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Immune thrombocytopenia (ITP) is a rare autoimmune disorder presenting with isolated thrombocytopenia. Splenectomy is still one of the treatment alternatives for these patients. Here we aim to analyze long term follow-up data of splenectomy in immune thrombocytopenia. This retrospectively designed study was conducted in a tertiary health clinic. Patients with ITP who were splenectomized between 1990 and 2015 were included. Response to treatment was interpreted as 'complete response', 'response' or 'no response'. The incidence of response loss was evaluated. Perioperative and long term complications and overall survival rates were determined. Out of 51 patients, who underwent splenectomy after 12 months of diagnosis, 47 achieved a response (92.2%). Of 47 patients who had a platelet count at least 30.000/µL, 41 (87.2%) had CR. Incidence of loss of response was 10.5% (95% confidence interval (CI): 4%-26.1%) at 30 months. Two patients died, and overall survival rate was 97.4% (95% CI: 82.8%-99.6%) at 30 months of follow up. Considering the complications: two patients had venous thromboembolism, 11 had minor bleeding episodes and 15 suffered from perioperative infections. Our study suggests that splenectomy promises a high level of response with acceptable complication rates. Although less preferred recently, splenectomy should still be taken into consideration when remission is not achieved especially after 12 months of disease.

With the advent of tyrosine kinase inhibitors (TKIs), patients with chronic myeloid leukemia (CML) have a life expectancy similar to those of age- and gender-matched healthy populations. Nevertheless, patients receiving TKIs report chronic adverse events such as fatigue, edema, and muscle cramps, which lead to a decrease in their quality of life (QoL). Therefore, the aim of this study was to assess the QoL and symptom burden in patients receiving original imatinib, generic imatinib, dasatinib, and nilotinib.A total of 121 patients with CML who received TKIs for at least 3 months were enrolled in the study. The QoL was assessed with the Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Quality of Life Questionnaire-Chronic Myeloid Leukemia (QLQ-CML24) modules. The symptom burden was assessed with MD Anderson Symptom Inventory for Chronic Myeloid Leukemia (MDASI-CML) and EORTC QLQ-CML24.The median age of the study population was 53 years (range, 28-90 years), and 83 (81.4%) patients had a low-to-medium Sokal risk score. The Eastern Cooperative Oncology Group performance status of most patients were good (2; 96%), and comorbidity scores were low (HCT-CI 3; 90.8%). There was no significant difference between the general health status of patients in terms of EORTC QLQ-C30 and QLQ-CML24. According to the results of the MDASI-CML and QLQ-CML24 modules, the most common symptom was fatigue (58.7%) in all groups, and there were no significant differences between the groups in terms of the effects on the daily life activities of the patients.Patients with CML receiving first- and second-generation TKIs were seen to have a similar QoL and symptom burden.

Philadelphia chromosome‐negative (Ph−) myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal disorders of the bone marrow, and are associated with a high disease burden, reduced quality of life (QOL), and shortened survival. This multinational, multicenter, non‐interventional registry “MERGE” was initiated with an objective to collect data on the epidemiological indices of classical Ph‐MPNs, existing treatment patterns, and impact of MPNs on health‐related QOL in various countries/regions in Asia, including the Middle East, Turkey, and Algeria. Of the 884 eligible patients with MPNs, 169 had myelofibrosis (MF), 301 had polycythemia vera (PV), 373 had essential thrombocythemia (ET), and 41 had unclassified MPNs. The median age was 58 years (range, 47‐66 years), and 50% of patients were males. The prevalence and incidence of MPNs were estimated to be 57‐81 and 12‐15 per 100 000 hospital patients per year over the last 4 years, respectively, in these countries. Total symptom score (mean [standard deviation; SD]) at baseline was highest in patients with MF (23.5 [17.47]) compared with patients with ET (14.6 [14.26]) and PV (16.6 [14.84]). Patients with ET had a lower mean (SD) number of inpatient visits (0.9 [0.77] days), and patients with MF had more outpatient visits (5.2 [3.17] days) on an average, compared with the entire MPN group. The study showed that patients with MPNs have a severe disease burden and reduced QOL. A discordance between physician and patient perception of symptom assessment was observed in this study (International clinical trials registry ID: CTRI/2014/05/004598)., This MERGE registry study provides epidemiological data on the distribution of MPNs and their diagnosis, management, and treatment patterns in developing emerging countries in Asia, including the Middle East, Turkey, and Algeria. The study showed that patients with MPNs have a severe disease burden and reduced quality of life. A discordance between physician and patient perception of symptom assessment was observed in this study.

Background Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease presenting with variable and various clinical findings. PNH might be overlooked and diagnosis may be delayed due to low awareness about PNH. This is the first multicenter study in Turkey, investigating the efficiency of diagnostic screening of PNH by multiparameter flow cytometry (FCM) according to consensus guidelines. Methods We evaluate the efficiency of consensus clinical indications for PNH testing with FCM in 1689peripheral blood samples from 20 centers between January 2014 and December 2017. Results Overall, at the 20 centers contributing to this study, PNH clone were detected in 62/1689 samples (3.6%) by FCM test. 75.8% (n = 47) of patients with PNH clone had aplastic anemia, 3.2% (n = 2) had Coombs (-) hemolytic anemia, 6.5% (n = 4) had unexplained cytopenia, 3.2% (n = 2) had MDS with refractory anemia, 1.6% (n = 1) had hemoglobinuria and 9.7% (n = 6) had others (elevated LDH, splenomegaly, etc.). In contrast, we detect no PNH clone test in patients who were screened for unexplained thrombosis. Conclusions Our study showed that current clinical indications for PNH testing are highly efficient and diagnostic screening of suspected patients for PNH with FCM is recommended. However, advanced screening algorithms are required for patients presenting with unexplained thrombosis and normal complete blood count.

The present study investigated the efficacy and safety profile of daratumumab monotherapy in 42 patients with relapsed refractory multiple myeloma through a Turkish early access program. the current findings have confirmed the efficacy of daratumumab monotherapy in heavily pretreated patients with refractory multiple myeloma because of the deep and durable responses and favorable safety and tolerability profile. Background: in countries where frontline drug approval is limited to first-generation proteasome inhibitors or immunomodulatory drugs, relapses have been both more frequent and less durable. We investigated real world data on the efficacy and safety of daratumumab monotherapy among patients with relapsed refractory multiple myeloma (RRMM) from Turkey using a prospective early access program. Patients and Methods: A total of 42 patients with RRMM after a minimum of 3 previous lines of proteasome inhibitor/immunomodulatory drug-based treatments were included from 25 centers across Turkey. Daratumumab monotherapy was administered intravenously at a dose of 16 mg/kg weekly (cycles 1-2), on alternate weeks (cycles 3-6), and monthly thereafter. Results: the median daratumumab monotherapy duration was 5.5 months (range, 0.2-28.7 months). the overall response rate was 45.2%, including 14 (33.3%) partial responses, 4 (9.5%) very good partial responses, and 1 (2.4%) complete response. the median duration of response was 4.9 months. the median progression-free survival (PFS) was 5.5 (95% confidence interval, 2.6-8.4 months) with 12- and 18-month PFS rates of 35.7% and 31.0%, respectively. the median overall survival was not reached; the 12- and 18-month overall survival rates were 64.3% and 59.5%, respectively. the depth of response had a significant effect on PFS (log-rank test, P = .026). Overall, of the 76 adverse events reported, 33 (43.4%) were grade >= 3; only 4 (9.52%) were grade 3 infusion-related reactions. No infusion-related reactions or adverse events led to treatment discontinuation. Conclusion: the present findings from our daratumumab early access program have confirmed the efficacy and safety profile of daratumumab monotherapy in heavily pretreated Turkish patients with RRMM., Janssen Pharmaceutica Turkey, The present daratumumab EAP was funded by Janssen Pharmaceutica Turkey. the authors would like to thank to Professor Sule Oktay, MD, PhD, and Cagla Ayhan, MD, from KAPPA Consultancy Training Research Ltd (Istanbul, Turkey), who contributed to the manuscript writing and statistical analyses.

Objectives To investigate the risk factors for rectal colonization with carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum s-lactamase-producing Enterobacteriaceae (ESBL-E) in hematological malignant patients with febrile neutropenia (FN); rate of rectal colonization and infection/colonization with CRE and ESBL-E; whether empirical treatment can be revised. Methods Adult patients receiving chemotherapy were included. Rectal swab cultures of patients were screened for CRE and ESBL-E using selective chromogenic agars. Results Fifty-seven FN episodes of 57 patients were studied. Rectal colonization rates were 40.4% (23/57) and 8.8% (5/57) for ESBL-E and CRE, respectively. ESBL-E bacteremia was diagnosed in 2 (8.6%) ESBL-E colonized patients, while CRE bacteremia was detected in 1 (20%) CRE colonized patient. Amikacin (100%) and carbapenem (93%) were the most effective antibiotics against gram-negative enteric bacteria. Beta-lactam usage within the last 3 months was a significant risk factor for ESBL-E colonization. Conclusions For the treatment of FN patients either colonized with ESBL-E or having significant risk factors for ESBL-E infection, aminoglycoside containing combinations may become an alternative to carbapenems due to their high sensitivity rates. When CRE colonized hematological cancer patients develop FN or if they are hemodynamically unstable, CRE covering empiric antibiotherapy should be preferred due to high mortality rates of CRE bacteremia.

Objective: The cases of diffuse large B-cell lymphoma, (DLBCL not otherwise specified (NOS)) which immunohistochemicallyexhibit MYC and BCL2 expressions are defined as double-expressor lymphomas (DELs). This study aimed to assess the prognosticimpact of DEL and the expressions of other proteins that may have role in tumorogenesis.Materials and Methods: In this study, 90 tumor samples from patients diagnosed with DLBCL NOS were evaluated retrospectively.Immunoexpressions of MYC, BCL2, activation-induced cytidine deaminase (AID), uracil-DNA glycosylase (UNG) and DNAmismatch repair proteins including MLH1, MSH2, MSH6 and PMS2 were analyzed.Result: Eleven cases (12.2%) which exhibited ≥40% MYC and ≥50% BCL2 immunexpressions were classified as DEL DLBCL. Patientswith MYC positivity displayed lower overall survival rate than MYC negative cases. A trend of lower overall survival was observed inthe double-expressor lymphoma group, however, this was not proven to be statistically significant. Significant relationship betweenAID, UNG and p53 immunexpressions with double-expressor lymphoma or overall survival was not detected. The correlationbetween immunexpressions of p53 and MYC was observed. The loss of expression of mismatch repair proteins was not observed inany cases.Conclusion: In this study, a relationship between low overall survival and MYC expression is detected. However, our result does notdemonstrate that double-expressor lymphoma can be associated with poor outcomes.

This study aimed to evaluate real-life data on patterns of hydroxyurea prescription/use in polycythemia vera (PV).This retrospective chart review study included PV patients who had received hydroxyurea therapy for at least 2 months after PV diagnosis. Data were collected from 10 representative academic medical centers.Of 657 patients, 50.9% were in the high-risk group (age ≥60 years and/or history of thromboembolic event). The median duration of hydroxyurea therapy was 43.40 months for all patients; 70.2% of the patients had ongoing hydroxyurea therapy at last follow-up. Hydroxyurea was discontinued in 22.4% of the patients; the most common reason was death (38.5%). The predicted time until hydroxyurea discontinuation was 187.8 months (standard error: ±21.7) for all patients. This duration was shorter in females (140.3±37.7 vs. 187.8±29.7) (p=0.08). This trend was also observed in surviving patients aged ≥50 years at hydroxyurea initiation (122.2±12.4 vs. 187.8±30.7, p=0.03). Among the patients who were still on hydroxyurea therapy, 40.3% had a hematocrit concentration of ≥45% at their last follow-up visit, and the rate of patients with at least one elevated blood cell count was 67.8%.Hydroxyurea prescription patterns and treatment aims are frequently not in accordance with the guideline recommendations. Its discontinuation rate is higher in females.Polistemia vera’da (PV) hidroksiüre reçete etme/kullanma şekilleri hakkındaki gerçek yaşam verilerini değerlendirmek.Bu retrospektif kayıt çalışmasına tanıdan sonra en az 2 ay hidroksiüre almış olan hastalar dahil edildi. Veriler ülkeyi temsil ettiği düşünülen 10 akademik tıp merkezinden toplandı.Altı yüz elli yedi hastadan %50,9’u yüksek risk (yaş ≥60 yıl ve/veya tromboembolik olay öyküsü) grubundaydı. Tüm hastalarda ortanca hidroksiüre tedavi süresi 43,4 aydı. Hastaların %70,2’si son kontrol tarihlerinde halen hidroksiüre kullanmaktaydı. Hidroksiüre en sık neden (%38,5) ölüm olmak üzere hastaların %22,4’ünde kesilmişti. Tüm hasta grubunda hidroksiüre kesmek için ortanca süre 187,8 ay ±21,7 standart hata olarak hesaplandı. Bu süre kadınlarda (140,3±37,7) erkeklere (187,8±29,7) göre daha kısa idi (p=0,08). Bu eğilim hidroksiüre başlandığında 50 yaş ve üstünde olan ve son durumda hayatta olan hastalarda da gözlendi (122,2±12,4 ve 187,8±30,7, p=0,03). Hidroksiüre devam etmekte olan hastalarda son kontrolde ≥%45 hematokrit %40,3 ve en az bir artmış kan hücre düzeyi %67,8 oranında gözlendi.Hidroksiüre reçete etme şekli ve tedavi hedefleri sıklıkla rehber önerilerine uymamaktadır. Hidroksiüre kesme oranı kadınlarda daha yüksektir.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disease that may lead to weakness and death of patients, if unrecognized and untreated. Although consensus guidelines were reviewed recently for the diagnostic screening of PNH with multi-parameter flow cytometry (FCM), until now, no study has investigated the efficiency of such clinical indications in older patients. Methods: Overall, 20 centers participated in the study and a total of 1,689 patients were included, 313 of whom were at geriatric age and 1,376 were aged 18 - 64 years. We evaluated the efficiency of consensus clinical indica-tions for PNH testing using FCM in peripheral blood samples and compared the results of older patients and pa-tients aged 18 - 64 years. Results: PNH clones were detected positive in 7/313 (2.2%) of the older patients. Five (74.4%) of the patients with PNH clones had aplastic anemia, 1 had unexplained cytopenia, and 1 patient had myelodysplastic syndrome (MDS) with refractory anemia. PNH clones were not detected in any older patients who were screened for unex-plained thrombosis, Coombs (-) hemolytic anemia, hemoglobinuria, and others (e.g., elevated lactate dehydroge-nase (LDH), splenomegaly). We detected PNH clones in 55/1376 (4%) samples of the patients aged under 65 years. Forty-two (76.4%) patients with PNH clones had aplastic anemia, 2 patients had Coombs (-) hemolytic anemia, 3 patients had unexplained cytopenia, 1 patient had MDS with refractory anemia, 1 patient had hemoglobinuria, and 6 (10.9%) had others (e.g., elevated LDH, splenomegaly). PNH clones were not detected in any patients who were screened for unexplained thrombosis. There was no statistical difference between the geriatric population and patients aged 18 - 64 years in terms of clinical indications for PNH screening with FCM (p = 0.49). Conclusions: Our results showed that the current clinical indications for PNH screening with FCM were also effi-cient in older patients. We suggest that older patients with unexplained anemia, myelodysplastic syndrome with refractory anemia, and unexplained cytopenia should be screened for PNH with FCM to identify patients who would benefit from treatment. © 2020 Verlag Klinisches Labor GmbH. All rights reserved.

WOS: 000491229800399 …

61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) -- DEC 07-10, 2019 -- Orlando, FL, Onec, Birgul/0000-0003-2824-1044; OZDOGU, HAKAN/0000-0002-8902-1283, WOS:000577164604216, [No Abstract Available], Amer Soc Hematol

Introduction Although many new drugs became available to treat multiple myeloma (MM), high-dose chemotherapy with auto-HCT remains the gold standard. Further intensification to improve disease control has been assessed in several trials. However, no clear consensus has emerged. Further evidence is therefore required to guide clinicians in choosing between single auto, tandem auto and auto-allo approaches. Materials and Methods We performed a retrospective analysis of MM patients (20-65 years) undergoing their first auto-HCT in EBMT centres (2002-2015). Our primary end-points were Progression-Free Survival (PFS) and Overall Survival (OS). We used 3 different statistical methods to avoid time bias and to account for time-dependent effects. We defined tandem transplants (auto-auto2 or auto-allo) given within 9 months in absence of progression. Single- and tandem-transplant groups were compared by a landmark analysis (1). In addition, two different dynamic prediction models (2, 3) were applied to predict long-term outcomes in all patients according to the treatment actually received while avoiding the loss of information that occurs in landmark analysis. The models incorporated a horizon time of 5 years for OS and PFS during the first 3 years following auto1. Since the effects of tandem transplants vary over time, these were split into "Recent", the first 100 days following the 2nd transplant, and "Past" for the longer term (2, 3), respectively. Age, disease status and calendar year of transplant at auto1 were also analysed. Furthermore, the third model incorporated the long-term time-varying effect of auto-allo or auto-auto2 and possible associated interactions with patients' characteristics. Results A total of 24,936 patients who received an auto as first transplant were included; 3,683 of these patients proceeded to an elective tandem auto and 878 to an auto-allo transplant. The median age of the entire cohort was 57.0 years (range 18.1.-65.0). 18% were in complete remission (CR) at first auto. The Tandem auto-allo group was younger (51.7 years). Both tandem groups (auto-auto and auto-allo) had fewer patients in CR at first auto (9% and 8%, respectively). There was no difference in CR rates at second transplant in the tandem groups (18% and 19%, respectively). In the tandem auto-allo group, 72% had HLA identical sibling donors and 25% matched unrelated donors. Reduced intensity conditioning was performed in 85% of the allogeneic transplants. The median follow-up of the entire cohort was 66.3 months. At 60 months following first auto, the PFS was 24.8% and OS 63.1%. All three statistical methods found that younger age and being in CR at first transplant were associated with superior PFS and OS. The long term results of the different transplant strategies were as follows: Landmark analysis at 4 months resulted in a reduction in the number of transplants analysed. Auto-allo only had an advantage in terms of very long term PFS (figure 1) and not for OS (not shown).Dynamic prediction (table 1, curves not shown) revealed that the tandem groups were superior regarding PFS in comparison to single auto (auto-allo and auto-auto: HR 0.56 and 0.85, both p Summary We here present a very large cohort of patients who have undergone auto and allo transplantation as first-line treatment for MM. Younger age and being in CR at first transplant were consistently found to be positive prognostic factors for PFS and OS. Tandem auto-allo was superior to single and tandem auto for long-term PFS. However, this PFS advantage only translated into a minor OS benefit for tandem auto-allo even when analysis was restricted to patients who were not in CR at the time of the first auto-HCT. Disclosures Schönland: Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Medac: Other: Travel Grant. Blaise:Pierre Fabre medicaments: Honoraria; Sanofi: Honoraria; Jazz Pharmaceuticals: Honoraria; Molmed: Consultancy, Honoraria. Chevallier:Jazz Pharmaceuticals: Honoraria; Daiichi Sankyo: Honoraria; Incyte: Consultancy, Honoraria. Mayer:AOP Orphan Pharmaceuticals AG: Research Funding. Gribben:Abbvie: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Acerta/Astra Zeneca: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Stelljes:MDS: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Amgen: Honoraria; Jazz Pharmaceuticals: Honoraria. Bloor:Abvie, Gilead, Novartis, Autolus, Celgene, etc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational grant. Beksac:Celgene: Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hayden:Amgen: Honoraria; Alnylam: Honoraria. Kröger:Celgene: Honoraria, Research Funding; DKMS: Research Funding; JAZZ: Honoraria; Medac: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Research Funding; Sanofi-Aventis: Research Funding.

Onychomycosis (OM) is a common fungal infection of the toenails and/or fingernails that is highly prevalent in the general population and also responsible for significant morbidity. OM is caused by dermatophytes, nondermatophytic molds, or yeast. Today systemic antifungal agents are considered as the gold standard for all types of OM. Here we report a case of aplastic anemia associated with oral terbinafine use and a review of the literature on hematological toxicities associated with terbinafine.

Summary This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycles of bortezomib 1·6 mg/m2 intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent-to-treat population included 104 patients (51 bortezomib, 53 observation). There were no meaningful differences in the primary endpoint of change from baseline to end of treatment in bone mineral density (BMD). End-of-treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P = 0·06); median progression-free survival was 44·9 months vs. 21·8 months (P = 0·22). Adverse events observed ≥15% more frequently with bortezomib versus observation were diarrhoea (37% vs. 0), peripheral sensory neuropathy (20% vs. 4%), nausea (18% vs. 0) and vomiting (16% vs. 0). Compared with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival.

Background The Philadelphia chromosome−negative classical myeloproliferative neoplasms ([MPNs], including essential thrombocythemia [ET], polycythemia vera [PV], and myelofibrosis [MF]), are generally associated with a substantial disease burden, often leading to a reduced quality of life (QOL) and shortened survival in many patients (pts). There has been a lack of estimates for the incidence/prevalence and treatment patterns of MPNs in many regions of the world, including countries from South Asia, Asia Pacific, Middle East, and Turkey. Hence, there is a need to establish databases like registries, which would provide information on the "real-world" data in these regions. The MERGE registry was initiated with an objective to collect data on the epidemiological indices of MPNs and existing treatment patterns in Asia, including Middle East, Turkey, and Algeria. This primary descriptive analysis from the MERGE registry was performed to estimate the incidence/prevalence, natural disease course, and treatment patterns of MPNs in these countries. Methods MERGE is a multinational, multicenter, nonintervention study that included adult pts with MPNs, who were diagnosed according to World Health Organization 2008 criteria. The data were collected retrospectively (since diagnosis) and prospectively after enrollment in the study. Disease assessments were scheduled every 6 months up to 5 visits, with a minimum of 2 years of follow-up. Pts who participated or were participating in a randomized clinical trial were allowed. Data were analyzed descriptively. Results In total, 884 MPN pts (ET=373, PV=301, MF=169, and unclassified=41) were included in the full analysis data set. The median age was 58 years (range, 47-66 years; younger compared to other regions) and 50% pts were males. Baseline pt characteristics by MPN subtype are summarized in Table 1. About 57% of pts were diagnosed by incidental finding of abnormal blood results followed by bone marrow evaluation. In these countries, the prevalence and incidence of MPNs are estimated to be 57-81 and 12-15 per 100.000 hospital-patients per year over the last 4 years, respectively. As assessed by MPN Symptom Assessment Form (MPNSAF), 92% of the pts reported at least 1 symptom. At baseline, fatigue was the most common symptom in all 3 MPN subtypes (71% MPN; 78% MF; 71% ET; and 68% PV). Inactivity (64%), early satiety (61%), abdominal discomfort (57%), bone pain (56%), weight loss (52%), night sweats (46%), and fever (29%) were more common in MF; whereas, itching in PV pts (50%). MF pts had the highest total symptom score at baseline (mean [SD], 23.5 [17.47]) as compared to ET (mean [SD], 14.6 [14.26]) and PV pts (mean [SD], 16.6 [14.84]). Overall, 64% of pts had ECOG performance status of 0 and 26% had ECOG 1. During study period, the most common nonpharmacological intervention was red cell transfusion in MF and ET pts, and phlebotomy in PV pts. Splenectomy (n=2) and stem cell transplantation (n=4) were rarely employed (6 MF pts). Hydroxyurea (HU) was the most common first-line therapy in all 3 MPN subtypes (overall, 54%; PV, 61%; ET, 54%; and MF, 39%), followed by aspirin. Other common first-line therapies were anagrelide (10%) and interferon (9%) in ET pts, antineoplastic (6%) and clopidogrel (6%) in PV, and JAK2 inhibitors in MF pts (15%). More than 75% of the induction therapies were monotherapies, with less than 3% of pts receiving 3 or more drug combinations as primary treatment. Patients with MF often received monotherapy (81%), than the other patients with MPN. Median duration of first-line therapy was about 6 months (95% CI, 1-21 months), and first-line therapy discontinuation rates of 35%, 36%, and 30% were noted in ET, PV and MF pts, respectively. Interferon was used in 8% of in the second-line setting. JAK2 inhibitors were more frequently (14%-17%) used in the second-and third-line settings. Conclusions The prevalence and incidence of MPNs in countries from Asia Pacific were derived using the number of pts visiting the corresponding hospitals. Thus, the resulting incidence and prevalence reported here are not directly comparable with the country-based prevalence/incidence and may overestimate the actual values. At baseline, pts with MPNs had significant disease burden. The most common first-line therapy was HU, though discontinuation rates of first-line therapies were high, and JAK2 inhibitors were mostly used in the second-line/third-line settings. Disclosures Yassin: Novartis: Research Funding. Taher:La Jolla Pharmaceutical: Research Funding; Ionis Pharmaceuticals: Consultancy; Celgene Corp.: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Protagonist Therapeutics: Consultancy. Kim:Novartis Korea: Honoraria. Rippin:Employee of IQVIA - doing consultancy for Novartis: Consultancy. Sadek:Novartis Pharmaceutical Corporation: Employment. Siddiqui:Novartis Pharma AG: Employment, Equity Ownership. Wong:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Background The Philadelphia chromosome−negative classical MPNs (myelofibrosis [MF], polycythemia vera [PV], and essential thrombocythemia [ET]) are associated with a pronounced symptom burden, including fatigue, night sweats, itching, and inactivity that may affect patients' HRQOL. There is a limited real-world evidence from many of the Asian countries, including Middle East, regarding the impact of MPNs on HRQOL, or the economic burden associated with these diseases. MERGE is a multinational, multicenter, nonintervention study conducted in adult patients with MPNs in Asia, including Middle East, Turkey, and Algeria. The present analysis evaluated the impact of MPNs on HRQOL of patients from MERGE and explored the association of HRQOL with the clinical outcomes and resource utilization. Method The MERGE registry included patients with MPN diagnosed as per the World Health Organization 2008 criteria. Patients were planned to be followed up for 2 years (5 visits over the course of study). MPN Symptom Assessment Form Total Symptom Score (MPNSAF TSS) was administered during the routine biannual follow-up visits to assess the HRQOL. MPNSAF TSS score was calculated only for patients who completed at least 6 of the 10 items on the MPNSAF TSS questionnaire. The level of inter-rater agreement between physicians and patients on the proportion of symptomatic patients was assessed through Cohen's Kappa coefficient. Further, an ANCOVA (Analysis of covariance) model was applied to estimate the influence of the baseline variables (age, sex, weight, height, family history of MPNs, comorbidities, time to initial MPNs diagnosis, type of MPN initial diagnosis, baseline hemoglobin and platelet count, Eastern Cooperative Oncology Group Performance Status [ECOG PS], and time since diagnosis to treatment initiation) on the TSS score. Variables with univariate P-value < 0.20 were included in the multivariate model. Furthermore, medical resource utilization was assessed by evaluating the inpatient and outpatient visits, hospice care, emergency room visits, and day care. Results Of the 884 eligible patients with MPNs, 169 had MF, 301 had PV, 373 had ET, and 41 had unclassified MPN. During the study, 64% of patients received hydroxyurea, 15% interferon, 15% JAK inhibitors, and 10% anagrelide either alone or in combination. At baseline, the proportion of patients presenting at least 1 of the symptoms was higher in the MF group (96.4%), compared to the total MPN patients (91.8%). In addition, the TSS (mean [SD]) at baseline was highest in the patients with MF (23.5 [17.47]) as compared to patients with ET (14.6 [14.26]) and PV (16.6 [14.84]). During the study duration and follow-up, the TSS remained approximately constant at subsequent visits. Physicians reported a lower proportion of symptomatic patients than the proportion self-reported by patients, although, there was better agreement between physicians and patients for pruritus and night sweats (Kappa, 0.61-0.80) (Table 1) than for other symptoms (Kappa, 0.41-0.60). Across MPN subtypes, inter-rater agreement was lowest for patients with MF compared to patients with ET or PV. In a multivariate adjusted mixed effect regression model, female gender, type of MPN (MF), presence of comorbidities, lower baseline hemoglobin were independently and positively associated with the symptom score values. Overall, 24.3% of the patients had at least 1 inpatient visit, with a mean duration of 11.1 days. Outpatient visits were the most commonly observed healthcare resource used (95.5%), without remarkable change during the follow-up period. Patients with ET had a lower mean number of inpatient visits (mean [SD]: 0.9 [0.77] days), and patients with MF had more outpatient visits (mean [SD]: 5.2 [3.17] visit) on an average, compared to the entire MPN group. Conclusion Despite being on treatment, patients with MPN in MERGE had substantial symptom burden, which did not change over the course of the study. A discordance between physician and patient perception of symptom assessment was seen in this study, indicating that in addition to spleen and hematological investigations, a more systematic assessment such as the use of MPNSAF TSS could help to better evaluate patients' symptoms and understand the disease and its treatment burden. Disclosures Taher: Celgene Corp.: Research Funding; Ionis Pharmaceuticals: Consultancy; Protagonist Therapeutics: Consultancy; La Jolla Pharmaceutical: Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Yassin:Novartis: Research Funding. Rippin:Employee of IQVIA - doing consultancy for Novartis: Consultancy. Sadek:Novartis Pharmaceutical Corporation: Employment. Siddiqui:Novartis Pharma AG: Employment, Equity Ownership. Wong:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Background The prognostic significance of complete cytogenetic response (CCyR) is well defined in patients with chronic phase chronic myeloid leukemia treated with imatinib as first-line therapy. However, the effect on outcomes of obtaining molecular response itself and the depth of it is not clear. In this study we aimed to determine the frequency of complete molecular response (CMR) during long-term follow-up and the clinical significance of CMR on patient outcomes and survival. Patients and Methods We retrospectively evaluated the files of 178 chronic phase chronic myeloid leukemia patients using imatinib therapy. Forty-seven patients with missing data were excluded from the study and the assessment was done in 131 patients. CMR was defined as undetectable BCR-ABL transcripts using real-time quantitative polymerase chain reaction with a sensitivity level of ≥ 10 4 in 2 consecutive analyses at least 3 months apart. Cytogenetic and molecular monitoring during treatment was performed according to the European LeukemiaNet recommendations criteria. Our primary objective was to analyze the association of deeper molecular response with differences in progression-free survival (PFS). Results Eighty-eight patients (67%) achieved CMR at any time in a median of 65 months of follow-up. The rate of CMR was higher in patients who achieved CCyR at 12 months and major molecular response (MMR) at 18 months. Fewer events occurred in the CMR group than the MMR group (26.1% vs. 50.0%). Overall survival was not different in both groups. CMR was associated with longer PFS with borderline significance. Conclusion Prolonged imatinib therapy helps to achieve a deeper molecular response in the long-term. Achieving deeper molecular response at any time positively affects maintaining the cytogenetic and molecular responses, and decreases the transformation to accelerated and/or blastic phase. The slight prolongation in PFS did not reach statistical significance.

PNH Education and Study Group (PESG) have been established in December 2013 as a non-profit, independent, medical organization www.pesg.org. Paroxysmal Nocturnal Hemoglobinuria (PNH) is a multi-systemic disease that should be treated with a multidisciplinary approach. Patients may apply to the clinics other than the hematology due to variability and diversity of clinical findings which lower the rate of diagnosis due to low awareness about PNH. PNH might be overlooked and diagnosis might be delayed. Regarding these, PESG was established with the collaboration of Immunology, Cardiology, Thorax Diseases (Pulmonology), Neurology, Gastroenterology, General Surgery and Urology specialists in addition to hematologists dealing with PNH. The PESG study group aims to increase the awareness about PNH, including training activities about PNH, strengthening the relations between clinics and planning of clinical studies as a goal. It is the first professional organization focusing on PNH, in Turkey.In this guideline, we want to facilitate the diagnosis attributes of physicians from all specializations that deal with PNH and its systemic complications. One can perceive this as a tailor made guideline of international guidelines but not a compilation.

A previously healthy 31-year-old female presenting with dyspnea, iron deficiency anemia, pancytopenia, splenomegaly, and abnormal coagulation tests was admitted to the hospital. Hematology consultation additionally revealed that 71% of cells were indicative of acute promyelocytic leukemia (APL) and the patient tested positive for a t(15;17) translocation, confirming APL. All-trans retinoic acid (ATRA) therapy was initiated immediately, but the patient exhibited severe dyspnea. This subsequently resulted in circulatory and respiratory arrest, followed by death. Just after death, fluorescein-labelled proaerolysin (FLAER) revealed a paroxysmal nocturnal hemoglobinuria (PNH) monocyteclone of 82%, confirming the diagnosis of PNH. Leukemia can be derived from non-PNH clones in PNH patients. Catastrophic thromboembolic events that could not be controlled with aggressive anticoagulation in a profoundly thrombocytopenic patient without overt disseminated intravascular coagulation (DIC) may suggest co-existent PNH.Keywords: Leukemia, Promyelocytic, Acute, Hemoglobinuria, Paroxysmal

The present study aimed to compare the efficacy and safety of azacitidine and decitabine in patients with myelodysplastic syndrome (MDS). A total of 88 patients diagnosed with refractory anemia with excess blast (RAEB) treated with azacitidine (n=57) or decitabine (n=31) were evaluated. Comparisons between azacitidine and decitabine groups were performed in the whole cohort, and in a 1:1 propensity score-matched cohort in order to reduce the simple selection bias. Patients who received azacitidine or decitabine had comparable overall response rates in both the unmatched (49.1% vs. 64.5%, p=0.166) and the propensity-matched cohorts (52% vs. 68%, p=0.248). The cumulative incidence of AML transformation at one year was comparable between azacitidine and decitabine in the unmatched (24.0% vs. 31.3%, p=0.26) and in the propensity-matched cohorts (18.7% vs. 31.5%, p=0.11). There was no difference in terms of transfusion requirement, febrile neutropenia episodes or the need for antifungal use during the treatment cycles in the propensity-matched cohort. The median overall survival was 20.4 months for azacitidine and 16.8 months for decitabine (p=0.59). Finally, we found that at least a four-cycle treatment with any HMA was a favorable factor. In conclusion, both azacitidine and decitabine have similar efficacy and toxicity profiles in the treatment of MDS-RAEB.

WOS: 000392282500002, PubMed ID: 27095141, Objective: In this study, we aimed to investigate the efficacy and safety of azacitidine (AZA) in elderly patients with acute myeloid leukemia (AML), including patients with >30% bone marrow (BM) blasts. Materials and Methods: In this retrospective multicenter study, 130 patients of >= 60 years old who were ineligible for intensive chemotherapy or had progressed despite conventional treatment were included. Results: The median age was 73 years and 61.5% of patients had >30% BM blasts. Patients received AZA for a median of four cycles (range: 1-21). Initial overall response [including complete remission (CR)/CR with incomplete recovery/partial remission] was 36.2%. Hematologic improvement (HI) of any kind was documented in 37.7% of all patients. HI was also documented in 27.1% of patients who were unresponsive to treatment. Median overall survival (OS) was 18 months for responders and 12 months for nonresponders (p=0.005). In the unresponsive patient group, any HI improved OS compared to patients without any HI (median OS was 14 months versus 10 months, p=0.068). Eastern Cooperative Oncology Group performance status of = 5 courses), and any HI predicted better OS. Age, AML type, and BM blast percentage had no impact. Conclusion: We conclude that AZA is effective and well tolerated in elderly comorbid AML patients, irrespective of BM blast count, and HI should be considered a sufficient response to continue treatment with AZA.

Renal failure is a common manifestation of multiple myeloma (MM). Bortezomib is primarily metabolized by cytochrome p450 isoforms. It also has a cytochrome-independent metabolism by excretion through the bile and kidney. Based on our observations, we aimed to explore the efficacy and toxicity profiles of bortezomib in 56 patients with MM, 24 of which had moderate to severe renal failure. Overall response and complete response, as well as very good partial response rates, were comparable between patients with normal renal functions and renal impairment. The median overall survivals for patients with estimated glomerular filtration rates of

The combination of melphalan-prednisone-thalidomide (MPT) has been investigated in several clinical studies that differed significantly with regard to patient characteristics and treatment schedules. This prospective trial differs from previous melphalan-prednisone (MP) vs. MPT trials by treatment dosing, duration, routine anticoagulation, and permission for a crossover. Newly diagnosed patients with multiple myeloma (MM) (n=122) aged greater than 55 yr, not eligible for transplantation were randomized to receive 8 cycles of M (9 mg/m(2) /d) and P (60 mg/m(2) /d) for 4d every 6 wk (n=62) or MP and thalidomide (100 mg/d) continuously (n=60). Primary endpoint was treatment response and toxicities following 4 and 8 cycles of therapy. Secondary endpoints were disease-free (DFS) and overall survival (OS). Overall, MPT-treated patients were younger (median 69 yr vs. 72 yr; P=0.016) and had a higher incidence of renal impairment (RI, 19% vs. 7%, respectively; P=0.057). After 4 cycles of treatment (n=115), there were more partial responses or better in the MPT arm than in the MP arm (57.9% vs. 37.5%; P=0.030). However, DFS and OS were not significantly different between the arms after a median of 23 months follow-up (median OS 26.0 vs. 28.0 months, P=0.655; DFS 21.0 vs. 14.0 months, P=0.342, respectively). Crossover to MPT was required in 11 patients, 57% of whom responded to treatment. A higher rate of grade 3-4 infections was observed in the MPT arm compared with the MP arm (22.4% vs. 7.0%; P=0.033). However, none of these infections were associated with febrile neutropenia. Death within the first 3 months was observed more frequently in the MP arm (n=8, 14.0%) than in the MPT arm (n=2, 3.4%; P=0.053). Long-term discontinuation and dose reduction rates were also analyzed (MPT: 15.5% vs. MP: 5.3%; P=0.072). Although patients treated with MPT were relatively younger and had more frequent RI, better responses and less early mortality were observed in all age groups despite more frequent discontinuation.

Eltrombopag was used in patients with chronic primary immune thrombocytopenia (ITP) who did not tolerate or were refractory to two or more previous treatments. The primary aims of the study were to determine the efficacy and safety of long-term eltrombopag treatment. Data were extracted from medical chart records retrospectively. Platelet count of at least 50 000/μl at any time point during the treatment was defined as the 'response'. Median duration of eltrombopag treatment was 29 weeks (11-74). The number of patients who had a platelet count of at least 50 000/μl at any time point was 26 (83.9%). The response was achieved by the second week in most of the patients. Concomitant ITP medications were withdrawn in nine out of the 11 patients. Eltrombopag was discontinued in one patient due to sustained response despite discontinuation of the treatment. Age, sex, concomitant ITP treatments, and previous ITP treatment failures had no impact on the treatment response. The treatment was discontinued due to thrombosis in only four patients. Four patients experienced a minor bleeding event. Hepatotoxicity and all other adverse events were mild and manageable. Eltrombopag is effective, safe, and well tolerated in the long-term treatment of chronic ITP patients.

Background/Aim: Low-molecular-weight heparin (LMWH) has been shown to prolong survival among patients with solid tumors, but its role among myeloma patients is unknown. Patients: Data from the GIMEMA (Gruppo Italiano Malattie Ematologiche dellʼAdulto), Nordic and Turkish myeloma study groups comparing melphalan and prednisolone with (MPT, n: 404) or without thalidomide (MP, n: 393) are analyzed for effects of LMWH. Forty percent (159/394) of the patients on MPT and 7.4% (29/390) in the MP arm received LMWH. Results: Thalidomide improved response and progression-free survival (PFS). Regardless of thalidomide treatment, response rate was higher among those receiving LMWH vs. none vs. other anticoagulants (58.1 vs. 44.9 vs. 50.4%, p = 0.01). PFS was significantly longer (median 32 vs. 21 and 17 vs. 17 months, p = 0.004) only among international scoring system (ISS) I patients receiving MPT ± LMWH vs. MP ± LMWH. The group of MPT patients who also received LMWH had a better OS compared to those who did not [45 months, 95% confidence interval (CI) 27.7-62.3, vs. 32 months, 95% CI 26.1-37.9; p = 0.034]. When multivariate analysis was repeated in subgroups, thalidomide was no longer a significant factor (response, PFS) among those receiving LMWH. Conclusion: Addition of LMWH to MPT, in particular in patients with low ISS, suggests additive effects, but the results are limited by the retrospective design of our study.

Hepatobiliary tuberculosis is uncommon even in endemic countries. It is associated with a high mortality and is even diagnosed early in the disease course. Acute liver failure (ALF) caused by tuberculosis bacilli has been reported in only a few reports. All previous cases have been diagnosed by postmortem examination. Time to antituberculosis treatment is very critical. In case of suggestive findings on clinical and radiologic examination, antituberculosis treatment should be initiated immediately. Drug use can be a challenge in patients with ALF. However, as long as the other possible causes of ALF can be excluded and hepatotoxic drugs were avoided during the early course of treatment, such a highly fatal presentation of tuberculosis can be treated safely. Here, we report a case of acute liver failure as a presentation of miliary tuberculosis. He was treated successfully with antituberculosis treatment.

The human JAK2 gene is mainly targeted by two types of genetic lesions that play roles in the pathogenesis of hematologic malignancies: intragenic mutations and chromosomal translocations. Chromosomal translocations of JAK2 are typically associated with myeloid or lymphoid malignancies with an aggressive course and poor outcome. Here we report a t(9;22)(p24;q11.2) translocation, in a MDS patient and review results associated with BCR-JAK2 fusion reported in the literature.

BK-virus (BKV) is an important etiological agent for late-onset hemorrhagic cystitis (HC) in patients undergoing hematopoietic stem cell transplantation. Late-onset HC causes significant morbidity among these patients. Therapeutic approaches remain predominantly symptomatic. Several treatment options have been used with variable success rates. Cidofovir has the highest specificity against BKV; however, its lack of availability in the majority of countries, high costs and potential nephrotoxic effects limit its use. The present study reports three cases of severe and prolonged BKV-associated HC (BKHC). HC was resolved in all three of the patients using oral levofloxacin. Thus, levofloxacin may be an effective treatment modality for achieving complete clinical and molecular response in patients with refractory, severe BKHC.

The aim of the present study was to investigate the relationship between PSGL-1 expression in the bone marrow and the known prognostic factors for multiple myeloma disease, disease stage, and survival. D162 staining and the staining degree, with the other standard immunohistochemical stains, were shown to be beneficial in the diagnosis of multiple myeloma disease. However, the results did not provide information about the disease course. Background: Changes occur in adhesion molecules in the disease course of multiple myeloma. P-selectin glycoprotein ligand-1 (PSGL-1, CD162) works as the ligand of selectin-neutrophil adhesion molecules. The aim of the present study was to investigate the relationship between PSGL-1 expression in the bone marrow and the known prognostic factors for multiple myeloma disease, disease stage, and survival. Materials and Methods: This research included 63 patients with multiple myeloma (26 women [41.3%]; 37 men [58.7%]). The bone marrow biopsy samples obtained at disease diagnosis for each patient were stained immunohistochemically in terms of CD162 expression using standard diagnostic immunohistochemical staining methods. The laboratory results, CD162 expression, overall survival, demographic characteristics of the disease, and the relationship between CD162 expression and the disease stage were evaluated. Results: Among the 63 patients included in the present study, the survival rate was 82.3% for 1 year, 73.2% for 2 years, 63.4% for 3 years, 51.7% for 4 years, 40.3% for 5 years, and 33.6% for 6 and 7 years. A statistically significant difference was not detected between the CD162 staining ratio and disease survival (P ¼ .232). A statistically significant difference was not detected between the CD162 staining degree and survival rate (P ¼ .184). However, the overall survival of the patients with no CD162 expression in the bone marrow was lower than that for the patients whose CD162 was stained 1, 2, and 3 degrees (12.33 � 11.49, 28.65 � 31.44, 37.25 � 29.32, and 47.92 � 45.29 months, respectively; P < .001). Conclusion: In the present study, CD162 staining and the staining degree, with the other standard immunohistochemical stains, were shown to be beneficial in the diagnosis of multiple myeloma disease. However, the results did not provide information about the disease course. Studies of a larger number of patients to examine P-selectin and interleukin-6 levels are needed to investigate the disease course.

Myelodysplastic syndrome (MDS) is mainly a disease of elderly population. Chronic cytopenias, especially anemia, frailty comorbidities, and age may alter the physical status significantly. Only a few proportions of patients can achieve long-term cure. In particular, but not limited to patients with low risk MDS; palliative/supportive care is the mainstay of the treatment. Erythropoietin-stimulating agents (ESAs) and red blood cell transfusions are the treatment options for patients suffering from anemia. Except one study, ESA-responders had a better quality of life (QoL) in three studies. Hematologic improvements should be assesses by patient-reported outcomes (PROs) as well as objective measures. Validated PROs those were used to assess QOL in patients with MDS included Functional Assessment of Cancer Therapy- Anemia (FACT-An) and European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC-QLQ C30) questionnaires and a MDS-specific questionnaire, QoL-E. All patients with MDS were screened. Patients with low-risk MDS were included in the study. One physician completed FACT-An, Hematopoietic Stem Cell Transplantation-Comorbidity Index (HCT-CI), and G8 frailty questionnaires in all patients. Demographic data were collected from patients' chart records. A total of 66 patients were screened. Fourteen patients were excluded due to high-risk MDS or indefinite diagnosis. In one patient, informed consent could not be obtained. Finally, 51 patients were included in the study. Median age was 66 years old (interquartile range [IQR]: 55-77). Twenty-one out of 51 patients (41.2%) were male. Most prevalent MDS subtype was MDS-refractory anemia (47%). All patients had very-low/low (86.3%) or intermediate-risk (13.7%) MDS according to age-adjusted IPSS-R (IPSS-RA). Median time from the diagnosis of MDS was 113 (IQR: 53-170) weeks. Twenty-eight patients (54.9%) were transfusion-dependent. Ten patients had a high transfusion burden, which was defined as transfusion requirement ≥4 units (U) over 8 weeks. Median transfusion duration was 112 (IQR: 31-173) weeks for transfusion-dependent patients. Median red blood cell transfusion during eight weeks was 1.5 (IQR: 0-4.5) U. Median hemoglobin concentration was 10.0 (7.9-11.3) g/dL for all patients. A total of nineteen patients (37.3%) were ESA-user/responder. Most of the patients (80.4%) had a low ( In univariate analyses, older age (β: -0.740, 95% CI: -1.138; -0.341, p Multivariate analyses revealed that age (β: -0.738, %95 GA: -1.101; -0.374, p Model stability was tested in 5000 bootstrap replicates of dataset. Age and being ESA-user/responder were included in 40.6% and 38.2% of all models (Table 1). These data indicates that age and ESA use are independent parameters of QoL in low-risk MDS. Impact of ESA use on QoL is independent from the hemoglobin level. Disclosures No relevant conflicts of interest to declare.

The combination of melphalan-prednisone-thalidomide (MPT) has been investigated in several clinical studies that differed significantly with regard to patient characteristics and treatment schedules. This prospective trial differs from previous melphalan-prednisone (MP) vs. MPT trials by treatment dosing, duration, routine anticoagulation, and permission for a crossover. Newly diagnosed patients with multiple myeloma (MM) (n=122) aged greater than 55 yr, not eligible for transplantation were randomized to receive 8 cycles of M (9 mg/m(2) /d) and P (60 mg/m(2) /d) for 4d every 6 wk (n=62) or MP and thalidomide (100 mg/d) continuously (n=60). Primary endpoint was treatment response and toxicities following 4 and 8 cycles of therapy. Secondary endpoints were disease-free (DFS) and overall survival (OS). Overall, MPT-treated patients were younger (median 69 yr vs. 72 yr; P=0.016) and had a higher incidence of renal impairment (RI, 19% vs. 7%, respectively; P=0.057). After 4 cycles of treatment (n=115), there were more partial responses or better in the MPT arm than in the MP arm (57.9% vs. 37.5%; P=0.030). However, DFS and OS were not significantly different between the arms after a median of 23 months follow-up (median OS 26.0 vs. 28.0 months, P=0.655; DFS 21.0 vs. 14.0 months, P=0.342, respectively). Crossover to MPT was required in 11 patients, 57% of whom responded to treatment. A higher rate of grade 3-4 infections was observed in the MPT arm compared with the MP arm (22.4% vs. 7.0%; P=0.033). However, none of these infections were associated with febrile neutropenia. Death within the first 3 months was observed more frequently in the MP arm (n=8, 14.0%) than in the MPT arm (n=2, 3.4%; P=0.053). Long-term discontinuation and dose reduction rates were also analyzed (MPT: 15.5% vs. MP: 5.3%; P=0.072). Although patients treated with MPT were relatively younger and had more frequent RI, better responses and less early mortality were observed in all age groups despite more frequent discontinuation.

Precursor B cell lymphoblastic lymphoma (B-LBL) is quite uncommon and it usually manifests as an extranodal disease. Although B-LBL may present with bone involvement, it is a very rare manifestation of B-LBL as a primary solitary bone tumor. Here, we report a case of precursor B-LBL presenting with solitary bone tumor and a review of a total of seven adult patients reported previously in the literature. We described demographic and clinical characteristics of these patients with unique presentation and discussed treatment options. Unlike previous reports except one case, our patient underwent allogeneic stem cell transplantation (allo-SCT) due to refractory disease. She is alive without evidence of disease by the post-transplant 12th month. B-LBL has an aggressive clinical course in adult patients and allo-SCT may be the best treatment option.

Protein Z (PZ) was found to be associated with pregnancy complications. There are no data implying an association between hemolysis (H), elevated liver enzymes (EL), and low platelet counts (LP) (HELLP) syndrome and changes in plasma levels of PZ. The aim of this study is to investigate whether HELLP syndrome is associated with plasma concentrations of PZ. Protein Z levels in 29 women with HELLP syndrome were compared with 29 healthy, nulliparous and 25 normal pregnant women. The median PZ levels in patients with HELLP syndrome were found to be significantly lower than those of pregnant women. No significant difference was found between HELLP and healthy groups. Protein Z levels correlated with platelet counts, lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) levels in patients with HELLP syndrome. Median PZ level was higher in partial HELLP than in complete HELLP. We calculated 1330 ng/mL as a cutoff value for PZ level to discriminate HELLP syndrome from normal pregnancy. Low PZ levels are associated with the pathobiology of HELLP syndrome.

A patient with idiopathic myelofibrosis with nephrotic syndrome is reported. Seven months after the initial diagnosis of myelofibrosis, the patient was presented with dyspnea, generalized edema, heavy proteinuria, massive pleural effusion, and ascites. Renal biopsy showed focal segmental glomerulosclerosis. After starting immunosuppressive therapy consisting of cyclosporine and steroids, his renal function and proteinuria improved and transfusion requirements decreased.

Fifty-seven adult patients with idiopathic thrombocytopenic purpura (ITP) were treated with either conventional-dose prednisolone (CDP) (1 mg/kg/d, 36 patients) or high-dose methylprednisolone (HDP) (30 mg/kg/d, 21 patients), as first-line treatment. Patients in the HDP arm responded more rapidly (4.7 v 8.4 d), with a higher response rate (80% v 52.7%), and without severe side-effects. One quarter of the patients (3/12) who were non-responsive to CDP achieved complete remission when they were treated with HDP. The findings suggest that HDP may be a more effective first-line treatment than CDP for adult ITP, and it may also be preferred for life-threatening cases of ITP. However, these results must be confirmed by a randomized study prior to any change in the current practice of employing CDP as first-line treatment for adult ITP.

Imatinib mesylate is the standard treatment of chronic myeloid leukemia (CML). Despite imatinib is being used in the treatment of other malignancies as well, its potential role on de novo tumor growth is not known. Secondary malignancies are rarely seen in patients with CML and particularly in those receiving imatinib. Here, we present a CML patient taking imatinib therapy that was diagnosed to have breast cancer and received adjuvant chemo-and radiotherapy with imatinib. We tried to explain co-occurrence of these rare events by probable pathogenetic mechanisms.

Abstract 3970 Background and aim: The anti metastatic effects of heparin have been known for many decades. Such effects are dependent on the protease activated receptor expression (PAR-1 and/or CD24) by the cancer cells. The genes controlling PARs are located on chromosome 5q13. Recurrent amplification of chromosome 5q and 5p have been shown to increase survival (Avet-Loiseau H et al 2009 and Tapper W et al 2011) in myeloma. Low molecular weight heparin (LMWH) either for prophylaxis or treatment of venous thromboembolism, is frequently used in the treatment of myeloma. With an aim to separate the effect of heparin from the response achieved following Melphalan and Prednisolone (MP) plus Thalidomide, this study was initiated. Patients and methods: Individual data on 797 patients who were randomized to MP(n:393) or MPT(n:404) and published by the GIMEMA, Nordic, and the Turkish Myeloma Groups were analyzed using the SPSS 15.0 windows version. Except for the Nordic trial, LMWH was given as routine for the MPT patients. Patients who received anticoagulation as routine or following a thrombotic event were assigned to the LMWH group. Response equal to and more than partial response was included in the analysis. Comparisons were made using the Chi-Square or Mann Whitney U tests. Assessment of risk factors for response was done by the Backward- Stepwise Logistic Regression analysis. Survival analysis was performed using the Kaplan-Meier test. Results: Treatment groups (MP vs MPT) were well balanced according to prognostic factors. LMWH was given as prophylaxis (n:124, n:4) or as treatment (n: 38, n:16) in the MPT and MP groups respectively. Patients who received LMWH in the MP group exerted similar characteristics to MP patients, but more patients in the MPT+LMWH group had advanced ISS (p=0.007) compared to MPT patients. Response (≥ PR) was observed more frequently among the patients who received MP and LMWH than those who did not receive LMWH (38.4 % vs 70.6%,p=0.022). Similar effect was not observed in the MPT group. Within the MP and MPT groups responders had lower b2mg (3.8 vs 4.2, p=0.068 and 3.9 vs 4.5, p=0.028). Higher s-albumin (3.7 vs 3.4, p=0.002) was associated with better response only in the MP group. When age, creatinine, b2mg, ISS, gender, and anticoagulation were introduced into the logistic regression model including all patients, LMWH (odds ratio (OR): 1.948, 95 % CI: 1.319–2.877,p=0.001) and b2mg (OR:0.956, 95% CI:0.925–0.988, p=0.007) were found to be independent risk factors. Logistic regression performed for MP or MPT groups revealed LMWH to be significant in the MP arm (OR: 4.168, 95% CI: 1.288–13.492, p=0.017) but not in the MPT arm (OR:1.031, 95% CI: 0.61–1.745, p=0.908). Within the MPT arm, creatinine (>2 mg/dL)(OR:0.453,95 %CI: 0.218–0.939,p=0.033) and advanced ISS (OR:0.764,95% CI:0.562–1.038,p=0.085) were additional risk factors. Survival was extended when LMWH was introduced to patients who were in the MPT group (p=0.046). Conclusion: In this study, based on individual data from three large randomized trials comparing MPT and MP, we found the addition of LMWH to be significantly associated with a better response in MP patients and improved survival in MPT patients. Although the cytogenetic and molecular profile of the patients are unknown and this is a retrospective analysis, improvement of response and survival following introduction of LMWH to the MP or MPT treatment suggests an anti-myeloma activity of LMWH. Disclosures: Beksac: Janssen Cilag: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau. Waage:Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Membership on an entity's Board of Directors or advisory committees. Bringhen:Celgene: Honoraria; Janssen-Cilag: Honoraria; Novartis: Honoraria; Merck Sharp & Dhome: Membership on an entity's Board of Directors or advisory committees. Gimsing:janssen Cilag: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Membership on an entity's Board of Directors or advisory committees. Juliusson:Merck Serono: Membership on an entity's Board of Directors or advisory committees. Palumbo:celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria; Amgen: Honoraria.