ALBERT

Description: Introduction: Chronic liver disease (CLD) results in thrombocytopenia [1]. Depression of thrombopoietin (TPO) levels in CLD leads to thrombocytopenia. Thrombocytopenia increases the risk of bleeding in patients undergoing invasive diagnostic or therapeutic procedures [2]. TPO agonists have been depicted to be safe and efficacious in the treatment of thrombocytopenia due to idiopathic immune thrombocytopenia and aplastic anemia. Several studies have evaluated the use of TPO agonist versus placebo for pre-procedural treatment of thrombocytopenic patients with chronic liver disease. These studies were of limited sample sizes. We conducted a meta-analysis to determine if TPO agonists reduce the need of platelet transfusions before procedures in chronic liver disease patients. Methods: We performed a computerized search of Medline, Cochrane and Google Scholar databases through March 2019 for studies evaluating the efficacy of thrombopoietin (TPO) agonists versus placebo in the treatment of thrombocytopenia of chronic liver disease patients undergoing procedures. We screened 295 studies and only 5 of them met our inclusion and exclusion criteria. Inclusion criteria were studies with adults 〉18 years old, English literature, randomized controlled trials utilizing a TPO agonists in chronic liver disease patients. Exclusion criteria were studies with patients

Description: Key Points A subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.

Description: Introduction Venous thromboembolism (VTE), is the second leading cause of death in patients with cancer. The risk of VTE in patients with cancer is 4 to 7-fold, when compared to the general population. Even during anticoagulant treatment, the cumulative incidence of recurrent VTE is 3.5 times higher in patients with cancer than in cancer-free patients. Low-molecular-weight heparin has been the "gold standard" for the of treatment for VTE in cancer associated thrombosis, following the landmark trial by Lee et al. Methods We conducted a meta-analysis to evaluate the safety and efficacy of direct oral anticoagulants in patients with cancer. We systematically searched Medline for randomized-control clinical trials and post-hoc analyses. For each study, data on recurrent VTE, major or clinically relevant non-major bleeding (CRNMB), and major bleeding (MB) were extracted. We included randomized control trials (RCT's) where interventions consisted of direct oral anticoagulants (DOA) versus vitamin K antagonists (VKA) or low molecular weight heparins (LMWH), in which all or a part of the study population had active cancer. We excluded studies that were not comparing DOA versus VKA/LMWH or did not have a subset of active cancer patients. Results Seven studies met our eligibility criteria. Data for recurrent VTE was extractable from all 7 RCT's. There were 2178 enrolled participants total. The pooled results show evidence for a lower incidence of recurrent VTE with the use of DOA versus VKA/LMWH. The pooled risk ratio for recurrent VTE was 0.68 (95% confidence interval 0.50 to 0.93; P = 0.01). There was negligible heterogeneity among the trials (I2 = 0%; P = 0.99). Data for major bleeds was extractable from 6 RCT's, including 1952 enrolled participants total. The pooled results show no evidence for a difference in frequency of major bleeds with the use of DOA versus VKA/LMWH. The pooled risk ratio was 1 (95% CI 0.53 to 1.87; P= 0.99). There was moderate heterogeneity among trials (I2 = 40%; P = 0.17) Data for clinically relevant bleeding was extractable from 6 RCT's, including 1952 enrolled participants total. The pooled results show no evidence for a difference in frequency of nonmajor but clinically relevant bleeds with the use of DOA versus VKA/LMWH. The pooled risk ratio was 1.06 (95% CI 0.80 to 1.42; P= 0.68). There was negligible heterogeneity among trials (I2 = 27%; P = 0.24). Data for all bleeds (major or nonmajor) was extractable from all 7 RCT's. There were 2178 enrolled participants total. The pooled results show no evidence for a difference in frequency of bleeds with the use of DOA versus VKA/LMWH. The pooled risk ratio was 0.95 (95% CI 0.68 to 1.32; P= 0.74). There was substantial heterogeneity among trials (I2 = 65%; P = 0.02). Conclusions Our results suggest that DOACs might reduce the incidence of VTE recurrence in patients with cancer without putting them at high risk for major bleeds or clinically relevant nonmajor bleeds. Table. Table. Disclosures No relevant conflicts of interest to declare.

Description: INTRODUCTION: Both solid and hematologic malignancies are associated with an increased risk of thromboembolic events, according to previous studies. One of the most common risk scoring systems was developed based on type of non-hematologic cancer, body mass index (BMI), WBC, hemoglobin, and platelet counts. However, compared to other solid tumors, acute leukemia patients commonly present with pancytopenia at the time of diagnosis and the Khorana Risk Score (KRS) has not been validated in patients with acute myeloid leukemia (AML). The goal of our study was to validate the KRS in AML patients. METHODS: Using Total Cancer Care (TCC), we retrospectively identified histologically confirmed AML patients from 2000 to 2018. Clinical and laboratory variables including age, gender, previous cancer history, use of growth factors, underlying coagulopathy, white blood cell counts, hemoglobin, and platelet counts were characterized at the time of AML diagnosis and annotated using descriptive statistics. The thrombotic event rate was estimated with the Kaplan-Meier method and compared using log-rank test. All statistical analyses were performed using SPSS v24.0 and GraphPad Prism 7. RESULTS: A total of 867 AML patients were included in this study. The median age at AML diagnosis was 75 (51-96) years and male patients were 65% (n=565). A total of 28% (n=241) patients had prior cancer history (hematologic malignancies, n=34; solid tumor, n=207). A total of 12% (n=101), 7% (n=58), and 1% (n=8) patients had EPO, G-CSF, GM-CSF treatment prior to AML diagnosis and 84% (n=728) patient were treated with any typed of growth factors after AML diagnosis. The median BMI was 27.1 (14.8-103) and 5% (n=47) patients had BMI higher than 35. A total of 26% (n=229) patients had WBC ≥11 x109/L (median 3.165 (0.08-413.74) x109/L), 67% (n=584) patients had hemoglobin 350 x109/L (median 46 (1-800) x109/L). A total of 22% (n=191) patients had Khorana score 0, 51% (n=445) patients had score 1, 24% (n=207) patients had score 2, and 3% (n=24) patients had score 3, respectively. A total of 42 thrombotic events were observed in the median follow up of 3 (0.1-307) months. Among these, a total of 3% (n=6/191), 5% (n=23/445), 6.3% (n=13/207), and 0% (n=0/24) thrombotic events occurred in patients with Khorana sore 0, 1, 2, and 3, respectively. Log-rank (Mantel-Cox) test showed no statistical difference between individual subgroup (p=0.1949). CONCLUSIONS: In AML patients, there was a higher incidence of thrombotic events in patients with higher Khorana score though the difference was not statistically significant. The proportion of patients with Khorana score ≥3 was relatively low, which could be due to pancytopenia, a common presentation in AML patients. These results suggest that the development of better thrombotic risk scoring system is warranted in patients with AML. Disclosures Komrokji: Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau.

Description: Introduction Primary central nervous system lymphoma (PCNSL) is a rare disorder with a poor prognosis. The mainstay of treatment is single agent or combination high dose (≥3.5g/m2) methotrexate (HDMTX) based regimens. There is no consensus as to which dose of HDMTX improves outcomes in patients with PCNSL but doses of MTX greater than 3 g/m2 intravenously achieve therapeutic cerebrospinal fluid (CSF) concentrations. Purpose To determine if there is an optimal or total dose of HDMTX in PCNSL therapies that results in improved progression free (PFS) or overall survival (OS). Methods Patients at Moffitt Cancer Center with PCNSL were identified using our institutional database between January 1, 2000 and September 30, 2011. Patients with complete treatment data who were treated with HDMTX were included in this study. HDMTX was defined as MTX at a dose ≥ 3.5g/m2. Patient demographics, clinical, and treatment data were collected and analyzed. Treatment information collected included the starting dose of HDMTX, IV rituximab use, MTX toxicity and clearance, cycles of MTX, and total amount of MTX administered (g/m2). Data were analyzed using descriptive statistics and the Kaplan-Meier (KM) method was used to estimate median PFS and OS using the log rank test. P value of

Description: Introduction: Central Venous Catheters (CVC) improve quality of life for patients with hematologic malignancy but long-term presence may result in CRT. Optimal treatment of CRT is uncertain. Here, we focus on a retrospective study of CRT in patients with hematologic malignancy to identify clinical features associated with increased risk for recurrent thrombosis. Methods: Demographic and management information of patients with CRT and hematologic malignancy was extracted from the medical record of a single academic medical center. Data was described using summary statistics. Nonparametric Cox proportional hazard models were utilized for thrombosis recurrence and bleeding occurrence. Unadjusted models were utilized for CRT treatment, type of anticoagulation, platelet count, and other factors. Results: 85 patients were included for analysis. Summary statistics are noted in Table 1. Median platelet count differed across initial treatment approach [Anticoagulation (AC): 177 (106.5- 662), Anticoagulation and Catheter Removal (AC+): 112 (61.75-304), Catheter Removal only 24 (20.25-35.5), No treatment 30.5 (16.75-10.8), p

Description: Abstract 256 BACKGROUND: Several recent reports indicated low response rates (20–30%) and poor outcome with standard anthracycline and cytarabine (3+7) induction regimen for sAML arising from MDS after azanucleosides failure (Bello et al. Cancer 2011 Apr 117) (Jabbour et al, Cancer 2010 August 15,116) (Prebt et al, JCO 2011 July) (Lin et al, ASH 2010 #2913). CLAG-M is an effective regimen in treating relapsed/refractory AML including relapsed/refractory sAML. The CR rate for CLAG-M was reported as high as 58% (Wrzesien-Kus, Robak et al. Eur J Haematol 2008 Feb). We compared the efficacy of CLAG-M to standard 3+7 as induction strategy in sAML after azanucleosides failure. METHODS: This was a retrospective case-control study. Data were obtained from the Moffitt Cancer Center (MCC) electronic records. Patients (18 years of age and older) with sAML who received primary induction therapy with the CLAG-M regimen (Cladribine 5 mg/m2/d intravenous (IV) over 2 hours(hrs) days (d) 1–5, Cytarabine (Ara-C) 2 g/m2/day IV over 4 hrs starting 2 hrs after cladribine d1-5, Mitoxantrone (Novantrone)10mg/m2/d IV d1-3, Filgrastim (Neupogen) 300 mcg subcutaneous d0-5), were compared to matched controls (sAML, prior azanucleoside failure) who received standard 3+7 regimen ((Ara-C) 100 mg/m2/d civi d1-7 and Idarubicin 12 mg/m2/d iv d1-3) or (Cytarabine (Ara-C) 100 mg/m2/d civi d1-7 and Daunorubicin 45–60 mg/m2/d iv d1-3)). Baseline characteristics collected included age, gender, race, ECOG performance status, prior treatments, MDS IPSS score, leukocyte count and myeloblast percentage at induction, karyotype risk group, and duration between original MDS diagnosis and sAML. The primary endpoint was overall survival (OS), and secondary endpoints included response rates defined by standard AML response criteria and feasibility of allogeneic stem cell transplantation (allo SCT). Descriptive statistical analyses were utilized. Chi square analysis and t- test were utilized to compare categorical and continuous variables, respectively. Kaplan-Meier method was used to estimate OS and log rank test was used to compare the 2 groups. All data were analyzed using SPSS version 19.0 statistical software. RESULTS: Twenty five patients who received CLAG-M were compared to a control of 24 patients treated with 3+7 for sAML arising from MDS after azanucleosides failure treated at MCC. The baseline characteristics were similar in the two groups with no statistically significant differences noted except that more patients had an ECOG PS 1 in 3+7 group (table-1). The CLAG-M cohort had a trend towards higher overall response rate (CR/CRi) 56% (N=14) compared to 29% (N=7) standard 3+7 (p=0.058). The median OS was 202 days (95%CI 97–307) versus 86 days (95%CI 30–142) (p=0.025) respectively in CLAG-M and 3+7 (Figure-1). The one year OS was 45% in CLAG-M group compared to 9% in 3+7 group. Seven patients (28%) in the CLAG-M cohort versus 1 patient (4.2%) in the 3+7group received allo SCT (p= 0.024). The median OS was not reached for patients who proceeded to allo SCT in the CLAG-M cohort compared to 112 days for patients who did receive allo SCT in the 3+7 cohort (p=0.007). The mean duration of hospitalization was 33 days with CLAG-M compared to 41 days with 3+7 (p=0.08). CONCLUSION: CLAG-M as an induction regimen for sAML from MDS after azanucleosides failure was associated with better OS compared to standard 3+7 therapy. There was a trend towards higher response rates with the CLAG-M regimen which allowed more patients to proceed to allo SCT. These results need to be confirmed in a randomized prospective clinical trial. Disclosures: No relevant conflicts of interest to declare.

Description: BACKGROUND: Venous thromboembolism is a well-known complication of malignancy. The Khorana Risk Score (KRS) utilizes the type of cancer, blood counts, and body mass index to predict risk of thrombosis in cancer patients. Patients with a KRS of greater than 3 are considered high risk for developing blood clots and may benefit from prophylactic anticoagulation. We wanted to determine if the use of the KRS would have led to prophylactic anticoagulation (AC) in these cancer patients prior to their thrombotic events. METHODS: This study utilized a group of 286 patients treated at Moffitt Cancer Center between May 1, 2010 and June 30, 2015 with a wide variety of cancer diagnoses with known venous thromboembolic events (VTE) (pulmonary embolism or deep venous thrombosis). We aimed to validate the KRS by retrospective analysis to determine if the KRS would have predicted VTE in these patients on the day of their venous thromboembolic event. The demographics are summarized using descriptive statistics. Wilcoxon rank-sum test is used for testing the difference in continuous variables. Fisher exact test is used for testing the difference in categorical variables. RESULTS: We found that the majority of these cancer patients with known VTE (89%) would have been classified as low risk of having VTE. Only 11% would have been classified as high risk to where prophylactic anticoagulation might have been indicated. CONCLUSIONS: We found that in a diverse group of cancer patients who had thrombotic events, the KRS did not appropriately stratify patients at the highest risk of VTE. The majority of patients with VTE were actually found to be low risk which would not have led to improved awareness or medication prophylaxis. Improved risk stratification methods are needed for cancer patients to implement an effective prophylactic strategy. Table Table. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Most patients (pts) with diffuse large B cell lymphomas (DLBCL) are cured with first line chemoimmunotherapy including an anthracycline and rituximab. Pts who obtain complete remission (CR) but latter relapse often can be cured with salvage therapy and autologous hematopoietic cell transplantation (auto-HCT). This management paradigm often is applied to pts with primary treatment failure (PTF). However, this group is heterogeneous and detailed data on outcomes in current era is needed to identify the DLBCL pts for whom novel therapeutic strategies should be designed. Methods: Fifteen US academic medical centers contributed pts to the REgistry of diFfuse large B cell lymphoma with prImary treatmeNt failurE (REFINE) collaboration. REFINE retrospectively captured patient, disease and treatment characteristics and treatment response as assessed by treating physician. Eligible pts were ≥ 18 years diagnosed with DLBCL during 2008-2015, who received upfront cheomoimmunotherapy including anthracycline and CD20-directed antibody and developed one of 3 patterns of PTF: relapse 〈 6 months following CR (early relapse- ER); only partial remission (PR) or stable disease (SD) with upfront therapy (residual disease-RD); progressive disease (PD) while receiving upfront therapy (primary progression-PP). Pts with HIV infection, primary CNS lymphoma or lymphoma transforming from a more indolent histology were excluded. Results: Patient characteristics for the 331 cases are summarized in Table 1. Median follow up of survivors was 18.9 months. R-CHOP was the upfront treatment for 87.6% of pts. Nearly all pts (94.6%) received salvage therapy after PTF and prior to any HCT, with a median of 1 and range 0 to 5 regimens. Response to first salvage regimen was CR in 19.9%, PR in 21.8%, SD in 9.0% and PD in 40.8%. Only 15.1% of pts were enrolled in clinical trials. One hundred and thirty-two pts (39.9%) underwent auto-HCT and 33 (10.0%) allogeneic-HCT (8 after failure of auto-HCT). Two-year overall survival (OS) from time of PTF was 45.5% (95% C.I. 34.5-56.5%) for ER, 30.6% (95% C.I. 20.0-41.2%) for RD and 18.5% (95% C.I. 11.4-25.6%) for PP (P