ALBERT

Description: Venous thromboembolism (VTE) is a major therapeutic issue in cancer. Advances in this field and heterogeneities in clinical practices prompted us to establish guidelines related to VTE treatment and to central venous catheter thrombosis (CVCT) management. in cancer patients according to the SOR Standards, Options: Recommendations (SOR) methodology for the development of evidence-based Clinical Practice Guidelines (CPG) as endorsed by the French National Cancer Institute. Methods: After reviewing the published studies on the topics between 1999 and 2007, a first version of the guidelines was based on the levels of evidence derived from analysis of the 38 out of 418 selected studies for VTE treatment and the 40 out of 175 selected studies for the CVCT management. The recommendations were classified as Standards or Options and then peer-reviewed by 65 independent experts. Detailed methodology is available at www.sor-cancer.fr Standards in cancer patients: The treatment of VTE should be based on Low Molecular Weight Heparins (LMWH) at curative doses for at least 3 months. During the initial treatment (up to 10 days), there are no specific requirements and all drugs approved (including LMWH, Unfractionnated Heparin (UFH), fondaparinux and danaparoid) may be used. Beyond the first 10 days, VTE treatment should be based on LMWH at curative doses for at least 3 and optimally for 6 months, as validated with the following drugs and dosage regimens: dalteparin 200 IU/kg once daily for one month, then 150 IU/kg once daily; enoxaparin 150 IU/kg once daily; and tinzaparin 175 IU/kg once daily. In case of: severe renal impairment, UFH should be used rapidly followed by Vitamins K Antaogonist (VKA) for at least 3 months; severe Pulmonary Embolism (hemodynamic failure), the indications and usages of thrombolytic drugs are the same as in non-cancer patients; absolute contra-indication to anticoagulation or VTE recurrence despite optimal anticoagulation, vena cava filters (VCF) should be considered; intracranial malignancies, VTE treatment is the same as in cancer patients with non-intracranial tumors. CVCT treatment relies on long term use of LMWH. In case of severe renal failure, UFH with early AVK must be used. Treatment is to be continued as long as the catheter is maintained. This can only be achieved if the catheter is functional, well positioned, not infected and if adapted anticoagulation has resumed the CVCT. If catheter withdrawal is necessary, there is no standard concerning the anticoagulation management. CVCT prophylaxis relies on positioning the catheter distal extremity at the “superior vena cava - right atrium” junction. Systematic CVCT anticoagulant prophylaxis is not recommended. Options: Treatment of VTE: If LMWH administration for 3 months is impossible, short-term use of LWMH followed by VKA for at least 3 months may be proposed. It is recommended to administer LMWH for 3 to 6 months; LMWH should be used according to the same curative dosage regimen as during the first 3 months. Beyond the first 6 months, the anticoagulant treatment should be continued as long as the cancer is active or treated. In the event of a first VTE episode secondary to a transient risk factor and if the cancer is not active nor treated, anticoagulation may be discontinued after 6 months. The choice between LMWH and VKA depends on their benefit-risk ratio (influenced by drug interactions, chemotherapy, invasive procedures, and general health status) and acceptability. If a VCF is considered, a retrievable VCF may be discussed. CVCT treatment: If another catheter has to be inserted, prior evaluation of the venous circulation by scanner or ultrasound examination is recommended. If prolonged use of LMWH is impossible, VKA can be proposed. In case of severe superior vena cava syndrome, fibrinolytics can be used in the absence of contra-indications. Treatment by LMWH can be stopped 6 weeks after catheter withdrawal in non active cancer or after 3 to 6 months of LMWH followed by VKA in the other cases. CVCT prophylaxis: Right side catheter insertion and vein localisation by ultrasonography are preferred. Conclusion: The French recommendations further support the 2006 Italian and the 2007 North American guidelines on VTE treatment in cancer patients and were extended to the use of VCF and treatment of patients with intracranial malignancies. In addition, we provide recommendations on CVCT treatment in cancer patients.

Description: Introduction Since 1996 a joint collaborative effort from the European Group for Blood and Marrow Transplantation (EBMT) and League against Rheumatism (EULAR) collected cases of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for patients (pts) with severe autoimmune diseases (AD). This retrospective observational study was designed to assess patients outcome and analyse the determinants of treatment responses after AHSCT. Methods All consecutive AD pts treated by AHSCT from 1996 to 2007 according to the EBMT-EULAR consensus statement with ethics committee approved protocol were included. Data were reported yearly via the electronic EBMT data management system PROMISE and outcomes updated as December 2007. Standard AHSCT techniques used either bone marrow (BM), peripheral blood stem cells (PBSC) or both. PBSC were collected with cyclophosphamide CY (CY 4 g/m2) + granulocyte-colony stimulating factor (G-CSF), or with G-CSF alone if cardiac function prevented CY. Cell selection used either CD34+ selection with or without monoclonal antibodies, particularly anti-CD52, anti-CD3, anti- CD19 or anti-CD20. Conditioning regimen used either Total Body Irradiation (TBI) or chemotherapy alone, with various combinations of CY, Busulfan, BEAM ± Antithymocyte Globulins (ATG), which were then subgrouped arbitrarily into high intensity regimen, including Busulfan or TBI, low intensity restricted to CY alone, Melphalan alone and Fludarabine-based regimens, or intermediate regimen with all the other combinations. Primary outcome measure was Progression Free Survival (PFS) defined as survival without evidence of relapse or progression. Secondary outcomes were the Overall Survival (OS) defined as time to death, irrespective of the cause and Transplant Related Mortality (TRM) at day 100, defined as death without ADs relapse or progression. Cumulative incidence curves were used for TRM, considering relapse or progression within 100 days as a competing event and compared using the Gray‘s test. Kaplan-Meier estimate was used to calculate PFS Probabilities and the log-rank test for univariate comparisons. For all pronostic analyses, continuous variables were categorised and the median was used as a cut-off point. Associations of patient, disease and graft characteristics with outcomes were evaluated in multivariate analyses, using Cox proportional hazards for PFS, and proportional hazard regression model of Fine and Gray for NRM. Results: From 1996 to December 2007, 900 AD pts (64 % female, median 35 years) from 171 teams in 27 countries treated by AHSCT were reported to the EBMT data base, mainly multiple sclerosis (MS, n=345), systemic sclerosis (SSc, n=175), systemic lupus erythematosus (SLE, n=85), rheumatoid arthritis (RA, n=89), juvenile idiopathic arthritis (JIA, n=65), vasculitis (VASC, n=26) and hematological immune cytopenia (HIC, n=37). PSC were used as stem cell source for 92% of the pts; 42 % of the pts had in vitro cell selection, mostly with CD34+ selection. All types of conditioning regimens were used in all disease categories with very few patients (7%) with TBI. On the overall population, the 5 years PFS was 43 ± 2 % and OS was 85 ± 1 %. Three years after AHSCT: PFS was 61±5 % for SSc, 55±3 % for MS, 54±6 % for SLE, 52±7 % for JIA, 53±15 % for PMDM, 47±11 % for VASC, 34±9 % for HIC and 23±5 % for RA,); OS was 98 ± 2 % for RA, 93 ± 2 % for MS, 82 ± 5 % for JIA, 83 ± 5 % for SLE and 77 ± 4 % for SSc, depending primarily on AD type (p 35 yrs (HR 0.73, 95%CI (0.59–0.89), p=0.002), AHSCT performed before December 2000 (HR 0.69, 95%CI (0.55–0.85), p=0.008) and number of AHSCT for ADs per centre £ 13 (HR 0.82, 95%CI (0.67–0.99, p=0.05) were associated with a lower PFS. The day 100 TRM was 5 ± 1% overall and appeared significantly lower for a number of patients per centre 〉 13 (HR 0.45, 95% CI (0.21–0.99), p=0.05). ConclusionThe EBMT registry allowed to collect 900 ADs pts with AHSCT after 10 years of collaborative effort. Although retrospective, this largest cohort studied worldwide so far showed that patient age, AD type and number of AHSCT per centre are important determinants of the response. AHSCT appeared a good therapeutic alternative for severe Ads unresponsive to conventional treatment, supporting the ongoing European and north American phase 3 trials comparing AHSCT to standard therapies in SSc, MS, SLE and Crohn’s disease.

Description: Abstract 3460 Autoimmune diseases (AD) have been reported after haematopoetic stem cell transplantation (HSCT) and most commonly autoimmune cytopenias (AIC) are observed. Proposed risk factors are unrelated donor HSCT and presence of chronic graft-versus-host disease (GVHD). Use of CB cells is increasing as an alternative source of adults HSC for allotransplant however incidence and risk factors of AD after CBT have not been described. Since CB lymphocytes are immature and most of the CBT are HLA mismatched, we hypothesize a high incidence and diversity of secondary AD and. Therefore, we conducted a retrospective study in order to describe incidence, nature and risk factors for secondary AD after CBT. We include CBT recipients reported to EUROCORD up to December 2008. All centres were asked to participate to the survey even if they did not observe any case of AD after CBT. For those with AD, detailed information on diagnosis, treatment and outcome were asked. Median follow-up was 44 months (3.2-217). 42 out of 651 patients (pts) from 35 centres had developed at least one secondary AD at a median of 198 days (27-4267) after CBT. The remaining 609 pts without secondary AD served as control group (nonAD). Characteristics of both groups are given in table 1. Cumulative incidence of secondary AD after CBT was 5±1% after 3 years and 6.5±1% after 10 years. Diagnosis of secondary AD were autoimmune haemolytic anemia (AIHA) in 16, autoimmune thrombopenia (ITP) in 9, EVANS syndrome in 6, autoimmune thyroiditis in 3, glomerulonephritis in 2, Graves disease, psoriasis, psoriasis arthritis, immune neutropenia, ulcerative colitis and vasculitis in 1 patient each. Three pts developed ITP followed by AIHA. Median time to develop a AIC was 180 days (27-4267) and non-hematological AD was 322 days (70-1117), respectively (p=0.13). At onset of AD, 3 pts had acute GvHD, 6 chronic GvHD and in 10 pts an infection. In multivariate analysis adjusted for differences between the two groups, the following factors were associated with higher incidence of secondary AD: 1) age

Description: Introduction Autologous Hematopoietic Stem Cell transplantation (AHSCT) is used since 1994 worldwide to treat severe autoimmune disease (AD) refractory to standard therapy. Despite early release and regular update of the European Society for Blood and Marrow Transplantation (EBMT) practice guidelines (Snowden JA et al BMT 2012, Alexander T et al BMT 2014) along with 3 randomised Clinical trials (CTs) for Systemic Sclerosis (SSc) ASTIS, Crohn's Disease (CD) ASTIC and Multiple sclerosis (MS) ASTIMS, the uptake of this approach varies according to each ADs and between countries. We therefore design this retrospective study to evaluate patients (pts) outcomes as reported to the French Bone Marrow Transplantation Society registry (SFGMT-TC) in light of the other States activity published or reported to the EBMTregistry. Materials and methods All AHSCT for adult AD pts (〉 18 years (yrs)) reported in France from 1997 to 2013 with at least one yr follow-up after AHSCT were included in the study. Primary data were derived from the EBMT registry (MED-A/B forms) with additional data obtained through a specific questionnaire (MED-C) for the study. Primary end point is overall survival (OS), defined as time since the day of transplant to death, irrespective of the cause. Secondary end points are Progression Free Survival (PFS), 100 day treatment related mortality (100-day TRM) and non-relapse related mortality (NRM). The probabilities were estimated using the Kaplan-Meier estimator for OS and PFS, cumulative incidence for NRM, relapse/progression being the competing event. All tests were two-sided. Statistical analyses were performed with IBM SPSS Statistics 22.0 and R version 3.1.2 (R Development Core Team, Vienna, Austria) software packages. Results 96 adult pts (55% Female), median age 45 yrs [20-71], underwent a first AHSCT for ADs in 19 HSCT Units. Most of the ADs were rheumatological(72%) with 55 SSc, 7 polymyositis-dermatomyositis, 3 polychondritis, 2 Lupus Erythematosus, 1 Rheumatoid Arthritis (RA), 1 Ankylosing Spondylitis, or neurological (15%) with 14 MS, whereas the others were 5 CDs, 5 immune thrombocytopenic purpura, 1 hemolytic autoimmune anemia, 1 IgM neuropathy and 1 POEMS syndrome. Two pts had 2 simultaneous ADs (1 SSc and RA, 1 CD and RA). Median duration between AD diagnosis and AHSCT was 3.5 yrs [1-33]. With a median follow-up of 7 yrs [

Description: Background: Autologous Hematopoietic Stem Cell Transplantation (AHSCT) has been shown more effective to treat severe forms of systemic sclerosis (SSc) than conventional immunosuppressive therapy.However, despite advances in clinical management, therapeutic mechanisms of AHSCT still need to be more completely understood. Furthermore, identification of biomarkers of therapeutic response may help to refine current clinical protocols and improve future therapeutic goals. Objective:To investigate immunological mechanisms associated with the therapeutic efficacy of AHSCT. Methods: Thirty-one patients with progressive SSc, refractory to first line therapy, were selected for AHSCT. Follow-up included clinical assessment of general health, skin thickness (modified Rodnan's Skin Score, mRSS), lung function (Forced Vital Capacity, FVC), levels of anti-Scl70 autoantibodies and C-reactive protein (CRP). Dermal fibrosis was evaluated by PicroSirius (PS), hematoxylin/eosin (HE) and Masson's-Trichrome (MT). Sixteen additional SSc patients under standard treatment were enrolled as controls. PBMCs were collected before and every 6 months, until 36 months post-AHSCT. Thymic function was measured by RT-qPCR quantification of β- and signal joint (sj)-T-cell receptor excision circles (sjTREC) and intra-thymic T-cell division (n) was calculated by the formula: n= LOG(sjTREC/βTREC)/LOG2. B cell replication history was quantified by coding-joint (Cj) and sj-kappa-deleting recombination excision circles (sjKREC), and B-cell divisions in the peripheral blood (N) were calculated by the formula: N= LOG(Cj/sjKREC)/LOG2. Telomere length was evaluated by multiplex RT-qPCR. CD19+CD24hiCD38hi Bregs, CD19+CD27-IgD+ naive, CD19+CD38lowIgD+ Bm2, CD3+CD4+CD31+CD45RA+ recent thymic emigrants (RTE), CD8+CD28-CD57+ exhausted and CD4+CD25hiFoxP3+ (GITR+/CTLA-4+) Tregs were quantified by FACS. IL-10-producing Tregs were quantified after 24h stimulation with anti-CD3/CD28 Dynabeads. IL-10-producing Breg counts were assessed after 24h stimulation with CpG and CD40L. Skin biopsies were stained for IL-10 expression. Results: Rodnan's score decreased at 6 months, remaining lower than baseline until 36 months after AHSCT. FVC values stabilized and anti-Scl-70 autoantibody titers and C-reactive protein (CRP) levels decreased after AHSCT. PS, HE and MT skin biopsy staining evidenced decreased collagen deposition. Immune reconstitution analyses evidenced that thymic function was significantly reduced at 6 months post-AHSCT, and higher than baseline at 24 months, never changing intrathymic T-cell division rates and strongly correlating with thymic-derived RTE exportation. Moreover, at 6 months post-AHSCT, increased numbers of exhausted T-cells correlated with reduced telomere T/S ratio, indicating that while thymic function is suppressed, early after AHSCT, the immune reconstitution is based on homeostatic proliferation of residual cells. Regulatory T-cells increased at 12 months post-transplantation, correlating with sjTREC values, with higher CD45RA expression and IL-10 production than at baseline. Bone marrow output of naive B-cells increased from 12 until 36 months post-AHSCT, resulting in reduced B-cell division in the periphery, as shown bypersistent increase of conventional naive as well as of non-conventional Bm2 naive B-cell counts. Finally, regulatory B-cell counts increased transiently from 6 to 12 months after AHSCT, presenting higher IL-10 production than at baseline. Skin biopsies evidenced higher IL-10 expression at 6 and 12 months post-transplantation as compared to baseline. Six transplanted patients presented disease reactivation with subsequent increase in Rodnan's score and/or worsening of lung function after AHSCT. These patients presented lower FoxP3, GITR and CTLA-4 expressions at 12 months post-transplantation. Regulatory B-cell counts after AHSCT were also lower in relapsing than in non-relapsing patients. Conclusions: Our results suggest that increased counts of newly-generated regulatory B- and T-cell after AHSCT are associated with clinical improvement in SSc patients. Clinical remission may be associated with amelioration of the immunoregulatory network and restoration of self-tolerance promoted by the procedure. Disclosures No relevant conflicts of interest to declare.

Description: Introduction Few data are available on the long-term LMWH prescription and treatment follow-up in clinical practice in patients with cancer-associated VTE. Study objectives were to document the prescription and use of treatment doses of LMWH in cancer patients and to assess adherence to established recommendations. Methods Adult cancer patients receiving antineoplastic treatment or palliative care, age ≥18 years, with recent symptomatic VTE in whom treatment with LMWH had been initiated within 7 days prior to inclusion, were eligible to participate in this prospective observational French multicenter study. Patients with a contra-indication to LMWH were not eligible for participation. Main study outcome was the description of LMWH use and prescription in usual medical care. Adherence to recommendations was measured as the proportion of patients receiving a prescription of a LMWH at treatment doses according to the approved dosing schedule and treated for at least 3 months in the absence of severe renal insufficiency (CrCl1 month in 47 (11.5%) patients, respectively. Four (1.03%) patients had severe renal insufficiency. VTE diagnosis at inclusion included lower-limb deep-vein thrombosis (DVT) in 193 (47.2%), pulmonary embolism in 145 (35.5%), CVC-associated thrombosis in 66 (16.1%), upper-limb DVT in 45 (11.0%) and visceral thrombosis in 16 (3.9%) patients, respectively. Most cancers were solid tumors gastro-intestinal (24.4%), lung (17.4%) or breast (15.9%); 81% of patients received chemotherapy and 61.4% were metastatic cancers. LMWH prescriptions included dalteparin in 42 (10.3%), enoxaparin in 61 (14.9%), nadroparin in 5 (1.2%) and tinzaparin in 301 (73.6%) patients. Only 4 (1%) patients received LMWH despite severe renal insufficiency. Table 1 –Prescription adherence to recommendations at inclusion [n (%)]Adherence criteriaTinzaparin (N=301)Other LMWH (N=108)All (N=409)Treatment duration 〉 3 months293 (97.3)108 (100)401 (98.0)Adequate dosing regimen*231 (76.7)14 (13.0)245 (59.9)Adequate dosing schedule296 (98.3)45 (41.7)341 (83.4)Overall adherence219 (72.8)7 (6.5)226 (55.3) *includes adequate treatment dose and dose adjustment according to recommendations A total of 274 (67.0%) patients received the recommended treatment dose, while 87 (21.3%) patients received doses exceeding this by more than 10% and 39 (9.5%) patients received doses more than 10% below the recommended doses. Based on the pre-defined adherence criteria, 226 (55.3%) [95% CI 50.4-60.1] patients had a LMWH prescription consistent with recommendations. Tinzaparin prescriptions were associated with higher adherence scores compared to other LMWH. During follow-up, actual mean treatment duration was 5.28 ± 2.07 months and 85.7% of patients were treated for 3 months or more Table 2 - Adherence to recommendations at inclusion according to cancer characteristics (N=409) [n (%)] Cancer characteristics Proportion of study population Proportion of adherence to recommendations Gastro-intestinal Lung Breast Hemato lymphopoietic Other Metastatic Chemotherapy (n=405)* 100 (24.4) 71 (17.4) 65 (15.9) 54 (13.2) 119 (29.1) 251 (61.4) 328 (81.0) 53 (53.0) 37 (52.1) 46 (70.8) 28 (51.9) 62 (52.1) 133 (53.0) 186 (56.7) *405 patients documented with chemotherapy At inclusion, the rate of prescriptions consistent with recommendations was low (55.3%) while the highest rate of adherence (70.8%) was observed in patients with breast cancer known to be at rather lower risk of VTE recurrence. Conclusion Adherence to treatment duration was adequate whereas dosing regimen was insufficiently compliant with recommendations. Overall adherence with tinzaparin seemed higher compared to other LMWH Management of patients with cancer-associated VTE requires further education and information of health care professionals. Farge D, J Thromb Haemost. 2013 Jan; 11(1):56-70. Disclosures Farge: Pfizer: Research Funding; LEO Pharma: Research Funding. Debourdeau:Pfizer: Research Funding; LEO Pharma: Research Funding. Cajfinger:Pfizer: Research Funding; LEO Pharma: Research Funding.

Description: Introduction Long-term treatment with LMWH is the standard therapy for patients with cancer-associated VTE. Recommended treatment regimen include the prescription of LMWH at treatment doses according to approved administration schedule for at least 3 months in the absence of severe renal insufficiency (CrCl 50% 15 2 17 Deaths n=301 n=107 n=408 All 102 (33.9) 44 (41.1) 146 (35.8) Cause of death* n=100 n=44 n=144 LMWH treatment** 1# 0 1## Cancer 87 39 126 Sepsis 4 1 5 Bleeding 4 1 5 Antineoplastic treatment 1 0 1 PE 0 1 1 Other 7 3 10 *Multiple causes of death may have been reported in the same patient; **fatal bleeding reported as LMWH-related; #n=99; ## n=143 Kaplan-Meier estimate of the probability of bleeding at 6 months was 15.9% while corresponding estimates were 18.1% for thrombocytopenia and 34.5% for deaths. Of the five (3.5%) patients who reported fatal bleedings one was reported as related to the LMWH treatment. No heparin-induced thrombocytopenia was reported in the study. Conclusion Clinical outcomes were consistent with previous observations in this patient population except a lower incidence of VTE recurrence compared with previous studies. Study results tend to confirm the favorable efficacy and safety profile of LMWH for the long-term treatment of patients with cancer-associated VTE, when used according to recommended treatment duration and respecting contra-indications. Schulman. J Throm Haemost. 2005 Apr;3(4):692-4.Farge J Thromb Haemost. 2013 Jan;11(1):56-70.Debourdeau P, J Thromb Haemost. 2013 Jan;11(1):71-80 Disclosures Farge: Pfizer: Research Funding; LEO Pharma: Research Funding. Debourdeau:Pfizer: Research Funding; LEO Pharma: Research Funding. Cajfinger:Pfizer: Research Funding; LEO Pharma: Research Funding.

Description: Introduction Long-term treatment with LMWH is the recommended standard for patients with cancer-associated VTE [1, 2]. Data on the long-term prescription of LMWH and treatment follow-up in clinical practice, and particularly the patient’s view on the treatment, are scarce. The main objective of TROPIQUE was to document the prescription and use of LMWH in these patients. A sub-study aimed to assess patients’ perception of long-term anticoagulant treatment with LMWH based on the validated Perception AntiCoagulant Treatment Questionnaire (PACT-Q) [2]. Methods Adult cancer patients with recent symptomatic VTE from the TROPIQUE study were asked to fill-in a PACT-Q at inclusion and at 6 months or study end. PACT-Q1 administered at study start included “Treatment Expectations” (7 items) measured by separate scores expressed on a 5-point Likert scale. PACT-Q2 performed at 6 months or at the end of the study included “Convenience” and “Anticoagulant Treatment Satisfaction” (13 and 7 items, respectively) measured by global scores on a 0-to-100 scale. Results A total of 409 patients (49.9% female), aged 65±12.1 years, were consecutively included from November 2012 to August 2013. Most of cancers were solid tumors; 81% of patients received chemotherapy and 60.9% of cancers were metastatic. Mean treatment duration was 5.28 ± 2.07 months and 98.0% of patients were treated for 3 months or more. PACT-Q1 and PACT-Q2 were collected on a voluntarily basis from 269 (67.8%) and 139 (34.0%) patients, respectively. At study start patients’ treatment expectations were high, particularly regarding the confidence in the treatment to prevent blood clots (mean 3.94 ± 0.75), the expectations of symptom relief (mean 3.98 ± 1.04) and the importance of ease of use (mean 4.22 ± 0.9) while 54.3% of patients had low or no expectations of treatment-related side effects (bruise, bleeding) (mean 2.45±1.1). The treatment was considered convenient (global score 79.7 ± 17.1), with the majority of patients reporting small or no difficulties with taking the treatment (subcutaneous injections) and with regards to impact on daily life. The impact of treatment-related side effects on activities was reported as low. A proportion of 69.1% of patients were overall satisfied or very satisfied with their anticoagulant treatment whereas the experience with treatment-related side effects was worse or much worse than expected for only 12.9% of patients. The “Anticoagulant Treatment Satisfaction” global score was 62.9 ± 16.7. Abstract 4272. Table 1: Cancer patient’s perception of long-term anticoagulant treatment with LMWH [n (%)] Selected perception items* Not at all or to a small extent Moderately Very much or extremely Mean score on Likert scale ± SD PACT-Q1 Treatment expectations (n=269) Confident in preventing clots Symptom relief Side effects (n=267) Importance of ease to use - 10 (3.7) 22 (8.2) 145 (54.3) 17 (6.3) - 45 (16.7) 38 (14.1) 76 (28.5) 14 (5.2) - 214 (79.6) 209 (77.7) 46 (17.2) 238 (88.5) - 3.94 ± 0.75 3.98 ± 1.04 2.45 ± 1.1 4.22 ± 0.9 PACT-Q2 Convenience (n=138) Difficulty in taking treatment (n=137) Difficulties regarding daily life Bother in follow-up required Difficulties on regular intake Side effects impact on activities - 92 (67.2) 101 (73.2) 101 (73.2) 114 (82.6) 116 (84.1) - 37 (27) 26 (18.8) 16 (11.6) 17 (12.3) 14 (10.1) - 8 (5.8) 11 (8.0) 7 (5.1) 7 (5.1) 8 (5.8) 79.7 ± 17.1 Treatment satisfaction (n=137) Experience with side effects (n=132) Worse or much worse 17 (12.9) As expected 55 (41.7) Better or much better 60 (45.5) 62.9 ± 16.7 Overall satisfaction (n=136) Unsatisfied or very unsatisfied 10 (7.4) Neutral 32 (23.5) Satisfied or very satisfied 94 (69.1) *Only some items selected from the PACT questionnaire are shown Conclusion Patients with cancer-associated VTE had high expectations regarding anticoagulant treatment and long-term treatment with LMWH is perceived as convenient with a high degree of patient satisfaction. These results suggest that cancer patient’s capability to accept long-term injectable anticoagulant treatment is probably underestimated. These encouraging observations of patient perception of the anticoagulant therapy are essential in view of improving health professional’s adherence to established treatment recommendations on cancer-associated VTE [3]. 1- Farge D, J Thromb Haemost. 2013 Jan;11(1):56-70. 2- Prins MH, Health Qual Life Outcomes, 2009. 7: p. 9. 3- Debourdeau P, Support Care Cancer. 2008 Dec;16(12):1333-41 Disclosures Farge: Pfizer: Research Funding; LEO Pharma: Research Funding. Debourdeau:Pfizer: Research Funding; LEO Pharma: Research Funding. Cajfinger:Pfizer: Research Funding; LEO Pharma: Research Funding.

Description: Abstract 2322 New onset of AD have been reported after autologous and allogeneic HSCT and AD patients (pt) treated by HSCT may be at higher risk for developing a secondary AD. A single US centre study showed that more profound T cell depleting conditioning with antithymocyte globulin (ATG) or alemtuzumab enhanced the risk of secondary AD after HSCT for primary AD. We therefore aimed at specifying the incidence, nature and risk factors for secondary AD after autologous or allogeneic HSCT for a primary AD. Methods: Retrospective analysis of AD pts treated by HSCT as reported to the EBMT data management system ProMISe until November 2009. Each EBMT participating centre was asked to identify all pts having developed at least one AD and those not having developed AD after HSCT as controls with complete detailed information on HSCT and outcome of original disease and treatment and outcome of secondary AD for cases. Cumulative incidence curves were used to estimate incidence of AD considering death as a competing event. Associations of patients and graft characteristics with secondary AD were evaluated by multivariate analyses, using Cox proportional hazards. All tests were two-sided. The type I error rate was fixed at 0.05 to determinate factors associated with time to event outcomes. Results (median, extremes): Out of 338 patients from 26 centres in 12 European countries, 33 developed at least one secondary AD within 569 (19-1489) days after HSCT, 305 pts without secondary AD served as controls. Characteristics of both groups are in table 1. The cumulative incidence of secondary AD after HSCT for primary AD was 6.5 (±1) % after 3 years and 11.1 (±2) % after 5 years. Diagnoses of secondary AD were thyroiditis (n=13), autoimmune hemolytic anemia (AIHA) (n=4), autoimmune thrombopenia (n=3), acquired hemophilia (n=3), Graves' disease, rheumatoid arthritis, sarcoidosis, antiphospholipid syndrome and psoriatic arthritis in 2 pts each and myasthenia gravis and vasculitis in 1 pt each. Two pts developed two secondary AD. After multivariate analysis age younger than 33 years p=0.016 (overall median age at HSCT), primary systemic lupus erythematosus (SLE) p= 0.003, ex vivo manipulation p= 0.015 and HSCT performed after the year 2002 p=0.02 remained as risk factors for secondary AD. At last follow-up within 5.9 years (0.25-15 years) after HSCT, 28/33 pts with secondary AD were alive and 257/305 nonAD pts. 0ne Systemic Sclerosis pt and one Multiple Sclerosis transplanted pt died from secondary embolic antiphospholipid syndrome and acquired hemophilia respectively. 26 primary AD pts received specific therapy after HSCT for their secondary AD. The pts with acquired hemophilia received steroids plus cyclophosphamide and additional Rituximab or ivIG or plasmapheresis, those with immune thrombocytopenia responded to steroids. One pt with thrombocytopenia followed by AIHA needed additional immunosuppression and Rituximab. Two pts with AIHA received steroids, cyclophosphamide and additional Rituximab, and one case also ivIG and ultimately allogeneic HSCT for secondary AID. At last follow-up, 12 pts remained in remission of secondary AD without treatment, 15 pts needed ongoing therapy, 3 pts had persistent secondary AD without therapy. This first multicenter study after HSCT for primary AD showed that secondary AD occurred in 10% of 338 pts after HSCT and led to death in 2 pts. Younger age and SLE as primary AD were significant risk factors for secondary AD, but contrary to previous single centre US experience, conditioning with ATG or alemtuzumab did not increase the secondary AD risk. Secondary AD after HSCT should be added to the post transplant follow up clinical parameters. Disclosures: Lenhoff: Celgene: Honoraria.