ALBERT

Description: Introduction Iron plays a critical role in patients with multiple myeloma (MM). The limited availability of iron to the developing erythroid precursors results in the characteristic anemia so frequently seen in these patients. Moreover, iron is also a determinant in growth of the malignant plasma cells that makes it one of the critical factors in progression of the disease. Iron is a key component in success of erythropoietin (EPO) therapy that is often used to maintain hemoglobin (Hb) level of 〉10g/dL in patients with MM. International Myeloma working group (2011) advised transfusing IV iron to aid in success of EPO therapy. However, apart from determining the iron stores on bone marraow aspirate, there is hardly any reliable clinical or lab indicator of the iron stores in the body. The utility of various iron indices in determining the bone marrow iron stores remains anecdotal. In this study we aim to determine the relation between iron indices and iron level in the bone marrow of patients diagnosed with multiple myeloma. Methods A total of 268 multiple myeloma patients, diagnosed from 2004 to 2015, were identified from tumor registry of John H. Stroger Jr. Hospital of Cook County, Chicago. Accuracy of ferritin, iron level, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC) and transferrin saturation (TSAT) was evaluated using receiver operating characteristic curves (ROC). Out of sampled patients, 167 patients had a concurrent bone marrow biopsy and aspirate, serum ferritin and iron panel, and were included in ROC analyses. Results The study population consisted of 57% African-Americans, 18% Caucasians and 16% Hispanics. Median age was 61 years and 51% were females. Past history was significant for hypertension (48%), diabetes (31%), co-existing inflammatory conditions (18%), smoking (25%), alcohol abuse (17%) and illicit drug abuse (8%). Median hemoglobin, mean corpuscular volume (MCV), leukocytes and platelets were 10g/dL, 90.3fL, 6,200/mcL and 219,500/mcL respectively. Bone marrow aspirates for iron were rated as absent (37%), mild/moderate (18%) and adequate/normal (45%). Anemia was found in 79% of males (Hb

Description: Introduction: Rivaroxaban is a target specific oral anticoagulant approved for treatment of deep venous thromboembolism (DVT), pulmonary embolism (PE) and risk reduction in patients with DVT/PE requiring continued anticoagulation. The XALIA study showed a reduced bleeding risk compared to standard anticoagulation therapy; however, there is paucity of data regarding correlates of bleeding risk amongst patients receiving rivaroxaban in the community setting. We aimed to investigate the clinical factors associated with bleeding events (BE) in patients receiving rivaroxaban for treatment of DVT/PE. Methods: A retrospective study was conducted at John H. Stroger, Jr. Hospital of Cook County. We screened the charts of 837 patients who received rivaroxaban from January 1, 2015 to April 01, 2018. Patients with DVT/PE were included in the study (n=271). Patients with atrial fibrillation and those receiving rivaroxaban for prophylaxis were excluded. Any reported BE was recorded as either major or minor bleeding event. Major BE was defined as events requiring hospitalization, blood transfusions or significant drop in hemoglobin (〉2gm/dL). Rest of the BE were classified as minor BE. Socio-demographic and clinical factors were collected. Chi-square test and fisher exact test were used as the tests of trend. Multivariate logistic regression models were used to quantify the independent predictors. Odds ratios (OR) and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were obtained. Results: The study included 271 patients, of which 68.3% were African-American, 14.4% were Caucasian, and 12.9% were Hispanic. Median age was 53 years and 60.9% patients were men. Bleeding events were reported in 11.4% (n=31) patients with 6.3% major bleeding events and 5.2% minor bleeding events. Only concurrent use of aspirin (23.8% vs. 9.2%; OR 3.10, 95% CI 1.34-7.17, P = 0.008) was significantly associated with bleeding events. None of the clinical parameters, like abnormal liver function tests (11.4%), cirrhosis (3.3%), chronic kidney disease stage 3 or worse (7.6%), prior use of warfarin (29.9%) or low molecular weight heparin (18.1%) were associated with bleeding events. In multivariate model adjusted for age, gender and race, concurrent use of aspirin (aOR 3.06, 95% CI 1.23-7.62, P = 0.017) remained independent predictor of bleeding events. Conclusion: In the community practice, aspirin (81mg or 325mg) is prescribed for cardio-protection. A recently concluded trial showed a better cardioprotective effect of combining rivaroxaban and aspirin, without increase in BE in patients with stable cardiovascular disease. However, such data is not evident in patients receiving rivaroxaban for DVT/PE. Our study shows an increased rate of bleeding events in such patients with concurrent use of aspirin. Our study population comprises of two-third African-American patients who are under-represented in the clinical trials. Based on our results we would suggest further investigation in safety of prescribing aspirin with rivaroxaban in patients with DVT/PE in prospective trials. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Fostamatinib, a spleen tyrosine kinase (Syk) inhibitor has been studied in clinical trials of chronic immunologic conditions such as Rheumatoid Arthritis (RA), chronic immune thrombocytopenic purpura (ITP), IgA nephropathy and certain lymphomas. It has recently been granted FDA approval for the treatment of ITP. Fostamatinib inhibits the Syk pathway which is also involved in platelet activation through collagen receptor and the integrin αIIbβ3, which, in theory, would increases the risk of bleeding. Also, by inhibiting Syk, fostamatinib reduces macrophage phagocytosis and may render them ineffective against certain bacteria, hence increasing the risk of serious infections. We sought to examine the side effect profile of Fostamatinib in published and unpublished studies randomized controlled trials (RCT). Methods: A systematic search of scientific databases, major conference abstracts and clinical trial registries was performed. Only Phase 2 and Phase 3 RCTs with a placebo arm were included. For dosing of fostamatinib, we preferentially used the 100mg BID dosing as this is the dose approved by the FDA for ITP and is the dose determined through the large trials in patients with RA, which strikes a balance between benefits and harms. When the 100mg and 150mg dosing were combined (as in the ITP trials), we used data from that arm for the analysis. All major and minor harms specified in the trials were pooled using a random effects model and the risk ratio (RR) and confidence interval (CI) was determined using the Mantel-Haenszel method. An I2 value of less than ≤ 40% was considered minimal heterogeneity. Results: The search found 12 studies involving 1,444 cases and 1,188 controls. Of these, 9 studies examined the use of fostamatinib for RA whereas 2 studies were on ITP, and 1 study was on IgA nephropathy. Commonly encountered side effects of fostamatinib therapy were diarrhea, headache, nausea and hypertension. When compared to placebo, fostamatinib was associated with 19% higher risk of any adverse event (9 studies, RR = 1.19, CI = 1.07 - 1.33, I2 = 40%). Patients who received fostamatinib had a significantly higher risk of developing neutropenia (ANC 〈 1500/microL) when compared to placebo (8 studies, RR = 4.34, CI = 1.82 - 10.31, I2 = 30%). There was only 1 case of febrile neutropenia in one of the ITP trials. There were no significant differences between the fostamatinib and placebo groups with regard to upper respiratory tract infections (7 studies, RR = 1.43, CI = 0.61 - 3.36, I2 = 49%), urinary tract infections (4 studies, RR = 1.6, CI = 0.78 - 3.28, I2 = 0%) or serious infections (7 studies, RR = 1.18, CI = 0.42 - 3.30, I2 = 0%). However, when compared to placebo, there was a 2.23 times higher risk of developing diarrhea (10 studies, CI = 1.46 - 3.41, I2 = 45%) and hypertension (9 studies, CI = 1.61 - 3.09, I2 = 13%) in the fostamatinib group. Most patients had hypertension at baseline and few needed either medication initiation or adjustment in the fostamatinib cohorts. Fostamatinib also significantly increased liver enzyme (ALT 〉 3 ULN) when compared to placebo (9 studies, RR = 2.21, CI = 1.18 - 4.14, I2 = 0%). There were higher bleeding events in the fostamatinib group, but there was no significant difference between the treatment and placebo arms (4 studies, RR = 1.06, CI = 0.16 - 6.94, I2 = 45%). There were no significant differences between the treatment and control groups with regard to serious adverse events and mortality. Treatment discontinuation rates due to adverse events were not significantly different between groups. Conclusions: Fostamatinib tends to have a relatively benign side effect profile, with few serious side effects. In congruence of the theoretical higher bleeding risk with Syk inhibition, the bleeding events were slightly higher in fostamatinib group, however there was no statistically significant difference between the treatment and the placebo groups. Similarly, the incidence of neutropenia, though higher in the Fostamatinib group, was rarely associated with fever (1 event among all 12 trials). The incidence of serious infections did not differ significantly between groups. Gastrointestinal and cardiac side effects were transient and did not lead to significantly more treatment discontinuations when compared to placebo. Larger longitudinal studies are needed to better examine the long-term side effects associated with Fostamatinib. Table Disclosures No relevant conflicts of interest to declare.

Description: Introduction US Food and Drug Administration has recently approved the use of rivaroxaban 2.5mg BID in patients with coronary heart disease based on Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial. However, it's unclear whether there is net clinical benefit with use of rivaroxaban in such patients. Therefore, we did a systematic review and meta-analysis to evaluate the effects of rivaroxaban on clinical outcomes in coronary heart disease patients. Methods: Embase, Ovid, Pubmed and Scopus were extensively searched from inception of these databases to April 2019 by two independent reviewers. Only randomized controlled trials of low dose rivaroxaban (2.5 mg BID) reporting mortality and cardiovascular outcomes of interest in baseline coronary heart disease patients (≥ 18 years) with at least 1000 patients and follow-up of ≥ 1 year were included. The co-primary outcomes were cardiovascular mortality and all-cause mortality. The secondary endpoints were myocardial infarction (MI), stroke, major adverse cardiovascular events, major bleeding and cerebral nervous system (CNS) bleeding. Cochrane Collaboration's tool was used for risk of bias assessment. Statistical heterogeneity was quantified using I2 statistics whereas publication bias was assessed with Eggers regression test. We combined estimates using DerSimonian and Laird random effects models. Outcomes were reported as hazard ratios (HR) with 95% confidence intervals (CI). Results: Five randomized control trials including 39,979 patients were included in our meta-analysis. Trials ATLAS and Commander HF used placebo as their control while COMPASS and GEMINI ACS-1 used aspirin as control. Pioneer AF-PCI used vitamin K antagonist as the control. Mean age (SD) of the patients was 65.6 ± 3.7 years with 74.3% females. Mean follow up in years was 1.6 ±0.5. Majority of the patients in each trial had hypertension. Our pooled analysis showed reduction in all-cause mortality (HR, 0.85, 95% CI, 0.72-1.00, P=0.05), cardiovascular mortality (HR, 0.83, 95% CI, 0.70-1.00, P=0.05), MI (HR, 0.88, 95% CI, 0.78-1.00, P=0.05) and stroke (HR, 0.70, 95% CI, 0.53-0.94, P=0.02) with low dose rivaroxaban. No significant difference in risk of bleeding was observed (HR, 1.45, 95% CI, 0.83-2.51, P=0.19). Our pooled analysis also showed reduction in major cardiovascular events (HR, 0.91, 95% CI, 0.85-0.98, P=0.01). CNS bleeding was only reported by ATLAS and COMPASS trials and net effect showed no statistically significant bleeding risk (HR, 1.63, 95% CI, 0.70-3.79, P=0.26). Conclusion: Our data suggest that the use of rivaroxaban is associated with reduction in all-cause and cardiovascular mortality in coronary heart disease patients without significantly increasing the risk of bleeding. To further decrease the residual risk of cardiovascular events in coronary heart disease patients, low dose rivaroxaban can be considered by clinicians. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Current expert recommendations recommend double therapy (DT) over triple therapy (TT) in atrial fibrillation patients post percutaneous coronary intervention (PCI) to prevent the incidence of stroke. Though previous studies have focused on DT (oral anticoagulant [OAC] + P2Y12 inhibitor (including clopidogrel, ticagrelor and prasugrel)) versus TT (OAC + P2Y12 inhibitor and aspirin) strategy, no study assessed which OAC was more effective in the prevention of cardiovascular events and stroke. To this end we performed a systematic review and meta-analysis to assess whether non-vitamin K oral anticoagulants (NOAC) based DT strategy is comparable with vitamin K antagonist-based TT in patients with AF after PCI. Methods: Embase, Ovid, Pubmed and Scopus were extensively searched for only phase 2 and 3 clinical trials comparing NOAC based DT with VKA based TT from inception of these databases till June 2019 by two independent reviewers. The endpoints were all-cause mortality, Thrombolysis in Myocardial Infarction (TIMI) major bleeding, cardiovascular mortality and myocardial infarction. Cochrane Collaboration's tool was used for risk of bias assessment. Statistical heterogeneity was quantified using I2 statistics. Publication bias was assessed with Eggers regression test. Estimates were reported as hazard ratios (HR) with 95% confidence intervals (CI) using random effect model. Rivaroxaban 15 mg once daily dose from PIONEER-AF was included. From REDUAL-PCI trial we included dabigatran 110 mg BID and 150 mg BID doses. AUGUSTUS trial used 5 mg BID or 2.5 mg BID dosing of apixaban. Results: 402 trials were retrieved in the initial search which were analyzed according to PRISMA (Preferred Reporting Items for Systematic review and Meta-Analyses) guidelines. Three trials (Augustus, PIONEER AF-PCI and RE-DUAL PCI) were extracted that met the inclusion criteria and included in the final analysis evaluating 8754 patients. Twenty seven percent were females. Mean age was 71 years. PCI was done for acute coronary syndrome in 44% of the patients. Mean calculated CHA2DS2-VASc was 4 which qualifies the use of oral anticoagulants. Only PIONEER AF-PCI and RE-DUAL PCI trials described the type of stent used for PCI. Drug eluting stents were used in 71% of the patients. There was no evidence of publication bias in our analysis (P=.78). The studies overall had low risk of bias. Our analysis showed no statistically significant difference in usage of NOAC + P2Y12 inhibitor compared to triple therapy consisting vitamin K antagonist in regards to all-cause mortality, (HR 0.92, 95% CI 0.72-1.18, P=.52), thrombolysis in myocardial infarction (TIMI) major bleeding (HR 0.91, 95% CI 0.38-2.16, P=.83), cardiovascular mortality (HR 0.95, 95% CI 0.71-1.28, P=.75), stroke (HR 1.07, 95% CI 0.67-1.71, P=.78),stent thrombosis (HR 0.72, 95% CI 0.42-1.23, P=0.23) and myocardial infarction (HR 0.88, 95% CI 0.68-1.13, P=.32). Conclusion: We conclude that there is no difference between the usage of NOAC including rivaroxaban, dabigatran and apixaban in dual regimen vs triple therapy with VKA (warfarin). However, some limitations need to be considered such as heterogeneity across patients in terms of indication for PCI (elective vs emergency), choice of P2Y12 inhibitor (clopidogrel vs ticagrelor vs prasugrel), mean duration of therapy (range 6-12 months) and mean length of follow-up (range 6-14 months). In future clinical practice, post-PCI antithrombotic regimens in AF will likely consist of a single P2Y12 inhibitor plus NOAC. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Liver cirrhosis is being increasingly recognized as a hypercoagulable state, mainly due to disproportionate reduction in antithrombotic factors (protein C, S and anti-thrombin III). Portal vein thrombosis (PVT) is a frequent sequala of liver cirrhosis that can lead to numerous complications and potential exclusion from transplant lists, at least until the resolution of the thrombus. The current evidence for anticoagulation (AC) for PVT in liver cirrhosis is limited to small retrospective studies. Major liver societies recommend limited anticoagulation with enoxaparin based on expert opinion (Category C). We sought to examine the incidence of bleeding after AC in cirrhotic patients with PVT. Methods: Data were obtained from a commercial de-identified database (Explorys, IBM, Inc.) that integrates electronic health records from 27 major integrated U.S. healthcare systems from 1999 to July 2019. Cases were defined as adult patients aged 〉=18 years having a new Systematized Nomenclature of Medicine Clinical Terms (SNOMED) diagnosis of PVT, had been anticoagulated for the first time following PVT and had experienced bleeding for the first time following AC. Controls were adults who had a diagnosis of PVT and did not get AC. We included older anticoagulants (warfarin and enoxaparin) as well as newer anticoagulants (apixaban, fondaparinux and rivaroxaban). We compared the incidence of bleeding (defined as bleeding from any site) in those with PVT who received AC to those with PVT who did not receive AC. In addition, we also compared the incidence of bleeding between older and newer anticoagulants, and also examined whether there were differences in gender, race, and insurance status for those who bled while on AC. Analysis comprised of calculating odds ratios (OR) and confidence intervals (CI) for the OR. Results: A total of 213,810 patients had liver cirrhosis and out of those, 7,570 (3.5%) patients had PVT. Four hundred and ten cases out of 1,430 patients who received AC bled for the first time whereas 980 cases out of 3,880 patients who did not receive AC bled for the first time. Cases on AC had 1.18 times higher odds of bleeding when compared to controls who did not receive AC (CI = 1.04 - 1.36). Newer AC were less likely to increase bleeding when compared to older AC (OR = 0.6, CI = 0.4 - 0.9). Females were significantly more likely to be first time bleeders on AC when compared to male first-time bleeders on AC (Table 1). However, race and insurance status did not seem to affect bleeding rates (Table 1). Conclusion: Anticoagulation for PVT in liver cirrhosis increases bleeding events. Newer AC were significantly less likely to increase bleeding when compared to older AC. Females were more likely to bleed on newer AC than males, but race and insurance status did not affect bleeding rates. Limitations of the study include the retrospective nature of the analysis that relied on diagnosis coding, and smaller numbers in our subgroup analyses which limits generalizability. Clinicians should be aware of the significant risk of bleeding when prescribing AC, particularly older AC to cirrhotic patients with PVT. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: The incidence of bone marrow involvement (BMI) in patients diagnosed with Hodgkin Lymphoma (HL) is relatively low varying from 4-14% in different series occurring mainly in patients with advanced disease (stage III-IV). Ann Arbor staging system with Cotswolds modification in 1989 recommend staging bone marrow in patients with clinical stage III-IV and stage II patients with adverse risk features. It’s utility is now questionable and no longer recommended by many authors as it does not alter the way patients are managed. The advent of 18F-fluoro-2 –deoxy-D-glucose positive emission tomography (FDG-PET) scan use in the staging of patients has improved the prediction of possible bone marrow involvement obviating further the need for bone marrow biopsy. While BMI is said to be an independent prognostic factor in the survival of patient with HL, more studies have shown that BMI alone in patients with Stage IV disease does not influence survival or freedom from disease progression. Because staging bone marrow biopsy (BMB) use in HL varies from one institution to another, we performed a retrospective review in our institution in order to determine its incidence, risk factors and effect in the management of patients. Methods: We performed a retrospective search in John H Stroger, Jr. Hospital database of patients with HL seen from 2004 to 2013. 237 adult (18yr and above) patients were screened. 185 patients had BMB done as part of work up. Results: BMI was detected in 21%(38 of 185) of patients who had BMB as part of work up. M:F ratio was 2.5:1. Mean age was 39.8 +/- 11.5yrs. 51%(95 of 185) of patients who had BMB had advanced disease. 94%(33 out of 35) of patients with BMI had advanced disease prior to BMB. 3 patients with BMI were incompletely staged. Advanced disease was significantly more likely to be associated with BMI than early stage disease (OR 20.2 95% CI 4.6-87.6 p=0.0001). Less than 1%(2 out of 78) of patients with early stage disease were upstaged .The 2 patients that were upstaged had Stage IIB disease prior to BMB.38%(14 of 37) of patients with BMI were HIV positive which was higher compared to 12%(16 of 129) of patients without BMI that were HIV positive (OR 5.8 95% CI 2.4-14.0 p=0.0001). 5 of 38 patients with BMI had staging FDG-PET and all showed positivity in the skeletal system. Patients with BMI in our review were managed with 6-8cycles of chemotherapy (CT)-Adriamycin, Bleomycin, Vinblastine and Dacarbazine regimen (ABVD). 5 cases were relapsed disease. 4 of these patients with relapsed disease received Platinum/Gemcitabine regimen and one patient received Mechlorethamine, Vincristine, Procarbazine and Prednisone regimen (MOPP). Radiation Therapy (RT) was part of the management in 4 patients done for cord compression (2), bulky mediastinal disease (1) and for residual disease after chemotherapy (1). Conclusions: The incidence of BMI was high in our retrospective review compared to other series, however majority of involvement were in patients with advanced disease as in most series. Patients were rarely upstaged from early stage to advanced stage with bone marrow biopsy. This occurred in less than 1% in our retrospective review. Staging FDG-PET although done in few of our patients with BMI was predictive. Management of these patients was not significantly altered based on BMI. They were managed mainly with CT. RT needed in some of these patients was justified (cord compression, and bulky mediastinal disease). RT for residual disease is not a standard of care. Risks factors identified for BMI includes advanced disease and associated HIV infection. BMB does not alter patient management and its sole prognostic significance in patients with stage IV disease is controversial. It is therefore not necessary in the staging of newly diagnosed patients with HL. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Spleen tyrosine kinase (Syk), a cytoplasmic tyrosine kinase, is a member of the non-receptor type protein kinase family. Apart from the hematopoietic cells, it is also expressed in the epithelial and endothelial cells. Fostamatinib, a Syk inhibitor, has been proven beneficial in autoimmune disease like rheumatoid arthritis (RA) and immune thrombocytopenia (ITP). Murine models have shown a direct correlation between hypertension and level of R406, the active metabolite of fostamatinib. In this study, we sought to examine the cardiovascular profile of fostamatinib in published and unpublished randomized controlled trials. Methods: A systematic search of Pubmed, Medline and Scopus databases were done from inception till date to identify all phase 2 and 3 clinical trials of fostamatinib in patients with ITP and RA by two independent reviewers. Trials were included if they reported side effects including but not limited to cerebral ischemia or infarction, myocardial ischemia and myocardial infarction, hypertension and cardiac rhythm disorders. 35 trials were retrieved in the initial search which were excluded according to PRISMA (Preferred Reporting Items for Systematic review and Meta-Analyses) guidelines. 11 trials met the eligibility criteria and were included in the final analysis. All statistical analysis was carried out using OpenMetaAnalyst software. Categorical variables from each study are presented as proportions. The proportions from each study were subjected to arcsine transformation and pooled using a random-effects model. This yielded the pooled estimate with 95% confidence intervals. The I2 statistic was used to assess heterogeneity and a value of I2 = 25%-50% was considered mild, 50%-75% as moderate, and 〉 75% as severe. A P value of

Description: Background: The utility of bone marrow biopsy (BMB) in patients with Hodgkin lymphoma (HL) has been a controversial topic. Clinical stage 4 (CS4) has been shown to be an independent poor prognostic marker and is also included in the International Prognostic Scoring (IPS) index for predicting both progression-free survival (PFS) and overall survival (OS). The current guidelines still recommend performing a BMB in patients with stage IIB (with unfavorable risk factors), III and IV HL, mainly for staging purposes. Though bone marrow involvement (BMI) upstages the HL to stage IV, the prognostic significance of BMI remains unclear. The study was aimed to determine the prognostic significance of BMI in underserved patients with HL and to determine the prognostic importance of other blood parameters. Methods: The study was conducted at John H. Stroger Hospital of Cook County, an inner city tertiary care hospital providing care to the underserved population of Chicago. Charts of 241 patients diagnosed with HL were screened from tumor registry. Patients with incomplete charts were not included in the study. Socio-demographic, clinical and pathologic factors were recorded at the time of diagnosis. For comparative purpose, CS4 disease did not include patients with BMI. Kaplan-Meier and bivariate analyses were performed. Cox regression analyses were conducted to explore predictors of OS and PFS. Hazard ratios (HR) with 95% confidence intervals (CI) were obtained. Results: The study included 192 patients of which 41% were Afro-Americans, 34% were Hispanics and 21% were Caucasians. Median age was 34 years with 25.5% patients being older than 45 years and 68% patients being women. Seventeen percent patients were positive for HIV. Nodular sclerosis was the most common histologic subtype (55%), bulky disease was recorded in 19% patients and 61.5% patients had B-symptoms. CS4 disease was seen in 12% patients while 28% patients were stage III, 47% were stage II and 13% were stage I. Single-site BMB was done in 96% patients. BMB was positive for involvement with HL in 19% patients (n=37). Out of these 37 patients, 84% (n=31) had advanced stage (III & IV) HL. BMI was seen in 5% patients with early-stage HL (stages I-II) and 41% patients with advanced-stage HL. Median IPS score was 2 (range 0-6). Median values for clinical factors were: hemoglobin-11.8 g/dL, platelets 314.5 x103/uL, leukocytes 8.3 x103/uL, neutrophils 6x103/uL, lymphocytes 1.2 x103/uL and albumin 3.7 g/dL. Mean OS was 143 months (95% CI 126-160) with 5-year OS of 89%. Significant correlates of OS included: age 45 years or older (HR 2.83, 95%CI 1.25-6.43, P =0.013), HIV (HR 2.80, 95%CI 1.19-6.61, P =0.019), nodular sclerosistype (HR 0.29, 95%CI 0.12-0.71, P =0.006), CS4 disease (HR 3.05, 95%CI 1.20-7.77, P =0.019), BM positive for involvement with HL (HR 5.76, 95%CI 2.56-12.98, P