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Aim: To compare alpha/beta T-cell depletion with posttransplant Cyclophosphamide (PTCy) in haploidentical allogeneic transplantation in adult hematological patients, this is the first study. Method: In our study, we reported 36 haploidentical allogeneic stem cell transplants which were performed in our clinic. Results: Twenty-six of these haploidentical transplants received standard treatment and transplanted either with PTCy (n=21, 81%) or with alpha/beta T-cell depletion (n=5, 19%). Less CD34+ stem cells were administered in the T-cell depletion group. When the two groups were compared in terms of survival, no difference was found in relapse-free and overall survival in each group. Acute GVHD cases developed in the PTCy group mostly developed after CMV infection, whereas acute GVHD did not develop in the T-cell depletion group. In the PTCy group, 8 cases developed graft failure and relapse; 4 cases developed graft failure or relapse in the T-cell depletion group, and 2 of them developed graft failure or relapse following EBV infection and 1 of them following CMV infection. Conclusion: We have a small number of patients in the T cell depletion group. Due to our long follow-up period, we believe that our patients with T cell depletion can be compared with those who underwent PTCy, and similar survival results can be achieved in adult patients having hematologic malignancies.

Extracellular RNAs (exRNAs) are actively secreted from cells in membrane-bound extracellular vesicles (EVs). Diverse classes of RNAs are secreted as exRNAs, including messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and transposable element RNAs (TE RNAs). However, the full composition and clinical utility of exRNAs secreted in response to oncogenic signaling are unknown. Here we use both affinity- and nanofiltration-based EV isolation approaches to show that mutant KRAS(G12C) signaling results in the secretion of specific lncRNAs, TE RNAs, and mRNAs, some of which are prognostic for lung adenocarcinoma (LUAD) patient survival. We found that inhibition of KRAS(G12C) signaling broadly reprograms the noncoding transcriptome, as evidenced by a substantial increase in TE RNA secretion. KRAS(G12C) inhibition also increased the abundance of secreted lncRNAs and retained intron-containing transcripts, while decreasing the mRNA content of EVs. Oncogenic KRAS(G12C) signaling was required for the secretion of mRNAs from a set of 20 genes that are significantly associated with unfavorable clinical outcomes in LUAD. Our study suggests that both coding and noncoding RNAs that are secreted in EVs may serve as KRAS(G12C)-specific signatures for diagnosing lung cancer.

Background Multiple myeloma (MM), characterized by extensive genomic instability and aberrant DNA damage repair, is a plasma cell malignancy due to the excessive proliferation of monoclonal antibody-producing plasma cells in the bone marrow. Despite the signifcant improvement in the survival of patients with the development of novel therapeutic agents, MM remains an incurable disease. Werner (WRN) helicase, a member of the RecQ helicase family that contributes to DNA replication, recombination, and repair, has been highlighted in cancer cell survival, yet the role and mechanism of WRN in MM remain unclear. Methods and results Increased mRNA expression of WRN in newly diagnosed and relapsed CD138+myeloma plasma cells than normal CD138+plasma cells and their matched CD138−non-tumorigenic cells were detected by qPCR. Using NSC19630, a specifc WRN helicase inhibitor, we further showed decreased cell viability, proliferation, and DNA repair and increased DNA damage and apoptosis in MM cells by MTT assay, cell cycle assay, apoptosis assay, and Western blotting. Conclusions The results of the present study demonstrate that WRN is essential in MM cell viability, proliferation, and genomic stability, indicating its inhibition may enhance the efcacy of chemotherapy in MM.

RAS genes are the most frequently mutated oncogenes in cancer, yet the effects of oncogenic RAS signaling on the noncoding transcriptome remain unclear. We analyzed the transcriptomes of human airway and bronchial epithelial cells transformed with mutant KRAS to define the landscape of KRAS-regulated noncoding RNAs. We find that oncogenic KRAS signaling upregulates noncoding transcripts throughout the genome, many of which arise from transposable elements (TEs). These TE RNAs exhibit differential expression, are preferentially released in extracellular vesicles, and are regulated by KRAB zinc-finger (KZNF) genes, which are broadly downregulated in mutant KRAS cells and lung adenocarcinomas in vivo. Moreover, mutant KRAS induces an intrinsic IFN-stimulated gene (ISG) signature that is often seen across many different cancers. Our results indicate that mutant KRAS remodels the repetitive noncoding transcriptome, demonstrating the broad scope of intracellular and extracellular RNAs regulated by this oncogenic signaling pathway.

Aim: The best treatment for patient with end stage kidney disease is kidney transplantation which improve their quality of life and survival rate. The aim of our study is to determine the factors that affect the results of early outcomes of graft function. Method: Twenty-eight adult patients who underwent renal transplantation from 2016 to 2017 were included in our university. Results: The median age of the recipients was 38.5 (range: 19-65) and 68% (19 patients) were male. Acute rejection was detected in 8 patients. Patients who developed rejection were found to have higher panel reactive antibody positivity and higher parathyroid hormone levels. Panel reactive antibody positivity was found to be 25% in patients who developed rejection and 0% in patients who did not develop rejection (p = 0.02). The parathyroid hormone level was calculated as 963.2 ± 587 in the rejection group and 378 ± 227 in the rejection group (p = 0.003). It was observed that 37.5% of DM patients had rejection and 10% in non-diabetic patients. The difference was statistically significant (p = 0.08). Conclusion: Panel reactive antibody positivity and parathyroid hormone levels increased the likelihood of rejection. The effect of the presence of diabetes mellitus in the patient on the development of rejection was observed to be limited. Our findings were consistent with the literature. Because of the number of patients and the short follow-up period, further studies are needed.

Any erythrocyte transfusion among humans having type A or B blood groups is impossible due to antibodies causing fatal transfusion complications. A cross-match test is performed to prevent immune transfusion complications before transfusion. Our hypothesis is that the fragment antibody (Fab) part of the antibody (incomplete antibody) may be used to prevent an immune stimulus related to the complete antibody. Therefore, we designed a pilot study to evaluate the effectiveness of these incomplete antibodies using cross-match tests.Pepsin enzyme and staphylococcal protein A columns were used to cut anti-A and anti-B monoclonal antibodies and purify their Fab (2) fragments, respectively. An Rh-positive erythrocyte suspension with purified anti-A Fab (2) solution and B Rh-positive erythrocyte suspension with purified anti-B Fab (2) solution were combined correspondingly. Cross-match tests were performed by tube and gel centrifugation methods. The agglutination levels due to the anti-A and anti-B Fab (2) antibodies and their effects on the agglutination normally observed with complete antibodies were then measured.No agglutination for the purified incomplete anti-A Fab (2) with A Rh+ erythrocyte and anti-B Fab (2) with B Rh+ erythrocyte combinations was observed in the tube cross-match tests. These agglutination levels were 1+ in two wells in the gel centrifugation cross-match tests. Fab (2)-treated erythrocytes were also resistant to the agglutination that normally occurs with complete antibodies.We determined that the Fab (2) fragments of antibodies may not only be used to obtain a mild or negative reaction when compared to complete antibodies, but they might also be used for decreasing ABO incompatibility. Incomplete antibodies might be a therapeutic option in autoimmune hemolytic anemia and they may also be used in solid organ or hematopoietic stem cell transplantation. Therefore, we have planned an in vivo study to prove these in vitro findings.Amaç: Tip A ve B kan grubuna sahip insanlar arasında herhangi bir eritrosit nakli öldürücü transfüzyon komplikasyonlarına neden olan antikorlar nedeniyle imkansızdır. İmmün transfüzyon komplikasyonlarını önlemek için transfüzyondan önce çapraz karşılaştırma testi yapılır. Hipotezimiz komplet antikorla ilişkili bağışıklık yanıtını önlemekte antikorun fragman antikor (Fab) parçasının (inkomplet antikor) kullanılabileceğidir. Bu inkomplet antikorların etkinliğini değerlendirmek için de çapraz karşılaştırma testlerini kullanarak bir başlangıç çalışması tasarladık. Gereç ve Yöntemler: Anti-A ve anti-B monoklonal antikorlarını kesmek ve saflaştırmak için sırasıyla pepsin enzimi ve stafilokokal protein A kolonları kullanıldı. A Rh pozitif eritrosit süspansiyonu ile saflaştırılmış anti-A Fab (2) solüsyonu ve B Rh pozitif eritrosit süspansiyonu ile saflaştırılmış anti-B Fab (2) solüsyonu sırasıyla birleştirildi. Çapraz karşılaştırma testleri tüp ve jel santrifügasyon yöntemleri kullanılarak çalışıldı. Sonrasında anti-A ve anti-B Fab (2) antikorlara bağlı aglütinasyon düzeyi ve bunların komplet antikorlarla normalde gözlenen aglütinasyon üzerine etkileri ölçüldü. Bulgular: Tüp yöntemi ile yapılan çapraz karşılaştırma testinde saflaştırılmış inkomplet anti-A Fab (2) ile A Rh pozitif eritrosit ve anti-B Fab (2) ile B Rh pozitif eritrosit kombinasyonlarında aglütinasyon gözlenmedi. Jel santrifügasyon yöntemi ile yapılan çarpraz karşılaştırma testinde bu aglütinasyon düzeyleri her iki kuyucukta da 1 pozitifti. Fab (2) ile muamele edilen eritrositler komplet antikorla normalde oluşan aglütinasyona da dirençliydiler. Sonuç: Antikorların Fab (2) fragmanlarının sadece komplet antikorlara kıyasla daha hafif veya negatif reaksiyonu elde etmekte değil, aynı zamanda ABO uyumsuzluğunu azaltmakta da kullanılabileceğini değerlendirdik. İnkomplet antikorlar otoimmün hemolitik anemide bir tedavi seçeneği olabileceği gibi aynı zamanda solid organ veya hematopoeitik kök hücre naklinde kullanılabilir. Bu nedenle in vitro bulguları doğrulamak için in vivo bir çalışma planladık.

Tyrosine kinase inhibitors (TKIs) have changed the indications for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia (CML). Therefore, we aimed to evaluate the effect of TKIs on allo-HSCT in CML.In this quasi-experimental study, we compared patient, disease, and transplantation characteristics as well as allo-HSCT outcomes between the pre-TKI era (before 2002) and the post-TKI era (2002 and later) in patients with CML. A total of 193 allo-HSCTs were performed between 1989 and 2012.Patients in the post-TKI era had more advanced disease (chronic phase 1) at the time of transplant and more frequently received reduced-intensity conditioning compared to patients in the pre-TKI era. Relapse/progression occurred more frequently in the year ≥2002 group than in the year2002 group (48% vs. 32% at 5 years, p=0.01); however, overall survival (OS) was similar in these two groups (5-year survival was 50.8% vs. 59.5%, respectively; p=0.3). TKIs (with donor lymphocyte infusions or alone) for treatment of relapse after allo-HSCT were available in the post-TKI era and were associated with improved OS. While the rates of hematologic remission at 3 months after allo-HSCT were similar between TKI eras, patients having remission had better disease-free survival (DFS) [relative risk (RR): 0.15, confidence interval (CI) 95%: 0.09-0.24, p0.001] and OS (RR: 0.14, CI 95%: 0.09-0.23, p0.001). Male allo-HSCT recipients had worse DFS (RR: 1.7, CI 95%: 1.2-2.5, p=0.007) and OS (RR: 1.7, CI 95%: 1.1-2.6, p=0.02) than females.TKIs are an effective option for the treatment of relapse after allo-HSCT in CML. Hematologic remission after allo-HSCT is also an important factor for survival in CML patients.Amaç: Tirozin kinaz inhibitörleri (TKİ) kronik myeloid lösemide (KML) allojenik hematopoetik kök hücre nakli (AHKHN) endikasyonlarını değiştirdi. Bu nedenle de biz KML’de TKİ’nin AHKHN üzerine etkisini değerlendirmeyi amaçladık. Gereç ve Yöntemler: Bu öncesi-sonrası çalışmasında KML’li hastalarda TKİ öncesi dönem (yıl2002) ve TKİ sonrası dönem (yıl ≥2002) arasında hasta, hastalık ve nakil karakteristikleri ile AHKHN sonuçlarını kıyasladık. Toplamda 193 AHKHN, 1989 ve 2012 arasında yapıldı. Bulgular: TKİ sonrası dönemdeki hastalar, TKİ öncesi döneme göre nakil sırasında daha ileri hastalığa (kronik faz 1’den ileri) sahipti ve daha sık azaltılmış yoğunluklu hazırlık rejimi aldı. Relaps/progresyon ≥2002 grupta2002 grubundan daha fazlaydı (5 yıllık %32’ye karşın %48; p=0,01); bununla birlikte toplam sağkalım (TS) bu iki grupta benzerdi (5-yıllık-sağkalım sırasıyla %50,8’e karşın %59,5; p=0,3). TKİ tedavisi (verici lenfosit infüzyonu ile birlikte veya tek başına) AHKHN sonrası relaps tedavisinde TKİ sonrası dönemde mevcuttu ve artmış TS ile ilişkiliydi. AHKHN sonrası 3. aydaki hematolojik remisyon oranları TKİ dönemleri arasında benzer iken; remisyonda olan hastalar daha iyi hastalıksız sağkalıma (HsS) [Göreceli risk (GR): 0,15; %95 güven aralığı (GA): 0,09-0,24; p0,001] ve TS’ye sahipti (GR: 0,14; %95 GA: 0,09-0,23; p0,001). Erkek AHKHN alıcılarının HsS (GR: 1,7; %95 GA: 1,2-2,5; p=0,007) ve TS’leri (GR: 1,7; %95 GA: 1,1-2,6; p=0,02) kadınlardan daha kötüydü. Sonuç: TKİ, KML’de AHKHN sonrası relapsın tedavisinde etkin bir seçenektir. AHKHN sonrası hematolojik remisyon da KML hastalarında sağkalımda önemli bir faktördür.

Introduction: Bendamustine is a synthetic alkylating agent made of both mustard and benzimidazole groups. It is used mainly in myeloma patients who have run out of classical treatment options and yet, have eligible performance status. Although data is still accumulating, there is not enough information to recommend a certain standard bendamustine dose or regimen in multiple myeloma. Melflufen is also an alkylator that is activated once metabolized by peptidases [1]. The logic this molecule selects and exterminates myeloma tumor cells by is that, myeloma cells overexpress aminopeptidases. Here, we have compared our and published bendamustine combination with melfufen data. Methods: We retrospectively analyzed our relapsed or refractory multiple myeloma patients who received bendamustine between 2002 and 2020 at Ankara University Medical School. All statistical analyses were performed via SPSS statistics version 20.0 software. After Pubmed search, all published bendamustine combination and melflufen clinical data among relapse refractory myeloma patients were included in the analysis. Results: Female/ male ratio was 14/ 18 (43.7 % / 56.3 %). Median age was 62 (36- 77) years. 22 (68.7 %) patients had Ig G myeloma, 6 (18.7 %) had Ig A myeloma and 4 (12.6 %) had light chain myeloma. ISS scores were as follows: I/ II/ III: 8 (25 %)/ 17 (53.1 %)/ 7 (21.9 %). FISH defined cytogenetics were available for 18 patients; 8 of them had normal chromosome analysis, 3 had only del13q, 1 had tri7. High risk cytogenetics was observed among 6 (33.3 %). R-ISS scores were as follows: I/ II/ III: 4 (22.2 %)/ 12 (66.7 %)/ 2 (11.1 %). Median prior lines of therapy was 3 (1- 6). 30 (93.8 %) patients had a history of bortezomib, 21 (65.6 %) had lenalidomide, 9 (28.1 %) had thalidomide. 21 (65.6 %) patients had undergone high-dose chemotherapy supported by autologous stem cell transplantation before bendamustine. 15 (46.9 %) patients were in treatment- refractory status at bendamustin initiation while 17 (53.1 %) used it for disease progression. Bendamustin was given either with Dexa (n= 13, 40.6 %) Bortezomib+ Dexa (n=6, 18.8 %), Lenalidomide+ Dexa (n=6, 18.8 %), Pomalidomide+ Dexa (n=5, 15.6 %) or Thalidomide+ Dexa (n= 2, 6.3 %). Bendamustine dose was 100- 120 mg/ m2/ day, 2 days monthly. 32 patients were followed up for median 26 months. Response to bendamustine treatment were as follows: Complete remission 4 (12.5 %), very good partial response 12 (37.5 %), partial response 8 (25 %), unresponsive 8 (25 %). Median progression free survival (PFS) was 5.6 (1- 40.6) months and overall survival (OS) was 17.3 (2- 79) months with bendamustine based treatment protocols. 15 (46.9 %) patients suffered grade ≥3 myelosuppression. Febrile neutropenia was experienced by 7 (21.9 %) patients, and 6 (18.7 %) had CMV reactivation during bendamustine treatment. There was no drug related mortality. Conclusion: Although bendamustine is effective among highly refractory myeloma patients, toxicity profile and immune plus myelosuppression prevents long term use. Bendamustine in our experience in combination has provided efficacy comparable to earlier publications. Current single agent Melflufen data in advanced stages may be even more promising if combined with proteasome inhibitors or IMIDs. References 1. Richardson, P.G., et al., Melflufen plus dexamethasone in relapsed and refractory multiple myeloma (O-12-M1): a multicentre, international, open-label, phase 1-2 study. The Lancet Haematology, 2020. 2. Knop, S., et al., The efficacy and toxicity of bendamustine in recurrent multiple myeloma after high-dose chemotherapy. haematologica, 2005. 90(9): p. 1287-1288. 3. Grey-Davies, E., et al., Bendamustine, thalidomide and dexamethasone is an effective salvage regimen for advanced stage multiple myeloma. British journal of haematology, 2012. 156(4): p. 552-555. 4. Damaj, G., et al., Efficacy of bendamustine in relapsed/refractory myeloma patients: results from the French compassionate use program. Leukemia & lymphoma, 2012. 53(4): p. 632-634. 5. Ludwig, H., et al., Bendamustine-bortezomib-dexamethasone is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma. Blood, The Journal of the American Society of Hematology, 2014. 123(7): p. 985-991. Disclosures Ozcan: Abdi Ibrahim: Other; Archigen Biotech: Research Funding; Amgen: Honoraria, Other: Travel support; Bristol Myers Squibb: Other: Travel support; Jazz Pharmaceuticals: Other; Sanofi: Other; F. Hoffmann-La Roche Ltd: Other: Travel support, Research Funding; Celgene: Research Funding; MSD: Research Funding; Janssen: Other: Travel support, Research Funding; AbbVie: Other: Travel support, Research Funding; Bayer: Research Funding; Takeda: Honoraria, Other: Travel support, Research Funding.

Purpose: Peripheral stem cell transplantation is used as a life-saving therapeutic option in hematological malignancies. As previously established, most hematological malignancies are seen in the elderly population. Therefore, possible HLA-identical sibling donors of elderly patients are generally of an advanced age. In this study, we aimed to evaluate the effect of old age on stem cell mobilization and quality in older adult healthy sibling donors. Materials and Methods: Between 2006 and 2014, we evaluated 38 healthy donors aged ≥55 years. The granulocyte-colony stimulating factor (G-CSF) analogs were used at a dose of 5 µg/kg/day and administered subcutaneously twice a day for five days. CD34+ cells were estimated in the peripheral blood before collection of the apheresis product. The National Marrow Donor Program selects healthy unrelated donors if they are younger than 60 years. Therefore, we compared the product quality in donors over the age of 60 to that in donors aged 60 years or less. Results: We collected sufficient products from all the donors with one to three apheresis procedures. No serious complication was detected in all donors. Reaching the target CD34+ cell count in one day were detected in 83% of younger and 79% of older donors (P = NS). Collected CD34+ cells x10e6/recipient body weight (kg) was same and 5.1 in the groups (P = NS). There were no correlation between the donor age and these parameters. Conclusion: Healthy donor apheresis in older adults can be performed effectively and possible donors should be evaluated regardless of their age. J. Clin. Apheresis 32:16–20, 2017. © 2016 Wiley Periodicals, Inc.

The increased risk of infection for patients caused by construction and renovation near hematology inpatient clinics is a major concern. The use of high-efficiency particulate absorption (HEPA) filters can reduce the risk of infection. However, there is no standard protocol indicating the use of HEPA filters for patients with hematological malignancies, except for those who have undergone allogeneic hematopoietic stem cell transplantation. This quasi-experimental study was designed to measure the efficacy of HEPA filters in preventing infections during construction.Portable HEPA filters were placed in the rooms of patients undergoing treatment for hematological malignancies because of large-scale construction taking place near the hematology clinic. The rates of infection during the 6 months before and after the installation of the portable HEPA filters were compared. A total of 413 patients were treated during this 1-year period.There were no significant differences in the antifungal prophylaxis and treatment regimens between the groups. The rates of infections, clinically documented infections, and invasive fungal infections decreased in all of the patients following the installation of the HEPA filters. When analyzed separately, the rates of invasive fungal infections were similar before and after the installation of HEPA filters in patients who had no neutropenia or long neutropenia duration. HEPA filters were significantly protective against infection when installed in the rooms of patients with acute lymphocytic leukemia, patients who were undergoing consolidation treatment, and patients who were neutropenic for 1-14 days.Despite the advent of construction and the summer season, during which environmental Aspergillus contamination is more prevalent, no patient or patient subgroup experienced an increase in fungal infections following the installation of HEPA filters. The protective effect of HEPA filters against infection was more pronounced in patients with acute lymphocytic leukemia, patients undergoing consolidation therapy, and patients with moderate neutropenia.Amaç: Hematoloji yatan hasta kliniklerinin yakınındaki inşaat ve tamiratların neden olduğu, hastalardaki artmış enfeksiyon riski büyük bir endişe kaynağıdır. Yüksek etkinlikte partikül emici (YEPE) filtrelerin kullanımı enfeksiyon riskini azaltabilir. Bununla birlikte allojenik hematopoetik kök hücre nakli yapılanlar dışında, YEPE filtrelerin hematolojik malignite hastalarında kullanımı konusunda standart bir öneri yoktur. Bu öncesi sonrası çalışma inşaat esnasında enfeksiyonların engellenmesinde YEPE filtrelerin etkinliğini ölçmek için kurgulandı. Gereç ve Yöntemler: Hematoloji kliniğinin yanında meydana gelen geniş çaplı bir inşaat nedeniyle hematolojik tümörlerin tedavisinin yapıldığı hasta odalarına portabl YEPE filtreler yerleştirildi. Portabl YEPE filtrelerin yerleştirilmesinden önceki ve sonraki 6 aydaki enfeksiyon oranları karşılaştırıldı. Bu 1 yıllık dönemde toplam 413 hasta tedavi edildi. Bulgular: Gruplar arasında antifungal profilaksi ve tedavi rejimleri açısından farklılık yoktu. YEPE filtrelerin yerleştirilmesini takiben tüm hastalarda enfeksiyon, klinik gösterilmiş enfeksiyon ve invaziv fungal enfeksiyon oranları azaldı. Ayrı ayrı analiz edildiğinde ise YEPE filtre yerleştirilmesi sonrası ve öncesi invaziv fungal enfeksiyon oranları nötropenisi olmayan veya uzun nötropeni süresi olan hastalarda benzerdi. Akut lenfoblastik lösemi hastalarının, konsolidasyon tedavisi alan hastaların ve 1 ile 14 gün arasında nötropenik kalan hastaların odalarına yerleştirilen YEPE filtreler enfeksiyonlara karşı belirgin bir şekilde koruyucuydu. Sonuç: Çevresel Aspergillus kontaminasyonunun daha sık olduğu yaz sezonuna ve ortaya çıkan inşaata rağmen, YEPE filtrelerin yerleştirilmesi sonrası dönemde ne hastalarda ne de hasta alt gruplarında fungal enfeksiyonlarda artış gözlenmedi. YEPE filtrelerin enfeksiyonlara karşı koruyucu etkisi akut lenfoblastik lösemi hastalarında, konsolidasyon tedavisi alan hastalarda ve orta derecede nötropenisi olanlarda daha belirgindi.

Although there is currently no consensus regarding the treatment of steroid-refractory acute graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation (HSCT), antithymocyte globulin (ATG) is one of the most widely used immunosuppressive drugs in this setting. We retrospectively summarized our transplant center’s experience with 35 steroid-resistant acute GvHD patients who were treated with three different ATG preparations. Severe (grade III-IV) acute GvHD was observed either during the posttransplantation period (n= 32) or after donor lymphocyte infusion (n= 3). For secondary treatment of acute GvHD, rabbit Jurkat cell linereactive ATG (ATG Fresenius®) (n= 22), rabbit thymus cell-reactive ATG (Thymoglobulin®) (n= 9) or equine antilymphocyte globulin (ALG) (Lymphoglobulin®) (n= 4) was administered at a dose of 2-10 mg/kg/day for five consecutive days. The median time from the diagnosis of acute GvHD to the first day of infusion of ATG or ALG was 15 days (3-70 days). An overall response was observed in 15 patients (42%), with similar response rates among patients treated with any of the three ATG preparations. The overall survival (OS) of the patients did not increase in any treatment group, though the severity of GvHD and the disease status before HSCT were shown to negatively impact OS. Although responses could be achieved in steroid-refractory acute GvHD using rabbit or horse ATG, survival rates did not increase because of high mortality rates due to infection during treatment.

Background Haemorrhagic cystitis (HC) is usually a serious complication in allogeneic haematopoietic stem cell transplantation (allo-HSCT) recipients. In this study, our aim was to define risk factors and outcomes for patients with HC in an allo-HSCT setting. Methods We retrospectively evaluated 249 allo-HSCTs performed between 2011 and 2016 in our centre. Results HC was diagnosed in 98 patients (39%) at a median of 119 days (range 5–580) and 91 (93%) of the patients had late onset disease. In univariate analysis, HC was related to cytomegalovirus (CMV) reactivation ( PConclusions This study suggests that CMV reactivation is associated with increased risk of HC in multivariate analysis, however, this result is not confirmed in patients with HC grade II and beyond.

Optimal duration of adjuvant trastuzumab therapy in early-stage HER2-positive, lymph node-negative breast cancer is unknown. To establish this, we compared 1-year and 9-week trastuzumab regimens in HER2-positive, lymph node-negative early-stage breast cancer patients.We retrospectively analyzed 4374 breast cancer patients. There were 181 early-stage, lymph node-negative breast cancer patients who were treated with adjuvant trastuzumab for either 9-week or 1-year schedule. A total of 101 patients received trastuzumab for 9 weeks and the remaining 80 patients received this adjuvant therapy for 1 year. Disease free survival (DFS) and overall survival (OS) rates of both groups were calculated.There was no difference between groups according to OS. Five-year OS rates were 95.5% in the 9-week group and 93.3% in the 1-year group (p=0.78). DFS was affected by age, having tamoxifen therapy and disease stage. Nine-week trastuzumab group was superior to 1-year group and 5-year DFS rates were 91% in 9-week group and 81.2% in 1-year group (p=0.02). However, the 1-year group had more stage II patients than the 9-week group. We did not find any difference between groups regarding developing congestive heart failure.It appeared that 9-week trastuzumab treatment was not inferior to 1-year trastuzumab treatment in early-stage, lymph node-negative breast cancer patients.

Peripheral stem cell transplantation is used as a life-saving therapeutic option in hematological malignancies. As previously established, most hematological malignancies are seen in the elderly population. Therefore, possible HLA-identical sibling donors of elderly patients are generally of an advanced age. In this study, we aimed to evaluate the effect of old age on stem cell mobilization and quality in older adult healthy sibling donors.Between 2006 and 2014, we evaluated 38 healthy donors aged ≥55 years. The granulocyte-colony stimulating factor (G-CSF) analogs were used at a dose of 5 µg/kg/day and administered subcutaneously twice a day for five days. CD34+ cells were estimated in the peripheral blood before collection of the apheresis product. The National Marrow Donor Program selects healthy unrelated donors if they are younger than 60 years. Therefore, we compared the product quality in donors over the age of 60 to that in donors aged 60 years or less.We collected sufficient products from all the donors with one to three apheresis procedures. No serious complication was detected in all donors. Reaching the target CD34+ cell count in one day were detected in 83% of younger and 79% of older donors (P = NS). Collected CD34+ cells x10e6/recipient body weight (kg) was same and 5.1 in the groups (P = NS). There were no correlation between the donor age and these parameters.Healthy donor apheresis in older adults can be performed effectively and possible donors should be evaluated regardless of their age. J. Clin. Apheresis 32:16-20, 2017. © 2016 Wiley Periodicals, Inc.

We evaluated 979 patients for the development of post-transplant lymphoproliferative disease (PTLD) and solid malignancies after allogeneic hematopoietic stem cell transplantations (allo-HSCT) as a late complication. We found 15 (1.5%) subsequent malignancies; three of these malignancies were PTLD, and twelve were solid tumors. The median time from allo-HSCT to the development of PTLD was 9 (3-20) months and that from allo-HSCT to the development of solid tumors was 93 (6-316) months. The cumulative incidence of evolving subsequent malignancy in patients was 1.3% (±0.5 SE) at 5 years and 3.9% (±1.2 SE) at 10 years. The Cumulative incidence of developing subsequent malignancy in patients with benign hematological diseases as the transplant indication was 7.4%±4.2SE at 5 years. More subsequent malignancy developed in patients having ≥1 year chronic GVHD (3.7% in ≥1 year chronic GVHD and 0.7% in

Background/Aim:Multiple Myeloma (MM), characterized by aberrant accumulation of terminally differentiated plasma cells in the bone marrow, is promoted by ongoing DNA damage and genomic instability. O6-methylguanine-DNA-methyltransferase (MGMT), a DNA repair protein, transfers the alkyl group from guanine to its cysteine residue and is implicated as an important chemoresistance factor particularly in chemotherapy-induced DNA alkylation. A growing body of evidence has shown that enhanced DNA repair capacity stimulates cancer cell survival and facilitates genomic instability. Thus, targeting DNA repair activities including MGMT seems to be a promising strategy for the treatment of MM. Materials and Methods: In our study, MGMT expression was evaluated in MGUS, SMM and MM patients compared to normal plasma cells using publically available gene expression data sets (Gene Expression Omnibus; GSE47552). Furthermore, MGMT mRNA and protein levels were determined in human MM cell lines (NCI H929, RPMI 8226 and U266), three samples of control PBMCs, matched CD138+ myeloma and CD138- non-tumorigenic cells obtained from bone marrow aspirates of same MM patients [newly diagnosed (ND, n=12) and relapsed / refractory (RR, n=8)] by RealTime Ready PCR Assay and Western blot, respectively. The experiments with human cells were approved by the Ethical Committee of Ankara University School of Medicine. Following treatment of MM cells with Lomeguatrib for 48 hours, cell viability, cell cycle progression and apoptosis were assessed by MTT and flow cytometry. DNA damage levels were examined by alkaline comet assay and immunoblotting of ΥH2AX phosphorylation. Results: Comparable MGMT expression was detected between MM cells and normal plasma cells, and between ND CD138+ and RR CD138+ myeloma cells. Inhibition of MGMT activity by Lomeguatrib reduced MM cell viability and induced apoptosis in MGMT proficient but not in MGMT deficient MM cells in a dose-dependent manner. In contrast, Lomeguatrib did not affect the cell viability of PBMCs from three healthy donors and CD138- non-tumorigenic cells from three MM patients. Furthermore, Lomeguatrib perturbed cell cycle and decreased phosphorylation of G1/S specific CyclinE1 in these cells and led to an increase in DNA damage. Western blot analysis revealed a reduction in protein levels of Fen1, Ku-70 and Rad51 which are involved in double-strand DNA break repair. Conclusion: These results revealed that MGMT promotes repair of DNA double-strand breaks in MGMT proficient MM cells and MGMT inhibition enhances DNA damage-induced apoptosis, suggesting that inhibition of MGMT by Lomeguatrib might be a useful strategy to overcome unfaithful DNA repair in MM. This research has been supported by The Scientific and Technological Research Council of Turkey (No:113Z383). Disclosures Beksac: Celgene, Janssen Cilag Amgen, Novartis, Takeda: Honoraria, Speakers Bureau.

To the Editor, Waldenstrom’s macroglobulinemia (WM) is a B cell lymphoplasmacytoid lymphoma, which is characterized by a presence of serum monoclonal immunoglobulin M and clonal lymphoplasmacytic cells in bone marrow.1,2 Lymphadenopathy, splenomegaly, leucopenia, thrombocytopenia, anemia, hyperviscosity and peripheral neuropathy are commonly seen in WM.2 B-symptoms (weight loss, fever or night sweats) may also be detected in WM patients.2 Although fever is a B symptom, WM is not considered as a diagnosis in a febrile patient.3 In literature fever accompanied with WM were reported either with other B-symptoms or due to infection. Thus, at the time of diagnosis most of WM patients have no fever.4-6 Here we would like to present a patient, who has been diagnosed with WM during an evaluation of fever. A 51-year-old Caucasian woman has been admitted to our hospital with a 4-day-fever and fatigue. She has been treated with inhaler steroid and s-2 agonist because of asthma. She had no dysuria, cough, sputum, weight loss, night sweats or diarrhea. In physical examination liver was palpable as 2 cm at the right mid

Psychological status of patients during epidural and intravenous (i.v.) morphine administration are not known enough. It's known that after administration of morphine epidurally and intravenously plasma concentrations are similar but the concentrations in cerebrospinal fluide are different. The effects of two postoperative analgesia treatment regimens on the psychological and mental functions of the elderly after major orthopedic surgery were investigated in this randomized, blinded study. Morphine was used epidurally in Group E and intravenously in Group IV with patient controlled analgesia method for postoperative analgesia treatment. All patients were assessed for psychological status the day before surgery and 2 days after surgery using the Brief Symptom Inventory (BSI). The results of the BSI were assessed with the Global Severity Index (GSI). Nine subscales were also derived: depression, somatization, obsessive-compulsive, anxiety, interpersonal sensitivity, hostility, phobic anxiety, paranoid ideation, and psychoticism. There was not significant difference between the groups for preoperative and postoperative GSI results (p0.05). Only interpersonal sensitivity subscale results in Group i.v. were decreased compared to the baseline (p0.001). Preoperative BSI and submeasurement test scores revealed no correlation with total morphine consumption in both groups (p0.05). Mental changes like agitation, time and place disorientation were seen equally in both groups. This study showed that after epidural and intravenouse morphine administration, no psychologycal changes were observed in the postoperative period compared with baseline. Patients who received morphine intravenously were showed less interpersonal sensitivity in the postoperative period.

Total knee replacement (TKR) is one of the most painful orthopedic surgical procedures. This study was aimed to investigate the effect of a single-shot preoperative 3-in-1 femoral nerve block on postoperative pain by using 0.375% ropivacaine, and on the consumption of morphine by using PCA following the TKR surgery. Side effects were also evaluated in this setting. 34 patients were included in this study. Group R (n=17) received a 3-in-1 femoral nerve block (FNB) with 40 mll of ropivacaine 0.375%. Group S (n=17) received only a 2 mg loading dose of morphine 30 minutes before the end of surgery, and no block was performed. Both groups received general anesthesia and postoperatively had a PCA pump programmed to deliver morphine. VAS scores at rest, morphine consumption and adverse effects were recorded. Two patients were excluded from each group. Pain scores at 0, 1, 2, 3, 4, 6, 8 postoperative hours were significantly lower in group R in resting position (p0.05). Group R experienced no pain at the recovery room and this state lasted 8 hours after the surgery while group S reached the acceptable score (VAS ? 3) one hour after leaving the recovery room. The morphine requirement was significantly lower in Group R at 12, 18, 24, 48 hr after TKR (p0.001). Side effects were also lower in this group. Preoperative single-shot 3-in-1 FNB with 40 cc of ropivacaine 0.375% provides better VAS scores, less morphine consumption and fewer side effects in elderly patients when compared to the group with no block.

articles do not necessarily reflect those of Informa Healthcare (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient.

To explore how satisfied family medicine residents are with their training in teaching hospitals and current postgraduate training program.We surveyed 135 family medicine residents in 5 teaching hospitals in Ankara region. The residents were asked to fill out the questionnaire at their work place. The questionnaire consisted of 23 open- and closed-ended questions about general demographic data, training conditions, appropriateness of training, and quality of training delivered by clinical teachers in family medicine. The response rate was 75%.Seventy percent of respondents found the order of rotation important. Most residents were satisfied with the duration of rotation. Eighty two percent of residents found basic skills taught during the course of the training to be insufficient. Fifty five percent of the participants felt that training in teaching hospitals was not sufficient, and majority desired training in family practice settings. Ninety-nine respondents suggested establishing a coordinating center for family medicine training and training of clinical teachers in topics relevant to family practice.Family medicine residents were generally dissatisfied with their training in major teaching hospitals in Turkey. Postgraduate family medicine curriculum needs to be changed and opinions of residents regarding their training should be taken into consideration.

INTRODUCTION: Though widely used and accepted as a first line regimen, published data regarding R-CODOX-M/IVAC is very limited. Up to date only three prospective studies and one case series have been reported. Herein, we present our institution’s experience with the management of Burkitt’s lymphoma with a special emphasis on the R-CODOX-M/IVAC regimen. METHODS: The files and electronic records of 35 patients diagnosed with Burkitt’s lymphoma between January 2005 and June 2014 were retrospectively revised. RESULTS: The median age at diagnosis was 40 (21-86 years). Male patients constituted 71.4 (n=25). Stage IV disease was present in 60.6% (n=20), and stage I disease in 27.3% (n=9) of the patients. ECOG performance scoring was < 3 in 70.6% (n=24) and Burkitt’s lymphoma risk scoring (availability of complete surgical resection, stage, serum LDH and CNS involvement) > 2 in 58.6% (n=17). The distribution of patients to administered regimens were as follows: R-CODOX-M/IVAC 10 patients (28.6%), HyperCVAD 5 patients (14.3%), R-CHOP 9 patients (25.7%), R-CVP 2 patients (5.7%), CALGB 10002 1 patient (2.9%) and other regimens (high dose methotrexate, high dose cytarabine, vincristine-prednisolone, etc.) 8 patients (23.0%). Median overall survival (OS) was 23.5 (1-114) months and median progression free survival was 17.0 (0-114) months. Relapses occurred in 7 patients (20.0%), mortality in 12 patients (34.3). R-CODOX-M/IVAC group (n=10) was compared to other rituximab containing regimens (R-CHOP, R-CVP) (n=11) and HyperCVAD (n=5) and other rituximab-free regimens (n=9) with respect to patient and disease characteristics, DFS and OS. The disease stage, ECOG performance score and Burkitt’s lymphoma risk score were similar between the four groups (p=0.6, p=0.2 and p=0.2, respectively). However, median OS was 13 (1-42) months in R-CODOX-M/IVAC group and it was significantly lower than other regimens (p=0.04 log rank test). Median PFS was 13 (0-42) months and also lower compared to other regimens, however, the difference was not statistically significant (p=0,1 log rank test). CONCLUSIONS: Burkitt’s lymphoma is currently one of the most aggressive mature B- cell origin lymphomas and there is no consensus on the standard of care. CODOX-M/ IVAC is one of the most frequently used regimen. Adding rituximab is also known to prolong overall survival in this patient population. Though the sample sizes are too small and the drawbacks of the retrospective study design exist, the inferior OS and PFS observed in this study with R-CODOX-M within patients having similar disease characteristics should be taken into account. Further studies comparing the efficiency of currently used regimens are needed to reach a clear conclusion. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Introduction: Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) is a biologically and clinically distinct variant of ALL and accounts for approximately 20 to 30 percent of ALL in adults. Ph chromosome and BCR-ABL fusion gene have been associated with a poor prognosis in ALL patients especially when patients were treated with chemotherapy alone. Better response rates have been reported with the introduction of tyrosine kinase inhibitors (TKIs) and incorporation of TKI into the treatment regimens. This development has allowed more patients to proceed to allogeneic hematopoietic stem cell transplantation (Allo-HSCT). In recent years some studies evaluated the efficacy of TKIs combined with steroids as first-line induction treatment in Ph+ ALL patients. Patients and methods: Here we present 5 patients who were newly diagnosed as Ph+ de novo (n=2) or secondary ALL transformed from chronic myeloid leukemia (n=3) and received TKI plus methylprednisolone (MP) as an induction regimen. All of our patients were male. Additional cytogenetic abnormality was detected in two patients (monosomy 7). This therapy was preferred in 3 patients due to comorbid disease and advanced age. Other patients received the therapy for bridging to allogeneic stem cell transplantation. Three patients received imatinib 800 mg daily and 40 mg/m2 MP for 45 days, one patient received dasatinib 140 mg daily and 60 mg/m2 MP for 32 days. TKI treatment after the induction has been continuing in maintenance therapy in all patients, except one patient whose TKI treatment was interrupted due to Allo-HSCT. One patient had a history of resistance to imatinib, nilotinib and dasatinib while he was in chronic phase of chronic myeloid leukemia. Therefore he was treated with bosutinib 500 mg daily plus MP 60 mg/m2 for 32 days. After completing of induction therapy 3 patients received 6-mercaptopurine 70mg/m2 daily, methotrexate 20mg/m2 weekly, vincristine 2 mg/day in every two months, MP 40mg/m2 for 5 days in every month and TKI daily as the maintenance therapy. Central nervous system (CNS) involvement was detected in two patients during the induction treatment on days 30 and 65, respectively. One of them received high dose methotrexate and then underwent Allo-HSCT from an HLA identical sibling donor at fourth month of diagnosis. The other patient was ordered cranial and spinal irradiation together with intrathecal chemotherapy. Results: Four patients achieved complete hematologic remission (CHR) at day 22 and one patient achieved CHR at day 45. Complete molecular remission was not obtained in our patients after the induction therapy. After a median follow-up of 7 months (range 3-22), four patients are alive currently. One patient died due to pulmonary infection after 22 months of diagnosis and he was still in CHR at the time of dead. Patient characteristics are given in table. Conclusions: Our observations suggest that TKI plus steroid therapy as the first line treatment for remission-induction in Ph+ ALL has been more tolerable and associated with less toxicity. Despite the poor prognostic effect of Ph chromosome in ALL patients, TKI plus steroid regimens may improve outcome and may allow to patients to proceed to Allo-HSCT. As shown among the elderly Ph+ ALL patients, this regimen might also be appropriate for younger Ph+ ALL patients. | | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | | -------------------------------------- | --------------------- | --------------------- | --------------------- | --------------------- | --------------------- | | Age | 69 | 65 | 38 | 70 | 29 | | WBC count at presentation (x10 9 /L) | 3500 | 46000 | 6000 | 26500 | 232000 | | BCR-ABL fusion protein (kD) | 190 | 190 | 210 | 210 | 210 | | TKI (dose) | Imatinib(800mg) | Imatinib(800mg) | Imatinib(800mg) | Bosutinib(500mg) | Dasatinib(200mg) | | BCR-ABL (FISH)% at presentation | 96 | 90 | 85 | 90 | - | | BCR-ABL ratio (RT-PCR) at presentation | 3,8 | - | 30,76 | 40,9 | 2,7 | | BCR-ABL ratio (RT-PCR) at day 22 | 0,0006 | 0,1411 | 0,2964 | 25 | 0,2794 | | Disease status at days 22&45 | Hematologic Remission | Hematologic Remission | Hematologic Remission | Hematologic Remission | Hematologic Remission | Table: Patient characteristics Disclosures No relevant conflicts of interest to declare.

Introduction Diagnosis and classification of acute myeloid leukemia (AML) are based on morphology and genetics. FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD), FMS-like tyrosine kinase 3 tyrosine kinase domain (FLT3-TKD) and nucleophosmin1 gene (NPM1) are most frequent mutations found in patients with AML. In this study, we aimed to identify the prognostic value of FLT3 and NPM1 mutations in our AML patients. Method We retrospectively evaluated 121 patients who had been diagnosed based on the WHO AML diagnosis criteria, between 2007 and 2014 in the Department of Hematology at Ankara University. FLT3 and NMP 1 mutations were detected by Polymerase chain reaction (PCR) amplification method. The overall survival (OS) and relapse-free survival (RFS) due to FLT3 and NMP1 mutations were analyzed using Kaplan Meier method and Long-Rank. P Results Of the 121 patients, 50 (41%) were female and 71 were male (59%). The mean diagnosis age of AML in the female patients was 50.52 ± 2.23, whereas the mean diagnosis age in the male patients was 50.62 ± 2.15. 115 of 121 patients (95%) received cytarabine (ARA-C) and an anthracycline ("7+3" protocol) as an remission induction therapy while 6 of the patients (5%) haven't received any therapy because of older age and poor performance status. 33 of 121 patients (33%) got cytarabine (ARA-C) and an anthracycline ("7+3" protocol) as a reinduction therapy. 67 of 121 patients (55%) were followed by consolidation therapy with high-dose ARA-C. Allogeneic stem cell transplantation (ASCT) was performed in 31 of 121 patients (31%) during follow-up. The donors were relatives in 21 of 31 patients (68%) while 10 ASCT were from unrelated donors (32%). 32 of 121 patients (26%) were dead during follow-up. The FLT3 and NMP1 mutations were studied from peripheral blood in 27 of 121 patients (22%) while in 94 of 121 (78%) patients samples from bone marrow were used. 27 of 121 patients (22%) had NMP1 mutation positive whereas 22 of 121 patients (18%) had FLT3 mutation positive. In 4 of 22 patients were FLT3-TKD positive others were FLT3-ITD positive.The FLT3 positive patients are significantly older than FLT3 negative patients (P.05)(Figure 1)(Figure 2). Conclusion In previous studies, FLT3-ITD mutation predicted an unfavorable prognosis whereas mutation in NPM1 gene was associated with favorable prognosis. Unexpectedly we detected no difference in either OS or RFS in FLT3 or NPM1 gene mutated patients. Figure 1. Kaplan Meier Curve of OS in FLT3 positive and negative group(dashed curve FLT3 positive). Figure 1. Kaplan Meier Curve of OS in FLT3 positive and negative group(dashed curve FLT3 positive). Figure 2. Kaplan Meier Curve of RFS in FLT3 positive and negative group (dashed curve FLT3 positive). Figure 2. Kaplan Meier Curve of RFS in FLT3 positive and negative group (dashed curve FLT3 positive). Disclosures No relevant conflicts of interest to declare.

Aim: We would like to present our center experiences in the approaches of relapsing and/or progressive acute leukemia patients after allogeneic hematopoietic stem cell transplantation (AHSCT). Patients: We have retrospectively evaluated 133 patients (86 Male; 47 Female) with acute leukemia who has been detected relapse and/or progression after AHSCT between June 1990 and October 2013. Median age was 30 years (16-63 years) at the transplant time. Their diagnosis were 89 AML (12 secondary AML), 41 ALL and 3 biphenotipic leukemia. Median time of relapse and/or progression was 165 days (13-4713 days) after ASCT. Relapse types were as extramedullary relapse (EMR) alone in 11, extramedullary with hematological relapse in 30 and hematological relapses (HR) alone in 92 patients. Results: Our treatment approaches were chemotherapy and/or donor lymphocyte infusion in 109, second ASCT from same or different donor in 16 and radiotherapy alone in two patients. However, six patients were not able to receive any therapy. We have observed that the numbers of donor lymphocyte infusion or second transplantation increased after the year of 1999 (Figure 1). The probability of three-month, six-month or one-year survival after the relapse&progression were calculated as 53.7%±4.4%, 35.1 %±4.3% and 24.2%±3.9%, respectively. Survival after the relapse or progression was median 102 days (ranging between 68.7 days and 135.3 days, 95% CI). The type of relapse (EMR alone, EMR plus HR versus HR alone) and leukemic types (AML vs ALL) did not effect survival (p>0.5). When we compared second transplantation with other approaches, survival after relapse did not change (p=0.8) (Figure 2). In addition, survival was not affected by the year of relapses as 1990-1999, 2000-2009 versus 2010-2014 (p=0.7). Conclusion: Treatment approaches in acute leukemia relapsing after transplantation vary from the cellular therapy to chemotherapy. But our experience was not able to show a difference between second transplantation and others. Moreover each center should be approached to the patients according to their experience and type of relapse until an effective treatment option will be defined. Figure 1. Treatment approaches according to years Figure 1. Treatment approaches according to years Figure 2. Overall survival according to treatment approaches Figure 2. Overall survival according to treatment approaches Disclosures No relevant conflicts of interest to declare.

Background and Aim: PET is a useful tool that allows deeper assessment of response beyond that measured by M protein levels. It has been reported to predict outcome following both ASCT and recently non-transplant setting too. To be able to integrate PET-CT negativity to internationally accepted response criteria the cut-off level needs to be validated by independent investigators. This prospective study was initiated to elucidate the prognostic role of PET-CT in the ASCT setting testing the cut-off level 4.2 initially reported by Zamagniet al versus the cut-off (3.35) based on our results. Patients and Methods: 139 consecutive patients diagnosed and transplanted in Ankara University with pre- and post-transplant (Tx) PET-CT imaging were included. Patients were: Median age 56.5 +/- 8.7 (M/F: 79/60), ISS I/II/III: 50/55/34, renal impairment (10.8%), bone involvement (90.6%), del13q (40.9%), t(4;14) and/or p53(26.5%), LDH high(12.9%), induction with Bortezomib (73.4%). Pre-Tx clinical response ³VGPR: 52.9%, post-Tx clinical response ³VGPR: 77.5%. Overall Survival (OS): median: 33 months (4.2-141 months). PASW statistics for Windows program was used for statistical analysis. Results: ROC analysis revealed 3.35 as a significant cut-off level (p=0.005; OS). PET-CR was defined FDG uptake less than 4.2 or 3.35 depending on the analysis. Pre-Tx PET-CR:17.4%, post-Tx PET-CR: 69.6% (4.2) was predictive for PFS (p=0.05) but not OS (p=0.096). However PET (>3.35) was predictive for OS (p=0.037) but not PFS. PET (>4.2) was predictive for OS (p=0.014) and PFS (p=0.019)among only ³VGPR patients. Similarly PET (>3.35) among ³VGPR patients was also predictive for OS (p=0.05) and PFS (p=0.04). PET-CR was not predictive among ³CR patients significantly. Cox regression analysis for PFS, when PET (>4.2) is used, ISS was significant only (OR: 1.99, p=0.049) when post-Tx clinical response (OR: 0.46, p=0.022) is not included in the model. For OS, clinical response both pre-Tx (OR: 0.35, p=0.015) and post-Tx (OR: 0.18, p3.35) increased the predictive value of PET. In addition to clinical response, PET-CR appeared as a borderline significant factor for OS: pre-Tx (OR: 2.2, p=0.078), post-Tx (OR: 2.26, p=0.067). In conclusion both PET (3.35) approached significance. To be able to integrate PET-CR to response criteria definition of PET-CR needs to be confirmed. Table 1PET cut-off 4.2PET cut-off 3.35Number of patientsnegativepositivenegativepositive Figure-1: PET( Figure-2. PET( Disclosures No relevant conflicts of interest to declare.

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare disorder of blood cells associated with mutations of X-linked gene called phosphatidylinositol glycan class A, and presenting as hemoglobinuria, signs of cytopenias (fatigue, easy bleeding) or thrombosis. In this study, 39 patients with PNH were retrospectively evaluated with regard to disease findings, laboratory investigations, complications and relationship between those and clone size. Median follow-up time was 26 months. Patients were divided into two groups. There were 24 classical PNH and 15 Aplastic Anemia (AA) or Myelodisplastic Syndrome (MDS) associated PNH patients. Evident signs of hemolysis at the time of diagnosis and thrombosis were seen in classical PNH patients. Sign of hemolysis developed in two AA patients. Hemoglobinuria, hemolysis test (increased reticulocyte and lactate dehydrogenase) were determined to be correlated with clone size. There was association between clone size and thrombosis. No patients with clone size smaller than 50% developed thrombosis and all patients with thrombosis were in classical PNH subtype which has greater clone size. PNH is a rare disease; therefore the effect of small number of patients on the statistical parameters must be taken into consideration. Over the entire course of follow-up time 8 patients died, 6 due to complications of allogeneic stem cell transplantation and 2 due to conditioning regimen before transplantation. Numbers of deaths are equal in each subtype. In summary, in this study there was a linear correlation between hemoglobinuria and LDH levels with clone size, which was statistically significant (p=0,031 and p=0,001 respectively). Other clinical signs did not correlate with clone size. Thrombotic complications were seen only in classical type PNH patients. No patients with clone size smaller than 50% developed thrombosis, MPV levels were significantly higher than others (p=0,04). There was also statistically significant correlation between reticulocyte and LDH levels with thrombotic events (p=0,009 and 0,003 respectively). In addition, after allogeneic stem cell transplantation 9 patients were evaluated for PNH clone and in 7 the clone was disappeared. Disclosures: No relevant conflicts of interest to declare.

e18009 Background: Building constructions around Hematology inpatient clinics are always a major concern for Aspergillus infections in immunocompromised patients. The use of HEPA (High Efficiency Particulate Arresting) filters can be helpful in reducing fungal infections. This quasi-experimental study was designed to measure the efficacy of HEPA filters in such a construction period. Methods: In May 2011, Portable HEPA filters have been placed in patient rooms where hematological malignancies were treated, because of the massive construction 10 meters from the clinic. Infection rates and survival 6 months before and after the installment were compared to see the effect of HEPA filters. A total of 413 patients were treated in the department during this 1-year period. Results: There were no statistical differences between antifungal prophylaxis or treatment regimens in groups. After HEPA filter installation the rates of fungal or non-fungal derived infection and pneumonia and length of hospital stay did not deteriorate in AML and ALL patients. Also, infection rates and infection-related mortality did not increase in AML group, moreover these rates decreased in ALL patients in the construction period. These findings were shown in Table. Conclusions: Despite the construction and the summer months, which environmental Aspergillus contamination is more frequently seen, there was no increase in fungal infections during Post-HEPA period. That may reflect a positive effect of HEPA usage even in AML patients. HEPA filters may be used as a protective system in hematology departments, in such a construction period. [Table: see text]

7038 Background: In this retrospective study we aimed to evaluate the rates and the clinical outcomes of allo-HSCT in CML following the advent of TKIs. Methods: We compared the transplantations (Txs) performed prior to 2002 (old era), the first year of TKIs, with the Txs during and after 2002 (new era). Results: Between 1989 and 2012 inour Tx unit a total of 189 allo-HSCTs were performed in 185 CML patients (second Tx for 4 patients). The ratio of Tx for CML among the whole Tx group decreased from 40 % to 12 % after 2002. The ratio also dropped to less than 5 % after 2008 and increased again to 15% in 2012. Time from diagnosis to Tx was longer in the old era than in the new era (9.2 months vs 15.4 months, p