ALBERT

Description: Abstract 5044 Introduction: Epidemiological studies are the base to evaluate the efficiency of medical interventions in the interest of the public health. Updated epidemiological data and effectivenes in the daily clinical practice are needed in Multiple Myeloma (MM). Materials and Methods: Epidemiological retrospective, longitudinal, multicenter nation wide Spanish study of an historical cohort of patients with MM. Data from patients aged ≥ 18 years, with a MM Stage II or III, who received a treatment on a daily clinical practice (not in clinical trials) for MM in the September'03-August'05 time frame were collected. The study protocol was approved by an Ethics Committee in 2009. Data were collected in 37 Spanish Centres during a 6 months period. Stratified effectiveness and survival analysis were performed (age

Description: Multiple myeloma (MM) is a heterogeneous disease. Evaluation of prognostic factors and risk stratification at diagnosis is necessary to compare outcome. Attempts have been made to apply a comorbidity score in the clinical sitting, but a standardized general approach is still lacking. We hypothesized that a comprehensive examination of every associated disease in a large cohort of patients could better highlight the prognostic impact of comorbidity in MM. All consecutive patients diagnosed in our institution, from 1993 to 2013, with symptomatic MM according to IMWG criteria were included in our population-based MM registry. Patients with plasma cell leukemia or with palliative management were excluded. Clinical variables analyzed were: age, sex, Durie-Salmon, International Scoring System (ISS), percentage of plasma cell in bone marrow by morphology (PC), serum creatinine (Cr) and estimated glomerular filtration rate according with Modification of Diet in Renal Disease (eGFR-MDRD). The following comorbodities were analysed: hypertension (HTA), diabetes (DM), obesity (OB) (body mass index 〉 30 Kg/m2), hyperlipaemia (HL), prior malignancy (PM), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), peptic ulcer (PU), thromboembolism (TE), renal transplant (RT), splenectomy (S), cutaneous disease (CD), amyloidosis (AM), heart disease (HD) (arrhythmia, congestive heart failure, coronary artery disease, other), lung disease (LD) (chronic obstructive pulmonary disease, asthma, other), liver disease (HE) (cirrhosis, non-alcoholic fatty liver disease, other), neurological disorder (ND), psychiatric disorder (PD) and rheumatologic disorder (RD). Kaplan-Meier method was used to estimate OS curves. Cox regression was used to determine the prognostic impact of each comorbidity in a univariate and multivariate model. 311 patients were eligible. Median age was 66 years (12-91), 148 men (47.6 %) and 163 women. Percentage of comorbidities was: HTA 45; OB 32.5; DM 20.4; HD 20.4; LD 15.2; PU 10; HL 9.7; ND 8; PM 7.8; PD 6.5; HBV 3.9; HE 3.9; TE 3.6; RD 3,5; AM 2.3; HCV 1.9; CD 1.6; S 1; RT 0.6; HIV 0.3. 63 patients (20.4 %) showed no comorbidities. Univariate analysis (table 1) demonstrated that AM (P=0.022), HCV (0.038), HIV (0.022), PD (0.015) and ND (0.05) were significantly associated with shorter OS. The variables associated with mortality in the multivariate analysis were age (p=0.002), ISS (III vs I: p=0.01), PC (p=0.05) and Cr (p=0.02). Results will be validated in another MM series and presented during the meeting. The overall prognosis of MM depends on a variety of host and disease-related characteristics. We confirm age, ISS, PC and Cr as robust and independent prognostic factors. Adjusting for these factors, no isolated comorbidity reach statistical significance; however, comorbidity seems to have a role in MM prognosis. More studies are warranted to define the prognostic impact of comorbidities in MM. Disclosures: No relevant conflicts of interest to declare.

Description: OBJECTIVES According to the World Health Organization, "Haemovigilance is required to identify and prevent occurrence or recurrence of transfusion related unwanted events, to increase the safety, efficacy and efficiency of blood transfusion, covering all activities of the transfusion chain from donor to recipient." The system should include monitoring, identification, reporting, investigation and analysis of adverse events near-misses and reactions related to transfusion and manufacturing. Transfusion-dependent patients receive iron overdose in each transfusion: one packed red blood cells containing 200-250 mg iron (1 mg/ml), which accumulates gradually in different tissues. Transfusions of packed red blood cells in a volume ≥120 mL / kg can cause iron overload, which correlates with ferritin levels in serum equal to or greater than 1000 g/L. The iron overload may be detected after 10 to 20 transfused packed red blood cells, increasing the risk of morbidity and mortality. PATIENTS, MATERIAL AND METHODS We studied the hematological patients with iron overload in 2013 and 2014, analyzing theirs levels of ferritin. The database of the transfusion service was also used, as well as the transfusion history of patients who had received more than 10 packed red blood cells, correlating with greater than 1000 mg/L ferritin. In 2013, 57 cases transfused with packed red blood cells were reported: 32 men and 25 women between 20 and 87 years (average: 56). Results vary between 10 and 73 concentrates (average: 25). Posttransfusion ferritin levels exceeded 1.000 mg/L, with an average of 2869 mg/L. The accountability and severity was recorded as non-assessable. In 2014, 76 cases were reported between the ages of 24 and 83 years (average: 56 years), with 50 men and 26 women. The number of packed red blood cells transfused ranged from 10 to 130 (average: 31). The ferritin posttransfusion quantities ranged from 1.041 to 15.190 mg/L. Regarding accountability, 23 were grade 2, 43 were grade 1 and 10 were not assessable. The severity was recorded as non-assessable. Table. Cases reported in 2013 and 2014 Year Cases (nº) Average Packed red blood cells average per patient Posttransfusion ferritin levels 2.013 57 56 25 2.869 μg/L (average) 2.014 76 56 31 Values between 1041-15190 μg/L CONCLUSIONS It is very important to keep track of ferritin levels in polytransfused patients. In order to reduce the risk of hemosiderosis, it is essential the optimal use of component (safe, efficient and clinically effective) and that the transfusion is performed when the patient needs it. Chelation reduce morbidity in patients with transfusional dependency and iron overload. In the annual report of Andalusian Health Service, the incorporation of Haemovigilance system of notifications of post-transfusion hemosiderosis stands out, although only 4 hospitals shared the information, therefore working in this field is necessary. We believe it is essential to establish protocols to improve the reporting of incidents by hemosiderosis Haemovigilance System. Disclosures No relevant conflicts of interest to declare.

Description: OBJECTIVES The low molecular weight heparins (LMWH) are typically administered at fixed doses like thromboprophylaxis or at doses adjusted to the weight of the patient in order to obtain a therapeutic effect. Generally they do not require laboratory monitoring, although it could be considered in special situations (renal failure, extreme weights, pregnant women). The LMWH do not affect the APTT, so it has been proposed to determine the anti-factor Xa activity when it is necessary to monitor its effect. The anti-factor Xa activity should be determined approximately 4 hours after sc administration of the LMWH that it is employed, concurring with the peak of activity. The therapeutic range of the anti-factor Xa activity is between 0.6 and 1 IU / mL when LMWH is administered every 12 hours. At single daily dose is less clear, although it seems that lies above 1 IU / mL. Nowadays, LMWH are the anticoagulant of choice during pregnancy. Numerous in vitro and in vivo studies have shown the existence of an antineoplastic effect of heparin. LMWH is commonly used for prolonged treatment of thrombosis associated with cancer. METHODS The main aim of our study is to evaluate the efficacy of tinzaparin sodium at therapeutic doses in preventing VTE in renal failure, active cancer and/or patients with contraindications to oral anticoagulation. The dose has been therapeutic and adjusting it has been made in terms of anti-factor Xa levels obtained monthly. Hemorrhagic or thrombotic complications and other possible side effects have been assessed. Until now, a total of 70 patients, 42 men and 28 women aged between 30 and 95 years old, have received tinzaparin sodium treatment. The main reason of anticoagulation are: atrial fibrillation and atrial flutter (with or without valve disease), VTE (with or without thrombophilia), stroke and transient ischemic attacks and mechanical prosthetic aortic and mitral valves (some of the patients carrying a double metal prosthesis). There was 1 resistance and 1 allergic reaction to anti-vitamin K. 4 of the patients were pregnant and 14 had renal failure. Prior to initiation of therapy, analytical determinations were performed, including: blood count, blood coagulation and biochemistry to assess renal function (urea and creatinine). 20 patients (14 were anticoagulated by atrial fibrillation, 2 for bearing a mechanical aortic prosthesis and 4 because of DVT, 1 of which had also a TEP) had active cancer or were in remission from their neoplasia (3 multiple myeloma, 1 LAM, 1 CMML, 4 renal tumors, 1 lung cancer, 5 prostate cancers, 1 hepatocellular carcinoma, 2 colon cancer, 1 endometrial adenocarcinoma and 1 retroperitoneal leiomyosarcoma). 1 with MDS was treated with LMWH because he had intra- and extrahepatic portal vein thrombosis. RESULTS Some of the patients had received prior treatment with anti-vitamin K (INR objective depending on pathology) but, in other cases, the low molecular weight heparin was the only treatment since the beginning of their anticoagulation. All the patients had received 175 IU / Kg of Tinzaparin Sodium once a day as initial dose, then the dose was adjusted according to the anti-factor Xa levels. They were controlled until 31/07/2015. In terms of side effects, 8 patients presented complications: 3 mucosal bleeding, 2 episodes of stroke in a patient, hemoptysis, deep vein thrombosis and 2 bleeding at the puncture site of heparin, which have not required discontinuation of therapy. When these complications occurred, we proceeded to the corresponding heparin dose adjustment based on new determinations of anti-factor Xa. CONCLUSIONS Although only in 70 cases, the results obtained confirm the efficacy, safety and cost-effectiveness of the continuous use of LMWH. Determination of anti-factor Xa levels are considered very useful for dose adjustment parameter. In our study, tinzaparin sodium has proved to be very useful in preventing venous thromboembolism associated or not with cancer, in patients with conditions requiring anticoagulation and presenting contraindications to the use of anti-vitamin K. The results obtained have demonstrated that tinzaparin is safe and, most likely, further studies will provide valuable confirmation data to support the use of low molecular weight heparins in the prolonged treatment of patients who require oral anticoagulation and can not receive it. Disclosures No relevant conflicts of interest to declare.

Description: Autologous stem cell transplantation (ASCT) has been successfully used in HIV-related lymphoma (HIV-Ly) patients on highly active antiretroviral therapy. We report the first comparative analysis between HIV-Ly and a matched cohort of HIV− lymphoma patients. This retrospective European Group for Blood and Marrow Transplantation study included 53 patients (66% non-Hodgkin and 34% Hodgkin lymphoma) within each cohort. Both groups were comparable except for the higher proportion of males, mixed-cellularity Hodgkin lymphoma and patients receiving granulocyte colony-stimulating factor before engraftment and a smaller proportion receiving total body irradiation-based conditioning within the HIV-Ly cohort. Incidence of relapse, overall survival, and progression-free survival were similar in both cohorts. A higher nonrelapse mortality within the first year after ASCT was observed in the HIV-Ly group (8% vs 2%), predominantly because of early bacterial infections, although this was not statistically significant and did not influence survival. Thus, within the highly active antiretroviral therapy era, HIV patients should be considered for ASCT according to the same criteria adopted for HIV− lymphoma patients.

Description: INTRODUCTION Allogeneic red blood cell (RBC) transfusions are vital and effective and effective to treat anemia. RBC transfusions increase hospitalizations in 2.5 days, risk of death in 1.7 times and risk of infection in 1.9 times. The cost of discharges from the hospital is 1.83 times higher and it represents 7.8% of the hospitalization total expenses. However, there is little awareness and knowledge about this transfusion practice, as well as an inexplicable and enormous inter-center variability. In attempt to reduce unnecessary transfusions and improve postoperative evolution, as well as to reduce hospital costs, "Patient Blood Management" (PBM) program has been developed, which includes hospital policies, procedures and protocols. In literature, evidence of PBM programs effectiveness is growing. METHOD In view of the need to evaluate these issues, the Maturity Assessment Patient Blood Management (MAPBM) project was constituted in 2014, which involves a group of clinical and management experts nationwide, with the participation of 35 Spanish hospitals (including our center since 2015). It evaluates and compares:The knowledge of professionals about transfusion practice and PBM programs (anonymous survey). Figure 1.The PBM process indicators of each participating center. Figure 2.Inter-transfusion variability and factors related to transfusion in different procedures adjusted by age, sex and comorbidity. Figure 3 We will analyze the results of our center comparing them with the rest of hospitals. RESULTS In general, there is a high awareness of the indication and minimization of transfusions in different procedures, as well as a dissemination of our PBM programs above the average, especially the protocol of preoperative anemia (Figure 1). Despite this, the results of our circuit for the correction of preoperative anemia are unfavorable, since they are detected in a higher percentage than the rest of the centers, but they are not effectively treated in the studied procedures (Figure 2). Our strategies to minimize bleeding, both spinal anesthesia in orthopedic and traumatological surgeries and perioperative use of tranexamic acid are noteworthy, except in the cases of hip fracture surgeries, where its use was contraindicated by multidisciplinary consensus. Our transfusion threshold is close to the standard. In all the studied procedures, transfusion with Hb ≥ 8gr / dl is not considered. Regarding the results of transfusion and factors related to transfusion (Figure 3), a globally superior transfusion rate is observed, mainly at the expense of cardiac and open colorectal surgery. Regarding other items, our mortality and complications rates are, in general, unfavorable. However, hospitalizations and readmissions are lower. CONCLUSIONS Although the dissemination of our PBM strategies is adequate, its implementation has not meant an improvement in the transfusion rate of the procedures studied, being even higher than the expected rate. We assume that the lack of efficacy of the circuit for the correction of preoperative anemia is due to the intrinsic obstacles of our center. Among them:Premature programming in some patients, especially the case of cardiovascular surgery, which determines that the time between the surgical indication and the preoperative visit, is very limited.Lack of adequacy of the treatment at the date of intervention caused by lack of knowledge, especially in general surgery.The rigid criteria for the delivery of carboxymaltose iron limit the inclusion of patients who are closer to the intervention date, or determine an insufficient dosage of iron sucrose.Lack of diffusion of our program to different services when correcting postoperative anemia with iron. Strategies will be established by the Transfusion commission to solve the problems identified. As for the unfavorable results on transfusion practice (transfusion index, mortality and complications), it is essential to introduce improvements and update the optimal use of blood products by our professionals. This contradicts the results of the Transfusion Practice Survey. Therefore, we will take this data with caution, insisting on the awareness of adequate transfusion policies and PBM strategies, with the support of the hospital's management, and the dissemination of knowledge about these programs to achieve the commitment of the professionals involved. Disclosures No relevant conflicts of interest to declare.

Description: INTRODUCTION Daratumumab is an anti-CD38 monoclonal antibody which is a recent success in the treatment of multiple myeloma (MM). It binds to the CD38 protein, which is highly expressed in MM tumor cells. It is indicated in monotherapy in patients with relapsed MM, being refractory to treatment and having previously received a proteasome inhibitor and an immunomodulatory agent, with progression of the disease since the last treatment. It can also be used, as stated recently in its data sheet, in combination with Lenalidomide and Dexamethasone or Bortezomib and Dexamethasone for the treatment of patients with MM who have received at least one previous treatment. It is being tested in combination with other drugs, which shows its enormous potential. OBJECTIVES We expose the experience with this drug in our center in recent years. MATERIALS AND METHODS We have evaluated patients treated with Daratumumab, recording: demographic data, previous number of lines of treatment, use in monotherapy or combination, date of initiation of treatment, response to it, date of suspension (if it occurred) and its cause, as well as total duration of the treatment (figure 1 and 2). RESULTS We studied 12 patients, 6 men and 6 women, treated with Daratumumab between 2016 and 2018. The average age is 63.75 years (range between 57 and 72). On average, it was used in the 4th line of treatment, ranging between 2 cases in which it was the 2nd and 1 in which it was the 7th. In all patients, it was used in monotherapy. Currently, 3 out of the 12 patients are still being treated with Daratumumab and they are in remission (objectified by PET-CT in 1 patient with only 4 months of treatment). 2 other patients are in partial remission (with 23 and 4 completed months of treatment, respectively). It was necessary to suspend the drug in 8 patients, in 7 cases due to progression of the disease. The remaining patient suffered, in the 1st administration, an adverse reaction of type III that was refractory to the symptomatic treatment and to the decrease of the infusion rate, which forced to withdraw the drug. In 4 cases, the drug was discontinued and the result was "stable disease", so it remained until progression was evidenced. The average maintenance of the drug until progression was 4 months, ranging between 2 and 6 months. In the remaining 3 patients the disease progressed, so the drug was discontinued. CONCLUSIONS The MM treatment has to be individualized and adapted to the risks. The data obtained from our patients indicate that Daratumumab is a potentially valuable drug among the therapeutic arsenal against this pathology. However, we believe that the results would be much better if the treatment is started in earlier lines. Disclosures Rios: Amgen, Celgene, Janssen, and Takeda: Consultancy.

Description: ASCT has been reported as a feasible, safe and effective treatment in HIV-Ly patients (pts) receiving Highly Active Antiretroviral Therapy (HAART). We hereby present an updated analysis of the EBMT experience on HIV-Ly pts treated with an ASCT since 1999. Sixty eight pts from 20 institutions [56 (82%) males, median age of 41 (29–62) years] were included. Twenty-two pts met AIDS criteria (other than lymphoma) at the time of HIV-Ly diagnosis. Forty-nine pts were diagnosed of NHL (31 DLBCL; 8 Burkitt/Burkitt-like; 4 plasmablastic; 3 anaplastic, 3 PTCL), 80% of them presenting with stage 〉II and 18 pts of HL, 61% of them presenting with stage 〉II. Median (range) lines of therapy before ASCT was 2 (1–5). Thirty-five pts were autografted in CR (16 in CR1), 25 in chemosensitive disease and 8 in chemoresistant disease. Sixty-five pts received the BEAM protocol as a conditioning regimen and the remaining three received TBI-based protocols. Two pts received more than 1 ASCT (censored at time of 2nd ASCT). At the time of ASCT the median number of CD4+ cells was 162 (8–1159)/mcl and 34 pts had undetectable HIV viral loads. HAART was given in 55/57 pts during conditioning but withdrawn in 25% of them. The median number of CD34+ cells infused was 4.5 (1.6–21.2) ×106/kg and G-CSF was used until engraftment in 60/67 pts for a median of 8 (2–21) days. All pts but one who died on day +15 reached neutrophils〉500/ml at a median time of 11 (8–36) days. Platelet count 〉20.000/ml was reached in 61 pts at a median time of 14 (6–455) days. Twenty three pts (34%) died: disease-progression (n=15), acute ASCT-related complications (n=6) [bacterial infections (n=4), multi-organ failure (n=1), other complications (n=1)] and 2 pts died from HIV-related complications. Cumulative incidence of NRM was 4.4% (95%CI 1.5–13.3) and 7.6% (95%CI 3.3–17.6) at 3 and 12 months, respectively. Age 〉 50 years at ASCT [RR 4.37 (95%CI 1.01–18.89), p = 0.05] was the only independent adverse prognostic factor for NRM. Relapse occurred in 19 (28%) pts giving a cumulative incidence of 23.6% (15.2–36.9) and 29.6% (20.0–43.8) at 12 and 24 months, respectively. Median time to progression was 4.5 (0.5–32) months. Histology (NHL other than DLBCL) [RR 3.2 (95%CI 1.0–9.6), p = 0.04], the use of 〉2 previous treatment lines [RR 2.7 (95%CI 1.0–7.2), p = 0.05] and not being in CR at ASCT [RR 3.5 (95%CI 1.2–9.7), p = 0.02] were significantly associated with a higher risk of relapse post-ASCT. With a median follow up time of 32 (2–81) months, PFS and OS were 56% (CI95% 43–70) and 61% (CI95% 48–74) at 3 years, respectively. Pts with refractory disease showed a poorer OS [RR 5.1 (95%CI 1.8–14.6), p = 0.002] and PFS [RR 5.3 (95%CI 2.0–13.7), p = 0.001]. One pt developed an in-situ epithelioma and myelodisplastic syndrome (+4y) and another one a kidney adenocarcinoma (+3y). The results of the largest experience on ASCT for HIV-Ly indicate that this approach is a useful treatment in terms of NRM, long-term OS, and PFS, with significantly better results in patients autografted with chemosensitive disease.

Description: INTRODUCTION Bridging therapy consists of the administration of a fast-acting anticoagulant such as the low-molecular-weight heparin (LMWH) during the period of cessation of oral anticoagulant therapy. The decision to continue with anticoagulant therapy or to discontinue the treatment with the establishment of the Bridging therapy have been carried out carefully and on an individual basis. While taking this decision, we have taken into account three factors: the urgency of surgery or invasive process, the risk of bleeding and thrombotic risk for the patient. In recent decades, there have been multiple studies supporting the LMWH treatment, at least as safe and effective and more cost-effective than unfractionated heparin (UFH) in the prophylaxis and treatment of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). Therefore, the LMWH is considered as the drugs of choice in the prevention of venous thromboembolism. There are several types of commercialized LMWH, with different pharmacological properties, such as molecular weight, anti-Xa/IIa ratio and average life. The sodium bemiparin is the LMWH with greater anti-Xa/IIa ratio, which implies a lower risk of bleeding. In addition, it has shown a low incidence of VTE and bleeding in actual clinical practice. OBJECTIVE There are few published data from bridging therapy at therapeutic doses in patients treated with oral anticoagulants (AVK) and perioperative management. It is intended to assess the efficacy (recurrence of thrombosis) and safe use of sodium bemiparin at anticoagulant doses on the bridging therapy and possible thrombotic and / or hemorrhagic complications (major and minor bleeding) resulting from this use. MATERIAL AND METHODS We have analyzed 550 bridging therapies at full dose in our clinic in the last year. They were made to a total of 345 patients (174 men and 171 women) with CHADSVASC 〉 2, aged between 15 and 90, with an average age of 64 years old. The reasons of anticoagulation in our patients were atrial fibrillation, mechanical prostheses, DVT, pulmonary embolism and recurrent thrombosis in patients with thrombophilia. In 70% of the cases, there were comorbidities, such as heart failure, chronic obstructive pulmonary disease, anemia, kidney failure, liver disease and long-term aftereffects of stroke. The bridging therapy has consisted on suspending AVK 4 (acenocumarol) to 6 days (warfarin) before the procedure, and replacing it by sodium bemiparin at full doses 100 kgr: 12.500 IU/24 h, and administration of a prophylactic dose of 3,500 IU, 12 hours before the procedure, and another dose 6-12 hours after the procedure, depending on the risk of bleeding of the intervention and the thrombotic risk of the patient's disease. The bridging therapy has been performed in 120 cases of major surgery (orthopedic surgery, ophthalmological procedures, valvular replacements etc), 210 cases of minor surgery (removal of nevus, complex dental extractions, dental implants), 140 cases of invasive procedures (colonoscopies, endoscopies ..), 30 cases of bleeding caused by AVK (epistaxis, petechiae and bruises, hemoptysis, menorrhagia and gastrointestinal bleeding), 15 cases of hospitalization with INR decompensation with various causes (infectious endocarditis, pneumonia, uncompensated heart failure...) and 35 cases for thrombophilia study. RESULTS: As complications of using bemiparin sodium, there have been: 1 case of heparin-induced thrombocytopenia, 20 cases of hematomas at the needle puncture sites and 2 cases of persistent uterine bleeding with progressive anemia with transfusional requirement. There was neither cases of major bleeding nor cases of thrombosis. CONCLUSIONS Sodium bemiparin administered at therapeutic doses (115 IU/kg/24h) in the perioperative period, according to the scheme described above, it is associated with a low incidence of recurrence of VTE and bleeding. The complications presented in our sample have been very few, in patients with associated co-morbidities. In our study, sodium bemiparin has shown to be safe and effective with minimal bleeding complications. Treatment should be administered on an individual basis according to each patient and factors related to surgery. Further studies will confirm our results. Table Table. Disclosures No relevant conflicts of interest to declare.