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Karakus, Volkan/0000-0001-9178-2850; Demirkan, Fatih/0000-0002-1172-8668; Demircioglu, Sinan/0000-0003-1277-5105; Arat, Mutlu/0000-0003-2039-8557; Cagliyan, Gulsum Akgun/0000-0002-2073-1949; Ozturk, Hacer Berna Afacan/0000-0001-9386-7604; WOS: 000473249400014 PubMed: 31036516 Therapeutic plasma exchange (TPE) is used to treat more than 60 diseases worldwide and has drawn growing interest. Little is known about the current situation of TPE activity in Turkey, so we developed a survey to obtain information about this timely topic. We collected data on TPE from 28 apheresis units throughout Turkey. We performed a total of 24,912 TPE procedures with 3203 patients over the past decade. Twenty years ago, the majority of procedures were performed for neurological and hematological disorders, and today, most TPE procedures are done for the same reasons. The only historical change has been an increase in TPE procedures in renal conditions. Currently, renal conditions were more frequently an indication for TPE than rheumatic conditions. Fresh frozen plasma was the most frequently used replacement fluid, followed by 5% albumin, used in 57.9% and 34.6% of procedures, respectively. The most frequently used anticoagulants in TPE were ACD-A and heparin/ACD-A, used with 1671 (52.2%) and 1164 (36.4%) patients, respectively. The frequency of adverse events (AEs) was 12.6%. The most common AEs were hypocalcemia-related symptoms, hypotension, and urticaria. We encountered no severe AEs that led to severe morbidity and mortality. Overall, more than two thirds of the patients showed improvement in the underlying disease. Here, we report on a nationwide survey on TPE activity in Turkey. We conclude that there has been a great increase in apheresis science, and the number of TPE procedures conducted in Turkey has increased steadily over time. Finally, we would like to point out that our past experiences and published international guidelines were the most important tools in gaining expertise regarding TPE.

Objective: The aim of this study was to evaluate the effectiveness of cryotherapy on the prevention of oral mucositis (OM) and on the oral pH value in patients with multiple myeloma undergoing autologous stem cell transplantation. Data Sources: This nonrandomized controlled clinical trial was carried out in Bone Marrow Transplant Centers of three hospitals with total 32 patients. In addition to standard oral care, a total of 80 minutes of cryotherapy was applied to the experimental group. OM was assessed according to the World Health Organization's Oral Toxicity Scale before chemotherapy and for 21 days after chemotherapy (every day in the first 14 days, then every other day until the 21st day [if not discharged]). Conclusion: According to the findings, cryotherapy did not change the incidence of oral OM, and neither affected the severity of nor decreased the duration of it. Oral pH value was found to be significantly different between the patient groups only before and 1 day after chemotherapy. Implications for Nursing Practice: Cryotherapy is an inexpensive, easy-to-use method with no side effects; it would be beneficial to continue cryotherapy to prevent the development of OM in patients with cancer receiving drugs with a short half-life such as melphalan. It is also recommended to conduct further studies with different chemotherapy drugs with short half-lives to determine its effect on the prevention of OM development. (c) 2021 Elsevier Inc. All rights reserved.

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.

It took several years to succeed safe hematopoietic stem cell transplantations. HLA-matched unrelated donors have become the most common donor source for allogeneic hematopoietic stem cell transplants worldwide. The sibling donor may have more comorbidity and decreased regenerative potential of stem and immune cells. The purpose of this retrospective study was to examine whether aging had any negative effect on aging donor or patient. 27 patients who received a hematopoietic stem cell transplantation (HSCT) from February 2013 to May 2016 and their donors were analyzed. We showed that transplantation from older relative donor was feasible. Adverse event rate was low. Donors tolerated the procedure very well. Good CD34+ cell harvest was possible.

Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD.We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56.A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]).Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy. (Funded by Novartis; REACH2 ClinicalTrials.gov number, NCT02913261.).

WOS: 000395365500020, PubMed ID: 28261298, Introduction: Chronic myeloproliferative disorders (CMPD) are chronic myeloid hematological disorders, characterized by increased myeloid cell proliferation and fibrosis. Impaired apoptotic mechanisms, increased cell proliferation, uncontrolled hematopoietic cell proliferation and myeloaccumulation may contribute to the pathogenesis of CMPD. The aim of our study was to show the possible role of FAS/FASL gene polymorphisms in CMPD pathogenesis and investigate the association with clinical parameters and susceptibility to disease. Material and methods: We included 101 (34 polycythemia vera (PV), 23 primary myelofibrosis (PMF), 44 essential thrombocythemia (ET)) CMPD patients diagnosed according to the WHO classification criteria and 95 healthy controls in this study. All the patients and the controls were investigated for FAS/FASL gene expression, allele frequencies and phenotype features, and also FAS mRNA levels were analyzed. Results: Chronic myeloproliferative disorders patients showed increased FAS-670AG + GG genotype distribution compared with the control group (p < 0.05). While the A allele was more frequent in both groups, AG genotype was more frequent in CMPD patients. There was no association between FAS-670A>G gene polymorphism and some clinical parameters such as splenomegaly and thrombosis (p > 0.05). No statistically significant difference in FASL+843C>T genotype or allele frequency was found between groups (p > 0.05). Moreover, no statistically significant difference was detected in FASL and JAK2V617F mutations (p > 0.05). FAS mRNA expression was 1.5-fold reduced in patients compared to healthy subjects. Conclusions: According to our findings, FAS/FASL gene expression may contribute to the molecular and immunological pathogenesis of CMPD. More investigations are needed to support these data.

Amac: Febril notropenik ataklar kemoterapi sirasinda ve sonrasinda onemli bir problemdir. Biz febril notropenik atak icin risk faktorlerini saptamak icin kemoterapi alan hastalarin kayitlarini geriye donuk olarak inceledik. Gerec ve Yontem: Toplam 154 (92 erkek ve 62 kadin) hastanin 2004-2006 yillari arasindaki 261 yatis periyodu geriye donuk olarak analiz edildi. Ortanca yas 49.5 (17- 80) idi. Hastalarin klinik ve demografik verileri toplandi. Febril notropenik atak ve klinik degiskenler (tani, yas, cinsiyet, kemoterapi rejimi, kok hucre transplantasyonu, notropeni suresi, santral venoz kateter varligi ve G-CSF kullanimi) arasindaki iliski logistic regresyon modeli kullanilarak analiz edildi. Bulgular: Febril notropenik atak 201(% 77) yatis periyodunda saptandi. Akut losemi tanisi (OR: 3.36, % 95 CI, 1.16- 9.78, p: 0.02), kok hucre nakli (OR:8.77, %95 CI,2.41-31.82, p:0.001), G-CSF kullanimi (OR: 8.46, 95% CI, 3.28- 22.04, p: 0.000) ve notropenik periyodun ≥ 10 gun olmasi (OR: 4.01, % 95 CI, 0.83- 19.24, p: 0.001) febril notropenik atak icin risk faktoru olarak saptandi. Sonuc: Akut losemi, kok hucre nakli, notropenik periyodun 10 gunden uzun olmasi ve G-CSF kullanimi febril notropenik atak icin risk faktoru olarak saptanmistir. G-CSF'nin febril notropeni icin risk faktoru olmasi ilacin ates yapici etkisine baglanmistir. Ozellikle infeksiyon semptom ve bulgusu olmayan febril notropenik hastalarda G-CSF kullanimi sorgulanmalidir.

Autologous hematopoietic cell transplantation (AHCT) is a routinely used procedure in the treatment of adult patients presenting with multiple myeloma (MM), Hodgkin lymphoma (HL) and various subtypes of non-Hodgkin lymphoma (NHL) in upfront and relapsed/refractory settings. Successful hematopoietic progenitor cell mobilization (HPCM) and collection are the rate limiting first steps for application of AHCT. In 2015, alinost 1700 AHCT procedures have been performed for MM, HL and NHL in Turkey. Although there are recently published consensus guidelines addressing critical issues regarding autologous HPCM, there is a tremendous heterogeneity in terms of mobilization strategies of transplant centers across the world. In order to pave the way to a more standardized HPCM approach in Turkey, Turkish Society of Apheresis (TSA) assembled a working group consisting of experts in the field. Here we report the position statement of TSA regarding autologous HPCM mobilization strategies in adult patients presenting with MM and lymphoma. (C) 2017 Elsevier Ltd. All rights reserved.

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.

Although peripheral blood stem cell (PBSC) products cryopreserved by non-controlled rate freezing and stored at -80 °C after overnight storage are used frequently, data regarding the rate of loss of CD34+ cells in these products are limited. In this prospective study, CD34+ cells were counted at three (fresh, post-overnight and post-thaw) points in 83 PBSC products from 41 patients by flow cytometry. Compared to fresh products, the mean losses of post-overnight and post-thaw total CD34+ cells are 16.3% and 38.4% (p = 0.02), and the mean losses of post-overnight and post-thaw viable CD34+ cells are 16.5% and 48.5%, respectively (p 0.001). The numbers of fresh viable, post-thaw total and post-thaw viable CD34+ cells were inversely correlated with the durations of neutrophil and platelet engraftment. Our results indicate that the mean loss of post-thaw total and viable CD34+ cells is approximately 20% higher than that observed in standard cryopreservation methods. In addition, fresh viable, post-thaw total and especially post-thaw viable CD34+ cell levels are valuable predictors of both neutrophil and platelet engraftments.

No detailed information currently exists about the immune phenotypic profiles of peripheral blood stem cells (PBSCs) obtained by different mobilization regimens. The effects of these profiles on the outcome of transplantation are largely unknown. In this prospective study, the surface immune phenotypic features (CD11a, CD18, CD31, CD38, CD44, CD62e, CD62L, CD90, CD117, CD135 and CD184 expression) of sorted PBSCs that had been mobilized by growth factor with (group I and group II) or without (group III) disease-specific chemotherapies were investigated. The immune phenotypic features on mobilized PBSCs in groups I, II and III were not significantly different. The CD31 (platelet endothelial cell adhesion molecule-1) positivity ratio on PBSCs inversely correlated with both the duration of neutrophil ( r =−0.32, p =0.03) and platelet ( r =−0.36, p =0.02) engraftment. No relationship was found between the engraftment (neutrophil and platelet) durations and CD184 (chemokine receptor CXC motif receptor 4 [CXCR4]) expression on PBSCs. We demonstrated that the surface immune phenotypic profiles on PBSCs obtained by several mobilization regimens were not different. To our knowledge, this is the first study to demonstrate that CD31 expression on human PBSCs may positively affect both neutrophil and platelet engraftment. Contrary to our expectations, CD184 (CXCR4) expression on PBSCs has no effect on neutrophil or platelet engraftment. Considered together, our results suggest that additional surface antigens (such as CD31) may be more effective in the homing process.

WOS: 000396896500001, PubMed ID: 28421151, Myeloid or granulocytic sarcoma (GS) is a tumoral lesion consisting of immature granulocytic cells. It is a rare entity during the course of CML patients especially after allogeneic stem cell transplantation (SCT). Relapse without bone marrow involvement is much rarer. We report a case of CML patient who relapsed with isolated granulocytic sarcoma after allogeneic SCT during cytogenetic and molecular remission. 28-year-old male was diagnosed as CML and allogeneic SCT was performed because of refractory disease to tyrosine kinase inhibitors. Complete cytogenetic and molecular response was achieved after allogeneic SCT followed by dasatinib treatment. Approximately 5 years after the transplantation, very rapidly progressive lesion was documented and diagnosed as GS although he was at molecular and cytogenetic remission. The patient died during chemotherapy due to sepsis. GS relapse after allogeneic SCT is a very rare type of relapse in CML patients with molecular and cytogenetic remission. Since it is a very aggressive disease with a poor prognosis, combined chemoradiotherapies with other possible options like DLI or second allogeneic SCT should be considered as soon as the diagnosis is confirmed.

As known, the world population is aging and as the life span increases the number of advanced-age lymphomas also shows an upward trend. Autologous hematopoietic stem cell transplantation (HSCT) is the standard treatment modality in chemotherapy-sensitive relapsed or refractory aggressive lymphomas. Increased morbidity and mortality related to both the transplant itself and comorbid diseases can be observed in elderly lymphoma patients. Patients who are 65 years or older and underwent autologous HSCT with B-cell non-Hodgkin lymphoma were retrospectively included in our study. In terms of survival analysis, median follow-up was 34.5 months (8-159) while the overall survival (OS) was 58%. In the univariate analysis of prognostic data in OS, patients who were referred to transplantation with complete response had a statistically significant survival advantage (p=0.043). In terms of the effect of pre-transplant conditioning regimens on survival, BEAM regimen yielded better results, though not statistically significant. Age, number of chemotherapy cycles received before mobilization and radiation therapy had no significant effect on the CD34 (+) cell count in the final product (p = 0.492, 0.746 and 0.078 respectively). In conclusion, autologous HSCT is a practicable treatment modality that provides survival advantage in suitable advanced-age patients with a diagnosis of B-cell non-Hodgkin lymphoma. (C) 2017 Elsevier Ltd. All rights reserved.

Autologous hematopoietic cell transplantation (AHCT) is an established treatment option for adult patients presenting with multiple myeloma (MM), Hodgkin lymphoma (HL) and various subtypes of non-Hodgkin lymphoma (NHL) in upfront and/or relapsed/refractory disease settings. Although there are recently published consensus guidelines addressing critical issues regarding autologous hematopoietic progenitor cell mobilization (HPCM), mobilization strategies of transplant centers show high variability in terms of routine practice. In order to understand the current institutional policies regarding HPCM in Turkey and to obtain the required basic data for preparation of a national positional statement on this issue, Turkish Hematology Research and Education Group (ThREG) conducted a web-based HPCM survey. The survey was designed to include multiple-choice questions regarding institutional practice of HPCM in adults presenting MM, HL, and NHL. The representatives of 27 adult HCT centers participated to the study. Here we report the results of this survey shedding light on the real world experience in Turkey in terms of autologous HPCM mobilization strategies in patients presenting with MM and lymphoma. (C) 2017 Elsevier Ltd. All rights reserved.

BACKGROUND: Autologous stem cell transplantation (ASCT) for adult acute myelogenous leukemia (AML) is a valid therapeutic option for patients with good-risk and intermediate-risk disease. The authors used the registry of the European Society for Blood and Marrow Transplantation to compare combined busulfan and melphalan (BUMEL) with combined busulfan and cyclophosphamide (BUCY) before transplantation. METHODS: From 2005 to 2013, 853 patients with available cytogenetics underwent ASCT in first remission, including 257 after receiving BUMEL and 596 after receiving BUCY. The proportion of patients with good-risk AML was lower in those who received BUMEL (14% vs 20% ; P = .02). More patients who received BUMEL underwent autograft in molecular remission (89% vs 78% ; P = .02). Three years after transplantation, the relapse incidence (RI) was 48.7%, the leukemia-free survival (LFS) rate was 47.7%, the overall survival (OS) rate was 66.2%, and the nonrelapse mortality (NRM) rate was 3.6%. RESULTS: Patients who underwent an autograft after receiving BUMEL fared better than those who underwent an autograft after receiving BUCY with a lower RI (39.5% vs 52.2% ; hazard ratio [HR], 0.65 ; 95% confidence interval [CI], 0.49-0.87 ; P = .003) a better LFS (55.4% vs 44.6% ; HR, 0.69 ; 95% CI, 0.53-0.89 ; P = .005), and a better OS (73.8% vs 63% ; HR, 0.62 ; 95% CI, 0.47-0.82 ; P = .0007). There was no difference in the NRM rate (BUMEL vs BUCY, 4.5% vs 3.2%, respectively). Among 74 patients in the BUMEL group and 187 in the BUCY group who underwent autograft in molecular remission, the RI was 30% versus 51%, respectively (univariate analysis ; P = .01), and the LFS rate was 66% versus 47%, respectively (univariate analysis ; P = .03). CONCLUSIONS: In patients with AML in first complete remission who undergo ASCT, the BUMEL combination is a better preparative regimen. Cancer 2017 ; 123:824-31. © 2016 American Cancer Society.

WOS: 000313935900012, PubMed ID: 24385728, Both leukocytoclastic vasculitis and metastatic pulmonary calcification are conditions that rarely occur during the course of multiple myeloma. We present a multiple myeloma patient that had severe dyspnea due to metastatic pulmonary calcinosis, and ulceronecrotic skin lesions caused by leukocytoclastic vasculitis. After 3 courses of standard-dose chemotherapy all skin and pulmonary lesions disappeared. Autologous peripheral stem cell transplantation was performed and during 1 year of follow-up the patient was in complete remission; after 1 year, laboratory test results indicated disease relapse. Although the patient was treated with bortezomib and dexamethasone, the disease progressed. Non-myeloablative allogeneic stem cell transplantation was performed, but despite of all treatment the patient died due to disease progression.

The diagnosis of Toxoplasma infection or disease in hematopoietic stem cell transplantation (HSCT) patients is achieved mainly by PCR screening; however screening did not find wide field of use in practice due to costly expenditures of PCR. This study aimed to determine patients at high risk of Toxoplasma infection or disease before transplantation by stem cell originated buffy coat PCR and subsequently to screen them. Buffy coats collected from 12 autologous and 18 allogeneic HSCT patients' donors were investigated by PCR before transplantation. After transplantation, blood and sera collected at fixed time intervals were screened by two PCR methods and serological assays. Screening results first time assessed a toxoplasmosis incidence level as 25% in autologous HSCT patients and increased incidence level in allogeneic HSCT patients to 22%. Importantly, buffy coat PCR was first time performed before transplantation, to determine the risk of toxoplasmosis. Buffy coat PCR results showed that four patients were at high risk of toxoplasmosis before transplantation. After transplantation, these patients experienced toxoplasmosis. In conclusion, for the determination of patients at risk of toxoplasmosis, clinicians should consider buffy coat PCR in combination with serology before transplantation. After transplantation, PCR screening can be initiated in high risk patients upon clinical suspicion.

Objective: Follicular lymphoma (FL) is one of the most common lymphomas, and is characterized by t(14;18)(q32;q21) in more than 80% of patients. The aim of this study was to determine the rate of t(14;18) positivity based onthe detection of mbr or mcr in paraffin-embedded tissue samples. Material and Methods: The study included 32 paraffin-embedded tissue samples collected from 32 consecutive FL patients that were diagnosed and followed-up at our hospital between 1999 and 2006. The MBR breakpoint wasidentified based on real-time PCR using a LightCycler v.2.0 t(14;18) Quantification Kit (MBR), multiplex PCR, and seminestedPCR. To identify the mcr breakpoint, real-time PCR was performed using specific primers and the FastStart DNAMaster SYBR Green I Kit. To detect t(14;18) via fluorescence in situ hybridization (FISH) nuclei from paraffin-embeddedtissue sections were extracted and used together with LSI IgH (immunoglobulin heavy chain) (spectrum green)/bcl-2(B-cell leukemia-lymphoma 2) (spectrum orange) probes. Results: The DNA and nuclei isolation success rate for B5 formalin-fixed, paraffin-embedded tissue sections (n = 12)was 42% and 33%, respectively, versus 95% and 60%, respectively, for 20 tissue sections fixed in formalin only. In all,24 paraffin-embedded tissue sections were analyzed and mbr positivity was observed in the DNA of 82.14% via seminested PCR, in 53.57% via multiplex PCR, and in 28.57% via real-time PCR. We did not detect mcr rearrangementin any of the samples. In all, 15 of 16 patients (93.75%) whose nuclei were successfully isolated were observed to bet(14;18) positive via the FISH method. Conclusion: Semi-nested PCR and FISH facilitated the genetic characterization of FL tumors. As such, FISH and PCR complement each other and are both essential for detecting t(14;18) translocation.

WOS: 000297962900009, PubMed ID: 27264588, Objective: The aim of this study was to examine Factor V G1691A (Leiden) (FVL) and prothrombin G20210A (PT) gene mutation status, and their relationship with thrombosis in patients with chronic myeloproliferative disorders (CMPDs). Materials and Methods: The study included 160 patients with a CMPD that were regularly followed-up between 1993 and 2009. FVL and PT mutation status was established based on blood samples analyzed via PCR using specific primers. Results: The frequency of FVL and PT mutation was 12.5% and 4.4%, respectively. In total, 27 episodes of thrombosis occurred in 24 (15%) of the patients, and there wasn't an association between the observed thrombotic events, and FVL or PT mutations. Hepatic vein thrombosis was noted in 3 patients that had FVL mutation, of which 1 also had PT mutation. Conclusion: We did not observe a relationship between thrombosis, and FVL or PT mutations in CMPD patients; however, 3 of the patients that had hepatic vein thrombosis also had FVL mutation. Larger studies are needed to more clearly determine if all CMPD patients with hepatic vein thrombosis need be investigated for FVL and PT mutation. (Turk J Hematol 2011; 28: 306-11)

To investigate the plasma levels of activated thrombin activatable fibrinolysis inhibitor (aTAFI) and thrombomodulin (TM) in Behçet disease (BD) and their relationship with thrombosis.Plasma aTAFI and TM levels were measured by ELISA in 89 patients with BD (18 having venous thrombosis) and in 86 healthy controls.Compared with healthy controls, the BD group had significantly lower levels of aTAFI (13.49+/-8.88 microg/ml vs. 26.76+/-11.57 microg/ml, p0.0001) and significantly higher levels of TM (3.26+/-1.85 ng/ml vs. 2.6+/-0.69 ng/ml, p=0.0003). Neither aTAFI, nor TM levels differed significantly between BD patients with and without thrombosis (p0.05). Despite a tendency to positive correlation (r=0.37, p=0.0004) between plasma levels of aTAFI and TM in healthy controls, there was a tendency for negative correlation (r=-0.51, p0.0001) between these two parameters in BD patients.The plasma aTAFI and TM levels do not seem to be related with the presence of thrombosis observed in BD. Increased plasma TM levels in BD may simply reflect endothelial cell activation and dysfunction.

PubMed ID: 18613872, [No abstract available]

15th Congress of the Interdisciplinary-European-Society-for-Haemapheresis-and-Haemotherapy (ESFH) -- OCT 05-09, 2005 -- Antalya, TURKEY, WOS: 000249175000017, PubMed ID: 17569591, We compared cryopreservation of peripheral blood progenitor cell (PBPC) products immediately and after overnight storage. There was no statistically significant difference in the groups regarding median CD34+ cell count of the product, storage duration at -80 degrees C, viability rates, neutrophil and platelet engraftment days. Overnight storage of products with leukocyte count > 300 x 10(9)/1 has longer leukocyte (P = 0.03) and platelet (P = 0.01) engraftment days compared to other groups. Overnight storage without adding any medium or plasma for the apheresis product with leukocyte count of less than 300 x 109/1 in a commercially available refrigerator can easily and safely be used in transplantation centers. (c) 2007 Elsevier Ltd. All rights reserved., Interdisciplinary European Soc haemapheresis & Haemotherapy

Autologous peripheral blood stem cells transplantation (PBSCT) is a therapeutic option which can be used in various hematological neoplastic disorders; and it can prolong disease free survival and total survival and at times it may be curative. In this study, we investigated variables influencing PBSCT in 91 patients who had undergone PBSCT between 1998 and 2002 in our center, retrospectively. PBSC collection was performed after mobilization with G-CSF or chemotherapy plus growth factor. Only high dose chemotherapy was used for conditioning regimes. The median number of CD34+ was 11.5 x 10(6)/kg. Posttransplant neutrophil engraftment (>500/microL) was requiring a median of 10 days, it was 13 days for platelet engraftment (>20,000/microL). For neutrophil and platelet engraftment, we investigated; sex, age, diagnosis and CD34+ cells, the time interval between diagnosis and transplantation, number of apheresis, conditioning regime, growth factor initiation day as independent variables. In univariate analysis CD34+ cell number (>10 x 10(6)/kg), time interval more than one year between diagnosis and transplantation and BEAM conditioning was found to be significant for neutrophil engraftment. But in multivariate analysis none of them was found to be significant. For platelet engraftment in univariate analysis CD34+ cell number (>7 x 10(6)/kg), primary diagnosis of multiple myeloma initiation day of growth factor (>2 day) was found to be significant. In multivariate analyses only CD34+ cell count was found to be significant (p=0.005). In conclusion, as in previous studies we found that the only predictor of engraftment kinetics was CD34+ cell count.

WOS: 000246827600005, PubMed ID: 17473386, Systemic mastocytosis is a disease characterized by multifocal mast cell proliferation in the bone marrow or other extracutaneous organs. Because of loosely scattered and hypo-/agranular mast cells, the diagnosis is sometimes very difficult. In the bone marrow, mast cell infiltration may be associated with prominent lymphoid infiltration leading to a misdiagnosis of a low grade non-Hodgkin lymphoma. A 49-year-old woman presented with right arm and leg pain, psychiatric symptoms, and diarrhea for four years. Physical examination and laboratory investigation revealed hepatosplenomegaly, anemia, mild thrombocytosis, mild leucocytosis and lymphacytosis. In the bone marrow biopsy, there was a prominent B lymphocyte proliferation reminiscent of a low grade non-Hodgkin lymphoma/leukemia and there were some spindle cells aggregates in paratrabecular location. The consecutive bone marrow biopsies were similar to the first. The subsequent splenectomy specimen exhibited striking fibrosis. In the lymph node sections, there was marginal zone hyperplasia. Multifocal accumulations of mast cells were strongly positive with mast cell tryptase and CD117 on immunohistochemical staining, though no metachromasia was identified in Giemsa and Toluidine Blue stained aspirates and tissue sections, probably due to hypo-/agranulation of mast cells. The case was presented to emphasize the importance of the antibody to mast cell tryptase in the diagnosis of mastocytosis and to discuss problems of differential diagnosis of systemic mastocytosis.

Background Infusion of cryopreserved and non-cryopreserved hematopoietic progenitor cells (HPC) is associated with a broad variety of symptoms. In this study, we have investigated infusion-related toxicity regarding temperature of cryopreserved autologous peripheral blood progenitor cells (PBPCs) transplanted in 31 and allogeneic non-cryopreserved PBPCs in 4 patients receiving high dose chemotherapy and stem cells transplantation for hematological malignancies. Study design and method A 24h ECG-Holter recording system was used to obtain cardiac arrhythmias. Two milliliters HPC were collected from entrance site of venous access to evaluate the temperature of infused HPC. Results We have detected arrhythmias in 17 (48.58%) of our patients before, during and after infusion. Median temperature of the infusat was 21°C (18–28.2). Arrhythmias during infusion were detected in 8 (22.85%) patients. The temperatures of infused HPCs were not statistically different in group with and without arrhythmias as 22°C and 21°C, respectively ( P >0.05). And also, volume, contents [dimethylsulphoxide (DMSO), red blood cells (RBC), platelet (PLT), and total nucleated cell (TNC)] of product, and rate of infusion speed did not have any effect on arrhythmias. Conclusion As a result of this study, we have concluded that the temperature of HPC does not cause any systemic hypothermia and does not have any relation to arrhythmias detected during infusion.

Multiple myeloma (MM) is a malignant disease resulting from an uncontrolled proliferation of a neoplastic plasma cell clone in the bone marrow, which might also be induced by the loss of control on apoptosis. Fas ligand (Fas-L), a member of the tumor necrosis factor family, induces apoptosis mediated via its transmembrane death receptor Fas (Apo-1/CD95) antigen. In the present study, immunostaining was performed on the initial diagnostic bone marrow biopsies of 36 MM patients (1 stage I, 5 stage II, 30 stage III), to evaluate the distribution of Fas receptor and Fas-L on malignant plasma cells. Both Fas and Fas-L were positive in 13 cases and negative in 3, whereas 10 cases were Fas-negative, Fas-L-positive and 10 were Fas-positive, Fas-L-negative. Although no association was found between the expression of Fas receptor or Fas-L and overall survival, Fas-L positivity was significantly associated with a shorter event-free survival (p = 0.0335). In this study, it has been shown that the expression of Fas-L, in malignant plasma cells of myeloma patients significantly shortens the event-free survival, indicating that the defect in apoptosis might be associated with disease progression in MM.

Currently, autologous peripheral stem cell transplantation used as a therapeutic modality in the treatment of various hematological malignancies is gaining more popularity day by day. In this method, the patient's own peripheral stem cells are collected by a proper method and stored at -80 degrees C until they are reinfused into the patient after being rewarmed in water bath at 37 degrees C. A number of complications have been reported related to reinfusion of the cryopreserved cells into the patient. These may include noncardiovascular complications such as nausea, vomiting, flushing, abdominal pain, chest discomfort, and headache, as well as cardiovascular complications like arrhythmias, hypotension, and hypertension. Hypothermia related to rapid infusion has been reported as the main factor underlying the cardiovascular complications. Electrocardiographic findings of hypothermia include sinusal bradycardia, prolonged QT and PR intervals, widened QRS complexes, and J wave, which is a ECG abnormality characterized by supraventricular and ventricular arrhythmias. We here present two cases of giant J wave caused by hypothermia during infusion of cryopreserved autologous peripheral stem cell that is detected by ECG and regressed after infusion ceased.

Thrombin activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase downregulating plasmin formation, thereby causing a tendency for thrombosis development. Since, Behçet's disease (BD) is a systemic vasculitis, which is commonly complicated by arterial and venous thrombosis, we aimed to find out plasma TAFI levels in BD, compared with healthy controls. We also searched whether plasma TAFI levels were significantly different between Behçet's subgroups with and without thrombosis.In this study, 105 BD patients (M/F: 64/41; mean age 36+/-1 years), followed up by Ege University Rheumatology Department were enrolled. The exclusion criteria were hemophilia, hyperlipidemia, diabetes mellitus, hepatic diseases renal failure, antiphospholipid positivity, oral contraceptive use and pregnancy. Age-and sex-matched healthy controls (n=53) were also included. Plasma TAFI levels were measured by ELISA. Since TAFI is also an acute-phase reactant, we also measured other inflammatory markers such as C-reactive protein (CRP).Plasma TAFI levels were significantly higher in Behçet's patients (91.1+/-7.4 ng/ml) compared with healthy controls (14.3+/-4.5 ng/ml) (P0.001), but there were no significant difference between the subgroups with and without thrombosis. In BD, there was no correlation between plasma TAFI levels and CRP.Regardless of manifest thrombosis, plasma TAFI levels in BD were significantly higher than in healthy controls. High TAFI levels might possibly contribute to the thrombotic tendency in BD. Future studies investigating TAFI gene polymorphism and functional activity are clearly needed, to clarify the exact role of TAFI in Behçet's thrombosis.

This is the last of a series of articles on invasive fungal infections prepared by opinion leaders in Turkey. The aim of these articles is to guide clinicians in managing invasive fungal diseases in hematological malignancies and stem cell transplantation based on the available best evidence in this field. The previous articles summarized the diagnosis and treatment of invasive fungal disease and this article aims to explain the risk categorization and guide the antifungal prophylaxis in invasive fungal disease.Bu makale Türkiye’de invazif fungal enfeksiyon ile uğraşan uzmanlar tarafından hazırlanan bir seri yazının sonuncusudur. Bu makaleler hematolojik malignitelerde ve kök hücre nakli hastalarında invazif fungal hastalıkların yönetimini eldeki kanıtların ışığında en iyi hale getirmeyi amaçlamaktadır. İlk yazılar tanı ve tedaviyi özetlerken, bu makale invazif fungal hastalıkta risk kategorizasyonu ve profilaksiyi ele almaktadır.

and showed evidence of disease in 145 (93%). After a median follow-up of 3.5 years, the median OS for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively. At least one previous line of therapy for MM and > 1 cytogenetic abnormality were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively. Conclusion: Neurological manifestations observed in patients with MM should raise a suspicion of CNS involvement. The diagnosis of CNS MM should be based on imaging studies and CSF cytology and flow cytometry. Although prognosis is generally poor, especially in patients with a long history of chemotherapy and unfavorable cytogenetic profile, survival of individuals free from these negative prognostic factors can be prolonged due to administration of systemic treatment and/or radiotherapy. Prospective multi-institutional studies are warranted to improve the outcome of patients with CNS MM. PO-089 Improved tumor response and survival outcomes with post-transplant bortezomib (Btz) consolidation versus observation (Obs) alone in patients with newly diagnosed multiple myeloma (MM): Results from a randomized, open-label, multicenter, parallel-group phase 2 study O. Sezer, E. Terpos, R. Hajek, G. Sucak, S. Cagirgan, W. Linkesch, O.M. Akay, G. Armbrecht, T. Plesner, J.A. Snowden, H. Nahi, Z. Gulbas, A. Potamianou, C. Couturier, R. Olie, C. Feys, N. Allietta, M. Beksac Department of Hematology and Stem Cell Transplantation, Memorial Hospital, Istanbul, Turkey; Department of Clinical Therapeutics, University of Athens School of Medicine, Alexandra General Hospital, Athens, Greece; Internal Medicine and Hematooncology, Masaryk University Hospital Brno and Faculty of Medicine University Hospital Ostrava, Czech Republic; Department of Hematology, Faculty of Medicine, Gazi University, Ankara, Turkey; Department of Hematology and BMT Center, Izmir Medicalpark Private Hospital, Izmir, Turkey; Department of Hematology, Medical University Clinic, Medical University of Graz, Graz, Austria; Hematology Department, Eskisehir Osmangazi University, Eskisehir, Turkey; Centre for Muscle and Bone Research, Charite e Campus Benjamin Franklin, Berlin, Germany; Department of Hematology, Vejle Hospital, Vejle and IRS/ SDU, Denmark; Department of Haematology, Royal Hallamshire Hospital, Sheffield, UK; Haematology Centre, Karolinska University Hospital, Stockholm, Sweden; Bone Marrow Transplantation Department, Anadolu Health Center, Kocaeli, Turkey; Janssen-Cilag Pharmaceutical SACI, Athens, Greece; Janssen-Cilag, Issy-lesMoulineaux, France; Janssen-Cilag AG, Zug, Switzerland; Janssen Research & Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium; Covance for Janssen-Cilag, Issy-les-Moulineaux, France; Department of Hematology, Ankara University, Ankara, Turkey Background: Induction therapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a standard frontline treatment for eligible MM patients (pts). PostASCT consolidation can improve depth of response and long-term outcomes. This phase 2 study evaluated the effects of Btz consolidation vs Obs alone on MM-related bone disease; pre-specified secondary endpoints of disease status (myeloma response), PFS, and OS are reported here. Methods: Eligible pts were adults with newly diagnosed MM who had achieved PR after single/double ASCT. Pts were randomized 1:1 (stratified by baseline bisphosphonate use and age) to receive 4 x 35-d cycles of Btz 1.6 mg/m2 IV on d 1, 8, 15, and 22, or Obs alone, followed by 18-mos’ follow-up for disease status and survival monitoring. Response was investigator-assessed per IMWG 2009 criteria. A last observation carried forward approach was used for missing assessments. PFS and OS were estimated using Kaplan-Meier analysis; exploratory p-values were determined using the log-rank test. Results: Between July 2009 and May 2012, 106 pts were randomized (52 Btz, 54 Obs). 2 pts were withdrawn prior to d 1, thus the modified intent-to-treat (mITT) population included 104 pts (51 Btz, 53 Obs): median age 58 vs 57 yrs; 71% vs 66% prior Btz-based induction. 41 (79%) and 46 (85%) pts completed the respective Btz consolidation and Obs phases as planned. CR+sCR rates at screening were 16% (Btz) and 15% (Obs). After the treatment/Obs phase, response rates were (Btz vs Obs): CR+sCR 22% vs 11%; VGPR 80% vs 68%; PD 8% vs 23%. PFS appeared longer with Btz consolidation vs Obs, both from randomization (median 44.9 vs 21.8 mos) and from first antiMM treatment (median 50.7 vs 35.0 mos) (Figure). After 21 (20%) deaths (11 Btz; 10 Obs), mean OS from randomization was 40.1 vs 36.6 mos and from first anti-MM treatment was 51.7 vs 47.1 mos; median OS was not reached in either arm at both time points. Pvalues for between-arm differences in response rates, PFS, and OS were all >0.05, likely due to small sample size. Conclusion: Compared with Obs alone, Btz consolidation was associated with trends for improved response depth and longer PFS and OS in newly diagnosed MM pts. Our response and PFS findings compare favorably with recent phase 3 data of Btz consolidation vs Obs in 15th International Myeloma Workshop, September 23-26, 2015 e129

WOS: 000318245800004, PubMed ID: 23503409, The risk of de novo malignancy is significantly higher in patients who have undergone organ transplantation than in the general population. Long-term immunosuppressive treatment, in addition to age, genetic pre-disposition and infectious agents, plays a major role in the development of malignancy. Although skin and hemopoietic system cancers are common, atypical presentations of malignancies may occasionally be seen during long-term follow-up in patients with functioning allografts. In this report, four cases, each with more than one different primary malignancy (one patient with three malignancies and three patients with two malignancies), are presented.

WOS: 000324224900001, PubMed ID: 23726928, In the 2008 WHO lymphoma classification, 'EBV-positive diffuse large B cell lymphoma (DLBCL) of the elderly is included as a new provisional entity. We aimed to evaluate the morphological, immunophenotypic, and clinical characteristics of the cases diagnosed as 'EBV-positive DLBCL of the elderly' in our center and compared them with the 'EBV-negative DLBCL' patients older than 50 years of age. EBV status was detected by Epstein-Barr early RNA (EBER) in situ hybridization analysis. By immunohistochemistry, a panel of antibodies for CD10, Bcl-2, Bcl-6, IRF4/MUM1, CD30, and Ki67 was performed. Out of 149 DLBCL patients older than 50 years, without any known history of immunodeficiency or prior lymphoma, eight patients who fulfill the criteria were re-evaluated. Five patients were male and three were female, with a median age of 67.6 years. Four patients presented with nodal involvement; others presented with bone and soft tissue, bone marrow, and spleen infiltrations. Five cases revealed predominantly monomorphic morphology, one also contained focal areas consistent with polymorphous subtype; and three patients revealed a polymorphous infiltrate. When classified according to 'Hans criteria', five were non-GCB, and three were of the GCB cell phenotype. All cases with polymorphous morphology were revealed to be of the non-GCB cell phenotype, and all expressed IRF4/MUM1. Two patients died with disease, four patients are alive and in complete remission following R-CHOP therapy, and two patients have just recently been diagnosed. When compared with the EBV-negative group, there are no reliable morphological and immunohistochemical features indicating EBV positivity. Therefore, EBER in situ hybridization analysis is necessary to identify 'EBV-positive DLBCL of the elderly'. Further studies are needed to fully understand the details of this disease, which can lead to new treatment modalities. (C) 2013 Elsevier GmbH. All rights reserved.

Reactive bone marrow plasmacytosis occurs in association with a variety of conditions. In such reactive cases, Plasma Cells (PCs) usually account for 10%-20% of cells in bone marrow trephine biopsy sections and rarely exceed 50%. Here in we report an unusual case of bone marrow aplasia associated with prominent atypical plasma cell proliferation and hypoplastic bone marrow.

Acquired activated protein C resistance (aAPCR) is seen more frequently in solid and hematological cancer patients. We aimed to investigate the presence of aAPCR and the frequency of clinically detectable thrombosis in sarcoma patients. Normalized activated protein C sensitivity ratio (nAPCSR), factor V Leiden (FVL) mutation, factor V (FV) levels and factor VIII (FVIII) levels were prospectively measured in 52 patients and in 52 healthy controls. Clinically detectable thrombosis was present in one patient (1.92%). Compared with healthy controls (106%), the sarcoma patients had significantly lower values of the nAPCSR at pre (87.25%) and post (94.35%) treatment period (P < 0.0001). aAPCR was found as 4.2, 13 and 0%, respectively. The post-treatment FV levels (178.1 U/dl) were significantly (P < 0.001) higher than the pretreatment levels (147.5 U/dl). Inverse correlation was found between post-treatment FV levels and nAPCSR values (r = -0.38, P < 0.02). We found out a slightly increased frequency of venous thromboembolism in sarcoma patients. As an original finding which has not been reported previously in the literature, we also found out a decrease in the nAPCSR, persisting even after treatment. Thirdly, we found out that the significantly higher rate of aAPCR at the time of diagnosis totally disappeared after treatment.

There is no detailed information about the clearance time of infused hematopoietic stem cell (HSC) from the blood circulation in humans. In this prospective study, peripheral blood CD34+ cell counts were detected during the 4days period following autologous HSC transplantation in 20 patients by means of flow cytometry. The median CD34+ cells were at the highest level in the first hour and decreased below pre-infusion values on the first day after HSC infusion. By nonparametric analysis, positive correlation was found between CD34+ cell levels at the first hour and the post-thaw CD34+ cell dose (r=0.57, p=0.01). An inverse correlation was determined between CD34+ cell levels at the first hour and neutrophil engraftment (r=-0.54, p=0.01). Compared with the patients having CD34+ cell count of ⩾2μL(-1) in the first hour following HSC infusion, the patients having CD34+ cell count of

We retrospectively reviewed peripheral blood stem cell (PBSCs) collections following 528 mobilization cycles over a 10-year period. A total of 206 (13.1%) AEs occurred in association with the 1572 procedures. One hundred and ninety-one (12.15%) of the AEs were classified as clinical AEs and 15 (0.95%) were classified as apheresis instrument related AEs. The most common clinical AE was numbness of the lips, tongue, or extremities (161 procedures, 10.2%) related to the infusion of acid citrate dextrose-A (ACD). Multivariate analysis revealed high amounts of ACD/weight (odds ratio [OR]=1.11, p=0.009), high numbers of procedures (OR=1.33, p0.001) and female gender (OR=2.83, p0.001) as being significantly associated with clinical AEs. Female gender was shown to be the most important risk factor for clinical AEs. Females who have a significantly increased risk of AEs would benefit from prophylactic calcium before and/or during PBSC collection.

Objective: Amyloidosis represents extracellular deposition of congophilic fibrils of similar morphology but different chemical composition. The types frequently involving the kidney are AA (serum amyloid A) and AL (light chain amyloid). Hereditary amyloidoses, which can also affect the kidney, are being described with increasing frequency. Distinguishing the type of amyloid is important because of the different treatments and outcomes. typing of amyloidosis by immunohistochemistry (iHC) is believed to be unreliable, except for AA amyloid. We reevaluated our cases in this study to draw attention to the nonAA amyloid deposits in renal biopsies with amyloidosis. Material and Method: renal biopsies diagnosed as amyloidosis between 997 and 2008 were stained for amyloid A with iHC. Cases with negative amyloid A staining were included in the study. Results: We found 90 cases of renal amyloidosis ( 98 biopsies) during the study period. Thirty cases (33 biopsies) with negative antiAA staining were studied. Among those 30 cases with nonAA amyloidosis, secondary AL amyloidosis was due to multiple myeloma in 8 cases and plasma cell dyscrasia in 2 cases. Hereditary renal amyloidosis was suspected in some cases. Conclusion: using amyloid A iHC on a routine basis and the clinical history are essential to diagnose AA amyloidosis. The differential diagnosis of nonAA amyloidosis may be inconclusive on iHC. The diagnostic approach should be multidisciplinary and requires careful clinical and pathological evaluation. The limitation of iHC may necessitate direct typing of the amyloid protein extracted from paraffin-embedded specimens in some cases.

Anti-TNF drugs may increase lymphoma risk in autoimmune rheumatic diseases, such as rheumatoid arthritis, but there have been no reports stating increased risk of lymphoma in ankylosing spondylitis (AS). Before 2 years, we had presented a case with AS developing Hodgkin's lymphoma following 6 months of etanercept treatment. Hereby, we present another case with AS developing non-Hodgkin's lymphoma (NHL), subsequent to 11 months of etanercept treatment. Pathological analysis revealed diffuse large B cell NHL. Although this is a report of a single case, cautious use of anti-TNF drugs is strongly recommended as they might cause lymphoma development even in AS.

We evaluated clinical features, management and survival of 12 patients with primary testicular non-Hodgkin's lymphoma presented to our hematology unit between January 1992 and July 2006, retrospectively. The median age of patients was 47 years at presentation (range 29-78 years) and > 80% of them were < 50 years old. In the majority of cases, orchidectomy was performed as diagnostic and first-line therapeutic procedures. Dominant histological subtype was diffuse large B-cell non-Hodgkin's lymphoma. Seven patients out of 12 (58%) were Ann Arbor stages I and II, and the remaining five patients (42%) were stages III and IV. All the patients received doxorubicin-based chemotherapy and achieved complete remission. The addition of rituximab and central nervous system prophylaxis with intrathecal combined chemotherapy containing methotrexate, cytarabine and dexametasone were applied to three patients who were recently admitted. The rate of relapse was 8% and progression-free survival (PFS) at 10 years was 88%. Median duration of response was 84 months (range 14-173 months), median 97.5 months of follow-up. All patients are alive and in case remission. Because of the spreading nature and relapse probability at different sites, including central nervous system and contralateral testis, systemic treatment with doxorubicin-based chemotherapy with or without prophylaxis for contralateral testis and the central nervous system seems to improve the outcome of primary testicular lymphoma.

We present a patient with an isolated oculomotor nerve palsy due to central nervous system leukemia with bone marrow findings consistent with myelofibrosis without any blasts. This has not been previously reported.

Hypocholesterolemia is seen in solid tumors and some hematological malignancies. We assessed cholesterol levels and the relationship between these levels and types and stages of multiple myeloma (MM) in the patients with MM. One-hundred two patients (60 male and 42 female) of mean age 59 +/- 11 years with MM were enrolled to this study. While 71.6% of the patients were Ig G type, 80.4% of the patients were at stage III. In the control group, there were 71 healthy persons (42 male and 29 female) of mean age 58 +/- 8 years. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in the patients with MM were significantly lower than the controls (p0.001). There was no difference for the levels of very-low-density lipoprotein cholesterol and triglyceride between the two groups (p0.05). Lipid parameters were not different between Ig types (p0.05). The levels of TC and LDL-C in the patients with stage I were higher than those of stages II and III (p0.001 and p0.005, respectively). The levels of TC and LDL-C in the controls were not higher than the patients with stage I (p0.05). HDL-C levels in the patients with stage III were lower than controls (p0.001). Hypocholesterolemia are seen in the patients with MM. Hypocholesterolemia may be due to increased LDL clearance and utilization of cholesterol by myeloma cells.

Rationale Autologous stem cell transplantation for adult acutemyelogenousleukemia (AML) is a therapeutic option for good and intermediate risk patients. New compounds and new formulations in conjunction with pre andpost transplant targeted therapy may improve outcome. A recent EBMT retrospective survey investigating on Busulfan administered IV (Nagler A et al:Haematologica. 2014 ) pre autologous stem cell transplantation (ASCT) suggested that the combination of Busulfan and High dose Melphalan (BUMEL) was associated with the best overall survival. To address this question, we compared this regimen with the historical Busulfanand Cyclophosphamide (BUCY) association. Methods Eligibilitycriteria consistedof all adult patients (age >18 years) with AMLautograftedin CR1, following a preparative regimen consisting of either BUCY or BUMEL, reported to the EBMT registry in the period from January 2005 to December 2013. The doses of Busulfan were either oral at 16 mg/kg over 4 days or IV at 12.8 mg/kg over 4 days. High dose Melphalan was 140mg/m². The data came from 231 centers 23 ofwhich usedboth regimens. The relationships between outcomes and patient, disease and transplant characteristics was evaluated in multivariate analyses using the Cox model. Results 1120 patients received BUCY and 436 BUMEL prior to autografting in first remission. Patients receiving BUMEL were older (median 52 years versus 50 years, p=0.01) with less good risk diseases by cytogenetics (16% versus 28%, p=0.001). They were autografted with a longer interval from CR1 to autografting (120 days versus 104 days, p=0.001) and they were more frequently in a negative minimal residual disease (MRD) status by molecular biology (89% versus 82%, p= 0.03). The nature of the pretransplant regimen interacted with the interval from diagnosis to autografting on both relapse incidence (p=0.005) and leukemia free survival (p= 0.02): the outcome post BUMEL was superior to BUCY only in patients transplanted within less than six months post diagnosis. In these patients, following BUMEL and BUCY respectively, the RI was 35%versus 50.6% (p< 10-3), the LFS 61.1% versus 46.2% (p< 10-3) and the OS 79.4% versus 64.8% (p= 0.003). There was no difference for NRM. When considering only patients autografted at the time when MRD detection was negative, the LFS at two years was 75.8% for 134 patients receiving BUMEL and 58.6% in the 371 patients receiving BUCY, with no significant difference (p= 0.1). The major cause of death in the two groups was leukemia recurrence. Conclusion We conclude that the BUMEL combination pre ASCT in AML CR1 is superior to BUCY when the transplant is performed less than 6 months after diagnosis. These registry data should be confirmed in a well designed two arm study assessing the role of ASCT in good risk and possibly intermediate -1 risk adult patients with AML. | | | p | HR | 95% CI | | --- | ------------------------------------------ | ----- | ----- | ------ | ----- | | NRM | BUMEL vs BUCY | 0.450 | 1.376 | 0.599 | 3.16 | | | Age atTx/ 10years | 0.001 | 1.064 | 1.025 | 1.10 | | | Time from diagnosis to Transplant. | 0.900 | 0.999 | 0.984 | 1.01 | | | Cytogenetics :Intermediatevs good | 0.610 | 0.709 | 0.191 | 2.63 | | | Poor versus good | 0.710 | 0.708 | 0.112 | 4.46 | | | Missing | 0.420 | 0.591 | 0.164 | 2.11 | | | centre (frailty) | 0.360 | | | | | RI | BUMEL vs BUCY | 0.001 | 0.602 | 0.445 | 0.816 | | | Age at Transplant / 10years | 0.005 | 1.012 | 1.003 | 1.020 | | | Time from diagnosis to Transplant: | 0.720 | 1.000 | 0.996 | 1.004 | | | Cytogenetics : Intermediatevs good | 0.510 | 1.145 | 0.764 | 1.714 | | | Poor versus good | 0.031 | 1.799 | 1.055 | 3.067 | | | Missingversus good | 0.480 | 1.150 | 0.779 | 1.699 | | | centre (frailty) | 0.110 | | | | | OS | BUMEL vs BUCY | 0.002 | 0.614 | 0.449 | 0.841 | | | Age at Transplant / 10years

WOS: 000245704500015, PubMed ID: 17236813, There are several side effects which have been reported during the infusion of peripheral blood progenitor cells (PBPCs) either due to the infusion or the content of the infusate. We have evaluated the side effects detected during PBPCs infusion in 194 autologous and 25 allogeneic transplantations. In autologous cryopreserved PBPCs infusion, we detected a total of forty-nine (25.25%) side effect events during and after the infusion period. Forty-six (23.71%) of these side effects were detected during the infusion period including fifteen (7.73%) cardiac side effects, which required stopping the infusion, and thirty-one (15.97%) non-cardiac side effects, which did not require cessation of the infusion. Sinus bradycardia after a minimum of 45 min after completing the infusion was seen in three (1.54'%) patients. The median volume, dimethyl sulfoxide (DMSO) and total nucleated cell (TNC) content of the product were found to be significantly higher in patients with side effects compared to the group without any side effects (P < 0.05). The median volume and DMSO content were found to be significantly higher in patients with cardiac side effects compared to non-cardiac side effects (P < 0.05). There was no cardiac side effects in patients treated with an infusate containing 100 x 10(9) L-1 leukocytes. We did not observe any infusion-related side effects in patients given allogeneic non-cryopreserved PBPCs. We have concluded that the volume, DMSO and TNC content of autologous cryopreserved PBPCs product are directly related to clinical side effects. (c) 2006 Elsevier Ltd. All rights reserved.

WOS: A1997WZ68100041, PubMed ID: 9175073

WOS: 000187184800027, PubMed ID: 14675333, Acute leukemias tend to affect a younger population and are much more common in pregnant patients than chronic leukemias are. We report a case of acute lymphoblastic leukemia diagnosed during the third trimester presenting with organomegaly and thrombocytopenia. Delivery of the fetus by cesarean section was decided because of the fulminant nature of the acute leukemia within days of admission. Bone marrow biopsy revealed acute lymphocytic leukemia, French American-British L-2 subtype B cell immunotype. A left ovarian mass was identified during the cesarean section which later proved to be lymphoblastic infiltration. The patient was started on induction chemotherapy consisting of vincristine, daunorubicin, prednisolone, and L-asparaginase immediately after the diagnosis. The patient died of Acinetobacter septicemia 18 days after the first admission.

WOS: 000259504600009, Hemophilia A (HA) is a hereditary, life-threatening and disabling disorder. In this study, we have examined 61 unrelated HA patients in order to identify the incidence of the intron 1 factor VIII (FVIII) gene inversion in the West Anatolian population. According to the results of DNA analyses of the 61 HA patients, no intron 1 inversion of the FVIII gene was found., Ege University Research Fund (EBIL TEM)Ege University, We are grateful to Dr. Cemal Un (Bogazici University, Istanbul, Turkey) for the mutant DNA sample. This study was supported by Ege University Research Fund (EBIL TEM).

In this report, we present a patient with chronic myeloid leukemia (CML) in blastic phase who had two consecutive episodes of spontaneous regression back to chronic phase without chemotherapy. Although, spontaneous remission (SR) is well documented in acute leukemia, SR in CML blastic phase is extremely rare and to the best of our knowledge only one case has been reported in the world literature. The factors possibly related to this phenomenon are discussed.