ALBERT

Description: BACKGROUND: Anthracycline based treatment for acute myeloid leukemia (AML) can be associated with significant morbidity and mortality amongst older patients or those with significant co-morbidities. Furthermore, for patients with previous anthracycline exposure or preexisting cardiac disease anthracyclines pose an increased risk of cardiotoxicity. For such patients intensive treatment options are limited. The FLAG (fludarabine, cytarabine and filgrastim) regimen is a non-anthracycline based chemotherapy useful for relapsed/refractory AML and as initial therapy for “fit” eligible patients. We present our experience using FLAG as first line therapy in a cohort of newly diagnosed AML patients with advanced age, significant co-morbidities or preexisting cardiac disease. METHODS: A single institution retrospective chart review was undertaken of patients treated with FLAG as frontline therapy from 2004 – 2013 with follow-up until June 2014. All patients were considered ineligible for standard ‘3+7’ treatment by the attending physician. RESULTS: Over the study period 56 patients received FLAG. Due to patient refusal or induction complications bone marrow assessments to ascertain remission status were not performed in 10 patients – to minimize bias these patients were evaluated for toxicity and overall survival (OS) but excluded from complete remission (CR) and relapse free survival (RFS) analysis. Of the 56 patients, 68% were males. The median age was 69 (21 – 80) with 79% aged ≥ 60 and 43% aged ≥ 70. Fifty-five percent (31) of the patients had primary AML and cytogenetics were favorable in 5% (3), intermediate in 66% (37), poor-risk in 21% (12) and failed in 7% (4). Forty-six percent (26) were treated with FLAG due to preexisting cardiac disease and others due to advanced age (20%), poor performance status (16%), co-morbidities (16%) or previous anthracycline exposure (2%). The ages of patients treated with FLAG due to cardiac disease or other reasons was similar (63.5 years vs. 66.9 years, p=0.27). Amongst patients with cardiac disease a pre-chemotherapy cardiac evaluation revealed wall motion abnormalities in 39% and an ejection fraction (EF) ranging from 33% - 81% with a borderline (≤ 50-51%) EF in 46%. Febrile neutropenia was observed in 82% (46) of patients, 27% (15) required intensive care support and the induction mortality was 16% (9). Amongst patients evaluated for a CR (46/56), 48% (22/46) obtained a CR. Although a CR was seen in 100% (3/3), 46% (15/33) and 37% (3/8) of patients with favorable, intermediate and poor-risk cytogenetics respectively there was no statistically significant difference (p=0.22) between groups. A CR was obtained in two additional patients following a second course of FLAG for an overall CR rate of 52% (24/46). Of these 24 patients, 8 (33.3%) received no additional treatment while 16 (66.7%) received consolidative chemotherapy. Of 10 eligible patients, 4 proceeded to an allogeneic stem cell transplant (allo-SCT) including two with preexisting cardiac disease. Of patients not transplanted 50% (10/20) eventually relapsed. There was no difference in relapse rates for those receiving FLAG for age/co-morbidities vs. cardiac disease (60% vs. 40%, p= 0.66) or for patients age

Description: Background: Heparin-induced thrombocytopenia (HIT) is associated with anti-platelet factor-4 (PF4)/heparin antibodies that activate platelets, resulting in thrombocytopenia and a pro-thrombotic state. At our institution antibody-mediated platelet activation is demonstrated by lumi-aggregometry, which is a method previously validated against the gold standard serotonin-release assay (SRA). Lumi-aggregometry does not involve radioactive isotopes, which is its major advantage over the SRA. The clinical course of HIT diagnosed via SRA and ELISA has been previously described, and clinical prediction tools such as the 4-T score were validated using these diagnostic tests. However, the clinical picture of HIT diagnosed by lumi-aggregometry has not been previously described. Aims: The objective of this study is to describe the clinical and laboratory presentation of patients diagnosed with HIT by lumi-aggregometry. Methods: Patients with clinically suspected HIT and quantitative anti-PF4 IgG-specific ELISA OD ≥0.400 (Gen-Probe, San Diego) received confirmatory HIT testing by lumi-aggregometry. Briefly, HIT antibody-induced activation of washed healthy donor platelets was tested at therapeutic (0.1U/mL and 0.5U/mL) and high (100U/mL) porcine heparin concentration. The degree of platelet activation was quantitated luminographically based on the light flash reaction of ATP (released from platelet dense-granules) with luciferin luciferase reagent. A ratio of therapeutic to high heparin luminescence amplitude of 〉5.0 and platelet aggregation at therapeutic, but not high, concentrations was considered a positive result. The results of assays performed by our regional HIT testing referral laboratory from June 2009 to July 2012 were reviewed to identify patients with positive HIT testing by lumi-aggregometry. Patient records were retrospectively reviewed to obtain predefined data on baseline patient characteristics, heparin exposure, platelet counts, and thrombotic events occurring in the 5 days preceding or the 30 days following the date of positive HIT testing. Results: We identified 43 patients diagnosed with HIT by lumi-aggregometry (median age 68.0, 49% male) while under the care of local academic (46%) or urban community hospitals (37.2% medical; 53.5% surgical; 9.3% intensive care). Median baseline platelet count was 187 (14-349). Median date of platelet drop post-heparin exposure was 6 days (range 3-14) in patients without prior heparin exposure or platelet transfusions (Figure 1). Platelet drop 〉50% and platelet nadir ≥20x109/L were present in the majority of patients (Table 1). Thrombocytopenia occurred prior to (70.5%) or the same day (23.5%) as thrombosis in 16/17 patients with serial platelet counts who developed HIT-associated thromboembolism. Conclusion: Patients diagnosed with HIT by lumi-aggregometry present with similar findings to those described in SRA-confirmed HIT. These findings lend support to the use of lumi-aggregometry as an accurate diagnostic assay for the clinico-pathologic syndrome of HIT. Figure 1 Figure 1. Table 1. Percentage platelet drop from baseline and platelet nadir Percent platelet drop Platelet nadir 〉50% 30-50%

Description: Background: The diagnosis of acute myeloid leukemia (AML), response to treatment and disease recurrence are most commonly assessed with bone marrow studies. Recommendations from leading experts (Bain, 2001) and guidelines of the European LeukemiaNET (Dohner, 2010) and the National Comprehensive Cancer network (O’Donnell, 2012) suggest that only the bone marrow aspirate (BMA) is necessary to assess residual disease while the trephine biopsy (TB) is necessary only when an aparticulate BMA is obtained. In contrast, guidelines of the International Council for Standardization in Hematology (Lee, 2008) suggest that BMA and the TB should be routinely performed together as they provide complementary information. Due to these conflicting recommendations we sought to determine whether the TB provides additional sensitivity for the detection of residual leukemia following intensive chemotherapy for AML. Methods: A single centre retrospective chart review was conducted of bone marrow studies of all AML patients who had received intensive chemotherapy from 2004 – 2013. Those lacking a TB were excluded. Residual disease was assessed by morphological examination of the BMA and TB +/- immunostaining but minimal residual disease (MRD) analysis was not performed. Results: 598 bone marrow studies from 227 patients were evaluated. The median age of the patients was 54.6 (range 18 -77) with 70% age 〈 60. Forty-four percent were female. Cytogenetics were favorable in 30 (13%), intermediate in 146 (64%), high-risk in 44 (19%) and failed in 7 (3%) of the patients. Of the 598 bone marrow samples 198 (33%) were interim marrows performed 14 days following initiation of induction or re-induction chemotherapy (D14 marrow), 251(42%) were recovery marrows following induction/re-induction chemotherapy (EOI marrow) and 149 (25%) were during follow-up. The BMA was considered to be acellular/hypocellular in 31%, hemodilute in 16.4% and aparticulate/pauciparticulate in 27.3% of samples. As per guidelines 〉 200 cells were counted in 99.8% of the aspirate samples to ascertain remission status. The median length of the TB segments was 1.85 cm (0.2 – 7.0 cm) and it was considered inadequate in 12.7%, of good or excellent quality in 24.9% and adequate for residual disease assessment in the remainder of cases. Approximately 19 % of TB samples had mild to significant hemorrhagic artifact. The bone marrow cellularity could not be assessed in 1.2% of samples but was patchy in 0.5%, aplastic in 2.8%, hypocellular in 36%, normocellular in 23.6%, hypercellular in 23.2%, packed in 6% and was not described in 6.7% of the cases. Residual leukemia was identified in 33.1% of BMA and in 33.3% of TB samples. The BMA and the TB findings were concordant in 562 of 598 (94%) of cases. In 3.5% (21) of cases residual leukemia was seen in the TB but not the BMA whereas in 2.5% (15) of cases the BMA detected residual disease but the TB failed to do so. The TB led to a change in diagnosis from ‘No Leukemia’ to ‘Residual Disease’ in 5.1% of D14 marrows, 3.6% of EOI marrows and in 1.3% of follow-up marrows with no statistically significant difference between the groups (p=0.178). There was no relationship between a change in diagnosis and whether patients received an anthracycline or a non-anthracycline based chemotherapy regimen (4.4% vs. 3.2%, p=1.0). The TB, however, led to a change in diagnosis more commonly in patients with favorable risk karyotype relative to those with intermediate risk karyotype (20% vs. 6.2%, p= 0.02) but not relative to those with unfavorable risk karyotype (20% vs. 13.6%, p=0.53). Hemodilute bone marrow samples were more likely to have a TB related change in diagnosis relative to undilute samples (8.2% versus 2.6%, p=0.01) as were aparticulate/pauciparticulate samples relative to particulate samples (8% vs. 1.9%, p=0.00046). However, in multivariate analysis, only an aparticulate/pauciparticulate sample was associated with TB related change in diagnosis (p=0.015, OR = 3.6). Conclusions: Our data demonstrate that, following intensive chemotherapy, the BMA alone may fail to identify residual leukemia particularly when the BMA is aparticulate/pauciparticulate. In these situations the TB provides additional sensitivity for the detection of residual disease. Further studies are required to evaluate the need for the TB in particulate samples when combined with MRD analysis. Disclosures No relevant conflicts of interest to declare.

Description: Rivaroxaban is an ideal potential alternative for treatment of heparin-induced thrombocytopenia because it is administered orally by fixed dosing, requires no routine coagulation monitoring and has been proven effective in the treatment of venous and arterial thromboembolism in other settings. The Rivaroxaban for HIT Study prospectively evaluated the efficacy and safety of patients with suspected or confirmed HIT who were treated with rivaroxaban [NCT01598168 - investigator sponsored study funded by Bayer] Methods: Canadian multicenter, single-arm, prospective cohort study of patients with confirmed or suspected HIT (4Ts score ≥4) treated with rivaroxaban 15 mg bid until the diagnosis was supported or refuted using the local HIT assay. Participants with HIT (positive local assay result) received rivaroxaban 15 mg bid until platelet recovery (or until Day 21 if the patient had acute thrombosis; HITT) then stepped down to rivaroxaban 20 mg daily until Day 30. Central testing with the serotonin-release assay (SRA) was performed (not in real-time at all centres). HIT positive was defined as a 4Ts score ≥4 plus serotonin release ≥50%. The primary outcome measure was the incidence of new symptomatic, objectively-confirmed venous and arterial thromboembolism in the combined cohort of patients with suspected and confirmed HIT at 30 days. Secondary objectives included incidence of symptomatic thromboembolism while on treatment with rivaroxaban (combined cohort) and the following outcomes among SRA-positive participants while on treatment with rivaroxaban: incidence of venous and arterial thromboembolism, incidence of major bleeding, and time to platelet recovery. Sample size of 200 participants (10 to 30 with SRA-confirmed HIT) was based on feasibility and an anticipated thrombotic event rate in the study population (combined cohort) of 6.5% at 30 days (5% in HIT negative; 11% in HIT positive while on rivaroxaban). Results: 22 participants (12 HIT positive) were enrolled between January 2013 and July 2015. The study was terminated early due to poor recruitment, but after enrolling the minimum expected number of HIT positive participants. Of the 12 HIT positive participants (SRA, mean release 95%), 3(25%) had HITT at time of study entry and 6 had received at least one dose of fondaparinux prior to study enrolment. Half of the HIT positive participants were enrolled in study after the SRA result had already been reported as positive. After 371 days of exposure to rivaroxaban (combined cohort), 1 HIT positive participant had possible symptomatic recurrent VTE (4.5%, 95% CI: 0 to 23.5%), 1 HIT positive participant had major bleeding (9 days after rivaroxaban was held) and there were 4 deaths (cancer 2, sepsis 1, end-stage COPD 1). The single episode of possible recurrent VTE was extension of previously documented apheresis catheter-related arm DVT in a HIT positive participant who presented on Day 7 with worsening arm pain. A repeat ultrasound showed extension of DVT; however a baseline scan had not been performed at time of study entry. Interestingly, the same participant failed treatment with fondaparinux prior to study enrolment (development of erythematous plaques at injection sites and failure of platelets to rise). His apheresis catheter was removed on Day 8, rivaroxaban was continued and complete resolution of his symptoms as well as platelet recovery was achieved. One HIT positive participant presented with evidence of bilateral lower limb arterial ischemia (HIT-related acute arterial thrombosis on documented chronic peripheral vascular disease) at the time of study enrolment. Despite achieving platelet recovery, he underwent bilateral below knee amputation on Day 16. Out of the 12 HIT positive participants, 11 achieved platelet recovery with mean time to recovery 9 days. The single participant who did not achieve platelet recovery received only 2 doses of rivaroxaban before it was held due to a transient rise in liver enzymes. Rivaroxaban was never restarted because he bled while receiving fondaparinux as an alternative. Conclusions: Rivaroxaban appears to be effective for treating patients with confirmed HIT, although lack of a comparator and a small sample size are limitations of our findings. The advantages of rivaroxaban over other agents currently used to treat HIT such as ease of administration, lack of routine coagulation monitoring and low cost make it an attractive option. Disclosures Linkins: Pfizer: Honoraria; Bayer: Honoraria, Research Funding. Off Label Use: rivaroxaban has not been approved for treatment of heparin-induced thrombocytopenia. Warkentin:W.L. Gore: Consultancy, Research Funding; Instrumentation Laboratory: Consultancy, Honoraria; Pfizer: Consultancy. Pai:Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS-Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Shivakumar:Bayer: Honoraria. Wells:Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS-Pfizer: Research Funding. Wu:Pfizer Canada: Membership on an entity's Board of Directors or advisory committees; Leopharma: Membership on an entity's Board of Directors or advisory committees.

Description: Introduction The D-dimer has been validated for use in the diagnosis of venous thromboembolism (VTE). The high sensitivity of the assay allows for safe exclusion of VTE in patients with low pre-test probability. Pre-test probability scores such as the Wells score for Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) have been established to help guide physicians on when to order a D-dimer in patients with suspected VTE. We sought to explore the landscape of D-dimer ordering at our institution and what clinical circumstances trigger D-dimer ordering. Methods We conducted a retrospective chart review of 237 patients in whom a D-dimer has been ordered over a 3-month period from January to March 2018 at the University of Alberta Hospital, Edmonton, Canada. Charts were reviewed for the following parameters: Specialty of ordering physician, apparent indication for ordering, patient risk factors for VTE and evidence of pre-test probability calculation. If no pre-test probability was recorded, we retrospectively calculated Wells DVT or PE scores depending on the apparent indication. We then reviewed subsequent investigations thought to be influenced by interpretation of the D-dimer. These included ventilation/perfusion scans (V/Q scan), ultrasound Doppler studies and Computerized Tomography pulmonary angiography (CTPA). Results Of the 237 charts reviewed, 84.4% of D-dimers were ordered in the Emergency Department while only 14.3% were drawn on admitted patients. Sixty-nine percent of the patients were identified as having at least one risk factor for the development of VTE with prolonged hospitalization (5.5%) and personal history of VTE (4.2%) being the most common. Indication for ordering was suspected VTE in 76.3% of patients while the indications was unclear in 12.7% of patients. An initial pre-test probability score was recorded for only 3 patients. Of the D-dimers ordered, 47.7% were above the upper limit of normal (≥ 0.50 mg/L) and considered a positive test. Forty five CTPAs and 27 V/Q scans were performed with only 4 (1.69%) and 6 (2.53%) confirming the presence of pulmonary emboli, respectively. Doppler ultrasounds were performed on 18 patients (7.6%) with only one confirming a DVT. Conclusions Our data shows that the majority of physicians at our institution fail to utilize pre-test probability tools prior to ordering a D-dimer. This leads to unnecessary costs, overuse of imaging studies and results in low rates of positive scans. Disclosures Wu: Bayer: Other: Local PI for trial ; BMS-Pfizer: Other: Local PI for trial ; Daiichi-Sankyo: Other: Local PI for trial .

Description: 1. Background Central venous catheters (CVCs) are a leading cause of upper extremity deep vein thrombosis (UE DVT). There is little data on patients with acute leukemia (AL). Long term CVCs are required for chemotherapy in AL. Concomitant severe thrombocytopenia makes anticoagulation for CVC related thrombosis a challenge. Incidence of UE DVT has been reported to be increased in those with peripherally inserted central venous catheters (PICC lines) vs those with centrally inserted lines. 2. Aims Our objective is to compare the incidence rate of VTE in leukemia inpatients with a PICC vs centrally-inserted CVC. 3. Methods We reviewed 420 charts for AL inpatients requiring a PICC line admitted to Hematology at the University of Alberta Hospital between 2003-2013. Baseline patient characteristics were recorded. All venous thromboembolic events were objectively confirmed on imaging studies. Incidence of catheter associated thrombosis was calculated. 4. Results 420 patients were identified. We present the preliminary results of the 337 patients that met our inclusion criteria, and received at least one PICC line insertion. 305 (90%) had AML, 144 (43%) were smokers, 126 (37.4%) had cardiovascular risk factor, and only 14 (4.2%) had previous VTE. Overall, there were 634 PICC line insertions, with the 5FR dual lumen being the most commonly used PICC line (80%). Out of the 634 insertions, there were 65 (10%) new ipsilateral upper extremity DVTs, 54 (83%) of which developed acutely (

Description: Introduction: Nearly 20% of all newly identified cases of VTE is associated with cancer. Hematologic malignancies are at increased risk of developing VTE. We aimed to identify the prevalence of hematologic malignancy in VTE patients and compare the survival between VTE and non-VTE patients with or without hematologic malignancy. Methods: Using linked administrative data and a validated algorithm we identified adult VTE cases in Alberta, Canada from 2003 to 2015. We also identified patients without VTE using the same database. Subjects having ICD-10 code for hematologic malignancy and solid tumor within one year before and after the VTE index event were further identified. Cox proportional hazard regression model was applied to estimate the hazard ratio (HR) of death. The Kaplan Meier survival analysis was performed to compare survival rate among patients with different diagnosis. Results: We identified 56,907 VTE patients. Of them 37,876 (66.6%), 18,502 (32.5%) and 529 (0.9%) cases were diagnosed as deep vein thrombosis (DVT), pulmonary embolism (PE), and both DVT & PE respectively. 57.4% of the VTE patients were female. Of all VTE cases, 1647 (2.9%) patients had hematologic malignancies and 5034 (8.8%) patients had solid tumor. Of the hematologic malignancy cases 853 (51.8%) , 164 (10%), 105 (6.4%), 302(28.3%) and 223 (13.5%) had Lymphoma, leukemia, myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN) and plasma cell dyscrasia respectively. We identified 27,664 patients without any diagnosis of VTE. Among them 586 (2.1%) and 4065 (14.7%) patients had hematologic malignancy and solid tumor, respectively. In VTE group, the hazard of death for patients with hematologic malignancy and solid tumor were 5.2 (95% CI: 4.8-5.5) and 7.5 (95% CI: 7.2-7.8) times greater than that of patients with no cancer, respectively. In the patients with no VTE, hazard of death among people with hematologic malignancy and solid tumor were 7.4 (95% CI: 6.4-8.5) and 12.4 (95% CI: 11.6-13.2) times greater than that of people with no cancer, respectively. In all hematologic malignancy and solid tumor patients, the hazard of death for patients with VTE were 1.8 (95% CI: 1.5-2.1) and 1.6 (95% CI: 1.5-1.7) times greater than that of patients with no VTE, respectively. In all patients without any cancer, those with VTE had 2.6 (95% CI: 2.4-2.7) times increased hazard of death than those without VTE. The Kaplan Meier survival analysis showed the lowest survival probability among VTE patients with solid tumor and hematologic malignancy (Log rank p

Description: Introduction: Hereditary macrothrombocytopenic disorders are rare syndromes characterized by mild to moderate thrombocytopenia, large platelets, and a variable bleeding phenotype. In general, the diagnosis must be made clinically and management is empiric. Because of the autosomally inherited nature of these disorders, peripartum management must take into account the risk of bleeding for both mother and baby, during the pregnancy and at delivery. Study Purpose: To describe the peripartum management and bleeding complications in pregnant women with suspected inherited macrothrombocytopenic disorders and their children. Study Design: We performed a retrospective review of all mothers referred to our tertiary care hospital from 2004 to 2007 for evaluation of macrothrombocytopenia in pregnancy where hereditary thrombocytopenia was suspected. The diagnosis was confirmed if at least 2 of the following clinical features were present: life-long thrombocytopenia; family history of thrombocytopenia that spanned at least 2 generations; and the lack of a platelet count response to IVIG or corticosteroids. Data relating to bleeding and therapies used to treat or to prevent bleeding before or during delivery for mother and child were extracted from medical charts. Blood films were reviewed with experts in morphology, and diagnostic testing was performed when possible. Results: A total of 5 mothers and 8 babies were included. The median platelet count of mothers at delivery was 54 x 109/L (range 15–83 x 109/L) and the median MPV was 9.8 fL (range 7.4–11.3 fL). Of the 8 babies, 4 were thrombocytopenic with a median platelet count at birth of 50 x 109/L (range 9–93 x 109/L) and a median MPV of 9.4 fL (range 8.9–9.6fL). One mother and her baby had neutrophilic Dohle body inclusions, and none had skeletal, neurologic or renal abnormalities. Three mothers were previously treated with IVIG, including one who also received prednisone, with no platelet count response. During pregnancy, fetal blood sampling for platelet count measurements was not done. None of the mothers had epidural anesthesia, all delivered vaginally and 7 of 8 labours were induced. Two mothers received prophylactic tranexamic acid at the time of active labour and 1 received DDAVP. Prophylactic platelet transfusions were not given. One mother had bleeding associated with spontaneous rupture of membranes, and one had a post partum hemorrhage associated with uterine atony and vaginal laceration. The latter was repaired surgically and treated with platelet transfusions and DDAVP. None of the babies bled, but 1 was given a platelet transfusion because of severe thrombocytopenia at birth (platelet count = 9 x 109/L) with persistent platelet clumping. Conclusions: The frequency of pregnancy-related bleeding in mothers with hereditary macrothrombocytopenia was low in this cohort even in the absence of prophylaxis. There is a need for improved diagnosis and risk stratification of mothers with hereditary macrothrombocytopenia. A multicentre prospective study would assist in determining optimal peripartum management.

Description: Introduction: The perioperative management of patients who are taking a direct oral anticoagulant (DOAC) for atrial fibrillation (AF) and require an elective surgery/procedure is uncertain. No studies have addressed the timing of perioperative DOAC interruption and resumption, and if perioperative heparin bridging and coagulation function testing are needed. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study hypothesized that a simple, standardized perioperative management strategy, based on DOAC-specific interruption and resumption intervals, that foregoes perioperative heparin bridging and coagulation function testing, is safe for patient care, with associated low rates of major bleeding (1%) and arterial thromboembolism (0.5%). We postulated that this management yields a high proportion of patients (〉90%) with a minimal to no DOAC level at surgery/procedure. Methods: PAUSE is a prospective study with 3 parallel DOAC cohorts of patients with AF taking apixaban, dabigatran or rivaroxaban and requiring anticoagulant interruption for an elective surgery/procedure. Patients were managed using a standardized protocol based on DOAC pharmacokinetic properties, procedure-associated bleeding risk (Appendix 1) and creatinine clearance (CrCl). DOACs were interrupted for 1 day before and after surgery for a low bleed risk surgery and 2 days before and after a high bleed surgery; longer interruption was done in patients on dabigatran with a CrCl

Description: Abstract 1090 Background: The incidence of venous thromboembolism (VTE) in patients with multiple myeloma (MM) is high in patients treated with thalidomide (T)- and lenalidomide (L)-based regimens containing dexamethasone (D) and/or cytotoxic chemotherapy (C). Consensus guidelines recommend routine thromboprophylaxis but reliable data from randomized controlled trials are lacking. Recent observational studies have suggested that thromboprophylaxis might be efficacious in decreasing the risk of VTE in this population. Purpose: To determine the absolute rates of VTE with and without different thromboprophylactic agents (ASA, warfarin, low-molecular-weight-heparin [LMWH]) in patients with newly diagnosed or previously treated MM receiving T- or L-based regimens. Data Source: A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews of published studies up to Jan 2010. Results: A total of 66 studies were included in the analyses. Of these, 61 (4264 patients) and 5 (1119 patients) assessed T- and L-based regimens, respectively. Thalidomide-based regimens The rates of VTE (per 100 patient-cycles) in patients with newly diagnosed MM treated with T-based regimens: The rates of VTE (per 100 patient-months) in patients with previously treated MM managed with T-based regimens: Lenalidomide-based regimens The rates of VTE (per 100 patient-cycles) in patients with newly diagnosed MM treated with L-based regimens: The rate VTE (per 100 patient-months) in patients with previously treated MM managed with L-based regimens: None of the studies reported major bleeding events. Limitations: The definition for VTE varied across studies. Most studies did not outline the diagnostic criteria for VTE. Data are not available (NA) for all prophylaxis regimens. Conclusion: Patients with newly diagnosed or previously treated MM receiving T- or L-based regimens are at high risk of VTE. It is uncertain whether thromboprophylaxis provides a clear benefit, especially in those receiving L-based therapy or have previously treated disease. Randomized controlled trials are needed to address this important clinical need. Disclosures: Lee: Eisai: Research Funding; Sanofi Aventis: Consultancy, Honoraria; Leo Pharma: Consultancy; Pfizer: Consultancy, Honoraria; Bayer: Honoraria; Boehringer Ingelheim: Consultancy, Honoraria, Speakers Bureau.