem Consortium from 1995 to 2002. We identified a total of 7,087 patients with hematologic malignancies undergoing allogeneic and autologous stem cell transplantation. The incidence of and risk factors for venous and arterial TE was analyzed in univariate and multivariate logistic regression analysis with adjusted odds ratios as estimates of relative risk. Results: TE was reported in 389 (5.5%) transplant patients with 4.8% patients developing venous and 0.7% arterial TE. The incidence of TE was greater in allogeneic (6.8%) compared to autologous (4.8%) transplant patients (p30 days (OR=1.66; 1.30–2.13; p Conclusions: This is the first substantive report on the incidence of thromboembolism in stem cell transplant patients. We found that thromboembolic events are a frequent complication in patients with hematologic malignancies undergoing stem cell transplantation. The incidence of TE is high among most subgroups studied. Prospective studies are needed to evaluate the efficacy and safety of thromboprophylaxis in this high-risk population.

Background: Cancer is associated with thrombosis, but the frequency of thromboembolism in hospitalized cancer patients receiving contemporary chemotherapy regimens is not known. We investigated the frequency of arterial and venous thromboembolism in hospitalized cancer patients receiving active therapy (as identified by the presence of neutropenia) and characterized its association with in-hospital mortality. Methods: We conducted a retrospective cohort study using the discharge database of the University HealthSystem Consortium. This included 66,106 adult neutropenic cancer patients with 88,074 hospitalizations between 1995 and 2002 at 115 academic medical centers. Patients were identified using ICD-9-CM codes that contained at least one diagnosis of malignant disease and agranulocytosis. Patients with thromboembolism were identified using codes for venous thrombosis, pulmonary embolism, arterial embolism, acute cerebrovascular disease, and acute coronary arterial disease. The association of VTE with clinical variables was studied in univariate analysis and in a multivariate logistic regression model. The chi-square test was used to compare categorical variables, and Cochran-Armitage test to determine trend. Results: Thromboembolism was reported in 5,272 patients (8%), with 5.4% patients developing venous and 1.5% arterial thromboembolism during the first hospitalization. There was a significant association between the occurrence of venous and arterial thromboembolism (OR 1.73, 95%CI, 1.38–2.16). Venous thromboembolism was more frequent in patients with metastatic disease (OR, 1.23, 95% CI 1.13–1.34), but arterial thromboembolism was not (OR, 0.59, 95% CI, 0.51–0.69). In-hospital mortality was significantly greater in patients with venous (OR 2.01, 95% CI 1.83– 2.22) or arterial thromboembolism (OR 5.04, 95% CI, 4.38–5.79), even in patients without metastatic disease. Patients with lymphoma or leukemia accounted for one-third of venous events and one-half of arterial events. Clinical variables most frequently associated with thromboembolism in a multivariate logistic regression analysis were age ≥ 65 years, primary sites of cancer including lung, gastrointestinal, gynecologic and brain, length of stay ≥ 10 days, and comorbidities including infection, pulmonary and renal disease, and obesity. From 1995 to 2002, there was a 36% increase in venous and a 124 % increase in arterial events (P for trend Conclusions: The incidence of thromboembolism is high across all cancer subgroups including patients with hematologic malignancies and with non-metastatic disease, commonly perceived to be at lower risk for thromboembolism. Of particular concern is the increasing frequency of venous and arterial thromboembolism. Prospective studies are necessary to characterize the risks and benefits of thromboprophylaxis in this patient population. Figure Figure