ALBERT

Description: Introduction: Most of the knowledge about treatments and outcome of CML patients originates from clinical studies. To get new and unbiased insights in the epidemiology, treatment and outcome of CML, the EUTOS population-based registry of newly diagnosed CML patients was established, - as part of the European Treatment and Outcome Study (EUTOS) for CML. The aim was to collect the data of all adults with newly diagnosed CML, irrespective of treatment and of enrolment in studies. Patients and Methods: The EUTOS population-based registry collected data of newly diagnosed CML patients, 18 years or older, over a specified period of time from 2008 till 2012 living in defined regions. The data were collected by 22 study groups in 20 European countries. Data were gathered via a web-based CRF-system. For comparison we used the already published data from five Company-sponsored registration studies IRIS (O’Brien et.all, NEJM, 2003), TOPS (Cortes et al, JCO, 2009) ENESTnd (Saglio et al, NEJM, 2010), DASISION (Kantarjian et al, NEJM, 2010) and BELA (Cortes et al, JCO, 2012), from three Investigator-sponsored studies GIMEMA (Castagnetti et al, JCO, 2010 and Gugliotta et al, Blood, 2011), French SPIRIT (Preudhomme et al, NEJM, 2010) and German CML IV (Hehlmann et al, JCO, 2011) and from two single referral centers HAMMERSMITH (De Lavallade et al, JCO, 2008) and MDA (Jain et al, Blood, 2013). Results: Till 15.05.2014 2978 patients were registered in the EUTOS Population-based registry. 94.3% of the patients were diagnosed in chronic phase (CP), 3.6% in accelerated phase (AP), and 2.2% in blastic phase (BP). For the calculation of the prognostic scores 361 patients had to be excluded because they were pretreated. For the comparison we used 2350 patients in Chronic Phase with laboratory values before any treatment. 54% of the patients in the EUTOS Population-based registry were male, less than in all studies (56.6 - 60.6%). The median age at diagnosis was 56 years, higher than in all studies (46 - 55). In EUTOS the proportion of patients more than 60 years and more than 65 years old was 40.4 % and 21.9 % respectively. Similar data were rarely reported in all other studies. Median value of the spleen size below costal margin was 0. 46.1% of the patients had a palpable spleen and 15.2% had a spleen size ≥ 10 (spleen size is always reported in cm under costal margin in this abstract). The % of palpable spleen is only reported by IRIS, 25.0% and by the FRENCH Spirit group, 49.8%. The median spleen is only reported by GIMEMA, 2.0. Spleen size ≥ 10 is reported by IRIS, 6.0%, ENESTnd, 12.4% and HAMMERSMITH 25.5%. While the median values for Platelets and Hemoglobin show no big differences, the median WBC in EUTOS is 83.9 x109/l and in the Company-sponsored registration studies: IRIS 18-20 x109/l , in ENESTnd 23-26 x109/l, in DASISION 23-25 x109/l , and in BELA 22-23 x109/l, in the Investigator-sponsored studies: GIMEMA 55 x109/l , in the FRENCH SPIRIT 83-104 x109/l , in the GERMAN CML IV 75-91 x109/l , and in the single referral center study HAMMERSMITH 140 x109/l, clearly indicating that in company-sponsored, registration studies, the reported values of the WBC were not recorded prior to any treatment. The median values for Blasts, Basophils and Eosinophils show also not so big differences. The % of Sokal low risk patients is in EUTOS with 34.5% lower than in all studies (35.2 - 60%) with the exception of HAMMERSMITH 28.9%. Discussion: The EUTOS Population-based registry provides the first European wide real-world series of patients with newly diagnosed Ph+, BCR-ABL+ CML. The age and sex distribution and some baseline characteristics such as Sokal Score as well as median WBC count in the EUTOS population-based registry are different from many prospective studies. This should be taken in due consideration before extrapolating the results of treatment studies to real life. Spleen size, which is known as an important value for prediction, is only very rarely reported in clinical studies. With further follow-up, this registry will provide a population-based insight on treatment, survival, and causes of death. Disclosures Baccarani: Novartis, BMS, Pfizer, Ariad: Consultancy, Honoraria, Speakers Bureau. Hoffmann:Novartis: Research Funding. Rosti:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Castagnetti:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy. Saussele:Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria. Steegmann:Novartis, BMS, Pfizer: Honoraria, Research Funding. Mayer:Ariad: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Turkina:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Zaritskey:Novartis: Consultancy. Clark:Novartis Pharmaceuticals Corporation: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Porkka:BMS: Honoraria; BMS: Research Funding; Novartis: Honoraria; Novartis: Research Funding; Pfizer: Research Funding. Hehlmann:Novartis: Research Funding; Bristol-Myers Squibb: Research Funding. Hasford:Novartis: Research Funding. Lindoerfer:Novartis: Research Funding.

Description: Abstract 4272 The incidence of Philadelphia positive (Ph+) chronic myeloid leukemia (CML) in Europe is still difficult to estimate, due to insufficient information. Currently, it is believed to range between 8 and 22 cases per million people per year, age adjusted. Prior to the introduction of the tyrosine kinase inhibitor (TKI) imatinib the annual death rate was about 10% for the first 2 to 3 years, and about 20% from the 4th year on, with less than 10% of patients alive after 10 years. Interferon-alfa treatment and allogeneic hematopoietic stem cell transplantation were very effective treatments but only in a minority of patients. Following the introduction of IM, and of the second generation TKI nilotinib and dasatinib the annual death rate has decreased to less than 5%, and more than 75% of patients are projected to be alive 10 years after diagnosis. Based on these figures, the prevalence of the disease is expected to double every 5 years and the management of the disease will rapidly become an important social and pharmacoeconomic issue. To govern this progress it is necessary to improve the level of information on the epidemiology of CML, on the treatment of CML in clinical practice, and on the outcome of treatment outside prospective, controlled clinical trials on which current outcome estimates are based. With that purpose, the European Leukemia Network (ELN) has established a registry of all new cases of Ph+ CML. In a public private partnership with Novartis Oncology Europe this registry has been expanded to also include treatment and quality controlled outcome (European Treatment and Outcome Study [EUTOS] for CML). The infrastructure of the registry is based on a EUTOS Central Scientific Headquarter (Dpt. Hematology-Oncology “L. and A. Seràgnoli”, University of Bologna, S.Orsola-Malpighi Hospital, Bologna, Italy) and a EUTOS Central Data Center (Dpt. For Medical Informatics, Biometric and Epidemiology, University of Munich, Munich, Germany), interacting with each national hub. Registry is population-based, covers completely most European countries with less than 12 millions inhabitants (Portugal, Belgium, Sweden, Finland, Lithuania, Latvia, Estonia, Czech Republic, Slovakia, Slovenia, Croatia, Serbia, Hungary, Austria, Greece, Cyprus), and covers partially (for larger countries, only sub-regions with roughly 10 millions inhabitants have been selected) most of the countries with more than 12 millions inhabitants, including Spain, the United Kingdom, The Netherlands, Germany, Poland, France, Romania, Russia and Italy. About 2500 newly diagnosed cases are planned to be registered over one year and to be followed for treatment and outcome including cytogenetic response, molecular response, and BCR-ABL KD mutations. Moreover, flanking projects have been implemented in the EUTOS frame: a network of standardized laboratories across Europe, to provide a molecular monitoring with quality controlled data, a central facility for imatinib blood level testing, soon in many European countries, and an educational effort (symposia, training workshops, internet platform). The EUTOS registry joins epidemiological and outcome data: its implementation requires considerable efforts and resources, but in the long run CML could become a model for epidemiologi and management of other cancers. Disclosures: Hasford: Novartis Pharma: Research Funding.

Description: Introduction Clinical studies clearly show that treatment with tyrosine-kinase inhibitors (TKI) greatly improve the prognosis of patients with CML. Detailed treatment recommendations have since been deduced from clinical trial results by the European LeukemiaNet (Blood 122:872-884). However, little is known about whether these achievements can also be transferred to routine health care. This work investigates if all CML patients are treated in agreement with current standards and wether they achieve outcomes at least as good as those in clinical trials. Methods The web-based registry aimed to collect all newly diagnosed adult patients with chronic phase Ph+ and/or BCR-ABL1+ CML in 20 countries or pre-specified regions covering ~ 92.5 million inhabitants. Overall 2904 patients were registered between 2008 and 2012. Cytogenetic and molecular responses were analyzed using cumulative incidences considering death and progression as competing risks. Survival was analyzed using Kaplan-Meier curves and log rank tests. Results 2342 patients were diagnosed in chronic phase and had follow-up data available. The median age was 55 years (range: 18 to 99 years) and 53% were male; 11% of the patients were at high risk of not achieving complete cytogenetic remission (CCyR) at 18 months according to the EUTOS score. According to the Euro score 10% of the patients were in the high risk group, 51% in the intermediate and 39% in the low risk group. 18% were included in clinical trials. Treatment data of 1701 patients were contributed from 15 countries (85% of 2042 patients registered in those countries). As a first-line therapy 80% of patients received imatinib 15% nilotinib, 3% dasatinib and 3% hydroxyurea (HU). Of the patients receiving nilotinib or dasatinib 56% had been enrolled into clinical trials. There were no significant differences between female and male patients regarding the first-line therapy. More than half of the patients who were treated with HU alone were aged 70 or older. Time to first CCyR is known for 62% of patients. Median time to first CCyR was 10 months; after 12 months 57% (95% CI 54%-60%) and after 18 months 76% (95% CI 74%-79%) had achieved CCyR. Time to first CCyR differed significantly regarding the EUTOS score. Median time to first CCyR was 9 months for the low and 13 months for the EUTOS high risk group (p 〈 0.0001). After 18 months 78% (95% CI 75%-80%) of patients in the low and 69% (95% CI 60%-76%) of patients in the high risk group had achieved CCyR. The patients' age did not have major influence on the time to first CCyR (p=0.8974, median time to first CCyR: 18 to 39 years: 9 months, 40-65 years: 9 months, older than 65 years: 11 months). Time to first major molecular remission (MMR) could be calculated for 54% of patients. Median time to first MMR was 15 months. Cumulative incidence of MMR after 12 months was 41% (95% CI 38%- 44%). The median observation time of living patients was 29 months. 187 patients died (8%). Probability of OS for all patients at 12, 24 and 30 months was 97% (95% CI 96% - 97%), 94% (95% CI 93% - 95%) and 92% (95% CI 90% - 93%), respectively. 108 patients progressed of whom 62 subsequently died, while 125 patients died without prior progression. Probability of PFS for all patients at 12, 24 and 30 months was 95% (95% CI 94% - 96%), 92% (95% CI 91% - 93%) and 90% (95% CI 88% - 91%), respectively. Of the 187 patients who died, 33% died after progression. 67% died without prior progression. The probability of progression and subsequent death was 1% (95% CI 1% - 2%) after 12 months and 2% (95% CI 2% - 3%) after 24 months. The probability of dying without prior progression was 2% (95% CI 2% - 96%) after 12 months and 4% (95% CI 3% - 5%) after 24 months. Discussion The EUTOS population based registry provides the first unselected sample of adult Ph+ and/or BCR/ABL1+ adult CML patients in Europe. It shows that in Europe the success reported from commercial and academic studies is transferred to the general population. The majority of patients were treated first-line with imatinib, which was the only TKI approved for first-line use by the EMA during most of the registration period. Probabilities of PFS and OS in the registry are comparable to those in clinical trials. The importance of calculating both overall survival and leukemia-related survival is highlighted, since many patients die from different causes related or unrelated to leukemia and to treatment, but without progression. Disclosures Hoffmann: Novartis Oncology Europe: Research Funding. Baccarani:PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ARIAD Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NOVARTIS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hasford:Novartis: Research Funding. Lindoerfer:Novartis Oncology Europe: Research Funding. Burgstaller:Novartis: Honoraria; Mundipharma: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; AOP Orphan Pharmaceuticals: Honoraria, Research Funding. Mayer:Novartis: Consultancy, Other: funding of travel, accomodations or expenses, Research Funding; BMS: Consultancy, Other: funding of travel, accomodations or expenses, Research Funding. Koskenvesa:GSK: Consultancy; Pfizer: Consultancy; Ariad: Other: funding of travel, accomodations or expenses; BMS: Consultancy, Other: funding of travel, accomodations or expenses; Novartis: Consultancy, Research Funding. Castagnetti:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria. Griskevicius:Novartis: Consultancy, Research Funding; Baxalta: Research Funding. Sacha:Angelini: Consultancy; Adamed: Consultancy; Novartis: Consultancy; BMS: Consultancy. Hellmann:Novartis: Consultancy, Other: funding of travel, accomodations or expenses, Research Funding, Speakers Bureau; BMS: Consultancy, Other: funding of travel, accomodations or expenses, Speakers Bureau. Turkina:Pfizer: Consultancy; Bristol Myers Squibb: Consultancy; Novartis Pharma: Consultancy. Zaritskey:University of Heidelberg: Research Funding; Novartis: Consultancy. Sninska:Novartis: Consultancy. Simonsson:Novartis Pharma: Research Funding. Saussele:Novartis Pharma: Honoraria, Other: Travel grant, Research Funding; ARIAD: Honoraria; Pfizer: Honoraria, Other: Travel grant; BMS: Honoraria, Other: Travel grant, Research Funding. Hochhaus:ARIAD: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Hehlmann:BMS: Consultancy; Novartis Pharma: Research Funding.

Description: Introduction The centerpiece of the European Treatment and Outcome Study (EUTOS) for Chronic Myeloid Leukemia (CML) is a registry collecting representative samples of CML patients in Europe. The In-Study section of the registry combines data of patients enrolled in investigator-sponsored prospective studies of treatment with imatinib-based regimens. The population-based (PB) section includes data of all newly diagnosed CML patients in specified regions of 27 European countries in an attempt to represent the general population of CML patients. Aims There is a common assumption that patients enrolled in prospective trials are highly selected, do not represent the ‘typical’ patient and that thus the results of such trials may not be easily generalized to all patients. Thus we analyzed possible differences in the baseline characteristics of the two patient groups. Available were age, sex, EUTOS score, phase of disease, spleen enlargement, platelets, leukocytes, and percentages of blasts, eosinophils, and basophils in peripheral blood. Methods For all analyzed factors we calculated distribution parameters or percentages depending on the scale of the factor. To identify significant differences we used χ2-tests and Mann-Whitney U-tests. Level of significance was 0.05. Results The In-Study section included 2346 patients from study groups in Germany, Italy, France, Spain, the Nordic study group, the Netherlands, and the United Kingdom, newly diagnosed from 2002 to 2006. The PB section of the registry included 3457 patients newly diagnosed with CML from 2008 to 2012 in 27 European countries. The median age at diagnosis of In-Study patients (51 years (18-88)) was significantly lower than the age of the general population newly diagnosed with CML (56 years (18-99), p

Description: INTRODUCTION Essential thrombocythemia (ET) is a classic Philadelphia chromosome-negative myeloproliferative neoplasm with low progression rate to secondary myelofibrosis and transformation to acute leukemia. Patient survival is prolonged and the main clinical focus in ET patients is prevention of thrombotic and hemorrhagic complications. Chronic inflammation may be one of the main reasons for progression and complications in ET. The somatic JAK2 V617F mutation found in about half of the patients with ET is associated with dysregulation and overexpression of inflammatory genes resulting in massive production of cytokines and other inflammatory mediators. In spite of knowing that chronic inflammation is an important risk factor for the development of atherosclerosis in patients with chronic inflammatory diseases, such as rheumatoid arthritis, type 2 diabetes mellitus and systemic lupus erythematosus no clinical study has been published in patients with ET about deterioration of arterial function. Therefore, we tested patients with JAK2 V617F positive ET in comparison with age-and sex-matched, apparently healthy control subjects whether they show more advanced progression of arterial stiffness and pulse-wave velocity - parameters that increase with age and are associated with adverse cardiovascular outcomes. PATIENTS AND METHODS Thirty six patients with JAK2 V617F positive ET, without clinically apparent atherosclerotic disease and 38 apparently healthy individuals were enrolled in our study after giving their informed consent. The 10-year risk for coronary disease was assessed at inclusion by the Framingham risk equation. All subjects underwent two separate clinical visits for ultrasound examination of the extracranial carotid arteries (using Aloka prosound α7, Hitachi Aloka Medical, Ltd., Japan). Echo-tracking of the common carotid arterial wall 2 cm proximal to the bulb was used to assess the β-stiffness index and to estimate the pulse wave velocity. The first measurement was done between January 2014 and August 2015 and the second 3-4 years later between January and July 2018. Continuous variables were tested for normality and are presented as median values and inter-quartile range (QR) or mean values and standard deviation (SD). The differences between groups were evaluated either by the Mann-Whitney test or the Student's t-test for continuous data, or by the chi-square test for the sex distribution. RESULTS Patients with ET and control subjects did not differ in age and sex distribution (age at inclusion 57.5 (QR 45.8 - 64.9) vs 59.2 (QR 53.6 - 67.8) years, p = 0.17, male/female 12/24 vs. 14/24, p = 0.76) or in the predicted 10-year risk of coronary disease by the Framingham equation (6.84 (3.27-11.82) vs. 7.20 (3.61-10.37), p = 0.87) at inclusion in the study. The mean β-stiffness index for patients with JAK2 V617F positive ET was 7.71 (standard deviation (SD) 2.42) at the first visit and 9.67 (SD 2.31) at the second visit, while the mean β-stiffness index for control subjects was 8.73 (SD 2.77) at the first visit and 8.97 (SD 1.91) at the second visit. Individual pairs of data are shown in Fig 1a. The increase in β-stiffness index between the first and the second visit for patient with JAK2 V617F positive ET was 1.95 (SD 2.17) and for control subjects 0.24 SD (1.96), p 〈 0.001 (Fig. 2a). The mean pulse wave velocity for patients with JAK2 V617F positive ET was 6.20 m/s (SD1.04 m/s) at the first visit and 6.92 m/s (SD 0.93 m/s) at the second visit, while in control subjects it was 6.57 m/s (SD 1.00 m/s) at the first visit and 6.66 m/s (SD 0.79 m/s) at the second visit. Individual pairs of data are shown in Fig 1b. The difference in pulse wave velocity between the first and the second visit for patients with JAK2 V617F positive ET was 0.72 m/s (SD 0.92 m/s) and for control subjects 0.09 m/s (SD 0.71 m/s), p 〈 0.001 (Figure 2b). CONCLUSIONS Patients with JAK2 V617F positive ET had accelerated progression of arterial stiffness of the carotid arteries and estimated pulse wave velocity in the 3-4 year observation period compared with control subjects matched for age, sex and Framingham cardiovascular risk score. Disclosures No relevant conflicts of interest to declare.

Description: Background Treatment-free remission (TFR) in patients with chronic myeloid leukemia (CML), who achieve a sustained and deep molecular response (DMR, MR4 or MR4.5) after treatment with BCR-ABL1 tyrosine kinase inhibitors (TKIs), is possible after TKI discontinuation (Rea and Cayuela. 2018). Nilotinib has been shown to elicit deeper and faster molecular responses compared to imatinib. More than 50% of patients who responded to imatinib, but did not achieve a DMR, achieved a DMR 1 year after they switched to nilotinib (Hughes et al. 2017). On attempting TFR, about 50% of patients lose response early and relapse (Mahon et al. 2019). The reason for this loss of response after achieving sustained DMR in patients has been attributed to residual and quiescent LSCs (Houshmand, et al. 2019). LSC for CML arises from the transformation of a hematopoietic stem cell through a t(9;22) translocation, leading to the Philadelphia chromosome [Ph1], and is characterized by the presence of the unregulated tyrosine kinase activity of the chimeric BCR-ABL1 protein together with specific surface antigens including CD26 and/or other aberrant markers (Bocchia, et al. 2018). The ENESTPath study is designed to evaluate the impact of duration of 24 or 36 months (mos) of consolidation treatment with nilotinib after switching from imatinib, on the rate of TFR. The LSC sub-study was designed to evaluate the correlation between duration of nilotinib therapy and LSCs. This interim analysis of the LSC sub-study presents preliminary data on characteristics of LSC-positive patients and their response after 24 mos of nilotinib therapy. Objectives To assess factors impacting LSCs and the effect of nilotinib therapy in patients with CML who switched from imatinib to nilotinib. Methods Patients from the ENESTPath study who switched from imatinib received 24 mos of nilotinib therapy (12 mos of induction and consolidation therapy, each). Patients who achieved stable MR4 (4/5 preceding quarterly real-time quantitative polymerase chain reaction [RT-PCR] assessments were ≥MR4 and last assessment was ≥MR4) at the end of the consolidation phase were randomized 1:1 to receive either an additional 1 year of nilotinib treatment or to start TFR, while those without stable MR4 were not randomized (NR), and followed-up until end of the study (5 years after baseline visit). For the current analysis, bone marrow samples collected at screening and at 24 mos were evaluated for the presence of Ph+ on fluorescence-activated cell sorting-purified CD34+CD38-/+ cells by fluorescence in situ hybridization and/or RT-PCR techniques. Results Of the 60 patients enrolled in the sub-study, 34 were randomized, 25 were NR, and 1 had protocol deviation (not included in the analysis). Overall, the mean age of the patients was 49.4 years. All patients had been previously treated with imatinib for a median duration of 59.7 mos. When analyzed for LSCs by RT-PCR or histone (HIS) at baseline, 10 patients were found to be positive, 23 were negative, 25 patients had data missing, and 1 was not evaluable. Sokal score categories and duration of prior imatinib therapy for LSC-positive and negative patients at baseline are presented in Table 1. More patients with low Sokal risk and longer duration of prior imatinib therapy (≥ 5 years) were negative for LSCs at baseline (Table 1). After treatment with nilotinib, the number of patients with Ph+ among CD34+CD38-, CD34+CD38+, and CD34+CD38-/+ LSCs was lower at 24 mos compared to baseline, except for aberrant CD34+ cells in the NR group (Figure 1). A decrease in the percentage of CD34+/CD38+ and immunophenotypically aberrant CD34+/- cells was observed for most of the patients analyzed at baseline and at 24 mos by HIS or RT-PCR. Overall, 11 and 10 patients in the randomized and NR groups, respectively, had ≥1 dose reduction/interruptions; adverse events led to dose reduction/interruptions in 9 patients each, in both arms. Conclusion This analysis indicates that treatment of CML patients with nilotinib after switching from imatinib may play a role in the reduction of LSCs over time. As the number of patients with available Sokal score at baseline and prior imatinib exposure was low, meaningful conclusions cannot be drawn, and further investigations are needed. Results of patients attempting TFR are awaited, and it would be interesting to analyze the correlation between the LSC count and rate of TFR in the final analysis of the sub-study. Disclosures Sanchez-Guijo: BMS: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Amgen: Honoraria; Roche: Honoraria. Plata:Novartis: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Crugnola:Novartis: Honoraria; Incyte: Honoraria. Caocci:Novartis: Honoraria; Celgene: Honoraria. Oakervee:Novartis: Honoraria; Bristol Myers-Squibb: Honoraria; Pfizer: Honoraria. Jedrzejczak:Amgen: Consultancy; Takeda: Consultancy; Novartis: Research Funding; Amgen: Other: Travel support for hematology meetings (ASH, EBMT, EHA) ; Celgene: Other: Travel support for hematology meetings (ASH, EBMT, EHA); Roche: Other: Travel support for hematology meetings (ASH, EBMT, EHA). Kiani:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Supekar:Novartis: Employment. Ferreira:Novartis: Employment. Shah:Novartis: Other: Service Provider. Steegmann:BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Baccarani:Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Takeda: Consultancy.

Description: Introduction As there are only few data available about the incidence, the stage of disease at diagnosis, the treatment and the outcome of chronic myeloid leukemia (CML) in Europe the European Treatment and Outcome Study (EUTOS) for CMLcollected such data in 27 European countries. The population-based registry was set up by EUTOS to further explore the epidemiology, characteristics, treatment and outcomes of CML in Europe. The present work focused on the estimation of incidence of CML in Europe, in the single countries participating in the registry and the comparison to existing incidence estimations from the US. Patients and Methods The EUTOS population-based registry aimed to document all newly diagnosed adult patients with Ph+ and/or BCR-ABL+ CML at any stage nationwide or in prespecified regions within countries of Europe. Croatia, Cyprus, Estonia, Latvia, Lithuania, Slovakia, Slovenia and Sweden were observed in total while for Austria, the Czech Republic[H1] , France, Germany, Italy, the Netherlands, Poland, Russia, Serbia, Spain, Sweden and the United Kingdom specified regions were selected. Population data from the United Nations database were used for calculations in countries that were observed nationwide, while the study groups provided the population numbers of the specified regions for countries that were observed partially only. The registration periodvaried between 12 and 60 months in the different countries, from January 2008 to December 2012, registration area covered over 92.5 million inhabitants overall. Raw and standardized incidenceswere calculated for the countries and regions and adjusted to the registration period. For standardization the Old Europe Standard Population was used (Waterhouse et al IARC 1976). The registry and the standard population were truncated so only patients from 20 years on were included for the calculation of standardized rates. To compare and validate the EUTOS estimations we chose the data of the Surveillance Epidemiology and End Results Program (SEER) which cover about 28% of the US population. The data were collected from 2007 to 2011. Results There were 2,936 patients registered into the EUTOS population-based registry. Raw incidences per 100,000 inhabitants per year ranged from 0.72 in Poland to 1.39 in Italy. The overall raw incidence for all countries was 1.02, with 0.90 in females and 1.14 in males. Estimations of standardized incidences ranged from 0.72 in the UK to 1.29 in Italy. Overall standardized incidence was 0.99, with 0.86 in females and 1.12 in males. Age specific incidences rose with age group. While the incidence in the 18 to 40 years old population was as low as 0.52 (0.61 in males and 0.42 in females) it increased to 1.61 (2.18 in males and 1.26 in females) in the population from 70 years up. Comparing the SEER data to our EUTOS results very similar incidences can be observed up to age group 55-59 years. From that age group up the SEER incidence estimations are considerably higher. The overall standardized SEER incidences ranged around 1.7 per 100,000 for the years observed. The higher rates can be explained by different inclusion criteria of the registries: While EUTOS includes only Ph+ and/or BCR/ABL+ patients, the SEER has more open inclusion criteria. Also patients without information on Ph-status, BCR-ABL1 negative patients and patients diagnosed with chronic myelomonocytic leukemia are included. Discussion The EUTOS population based registry is the first paneuropean prospective study of incidence of CML in Europe. For the first time data about the incidence of CML are available now for most European countries. Raw and standardized incidences from the EUTOS registry fit in well with earlier findings of study groups from countries like the UK (Bhayat et al., BMC Cancer 2009; 9; 252) (Phekoo et al Haematologica 2006), Sweden (Höglund et al Blood 2013), Germany (Nennecke et al Bundesgesundheitsblatt 2014) and France (Corm et al J Clin Oncol 2008) that range between 0.7 and 1.1 per 100,000 inhabitants. Thus the estimation of incidence over all regions participating in the EUTOS project can serve as a robust estimation of the incidence of CML in Europe. [H1]Wurde zwar voll beobachtet, zwei Regionen wurden aber ausgeschlossen, da sie nicht garantieren konnten pop-based gewesen zu sein! Disclosures Hoffmann: Novartis: Research Funding. Lindoerfer:Novartis: Research Funding. Castagnetti:Novartis, BMS,: Consultancy, Honoraria; Pfizer: Consultancy. Griskevicius:NOvartis: Research Funding. Steegmann:Novartis, BMS, Pfizer: Honoraria, Research Funding. Hehlmann:Novartis, BMS: Research Funding. Hasford:Novartis: Research Funding. Baccarani:Novartis, BMS, Pfizer, Ariad: Consultancy, Honoraria, Speakers Bureau.

Description: The treatment of auto-immune thrombocytopenic purpura (AITP) remains unsatisfactory in patients refractory to first-line management such as corticosteroids and/or splenectomy. Those patients usually require unacceptably high doses of corticosteroids to maintain a safe platelet count and thus have refractory AITP. Relativelly new immunosupressive treatment modality is cyclosporin A (CsA) and no large studies involving these drug have been conducted. We treated 7 refractory AITP patients with CsA. Their platelet count were without any therapy below 20x109/L and mostly they had signs of subcutaneous and mucosal bleeding. In 6/7 patients splenectomy was performed earlier. In order to maintain »safe« platelet count, they all needed methylprednisolon (MP), at least 32 mg/daily. So at the time treatment with CsA began, all patients were on MP. During next months MP dosage was tapered or withdrew, according to patients platelet count and treatment efficacy. At the endpoint, in 4/7 patients complete remission (CR) was achieved and later CsA was slowly ceased. 3/7 patients are currently in partial remission (PR) of the disease. Also one of them who has more than 30 years history of the disease is in stable PR, on low dose CsA and low dose MP maintanance therapy. Her platelet count is well above 20x109/L. Among CsA treatment related side effects painful lower limb edema was most frequent. Based on our experience we suggest, that CsA should be recommended in refractory (chronic) AITP patients, because it shows long-term efficacy and good safety profile and is able to sustain remission at low doses or even after CsA discontinuation.