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Introduction and Objectives: For patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP), four baseline prognostic scores are commonly used including the Sokal score and the most recently introduced EUTOS long-term survival (ELTS) score. The ELTS score was shown to be superior to the Sokal score for predicting survival. The aim of the study is to evaluate the value of ELTS score on predicting disease progression and survival in Turkish pts with CML-CP. Material and Method: Demographic, laboratory and clinical features, disease responses to tyrosine kinase inhibitor (TKI) therapy and survival of CML-CP pts, who received upfront imatinib (IM) between 2003 and 2018 were analyzed retrospectively. Treatment responses were reevaluated according to European LeukemiaNet 2013 recommendations. Risk groups analysis, discrimination and hazard ratios (HRs) were evaluated with Cox regression and Kaplan-Meier survival analysis. Receiver operating characteristic (ROC) analysis was performed to examine the effects of scores on predicting overall survival (OS) and progression-free survival (PFS). Results: A total of 185 pts were included, of which 103 (55.7%) were male and median age was 47 years (range, 16 - 81 years) (Table 1). The percentages of pts with low-, intermediate-, and high-risk ELTS scores were 60.5%, 25.9%, and 13.5%, respectively. For the Sokal score, these percentages were 37.3%, 40.5%, and 22.2% respectively. For Sokal high-risk pts, only 46.3% were classified as high-risk according to the ELTS score. Similarly, 44% of pts with intermediate Sokal risk had low-risk ELTS score (Fig. 1). Seventy-seven pts (41.6%) had at least one comorbidity, and the most common comorbidities were hypertension (21.6%), diabetes mellitus (13%), and ischemic heart disease (12.4%) (Table 1). The median durations of IM therapy and follow-up were 2728 (range, 14 - 6320 days) and 3473 (range, 71 - 6320 days) days, respectively. Complete hematologic and early molecular (BCR-ABL1 IS Conclusion: In our study, we showed that the ELTS score could successfully predict high-risk pts compatible with the literature. With higher hazard ratios and better risk group stratifications, the ELTS score outperformed the Sokal score. The ELTS score can help clinicians to better discriminate poor prognostic pts and can promote optimal treatment strategies for these pts with potentially worse prognosis. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background The biosimilar rituximab (Redditux) was approved in Turkey for all indications of the reference molecule (MabThera) in March 2018. Large clinical trials and real-life experiences are lacking in hematological malignancies. Aims We aimed to evaluate the efficacy and safety of Redditux in de-novo diffuse large B-cell lymphoma (DLBCL). Methods Our institution decided to provide Redditux for hematological indications since February 2019. We retrospectively analyzed medical records of 51 consecutive de-novo DLBCL patients (pts) diagnosed between February 2019 and September 2019 in the hematology department of Istanbul University Istanbul Medical Faculty. We compared the response rates with historical controls treated with MabThera-CHOP at Cerrahpaşa Medical Faculty. Our study was approved by I.U. Istanbul Medical Faculty Ethical Committee (2019/1454). Results A total of 51 pts without CNS involvement received Redditux-CHOP. Median follow-up was 24 months (range: 8-31). A median of 6 cycles of biosimilar (range: 4-8) was administered. Four pts with high CNS-IPI score received four intrathecal methotrexate injections and 13 pts had additional radiotherapy for their initial bulky disease. The patient characteristics and response rates of the Redditux and historical MabThera cohorts are summarized in Table 1. Apart from 6 cases who were refractory to Redditux-CHOP, 8 pts had progressive disease (6 with CR, 1 with PR and 1with SD) in the follow-up. The median time to relapse was 11.5 months for 6 cases who had CR following first-line treatment. Five of 8 cases with PD experienced CNS relapse. Their CNS-IPI score (Schmitz et al. J Clin Oncol 2016) were low in 2 pts, intermediate in 2 pts and high in 1 patient. Of 11 pts with bone involvement at the time of diagnosis, three cases had CNS relapse (p=0.028). Two pts with CNS relapse were treated with intrathecal chemotherapy only due to their poor performance status. Eight pts received salvage combination chemotherapy [R-ICE (n=3); R-benda (n=3); R-DHAP (n=1); MATRix (n=1)] and two of them responded. One of these 2 cases underwent auto-SCT and the other proceeded to allo-SCT; however, he died during conditioning treatment. Ten pts died in the follow-up. Causes of death were progressive disease (n=7, two cases with CNS involvement), infection during allo-conditioning (n=1), post-COVID herpes zoster infection (n=1) and unknown (n=1). The 24 month PFS and OS rates were 75.8% (95% CI: 0.61-0.85) and 80.3% (95% CI: 0.67-0.89) for Redditux cohort, respectively. In the historical MabThera group, the 24 month PFS and OS rates were 85.2 (95% CI: 0.79-0.90) and 81.4% (95% CI: 0.75-0.86), respectively. For pts with high R-IPI score in the Redditux cohort (3-5); the 24-month PFS and OS rates were 54.2% (95% CI: 0.29-0.74) and 55.6% (95% CI: 0.31-0.75), respectively. In the historical Mabthera group, the 24-month PFS and OS rates were 68.7% (95% CI: 0.53-0.80) and 59.4% (95% CI: 0.47-0.70), respectively. Although the PFS rates seems to be worse in high R-IPI cases receiving Redditux, the difference was not significant (p=0.18; Figure 1). AEs were reported in 51% (n=26) of patients. Most common AE was grade 2 infusion reactions (shivering, nausea, fever) requiring medical intervention in 20% of pts, accompanied with rash in half of them. Grade 3&4 AEs were leucopenia (n=2; 4%), neutropenia (n=20; 39%) febrile in 2 cases, anemia (n=6; 12%), thrombocytopenia (n=3; 6%). Grade 2 pneumonia (n=2) and urinary tract infections (n=2) were other infectious complications. Conclusion Although the PFS rate at 24 months in high-IPI group treated with Redditux seems to be lower compared to MabThera treated historical control group, survival rates were not significantly different. Our results should be cautiously evaluated due to small sample size. Compared to the original trial of MabThera added to CHOP based regimen, (Coiffier et al N Eng J Med. 2002), our CR rates in stage 2-4 pts seem to be slightly lower (70.7% vs 76%), although the OS rates are quite similar (86.3% vs 82%). Grade 3&4 neutropenia requiring empirical administration of G-CSF was 39% in our cohort. Infusion reactions were observed in 20% of pts, which was reported to be around 30% with original molecule (Patel et al. Clin Lymphoma Myeloma Leuk 2019). The CNS relapse rate was relatively high (9.8%) in our cohort. Prospective randomized clinical trials are needed to determine the efficacy and safety profile of Redditux. Figure 1 Figure 1. Disclosures Ferhanoglu: Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

Background: Ibrutinib has become a widely used drug in the management of B-cell lymphoproliferative neoplasms (BLPNs). Past or active HBV infection is an exclusion criteria for the clinical trials of ibrutinib and for patients (pts) treated outside clinical trials there are contradictory data or suggestions concerning hepatitis B virus (HBV) prophylaxis. In this study, we evaluated the real-life data on the outcome of HBV infection status of pts with BLPNs receiving ibrutinib. Methods: Demographic features, previous treatments (including rituximab (RTX)) and follow-up durations, HBV infection and reactivation status, prophylaxis information, serum transaminase and total bilirubin levels of the pts were noted retrospectively. Past HBV infection was defined as concurrent detectable HBV core IgG antibody (Ab) (anti-HBc IgG) and undetectable HBV surface Ag (HbsAg) ± HBV surface Ab (anti-HBs). Active HBV infection was defined as HbsAg and/or HBV core IgM Ab (anti-HBc IgM) positivity. Quantitative HBV-DNA PCR results are also recorded, when available. Results: Twenty-seven consecutive pts were included, and pts' characteristics are displayed in Table 1. Median durations of ibrutinib therapy and entire follow-up were 9 and 108 months, respectively. All pts had received RTX prior to ibrutinib. Among the 27 patients, 8 had past HBV infection, while 2 had active HBV infection. HBV prophylaxis or treatment was started before ibrutinib in 5 pts, and simultaneously with ibrutinib in one. The remaining 4 pts with past HBV infection were not given any prophylaxis. Among these 4 cases with anti-HBc IgG positivity, three were also positive for anti-HBs. Currently, these 4 pts, including the one with a negative anti-HBs status, are at the 2nd, 4th, 12th, and 16th cycles of ibrutinib. To date, no signs of HBV reactivation was detected in our cohort. Discussion & Conclusion: All pts in our cohort had received RTX containing regimens prior to ibrutinib. In our analysis, 5 pts were under HBV prophylaxis or treatment when ibrutinib was started. Two of these had active HBV infection. Simultaneous HBV prophylaxis was started with ibrutinib for one pt and the remaining 4 pts with past HBV infection (anti-HBs + anti-HBc IgG positivity) did not receive any prophylaxis, but they were planned to be followed by monitoring the anti-HBs titers. In a study, 21 BLPN pts (10 treated with RTX previously) with occult HBV infection with a median follow-up of 9.5 months treated with ibrutinib without anti-HBV prophylaxis, and only two HBV reactivations were reported (Hammond et al. Blood. 2018;131(17):1987-1989). In another study, no HBV reactivation was detected in 7 CLL pts with past HBV infection, with a median follow-up duration of 25 months under ibrutinib, without any anti-viral prophylaxis (Tedeschi et al. Leuk Lymphoma. 2017; 58(12):2966-2968). The increase in the number of pts treated with ibrutinib, is followed by the awareness about the infectious complications including HBV reactivation. The consecutive use of RTX and ibrutinib has increased the risk of HBV-related complications. This issue has become more important in areas with a higher prevalence of HBV. Although the number of pts is limited and follow-up periods are relatively short, our results may indicate that pts with occult HBV infection treated with ibrutinib for BLPNs, might only be closely followed for HBV reactivation, rather than routine anti-HBV prophylaxis. Since pts with previous RTX exposure are likely to lose anti-HBs antibodies, ibrutinib-treated pts with both anti-HBs and anti-HBc IgG positivity should be closely monitored for possible risk of HBV reactivation. Anti-viral prophylaxis under ibrutinib therapy might still be an option for the selected cases. Disclosures No relevant conflicts of interest to declare.

Background: Although it may vary between different registries, the median age of chronic myeloid leukemia (CML) at diagnosis is between 50-60 years, and approximately 40% of the patients (pts) are diagnosed after age 60 [Hoffmann et al. Leukemia. 2015;29(6):1336-43]. Tyrosinekinase inhibitors (TKIs) have revolutionized the treatment of CML and currently pts with CML may expect to live close to normal lifespan. So the number of elderly CML pts with various potentialcomorbidities started to increase, which then brings out the issues regarding TKI toxicities, medication adherence and responses to TKI treatment. Aim: The aim of this study was to evaluate the efficacy and safety ofimatinib treatment in the elderly population (pts equal to or older than 60 years) with CML and to compare these data with younger pts (pts < 60 years). Patients and Methods: Pts diagnosed and followed in our clinic with CML were enrolled in the study. Patient demographics, dose and duration ofimatinib therapy, disease risk scores, cytogenetic and molecular responses,comorbidities, adverse events (AEs), follow-up durations and outcomes were evaluated from files of the pts, retrospectively. TheCharlsoncomorbidity index (CCI) of each patient was calculated as stated before [Breccia et al.Haematologica. 2011;96(10):1457-61]. Results: The patient cohort was consisted of 158 pts with a median age of 44 years (range, 18 - 83 years). Group A consisted of thirty-three pts who were equal to or older than 60 years (Fig. 1), and there were 125 pts (Group B) who were < 60 years of age (Table 1). The two groups were balanced regarding gender, disease stage, treatments prior to TKI therapy, and the starting dose ofimatinib. There were more pts with intermediate and highSokal risk scores in Group A than that of Group B (p Discussion: TKI therapy is relatively safe in elderly pts with CML, and cytogenetic and molecular responses are comparable with that observed in younger pts. In our institute, where pts are followed in a dedicated outpatient CML clinic, cytogenetic and molecular responses were similar in both elderly and younger pts leading to similar percentages of pts who were switched to 2GTKI therapy in both groups. Comorbidities can be problematic in elderly pts in whom CML and TKI relatedAEs are more common. However proper management of theseAEs including careful follow-up and timely TKI dose reductions may lead to successful outcomes. Inferior OS rates were observed in elderly pts with CML, but OS rates were similar in both groups when non-CML related deaths were excluded. Disclosures No relevant conflicts of interest to declare.

Background: Drug-induced pulmonary arterial hypertension (PAH) can be observed as an adverse event (AE) during the administration of dasatinib (DAS), which is a second generation tyrosine kinase inhibitor (TKI), used in the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The occurence of DAS-induced PAH at a late onset in most of the cases suggests a chronic pathological mechanism rather than an acute inflammatory or cardiac etiology. The treatment strategies of DAS-induced PAH include the cessation of the drug and PAH-specific therapies. Aim: The aim of the study was to evaluate the frequency, clinical features, management strategies and outcomes of patients with DAS-induced PAH among a cohort consisted of CML and Ph+ ALL patients who had received DAS as a salvage treatment after imatinib (IM) failure or intolerance. Patients and Methods: Forty patients with Ph+ leukemias who received second-line DAS were enrolled. Patients' demographics, Sokal risk scores, molecular and cytogenetic responses, comorbidities [including preexisting cardiac disease, renal insufficiency, hypertension and chronic obstructive pulmonary disease (COPD)], DAS dose, dosing intervals and treatment durations, durations of IM therapy prior to DAS, and if any, treatments prior to IM (interferon (IFN), cytarabine (Ara-C), and hydroxyurea (HU)) and follow-up periods were noted retrospectively. TKI response criteria were based on the recommendations of European LeukemiaNet, and the definitions of the CML phases and responses were as described elsewhere. Results: Twenty-four patients were male, and the median age was 45 years (range, 18-81 years). There were 39 patients with CML and one with Ph+ ALL. Among the thirty-nine CML patients, 3 were in accelerated phase (CML-AP), two with blast crisis (CML-BC), and the rest were in chronic phase (CML-CP). The percentanges of low, intermediate, and high Sokal risk scores were 46%, 33%, and 21%, respectively. Thirteen patients received only IM prior to DAS, whereas the others had used HU, IFN and Ara-C prior to IM. After a median duration of 41.5 months (range, 1-93 months) of IM, the reason for switching to DAS were IM failure and intolerance in 37 and 3 patients, respectively. DAS was administered with a median of 50 months (range, 2-78 months). During DAS treatment hematological AEs were observed in 6 patients, whereas in twenty-one pulmonary complications including exacerbation of COPD and pneumonia (n=1), pleuro/pericaridal effusions (n=19), PAH (n=5) and gastrointestinal bleeding (n=1) were detected. DAS therapy was ceased in 13 patients, of which ten were switched to nilotinib (NIL) due to AEs (n=7) and failure (n=3). Also, two patients received cytotoxic treatment due to BC and one had allogeneic hematopoietic stem cell transplantation (allo-HSCT). Five patients (12.5%) had DAS-induced PAH (Table 1). Four of them were in CML-CP at diagnosis, and one was in CML-AP. All cases received DAS due to IM failure. At the time of DAS initiation, 4 cases were in CML-CP and one in CML-BC. PAH was diagnosed by transthoracic echocardiography (TTE) in 3 patients, and by right heart catheterization (RHC) in 2, and it was observed after a median of 8 months (range, 2-25 months) of DAS. Three patients had accompanying pleuro/pericardial effusions. All patients with DAS-induced PAH were alive at the time of the analysis, and the management of PAH included dose reduction in two, and DAS was switched to NIL in 2 cases and allo-HSCT was performed in one. Conclusion: DAS-induced PAH seems to be reversible with the cessation and/or modification of DAS ± PAH-specific treatments. As pulmonary vascular toxicity related to DAS is thought to be molecule-related rather than class-related, it seems reasonable to switch to another TKI. The patients in our cohort had good responses to dose modification and drug cessation and none received PAH-specific therapy. Although DAS-induced PAH is mainly defined as a late complication, we detected that PAH can be observed even after 2 months of drug exposure. PAH can be observed during DAS treatment and physicians should be aware of this AE. Routine cardiopulmonary evaluation prior to and/or during DAS may be beneficial. Mechanisms under this pathological condition, preceding and prognostic factors, and treatment strategies are needed to be evaluated with prospective trials. Disclosures No relevant conflicts of interest to declare.

Introduction: Imatinib mesylate (IM) is the first tyrosine kinase inhibitor (TKI) licensed for the treatment of chronic myeloid leukemia (CML). Severe bone marrow fibrosis (BMF) has been reported in excess of 40% of the patients with CML at diagnosis. Before TKIs became available, BMF which emerged at diagnosis and/or in the late periods of the disease was defined to be a poor prognostic factor, and it contributed significantly to morbidity and mortality from 10% to 30% in patients with CML. The relationship between BMF and both disease progression and prognosis has been the subject of re-evaluation after the introduction of IM therapy. In patients with CML, it has not been clearly demonstrated yet, whether IM improves the poor prognostic effect of fibrosis, and prevents the new BMF development or not. Aim: The purpose of this study was to evaluate the effects of IM therapy on BMF formation, and the prognostic significance of BMF in patients with CML. Material and Methods: One hundred and thirty-five CML patients were enrolled in the study. Patients' demographics, Sokal risk scores, molecular and cytogenetic responses and follow-up periods were noted from the patients' files retrospectively. All pre- and post-IM bone marrow biopsy samples, which were stained with hematoxylin and eosin, were re-evaluated for the current analysis. Grading of BMF was according to the European consensus decisions, graded as 0-III. The term "last bone marrow biopsy" (LBMB) is referred to a biopsy, which was performed at 18th months or later on during IM treatment. Results: The median age was 44 years (range, 18-92 years), and 78 patients (58%) were male. One hundred and twenty-eight patients (95%) were in chronic phase [CP], 4 patients (3%) were in accelerated phase [AP], and 3 patients (2%) were in blast crisis [BC] at the time of IM initiation. Out of 128 CML-CP patients, one hundred and twenty patients (93%) were in early CP, whereas 8 (7%) were in late CP. The percentage of low, intermediate, and high Sokal risk scores were 35%, 43%, and 22%, respectively. Before IM was initiated, thirty-one patients had received previous treatment modalities (hydroxyurea (HU) in twenty-one, and 10 patients had received interferon plus HU. he median duration of IM treatment was 45 months (range, 2-106 months). The rates of complete hematological response (CHR) at 3rd month, complete cytogenetic response (CCyR) at 12th month, and major molecular response (MMR) at 18th month were 92.4%, 71.6%, and 67.6%, respectively. BMF before the initiation of IM therapy was grade 0 in 52 patients (39%), grade I in 39 patients (29%), grade II in 28 patients (21%), and grade III in 16 patients (12%). There was a positive correlation between the Sokal risk scores and the grades of BMF at diagnosis (r:0.313, p The CCyR rates at 12th month did not differ according to the pre-imatinib BMF grades (p =0.127). There was no significant difference between patients with or without CCyR at 12 months of IM regarding grades of BMF (p =0.785). The MMR rates at 18 months did not differ according to pre-treatment grades of BMF (p =0.112). There was no significantly difference in overall survival rates between initial BMF mild (grade 0-I) and severe (grade II-III) groups (p =0.278). Conclusion: IM can reduce BMF after a long period of follow-up, independently from the molecular and cytogenetic responses. The BMF grades at diagnosis does not have a negative impact on the response to IM treatment. Therefore, the adverse prognostic impact of the marrow fibrosis among CML patients seems to disappear in the era of the TKIs. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) is an effective treatment for malignant and nonmalignant diseases. Improved long-term survival after HSCT translates into coming across secondary neoplasms. Contributory factors include primary disease, male sex, young age, prior therapies, conditioning regimens. The secondary neoplasms are particularly solid tumors, as well as lymphoproliferative disorders. Chronic graft-versus-host disease (GvHD) and immunosupressive therapy have also been reported to contribute to neoplasia risk. OBJECTIVE: The purpose of this study was to evaluate the frequency and distribution of the posttransplant secondary neoplasms in our center, to determine the possible contributory factors and relative effect of GvHD. METHODS: From 457 patients who received a HSCT between 1994-2014 clinical records of 312 patients were available to review retrospectively. 21 patients diagnosed with a secondary neoplasia in the posttransplant period are included in the study. Age, sex, primary diagnosis and treatment, time of HSCT, GvHD and immunosupressive treatments, localisation of neoplasms and outcomes were reported. RESULTS: Twenty-one cases of secondary neoplasms were observed (%6,7). The median age at diagnosis and transplantation were 44 and 47, respectively. The median follow-up time was 122 months (32-304). The most common primary diagnosis was Hodgkin's disease (HD). The most commonly used pretransplant conditioning regimen was BEAM. There were no cases of acute GvHD, chronic GvHD was observed in 3 cases. The most common secondary neoplasm was skin cancer followed by urogenital system cancers. The secondary malignancies seen in cases with chronic GvHD are concordant with GvHD sites. Three patients had benign neoplasms comprising fibroadenoma, mol hydatiforme and hibernoma; 2 patients developed preinvasive lesions of vulva (VIN 3) and oral cavity (squamous papilloma). For 20 patients the median time interval between the date of HSCT and diagnosis of a secondary neoplasia is 62 months (5-118); data is missing for 1 case. Two deaths were observed, 1 due to disease progression, 1 due to secondary colorectal malignancy. %90,4 of the study group are alive and in remission. Details are listed in Table 1 and 2. CONCLUSION: Patients undergoing HSCT have an increased risk of secondary cancers later in life. Known risk factors are primary disease, age at transplantation, pretransplant therapies, pretransplant conditioning regimens like total body irradiation, chronic GvHD and immunosuppressive therapies. Our study group is small to comment on these risk factors. Coherent with the literature skin cancer was the most common secondary cancer in our cohort as well. Interestingly we observed a trend towards increased urogenital cancers in comparison to reported data. This finding can be incidental because of the small number of study population or needs to be clarified yet. The increased risk of secondary neoplasms over time after transplantation and the greater risk among younger patients indicate the need for lifelong surveillance. Table 1 Characteristics of patients with secondary neoplasms after HSCT Characteristic n (%) Sex Female 10 (%47) Male 11 (%53) Primary diagnosis Acute myeloid leukemia 1 (%4,7) Acute lymphoblastic leukemia 3 (%14,3) Chronic myelogeneous leukemia 3 (%14,3) Multiple Myeloma 5 (%23,8) Hodgkin’s disease 6 (%28,6) Non-Hodgkin’s lymphoma 3 (%14,3) Prior therapy Chemotherapy 9 (%42,7) Chemoimmunotherapy 3 (%14,3) Chemoradiotherapy 5 (%23,7) Combination treatment* 3 (%14,3) Type of HSCT Allogeneic 5 (%23,8) Related 5 Unrelated 1 Autologous 15(%71,5) Both 1(%4,7) Conditioning regimens TBI+Cy 3 (%14,3) BEAM 8 (% 38,1) MEL 6 (% 28,6) BU+Cy 2 (% 9,5) Unknown 2 (%9,5) Acute GvHD 0 Chronic GvHD 3 (%14,3) Skin 3 Oral cavity 2 Eye 2 Pulmonary 1 Hepatic 1 Acute GvHD prophylaxis 7 (%33,3) CsA 1 MTX+CsA 6 Chronic GvHD treatment 3 (14,3) Steroid+CsA 2 CsA 1 Table 2 Characteristics and risk factors of patients who had secondary malignancy undergoing HSCT Breast Skin GIS Urogenital Lung Lymphoma Risk factors (n:2) (n:6) (n:2) (n:3) (n:2) (n:1) Prior therapy Chemotherapy 0 4 0 2 1 0 Chemoimmunotherapy 1 1 1 1 0 0 Chemoradiotherapy 1 0 0 0 1 1 Combination 0 1 1 0 0 0 Allogeneic Related 1 3 0 1 0 0 Unrelated 0 1 0 0 0 0 Autologous 1 3 2 2 2 1 TBI+Cy 0 1 0 0 0 0 BEAM 1 2 1 0 1 1 MEL 0 1 1 2 1 0 BU+Cy 0 1 0 1 0 0 Unknown 1 1 0 0 0 0 Chronic GvHD 0 2 0 0 0 0 Sex Female 2 2 2 1 0 0 Male 0 4 0 2 2 1 Disclosures No relevant conflicts of interest to declare.

Introduction: Recent studies indicate an increased risk for developing low bone mineral density (BMD) in patients with haemophilia. This has been suggested to result from less physical activity, and impaired vitamin D metabolism due to viral liver disease. Here we present the preliminary results of an ongoing study aiming to identify the risk factors for impaired bone health in adult haemophilia patients. Material and Method: Twenty-nine severe and 7 moderate haemophilia A and B patients were included in the study. Patient characteristics were given in Table-1. All patients had haemophilic arthropathy in ≥1 joints and were on prophylactic factor replacement therapy except 2 on demand patients. None of the patients had decompensated chronic liver disease. Eleven patients had a history of joint intervention (RAS or joint replacement). None of the patients had received on vitamin D supplementation. DEXA scans to screen BMD, blood chemical analysis including liver and kidney function tests, vit. D (25 hydroxy vitamin D) calcium, parathormone, alkaline phosphatase were obtained from all patients at study entry. Results: Osteoporosis and/or osteopenia according to WHO criteria were detected by DEXA scans in 2/3 of the patients. Twenty-six patients (72%) had vit. D levels below 20ng/mL, with half of them having levels less than 10ng/mL. Median lumbar and femur T scores were in the osteopenia range, being -1.2 and -2.2, respectively. Osteoporosis/penia rates and vit. D levels did not significantly differ between patients with severe and moderate haemophilia. However, patients with severe haemophilia had lower lumbar T scores (p=0.048) and seemed to acquire low BMD 2 times more likely than moderate haemophiliacs. Patients with a history of joint intervention had significantly lower vit. D levels (p=0.005) and 1.4 times more risk for low BMD. Conclusion: Preliminary results of our study are in line with the recent literature indicating an increased frequency for osteopenia and osteoporosis in patients with haemophilia. Despite their young age our cohort of patients had lower BMD and vitamin D levels than the age-matched healthy population. This is an interesting finding in a country like Turkey where the average yearly total number of hours of bright sunshine is over 3000. Data at hand suggest increased risk for reduced BMD especially in severe haemophiliacs with impaired joint mobility. The most probable underlying cause for reduced BMD seems to be haemophilic arthropathy related inactivity. Furthermore, impaired bone health seems to be partially associated with less sunlight exposure, which is probably a result of increased home confinement of patients with haemophilia due to joint disease. The study is still recruiting. We hope to clarify other questions regarding factors influencing bone health in haemophiliacs when the study is completed and additional data on radiological and physical examination as well as on quality of life are obtained. Table. Patient Characteristics (n=36) Age, years (median [range]) 35 [20 - 55] Type of haemophilia ( A/B), n 32/4 Genotype (severe/moderate), n 29/7 Factor activity level, % (median [range]) 0.4 [0.1 - 4.2] Type of treatment (prophylaxis/on demand) 34/2 Annual bleeding rate (median [range]) 4 [1 - 12] Joint replacement, number of patients (%) 7 (19) Radioactive synoviectomy, number of patients (%) 7 (19) Any joint intervention, number of patients (%) 11 (30.5) Lumbar T scores (median [range]) -1.2 [-5.2 - 1] Femur T scores (median [range]) -2.2 [-3.9 - 0.6] Vit. D, ng/mL (median [range]) 10.5 [1.3 - 45] Calcium, mg/dL (median [range]) 9.6 [8.9 - 10.2] Alkaline phosphatase, U/L (median [range]) 91.5 [53 - 177] Parathormon, pg/mL (median [range]) 39 [20 - 179] Haemoglobin, g/dL (median [range]) 14.75 [8.9 - 16] Osteopenia, number of patients (%) 12 (33) Osteoporosis, number of patients (%) 12 (33) HBV/HCV/HIV, n 1/11/0 Disclosures No relevant conflicts of interest to declare.

Abstract 4603 Background Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in the Western world with an annual incidence of 5/100,000. The clinical course of the disease is highly variable; while some CLL patients experience a stable clinical course that will never affect their morbidity or mortality, some of them will eventually progress and require chemotherapy. In addition to the traditional prognostic markers (e.g. Rai and Binet staging systems), more recently, mutational status of the variable regions of the immunoglobulin heavy chains (IgVH), chromosomal aberrations, CD38 expression and Zeta-chain-associated protein kinase 70 (ZAP-70) expression are used to better determine the prognosis in CLL patients. A novel CLL-specific gene, CLL Up-regulated gene 1 (CLLU1) that uniquely overexpressed in CLL patients, was recently demonstrated. It has been shown that CLLU1 mRNA expression levels in CLL patients predict time to initiation of therapy as well as overall survival (OS), and CLLU1 is highly up-regulated in poor-risk groups. The aim of this study is to investigate the relationship between CLLU1 levels and well known prognostic parameters and, to determine the importance of CLLU1 gene on prognosis and clinical course in our CLL patients. Methods 116 (46 female, 70 male) CLL patients who consecutively visited our outpatient clinic between May 2009 and March 2010 were enrolled in the study. Median age was 60 years (range, 30–87 years). Blood samples were drawn from the patients for CLLU1 determination, and CLLU1 levels were determined by RT-PCR method. CLLU1 expression level was counted both in CLL patients and healthy B cells as the difference between CLLU1 and abl (taken as an house keeping gene) gene. Then, they are transformed as folds which is the ratio between CLLU1 level in CLL patients and that in healthy B cells. Patients with CLLU1 expression exceeding the CLLU1 expression of normal (CD19+) B-cells were taken as positive. Each patient was followed for at least one year for survival data. For the statistical analysis, student’s t-test, Mann-Whitney U test and Pearson correlation were used. p Results There was no relationship between CLLU1 levels and, sex, age, modified RAI and BINET stages, lymphocyte counts and LDH levels at the time of diagnosis. Patients with nodular bone marrow infiltration had lower CLLU1 levels than patients with non-nodular infiltration (57.6 vs 498). Patients with high β2 microglobulin levels had higher CLLU1 levels than the ones with low β2 microglobulin levels (356.7 vs 13.6, p Conclusion With a limited number of patients we could demonstrate that CLLU1 levels correlated with β2 microglobulin levels and ZAP-70. Although there were similar findings also with CD38 levels; the association was not statistically significant due to the limited number of cases. Time to treatment was shorter in patients with CLLU1 levels above the median value than patients with CLLU1 levels below the median value. CLLU1 is a promising and specific new prognostic parameter in patients with CLL, and further studies in larger series are needed to define the impact of CLLU1 in the prognosis and clinical course of CLL patients. Disclosure This study was supported by Istanbul University Research Fund. Disclosures: No relevant conflicts of interest to declare.

Abstract 5223 Background Non-Hodgkin's Lymphoma (NHL) is the most common type of hematopoietic cancers and it constitutes 4% of all cancers. It is the seventh most common type of all cancers in Turkey. The NHL is 1.5 times more common among males and the median age of most subtypes is equal to or more than 50. About 85% of NHL has B cell origin and 5-year overall survival is around 60%. Tumor volume, histology, patient's age and performance, serum lactate dehydrogenase (LDH) and beta-2 microglobulin levels, stage of disease and presence of extranodal disease are related to prognosis of NHL. International Prognostic Index (IPI) includes five of these factors to predict prognosis: patient's age and performance, stage of the disease, serum LDH level, extranodal disease. Methods The aim of this study is to evaluate the responses to actual treatments applied and survival periods of our Diffuse Large B Cell Lymphoma (DLBCL) patients. Non-Burkitt's, aggressive non-Hodgkin's lymphoma records obtained from our hematology department, which belong to the period between January 2000 and May 2011 were retrospectively analyzed. 278 patients diagnosed morphologically/immune-histochemically as CD20 positive DLBCL were included in this study. 153 of 278 paraffin blocks of diagnostic tissue were accessible and two subgroups of DLBCL were determined as Germinal Center B cell (GC) and Activated B cell (AB). From the remaining 125 cases, paraffin blocks of diagnostic tissue could not be accessed 115 cases, so any subgroup could not be determined (ND) and Mediastinal Large Cell Lymphoma (MLCL) were assessed in 10 cases. The subgroups were compared in order to evaluate the survival and also the responses to treatment. In the non-parametric comparison process, we used Mann-Whitney-U test. Results Patient characteristics according to the subgroups are detailed in Table 1. Complete remission was achieved with the first line treatment in 75% of patients and from those, 20% were relapsed at the median of 9 months. Overall Survival (OS) was significantly longer in GC than in AB patients (median OS: 27 vs 24 months, p=0.006). The Time to Relapse (TTR) is two times longer in GC group than in AB group, however this data is not statistically significant (median TTR: 12 vs 5.5 months, p=0.221). Survival curve of ND patients is not significantly different from GC curve (p= 0.436). Nevertheless, AB subgroup survival curve is significantly worse than ND group (p= 0.024, Figure 1). Regarding all patients, IPI predicts the survival of DLBCL independent from subgroups and treatment modalities (p Conclusion The data should be analyzed carefully because all data could not be accessed in some patients as this is a retrospective analysis. However, our data is valuable at the point that it reflects “real-life” patient data. Disclosure This study was supported by Istanbul University Research Fund. Disclosures: No relevant conflicts of interest to declare.

Abstract 1692 Background: There has been a remarkable improvement in the management of chronic myeloid leukemia (CML) after imatinib mesylate (IM) became available in the market, but there is still a group of patients who are resistant to imatinib. Although point mutations in the BCR-ABL kinase domain is the most common mechanism for resistance in patients with CML receiving tyrosine kinase inhibitor (TKI) therapy, there are several mechanisms that can play a role in the resistance to TKIs. Multi drug resistance gene (MDR1) [ABCB1 (ATP-binding cassette, sub-family B (MDR/TAP), member 1) ] product is an ATP-driven efflux pump contributing to the pharmacokinetics of drugs that are P-glycoprotein (P-gp) substrates and to the multidrug resistance of cancer cells. More than 50 single nucleotide polymorphisms (SNPs) have been identified concerning the MDR1 gene, and SNP polymorphisms may affect the expression and function of the P-gp. The SNPs T1236C, G2677T/A, and C3435T are the most common variants in the coding region of ABCB1. Imatinib is a substrate of P-gp-mediated efflux, and P-gp mediated drug efflux can play a role in IM resistance. So identifying these SNPs may allow to predict the drug disposition and responses to IM in CML patients. The aim of the study was to identify the C3435T SNP variants, and the associations between MDR1 C3435T polymorphism and IM efficacy in our CML patients. Methods: Between December 2010 and March 2011, 110 chronic phase (CP) CML patients who consecutively visited our outpatient clinic were enrolled in this study. Hematologic, cytogenetic and molecular response patterns to IM as well as the association between MDR1 C3435T polymorphism and responses to imatinib were evaluated in our patient cohort. MDR1 C3435T polymorphisms were detected by real-time polymerase chain reaction (RT-PCR). We could assess complete cytogenetic response (CCyR) and major molecular response (MMR) in one hundred and six patients (96%) among these 110 patients. The differences in genotype frequencies in all patients taking imatinib treatment was determined by using the chi-square test. All tests were two-sided, and p Results: 59 patients were male (54%), and fifty-one were female (46%). Median age was 50.5 years (range, 19–84 years). 37.6% of the patients were low, 45% were intermediate, and 17.4% were high risk according to Sokal risk score. The CCyR rate was 71%, and MMR rate was 60%. The frequencies of MDR1 3435 CC, CT, and TT genotypes were 22.5%, 55%, and 22.5%, respectively. No statistically significant difference was observed between the frequencies of the genotypes according to gender. The CCyR rates in patients with CC, CT, and TT genotypes were 88%, 62%, and 75%, respectively (Figure 1). The patients with CC genotype had significantly higher CCyR rates when compared to patients having CT/TT and CT genotypes (p =0.04 and p =0.023, respectively) (Table 1). The patients with CC, CT, and TT genotypes did not differ significantly between each other regarding the MMR rates. There were no significant difference between the C3435T genotypes and second generation TKI usage regarding both CCyR and MMR. Conclusion: Before starting IM therapy, the individual patientÕs MDR1 gene polymorphism pattern can be important in determining the treatment strategy in patients with CML. Among our patient cohort, the patients with CC genotype had significantly higher CCyR rates than patients with CT/TT and CT genotypes. Up to now, there are a few studies in CML patients with different results regarding MDR1 gene polymorphisms, and since racial differences can be seen in the frequencies of MDR1 gene polymorphisms, further studies in larger series are needed to define the genetic polymorphisms with therapeutic relevance in patients on imatinib. Disclosure: This study was supported by Istanbul University Research Fund. Disclosures: No relevant conflicts of interest to declare.

Abstract 4429 Background Imatinib mesylate (IM) is considered the mainstay of chronic myeloid leukemia (CML) treatment for almost a decade. The primary goal of the study is to share data of a substantial number of CML patients followed at one center. Methods We analyzed data from 177 CML patients who were treated in our institution and received IM for at least 24 months. They were stratified into low, intermediate and high risk groups based on Sokal score. Early chronic phase (ECP) (within one year from diagnosis to IM start), late chronic phase (LCP) (≥ 12 months from diagnosis), and accelerated phase (AP) CML patients were included in the study. Patients were evaluated for hematologic, cytogenetic and molecular responses, event-free survival (EFS) and overall survival (OS), frequency of adverse events. Results The median age was 51.2 years (range, 22–86 years), with 77 females and 100 males. Patients were followed for a median of 60 months (range, 24–116 months). IM was started at a dose of 400 mg daily. 97.7% were in chronic phase, and 2.3% were in accelerated phase.75.1% of chronic phase CML patients were in early and 24.9% in late chronic phase. 42% of patients were low Sokal risk, 44% intermediate and 14% were high risk patients. 12% of the patients did not receive any prior therapy, 1% had received prior therapy with interferon (IFN), 73% were treated with hydroxyurea (HU) (mostly short course) and 14% with both HU and IFN. Complete hematologic response (CHR) was achieved in 90% of patients at 3 months (median time, 2.02 months). Cumulative rates of cytogenetic and molecular responses at 6, 12, 18 and 24 months are summarized in Table 1. Complete cytogenetic response (CCyR) was achieved in a significantly higher proportion of patients within the low and intermediate Sokal risk group (79.4%, 85.2%) compared with the high risk patients (14.3%, p=0.001). There was a significant difference in the complete molecular response (CMR) ratio achieved by low, intermediate and high Sokal risk patients (70.4%, 63.8% and 33.3%, p Conclusion In the current report, we described the outcome of unselected CML patients, treated outside of clinical trials. Grouping patients according to their Sokal prognostic score predicted IM response in this cohort. A longer interval from diagnosis to the start of IM and high Sokal risk score were adverse prognostic factors. 'Real life' data of our study are in accordance with the previous data reflecting the prognostic impact of cytogenetic and molecular responses on survival. Close follow-up of the responses and timely initiation of second-generation tyrosine kinase inhibitors were associated with high survival rates. Disclosures: No relevant conflicts of interest to declare.