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Bortezomib (Vel)- Melphalan 200 mg/m2 (Mel200) (Vel-Mel) has been utilised to intensify conditioning in autologous hematopoietic stem cell transplantation (AHCT) for multiple myeloma (MM). This EBMT registry-based study compared Vel-Mel with Mel200 during upfront AHCT. Between 2010 and 2017, MM patients who received Vel-Mel (n = 292) conditioning were compared with 4,096 Mel200 patients in the same 58 centres. Pre-AHCT, compared to Mel200 patients, Vel-Mel patients had similar International Staging System (ISS) scores and cytogenetic risk profiles; a similar proportion had received bortezomib-based induction (85% and 87.3%, respectively) though they were younger with a better performance status. Vel-Mel patients were more likely to achieve CR post-induction (40.6% vs 20.3%, p < 0.001) and by day 100 of AHCT (CR/VGPR: 70.2 % vs. 57.2%, p < 0.001). There was no difference in 3-year PFS (49% vs 46%, p = 0.06) or early post-AHCT mortality. In multivariable analysis, Vel-Mel associated with inferior PFS (HR: 1.69 (1.27-2.25, p < 0.001) and OS (HR:1.46 (1.14-1.86,p = 0.002), similar to negative effects on PFS of advanced ISS (HR:1.56 (1.33-1.83, p < 0.001), high-risk cytogenetics (HR:1.43(1.18-1.74, p < 0.001) and poor post-induction response(<=PR)(HR: 1.43(1.25-1.62, p < 0.001) Overall, despite superior pre- and post-AHCT responses, there was no improvement in PFS or OS following Vel-Mel. This data supports the findings of the smaller prospective IFM study., (© 2024. The Author(s).)

We retrospectively compared outcomes of 404 MDS patients undergoing 1st matched sibling donor allo-HCT receiving either PTCy-based (n = 66) or other "conventional prophylaxis" (n = 338; mostly calcineurin inhibitor + methotrexate or MMF). Baseline characteristics were balanced, except for higher use of myeloablative regimens in the PTCy group (52.3% vs. 38.2%, p = 0.047). Incidences of neutrophil (Day +28: 89% vs. 97%, p = 0.011) and platelet (Day +100: 89% vs. 97%, p < 0.001) engraftment were lower for PTCy-based. Day +100 cumulative incidences of grade II-IV and III-IV aGVHD, and 5-year CI of extensive cGVHD were 32%, 18% and 18% for PTCy-based and 25% (p = 0.3), 13% (p = 0.4) and 31% (p = 0.09) for the conventional cohort. Five-year OS (51% vs. 52%, p = 0.6) and GRFS (33% vs. 25%, p = 0.6) were similar between groups. Patients receiving PTCy had a trend to a lower cumulative incidence of relapse (20% vs. 33%, p = 0.06), not confirmed on multivariable analysis (p = 0.3). Although higher NRM rates were observed in patients receiving PTCy (32% vs. 21%, p = 0.02) on univariate analysis, this was not confirmed on multivariate analysis (HR 1.46, p = 0.18), and there was no resultant effect on OS (HR 1.20, p = 0.5). Based on these data, PTCy prophylaxis appears to be an attractive option for patients with MDS undergoing MSD allo-HCT., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Extracorporal Photophoresis (ECP) is in clinical use for steroid-refractory and steroid-dependent acute GVHD (SR-aGVHD). Based on recent Phase-III study results, ruxolitinib has become the new standard of care for SR-aGVHD. Our aim was to collect comparative data between ruxolitinib and ECP in SR-aGVHD in order to improve the evidence base for clinical decision making., Methods: We asked EBMT centers if they were willing to participate in this study by completing a data form (Med-C) with detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient., Results: 31 centers responded positively (14%) and we included all patients receiving alloSCT between 1/2017-7/2019 and treated with ECP or ruxolitinib for SR-aGVHD grades II-IV from these centers. We identified 53 and 40 patients with grades II-IV SR-aGVHD who were treated with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-aGVHD (steroid dependent vs. refractory). At day+90 after initiation of treatment for SR-aGVHD we found no statistically significant differences in overall response. The odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.13 (95% CI = [0.41; 3.22], p = 0.81). In line, we detected no statistically significant differences in overall survival, progression-free survival, non-relapse mortality and relapse incidence., Discussion: The clinical significance is limited by the retrospective study design and the current data can't replace prospective studies on ECP in SR-aGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-aGVHD., Competing Interests: Author OP has previously received honoraria from Mallinckrodt Pharmaceuticals, but not for the current project. Author OP has received honoraria or travel support from Gilead, Jazz, MSD, Novartis and Pfizer. He has received research support from Incyte and Priothera. He is member of advisory boards to Equillium Bio, Jazz, Gilead, Novartis, MSD, Omeros, Priothera, Sanofi, Shionogi and SOBI. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This study received funding from Mallinckrodt Pharmaceuticals. The funder had the following involvement with the study: study design was done by EBMT experts and was approved by the funder; interpretation of data was discussed by EBMT experts and was communicated with the funder. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Penack, Peczynski, Boreland, Lemaitre, Afanasyeva, Kornblit, Jurado, Martinez, Natale, Pérez-Simón, Brunello, Avenoso, Klein, Ozkurt, Herrera, Wichert, Chiusolo, Gavriilaki, Basak, Schoemans, Koenecke, Moiseev and Peric.)

Maintenance therapy in APL is still a standard especially in high-risk patients treated with chemotherapy+ATRA combination whereas the role of the maintenance therapy in low-risk patients is controversial. This study aims to compare the efficacy and toxicity of ATRA monotherapy and ATRA+MTX+ 6-MP combination as the maintenance treatment for 2 years in APL patients who achieved molecular complete response after induction and consolidation with ATRA+chemotherapy. A total of 71 patients from 4 different centers were included in this study. After a median follow-up of 54 months (5-180 months), the 5-year RFS was 89 % in the ATRA monotherapy arm, the 5-year RFS was 78.5 % in the combined treatment arm (p = 0.643, HR:1.3, 95 % CI: 0.35-5.3). Hematological toxicity in all grades and Grade III/IV hematological toxicity was observed significantly more in the combined treatment arm than in the ATRA monotherapy arm (All grades: 76.9 % vs 18.9 %, p < 0.001; Grade III/IV: 20.5 % vs. 3.1 %, p = 0.035). Hepatotoxicity at all levels was significantly higher in the combined treatment arm than in the ATRA monotherapy arm (61.5 % vs 25 %, p = 0.002). Our study concluded that two years of ATRA monotherapy and combined maintenance therapy, both of which were found to be similar in terms of disease control and long term survival, ATRA Monotherapy could be a safer maintenance treatment option since both hematological and non-hematological toxicities were observed less often in the ATRA monotherapy arm., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Ethical approval was waived by the local Ethics Committee of University of Health Sciences Gulhane Faculty of Medicine with its approval dated 27.06.2022 and numbered 46418926, in view of the retrospective nature of the study and all the procedures being performed were part of the routine care. Informed consent was obtained from all individual participants included in the study., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The role of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in the treatment of myeloma (MM) patients with severe and/or dialysis-dependent renal impairment remains uncertain. We report on the outcomes of 110 patients (median age 57 years) who had become dialysis-dependent pre-ASCT and who underwent a first ASCT between 1997 and 2017. Sixty-three (57%) patients had light chain MM. All patients required dialysis (94% hemodialysis and 6% peritoneal). Forty-four of 71 (62%) patients received bortezomib-based induction regimens and 42 (39%) patients had achieved at least a very good partial response (VGPR) pre-ASCT. Melphalan dosing was as follows: ≤140 mg/m 2 (82%), and >140 mg/m 2 (18%). The median PFS after ASCT was 35 months (95% CI: 21.5-42.2) and the median OS 102 months (95% CI: 70.4-129.1). At 1, 2, and 5 years after ASCT, 8% (95% CI 3-14%), 13% (6-20%), and 20% (12-29%) of patients, respectively, had achieved dialysis independence. In multivariate analyses of OS and PFS including age at ASCT, response at ASCT, and year of ASCT, younger age at ASCT and better response at ASCT (CR/VGPR/PR vs. MR/SD/progression) were significantly associated with better OS and PFS., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Therapeutic apheresis is an extracorporeal treatment that selectively removes abnormal cells or harmful substances in the blood that are associated with or cause certain diseases. During the last decades the application of therapeutic apheresis has expanded to a broad spectrum of hematological and non-hematological diseases due to various studies on the clinical efficacy of this procedure. In this context there are more than 30 centers performing therapeutic apheresis and registered in the apheresis database in Turkey. Herein, we, The Turkish Apheresis Registry, aimed to analyze some key articles published so far from Turkey regarding the use of apheresis for various indications., Competing Interests: Conflicts of interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Autologous hematopoietic cell transplantation (auto-HCT) may be performed in multiple myeloma (MM) patients relapsing after a previous auto-HCT. For those without an adequate dose of stored stem cells, remobilization is necessary. This retrospective study included patients who, following disease relapse after the first auto-HCT(s), underwent stem cell remobilization and auto-HCT performed using these cells. There were 305 patients, 68% male, median age at salvage auto-HCT was 59 years. The median time to relapse after the first-line penultimate auto-HCT(s) was 30.6 months, the median follow-up after salvage auto-HCT 31 months. The 2- and 4-year non-relapse mortality (NRM) after the salvage auto-HCT was 5 and 9%, the relapse incidence 56 and 76%, respectively. Overall survival (OS) after 2 and 4 years was 76 and 52%, progression-free survival (PFS) 39 and 15%. In multivariable analysis an increasing interval between the penultimate auto-HCT and relapse was associated with better OS and PFS, later calendar year of salvage auto-HCT with better OS. In conclusion, salvage auto-HCT performed with cells remobilized after a previous auto-HCT was associated with acceptable NRM. The leading cause of failure was disease progression of MM, which correlated with a shorter interval from the penultimate auto-HCT to the first relapse., (© 2022. The Author(s).)

The AETHERA trial reported an increased progression-free survival (PFS) when brentuximab vedotin (BV) was used as maintenance therapy in high-risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). Thus, we aimed to determine the impact and safety of BV as maintenance after ASCT in real-world patients. Seventy-five patients with relapsed/refractory HL started on BV consolidation therapy after ASCT due to high risk of relapse, between January 2016 and July 2019, from 25 institutions, were included in the study. The median follow-up time was 26 months. The most common high-risk features were primary refractory or relapsed disease <12 months (n = 61), lack of complete response (CR) to the last salvage regimen (n = 51), and having had at least two salvage regimens (n = 29). At the time of analysis, 42 patients completed consolidation courses, and BV was discontinued in 33 patients. Fifty patients had an ongoing response (CR in 41, PR in 6, and SD in 3 patients), 25 had progressed. Ten died in the follow-up, eight with progressive disease and two due to infection while in CR. The 2-year PFS and OS rates were 67.75% (95% confidence interval [CI]: 0.55-0.77) and 87.61% (95% CI: 0.76-0.94), respectively. Seventeen patients (23%) received BV in the pre-ASCT treatment lines, and there was no survival difference between the BV-naïve and BV-exposed groups. The most common adverse events were neutropenia (27%) and peripheral neuropathy (21%). Sixteen patients (21.3%) experienced grade 3 or 4 toxicity. BV was discontinued due to adverse event in 12 patients. Consolidation with BV after ASCT can achieve a 2-year PFS of 67.75% (95% CI: 0.55-0.75) with an acceptable toxicity profile., (© 2021 John Wiley & Sons Ltd.)

We retrospectively compared outcomes of a large series of adult patients with APL in CR2 receiving alloHSCT (n = 228) or autoHSCT (n = 341) reported to the European Society for Blood and Marrow Transplantation from January 2004 to December 2018. The 2-year cumulative incidence of non-relapse mortality was significantly higher for alloHSCT 17.3% (95% CI 12.5-22.8) compared with autoHSCT 2.7% (95% CI 1.2-5) (p = 0.001), while differences in relapse rate were not significant (28% versus 22.9%; p = 0.28). Leukemia-free survival (LFS) and overall survival (OS) favored autoHSCT with 74.5% (95% CI 69-79.2) and 82.4% (95% CI 77.3-86.5) compared with alloHSCT with 54.7% (95% CI 47.5-61.3) (p = 0.001) and 64.3% (95% CI 57.2-70.6), respectively (p = 0.001 and p = 0.001). Multivariable analysis showed significantly worse LFS after alloHSCT (HR 0.49; 95% CI 0.37-0.67; p < 0.0001), older age (p = 0.001), and shorter time from diagnosis to transplant (p = 0.00015). Similar results were obtained for OS. The study shows that autoHSCT resulted in better survival outcomes (LFS and OS) for APL in CR2. These results were mainly due to reduced NRM in the autoHSCT as compared to alloHSCT.

Introduction: Epstein-Barr virus (EBV) is associated with different types of human malignancies, including Burkitt lymphoma, nasopharyngeal carcinoma, and lymphomas. We retrospectively investigated the presence of EBV-DNA by real-time PCR in clinical samples of patients diagnosed as having hematologic malignancies while investigating the cause of lymphoproliferative disorders, and investigated its relationship to clinical manifestations., Patients and Methods: Fifty clinical samples sent to Gazi University's hematology clinics between November 2013 and March 2018 were included. EBV-DNA was investigated by real-time PCR method, and EBV-IgM and EBV-IgG antibodies were investigated by ELISA., Results: Fifty serum samples were investigated, and 10% (5/50) EBV-DNA positivity was determined in patients. Of the 5 patients with EBV-DNA positivity, 2 had acute lymphoblastic leukemia, 1 lymphoma, 1 T-cell lymphoma, and 1 B-cell lymphoma. Concomitant EBV-DNA and viral capsid antigen (VCA)-IgM positivity was not detected. The VCA-lgM test results of the all EBV-DNA-positive patients were negative and VCA-IgG positive (except for 1 patient). Regarding virus load, of the 5 samples, 2, 1, 1, and 1 of the samples had a virus load of 10 2 , 10 3 , 10 4 , and 10 5 copies/mL, respectively., Conclusion: EBV infection is threatening in patients with hematologic malignancies and are diagnosed by serologic and molecular methods. As a result of the study, we suggest that the detection of EBV-DNA by real-time PCR in patients being admitted with lymphoproliferative diseases and diagnosed as acute lymphoblastic leukemia and lymphomas may be useful in follow-up and treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Relapse of acute lymphoblastic leukemia (ALL) remains a major therapeutic challenge. Despite the consensus for proceeding to allogeneic stem cell transplantation (HSCT) in relapsing patients with ALL who achieve second complete remission (CR2) with salvage therapy, most patients lack a suitable matched-related histocompatible donor. The present multicenter retrospective study compared, for ALL patients in CR2, the HSCT outcome from all four possible alternative hematopoietic stem cell sources, namely matched unrelated 10/10 (n = 281), mismatched unrelated 9/10 (n = 125), haploidentical (n = 105), and cord blood (n = 104) donors. The 2-year outcomes were not statistically different between the four donor sources with respect to overall survival (38.3-47.2%), leukemia-free survival (30.5-39.6%), relapse incidence (32.6-37.6%), nonrelapse mortality (27.5-34.6%), and graft-versus-host disease-free relapse survival (21.4-33.1%). Donor choices for ALL patients achieving CR2 post first relapse are broad, ensuring that most patient in need secures a graft. Therefore, in practice, the donor choice should depend on timely availability and policy center.

Objectives: Several studies described single nucleotide polymorphisms (SNPs) on pattern recognition receptor (PRR) such as toll-like receptors (TLRs), dendritic cell-associated C-type lectin-1 (Dectin-1/CLEC7A) genes of patients with invasive fungal infections (IFIs) caused by Candida and Aspergillus. We screened TLR4, Dectin-1 and PTX3 polymorphisms in a Turkish population with invasive aspergillosis (IA) underlying haematological malignancies., Methods: In this case-control study, a cohort of 59 patients with haematological malignancies were included. There were 26 IA patients assigned by the EORTC-MSG criteria and 33 patients with no evidence of fungal disease. DNA and RNA were isolated from frozen bone marrow and serum samples. RNA levels and polymorphisms of TLR4 (rs4986790, rs4986791), Dectin-1 (rs16910526, rs7309123) and PTX3 (rs2305619, rs3816527) were determined. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by unconditional logistic regression analysis., Results and Conclusions: TLR4, PTX3 and Dectin-1 genes were downregulated in aspergillosis cohort under similar haematological conditions. TLR4 expression was 0.0626 ± 0.032 in controls when compared to IA patients as 0.0077 ± 0.014, and the difference was significant (P = .026). There was a difference in also the PTX3 gene among IA (0.0043 ± 0.004) and control (0.5265 ± 0.0043) groups (P = .035). The Dectin-1 (CLEC/A) expression was downregulated in IA group (0.1887 ± 0.072 & 0.0655 ± 0.010) but not statistically significant (P > .05). Conditional logistic regression analyses indicated that the GT genotype of rs16910526 polymorphism in Dectin-1 gene was associated with lower risk of IA (odds ratio = 3.635, 95% confidence interval = 0.690-3.138, P = .04)., (© 2020 Blackwell Verlag GmbH.)

Most myelodysplastic syndromes (MDS)-patients receive multiple red blood cell transfusions (RBCT). Transfusions may cause iron-related toxicity and mortality, influencing outcome after allogeneic HSCT. This prospective non-interventional study evaluated 222 MDS and CMML patients undergoing HSCT. Overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), and relapse incidence (RI) at 36 months were 52%, 44%, 25%, and 31%, respectively. Age, percentage of marrow blasts and severe comorbidities impacted OS. RFS was significantly associated with RBCT burden prior to HSCT (HR: 1.7; p  = .02). High ferritin levels had a significant negative impact on OS and RI, but no impact on NRM. Administration of iron chelation therapy prior to HSCT did not influence the outcome, but early iron reduction after HSCT (started before 6 months) improved RFS significantly after transplantation (56% in the control group vs. 90% in the treated group, respectively; p  = .04). This study illustrates the impact of RBCT and related parameters on HSCT-outcome. Patients with an expected prolonged survival after transplantation may benefit from early iron reduction therapy after transplantation.

The use of antihuman T-lymphocyte immunoglobulin in the setting of transplantation from an HLA-matched related donor is still much debated. Acute and chronic graft- versus -host disease are the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. The aim of this study was to evaluate the effect of antihuman T-lymphocyte immunoglobulin in a large cohort of patients with myelofibrosis (n=287). The cumulative incidences of grade II-IV acute graft- versus -host disease among patients who were or were not given antihuman T-lymphocyte immunoglobulin were 26% and 41%, respectively. The corresponding incidences of chronic graft- versus -host disease were 52% and 55%, respectively. Non-adjusted overall survival, disease-free survival and non-relapse mortality rates were 55% versus 53%, 49% versus 45%, and 32% versus 31%, respectively, among the patients who were or were not given antihuman T-lymphocyte immunoglobulin. An adjusted model confirmed that the risk of acute graft- versus -host disease was lower following antihuman T-lymphocyte immunoglobulin (hazard ratio, 0.54; P =0.010) while it did not decrease the risk of chronic graft- versus -host disease. The hazard ratios for overall survival and non-relapse mortality were 0.66 and 0.64, with P -values of 0.05 and 0.09, respectively. Antihuman T-lymphocyte immunoglobulin did not influence disease-free survival, graft- versus -host disease, relapse-free survival or relapse risk. In conclusion, in the setting of matched related transplantation in myelofibrosis patients, this study demonstrates that antihuman T-lymphocyte immunoglobulin decreases the risk of acute graft- versus -host disease without increasing the risk of relapse., (Copyright© 2019 Ferrata Storti Foundation.)

Objective: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (AHSCT) recipients. Current practice includes prophylactic and preemptive treatment modalities, which have risks, side effects, and costs of their own. There is no established risk scoring system that applies to all patients. We aimed to investigate the risk factors for CMV reactivation in AHSCT recipients., Materials and Methods: We retrospectively analyzed the risk factors for CMV reactivation in 185 consequent AHSCT recipients transplanted between September 2003 and December 2009 at the Stem Cell Transplantation Unit of Gazi University. Besides the standard transplant-related parameters, HLA antigens were also included among the variables analyzed., Results: Despite the very high rate of donor (94.6%) and recipient (100%) seropositivity, which are the so-called major risk factors in previous reports, our reactivation rate was much lower, with a frequency of 24.9%. The underlying disease, sex, conditioning regimen, and presence of antithymocyte globulin or fludarabine in the conditioning regimen had no impact on reactivation rate. CMV reactivation was significantly more frequent in recipients with graft-versus-host disease (GVHD) compared to those without GVHD (p<0.0001). CMV reactivation was significantly more frequent (p<0.05) in patients with HLA-B14, HLA-DRB1*01, and HLA-DRB1*13 antigens and less frequent in recipients with HLA-A11 and HLA-DRB1*04 antigens (p<0.05)., Conclusion: Universal risk factors/scores that apply to all transplant recipients are required for tailored prophylaxis and/or treatment strategies for CMV reactivation. Uncovering the role of genetic factors, including HLA antigens, as possible risk factors might lead the way to risk-adaptive strategies for adoptive cellular therapy and/or vaccination.

This prospective study was planned to determine the intercourse between translationally controlled tumor protein (TCTP)/histamine releasing factor (HRF)/histamine pathway and angiogenesis in chronic lymphocytic leukemia (CLL). A total of 153 CLL patients were included. Serum histamine levels were higher in CLL patients. A positive correlation was found between microvessel density (MVD)-mast cell (MC) count; MVD-TCTP/HRF and MC count-TCTP/HRF. Microvessel density, MC and ZAP 70 were significantly higher in TCTP/HRF-positive group. Time to first treatment was shorter in patients with increased MVD and TCTP/HRF. Further data is essential to ascertain the role of TCTP/HRF pathway in tumor angiogenesis and CLL prognosis., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Iron overload is considered as a significant cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. The presence of hemochromatosis gene (HFE) mutations might exacerbate iron toxicity in the post-transplant setting. This prospective study was planned to evaluate the genetic spectrum of HFE mutations in Turkish patients undergoing HSCT and the impact of HFE genotype on transplant morbidity and mortality. HFE genotypes of 102 patients [median age, 27.5 years (16-64 years); male/female, 73:29], who underwent allogeneic HSCT, were analyzed. Twenty-two patients were heterozygous and 1 patient was homozygous for the H63D mutation, while the C282Y mutation was observed in none of our patients. The frequency of invasive fungal infections (IFI) was significantly higher in H63D-mutated patients (p=0.004). H63D mutation was identified as an independent risk factor for the development of IFI (p=0.006, OR=0.554, SE=0.208), without an impact on overall survival and transplant-related mortality. The multifactorial iron-overloaded state in HSCT recipients might affect the phenotypic expression of HFE mutations and alter the severity of clinical presentation. The impact of HFE genotype on iron parameters and transplant-related morbidity and mortality should be validated with further studies.

Objective: Recent reports show the adverse impact of pre-transplantation iron overload on the outcome of haematopoietic stem cell transplantation (HSCT). We studied the pre-transplantation serum iron (SI) parameters including prohepcidin levels - a regulatory peptide of systemic iron homeostasis - and their role in early post-transplantation toxicities in allogeneic HSCT recipients., Patients and Methods: One hundred consecutive patients [36 women and 64 men; median age 27·5 years (range 16-63 years)] who underwent allogeneic HSCT between September 2003 and October 2007 at Gazi University were included in the study., Results: Pre-transplantation serum prohepcidin levels did not show correlation with SI parameters and interleukin-6 levels (P>0·05). Prohepcidin levels were inversely correlated with the National Cancer Institute grade of mucositis (P=0·060), neutropenic fever (P<0·001), and the number of days with febrile neutropenia (P=0·003). SI levels were correlated with the severity of hepatotoxicity (P=0·015) while pre-transplantation transferrin saturation levels were positively correlated with the severity of hepatotoxicity (P=0·055), pulmonary toxicity (P=0·032), and sinusoidal obstruction syndrome (P=0·049). Pre-transplantation serum ferritin levels were positively correlated with the development of sinusoidal obstruction syndrome (P=0·010) and inversely correlated with the day of neutrophil engraftment (P=0·012). Overall survival was 41·26% with a median follow-up time of 13 months (range 0·0-60 months). Pre-transplantation serum prohepcidin levels and iron overload were not associated with survival in Cox regression analysis., Conclusion: Our results suggest that pre-transplantation iron parameters and prohepcidin levels might predict some of the early post-transplantation toxicities, however, without an impact on overall survival.

Purpose: We assessed the role of the maximum standardized uptake value (SUV(max)) of bone marrow and the extramedullary lesion with the highest SUV(max) in positron emission tomography/computed tomography (PET/CT) of newly diagnosed multiple myeloma (MM) patients in predicting overall survival (OS)., Methods: A total of 61 newly diagnosed patients (55 MM and 6 plasmacytoma) were enrolled in the study [37 men and 24 women with a median age of 57 years (range 28-80 years)]. The SUV(max) of bone marrow and the extramedullary lesion in PET/CT was correlated with the levels of β(2)-microglobulin, C-reactive protein (CRP), albumin, creatinine, per cent of bone marrow plasma cells, serum free light chain (FLC) ratio, International Staging System (ISS) score and Durie-Salmon stage., Results: The extramedullary lesion with the highest SUV(max) showed significant correlation with bone marrow fluorodeoxyglucose (FDG) uptake (p = 0.027) and near significant correlation with ISS (p = 0.048). Bone marrow SUV(max) correlated significantly with the per cent of bone marrow plasma cell count (p = 0.024), CRP (p = 0.012) and ISS (p = 0.013). In stage III MM the mean values of SUV(max) in extramedullary lesions were significantly higher than stages I and II (6.23 ± 6.32 vs 2.85 ± 3.44, p = 0.023). The serum FLC ratio did not show any correlation with SUV(max) of lesions and bone marrow (p > 0.05). Forty-four MM patients with FDG-positive lesions in PET/CT showed inferior 5-year estimated survival (61.73%) when compared to 11 patients without FDG-positive lesions, all of whom were alive (p = 0.01). In multivariate analysis an extramedullary lesion with the highest SUV(max) was the only independent predictor of OS (p = 0.03)., Conclusion: PET/CT allows identification of high-risk myeloma patients, and extramedullary lesions with the highest SUV(max) independently predict inferior OS.

Fungal pulmonary infections (FPIs) are frequent causes of mortality in hematopoietic stem cell transplantation (HSCT) recipients. Determination of the specific risk factors may improve the prognosis. The aim of this study was to evaluate the risk factors of FPIs due to HSCT. Patient history, physical examination, chest X-rays and the consultation records of the pulmonary disease department which were a part of the routine evaluation before and at first, third, sixth, ninth and twelfth months of HSCT were retrieved in 148 adult HSCT recipients. Results of the high-resolution computed tomography, fiber-optic bronchoscopy and the microbiological data were also included. FPI was diagnosed in 22 patients (14.9%). Multivariate analysis showed that increased ferritin levels (>1000 ng/ml; OR: 3.42, 95% CI 1.03-11.42, P=0.045) and the development of sinusoidal obstruction syndrome (SOS; OR: 5.09, 95% CI 1.53-16.90, P=0.008) were significant risk factors for FPIs. The sensitivity and specificity of ferritin >1000 ng/ml for the prediction of FPIs were 67 and 70%, respectively. There was a positive correlation between the increased risk of FPIs and pretransplantation ferritin levels (r=0.413, P<0.001) and increased ferritin levels and SOS (r=0.331, P<0.001). Increased pretransplantation ferritin levels and development of SOS are predictive factors of FPIs during HSCT.

Objectives: Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. Hepatosplenic candidiasis (HSC) is defined as a distinct form of invasive candidiasis, with liver, spleen, and kidney involvement, in patients with hematological disorders., Methods: The charts of 255 patients (male/female 168/87; median age 35 (range 16-71) years) who were evaluated pre-HSCT at the Gazi University Hospital Stem Cell Transplantation Unit between 2003 and 2008, were retrospectively reviewed., Results: HSC, which was demonstrated in six (2.3%) patients, was found to be more common in allogeneic HSCT recipients than in autologous HSCT recipients and in patients who had received two or more previous chemotherapy courses than in patients who had received fewer than two (p>0.05). Patients with HSC tended to have a worse performance status than patients without HSC according to the World Health Organization (p=0.001) and Karnofsky scale (p=0.007). Pre-transplantation ferritin (p=0.008) and acute phase reactant levels, including erythrocyte sedimentation rate (p=0.025) and C-reactive protein (p=0.007), were significantly higher in patients with HSC than in patients without HSC., Conclusions: This study shows the predictive role of pre-transplantation ferritin levels in selecting a subset of patients at increased risk for HSC. Pre-transplantation risk assessment and targeted strategies might lower the morbidity and mortality of IFI in HSCT recipients., (Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We retrospectively analyzed the data of 175 patients who underwent autologous (n = 69) or allogeneic hematopoietic stem cell transplantation (HCT) (n = 106) including 19 (27.5%) and 38 (35.8%) recipients who had bone marrow fibrosis (BMF) prior to transplantation, respectively. We investigated the effects of BMF on engraftment, graft-versus-host disease (GVHD), early posttransplant complications, and survival. Pretransplantation BMF did not delay engraftment and showed no impact either on early posttransplant complications or on the development of acute and/or chronic GVHD. Probability of 1-year overall survival (OS) and progression-free survival (PFS) of autologous HCT recipients were similar, namely 76.7% versus 88.6% (P > .005) and 26.33% versus 16.5% (P > .05) among patients with versus without fibrosis, respectively. In allogeneic HCT recipients, the probability of 1-year OS was 35.2% among patients with versus 48.9% among those without fibrosis (P = .004) PFS at 1 year was inferior among allogeneic HCT recipients with BMF: 27.8% versus 51.2% (P = .0008). Cox regression analysis revealed BMF to be independently associated with age, Sorror comorbidity index, primary disease, and disease status during HCT (P = .045)., (2010 Elsevier Inc. All rights reserved.)

Reactivation of hepatitis B virus (HBV) is a frequent complication of chemotherapy (CT) in patients with HBsAg carriers. In this prospective study, we documented CT induced HBV reactivation risk in patients with hematological malignancies. HBV reactivation risk is influenced by baseline viral load. Therefore, we divided our study population into two groups according to HBV-DNA status. HBV-DNA negative patients (n=18) were treated with nucleoside analogues once HBV reactivation was observed. HBV-DNA positive patients (n=12) commenced lamivudine before the initiation of the CT. In HBV-DNA negative patients HBV reactivation was found in 10 patients (55.5%). HBV reactivation was significantly more frequent in chronic lymphocytic leukemia (CLL) patients (P=0.008) and in patients receiving rituximab containing chemotherapy regimens (P=0.06). Eight patients (80.0%) responded to antiviral treatment after HBV reactivation. Two CLL patients experienced a flare-up after the withdrawal of antiviral therapy. In HBV-DNA positive patients, HBV reactivation was observed in four patients (33.3%) during lamivudine treatment and in two patients after lamivudine withdrawal. This study demonstrated the increased risk of CT-induced HBV reactivation in CLL patients, for the first time.

Introduction: Iron overload is an important problem in candidates for and survivors of hematopoietic stem cell transplantation (HSCT), and affects long-term outcome and survival. The objective of the present study was to determine the effect of iron overload on early toxic or infectious complications and survival., Patients and Methods: We retrospectively reviewed the medical records for 250 adult patients (162 men and 88 women; median [range] age, 34 [16-71] years who underwent HSCT between September 2003 and August 2008. The HSCT grafts were autologous in 102 patients, and allogeneic in 148., Results: Follow-up was 315 (1-1809) days. Mean (SD) pre-HSCT serum ferritin concentration was 1402.6 (5016.2) ng/mL in the entire group, 647.6 (1204.3 ng/mL in autologous recipients, and 1410.6 (2410.4) ng/mL in allogeneic recipients. Twenty-eight autologous graft recipients (27.4%) and 102 allogeneic recipients (68.9%) demonstrated serum ferritin concentrations of 500 ng/mL or greater, and were classified as the high-ferritin group. High ferritin concentrations were significantly associated with toxic or infectious complications including mucositis, fungal infections, pneumonia, and sinusoidal obstruction syndrome in the early post-HSCT setting. A significant effect of pre-HSCT ferritin concentration on overall survival and transplant-related mortality was observed. The effect of pre-HSCT ferritin on survival was independent of the comorbidity index at Cox regression analysis. In the entire study population, the probability of survival was significantly lower when ferritin concentration was greater than 500 ng/mL., Conclusion: Transplant-related mortality has decreased substantially with the development of supportive treatments. Pretransplantation risk assessment and risk-adapted strategies such as decreasing iron overload might further improve transplant-related complications.

Leukemia relapse is a serious therapeutic challenge following hematopoietic stem cell transplantation (HSCT). In this retrospective study, 23 patients [15 (65.2%) AML, 8 (34.8%) ALL] who received DLI+/-reinduction chemotherapy for post-transplant relapse were reviewed. The overall response rate of DLI was 66.7% for AML and 50% for ALL. A total of 15 patients (65.2%) developed acute graft versus host disease (GVHD). Response rates were higher in patients with GVHD (80% versus 25%; p=0.01; OR: 12.0). The probability of OS was better in patients who respond to DLI (p=0.04). Further strategies are required to improve the anti-tumor properties of alloreactive donor lymphocytes and to obtain durable responses with DLI in patients with relapsed acute leukemia after allogeneic HSCT., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Objectives: Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. This retrospective study is planned to assess the prognostic value of serum free light chain (sFLC) levels and FLC ratio (FLCR) in CLL., Methods: Quantitative levels of sFLC were measured nephelometrically in sera collected at diagnosis. The expressions of ZAP70 and CD38 were quantified by flow cytometry. Chromosomal abnormalities were determined by interphase fluorescence in situ hybridization (FISH)., Results: In a cohort of 101 patients with a median follow-up of 29 (1-234) months, sFLC levels were found to be high in 55 patients (54.5%). An abnormal FLCR was found in 30 patients (29.7%). FISH-based genetic risk groups did not differ significantly with respect to sFLC and FLCR (P > 0.05). Median time to first treatment was shorter in patients with high sFLC levels (P = 0.02). Median overall survival (OS) was shorter in patients with high sFLC levels (P = 0.01) and abnormal FLCR (P = 0.05). In patients with early stage disease, median OS was shorter in high sFLC (P = 0.03) and abnormal FLCR groups (P = 0.048). A relationship was observed between abnormal sFLC levels and CD38 positivity on logistic regression analysis (P = 0.003; OR: 4.44; 95% CI: 1.66-11.8)., Conclusions: This study highlighted the adverse prognostic impact of high sFLC levels and abnormal FLCR with regard to survival in CLL, even in early stage patients. Prospective studies are warranted to validate the adverse impact of sFLC and FLCR on clinical outcome.

Aim: To investigate the frequency of occult hepatitis B, the clinical course of hepatitis B virus (HBV) reactivation and reverse seroconversion and associated risk factors in autologous hematopoietic stem cell transplantation (HSCT) recipients., Methods: This study was conducted in 90 patients undergoing autologous HSCT. Occult HBV infection was investigated by HBV-DNA analysis prior to transplantation, while HBV serology and liver function tests were screened prior to and serially after transplantation. HBV-related events including reverse seroconversion and reactivation were recorded in all patients., Results: None of the patients had occult HBV prior to transplantation. Six (6.7%) patients were positive for HBV surface antigen (HBsAg) prior to transplantation and received lamivudine prophylaxis; they did not develop HBV reactivation after transplantation. Clinical HBV infection emerged in three patients after transplantation who had negative HBV-DNA prior to HSCT. Two of these three patients had HBV reactivation while one patient developed acute hepatitis B. Three patients had anti-HBc as the sole hepatitis B-related antibody prior to transplantation, two of whom developed hepatitis B reactivation while none of the patients with antibody to HBV surface antigen (anti-HBs) did so. The 14 anti-HBs- and/or anti-HBc-positive patients among the 90 HSCT recipients experienced either persistent (8 patients) or transient (6 patients) disappearance of anti-HBs and/or anti-HBc. HBsAg seroconversion and clinical hepatitis did not develop in these patients. Female gender and multiple myeloma emerged as risk factors for loss of antibody in regression analysis (P < 0.05)., Conclusion: Anti-HBc as the sole HBV marker seems to be a risk factor for reactivation after autologous HSCT. Lamivudine prophylaxis in HbsAg-positive patients continues to be effective.

Cytokines like interleukin (IL)-6 and IL-1beta are both implicated in multiple myeloma (MM) pathogenesis and megakaryopoiesis. The dynamic interaction between thrombopoiesis and thrombopoietic cytokines in MM may affect platelet (PLT) counts. Sixty-eight patients with MM (30 female, 38 male; median age 58 (40-79), 38 newly diagnosed, 15 in plateau, and 15 relapse and/or refractory patients) and 21 controls were included in the study. Plasma levels of thrombopoietin (TPO), IL-1beta, IL-11 and IL-6 were measured by ELISA. PLT counts were not different between the control group and MM patients with various disease stages and activity. IL-6 and TPO levels were higher in MM patients than healthy subjects (p < 0.001). PLT counts were inversely correlated with TPO (r = -0.566; p < 0.001) and positively correlated with IL-6 (r = 0.263; p = 0.04) levels in MM patients. TPO and IL-6 levels were significantly correlated (r = 0.305; p < 0.001). Disease activity has no effect on plasma cytokine levels. TPO levels were higher in stage III than stage I (p = 0.05) and stage II (p = 0.03) patients in newly diagnosed MM. High TPO levels induced by IL-6 may sustain normal PLT counts despite bone marrow infiltration by plasma cells and decreased PLT half-life.

High-dose chemotherapy with autologous stem cell transplantation (ASCT) is curative treatment in various hematologic malignancies. Mobilization and collection of peripheral blood stem cell is the essential part of ASCT. The aim of this study was to evaluate the effectiveness of various mobilization regimens, determine the risk factors associated with mobilization failure (MF). We also investigated whether iron overload, which has an adverse impact on various aspects of HSCT including overall survival had any impact on mobilization kinetics. A total of 118 consecutive patients were included in this study. The rate of MF was 11.8 % with the first mobilization regimen. Frequency of MF was higher in lymphoma (P < 0.001) patients and in those receiving G-CSF alone (P= 0.01). Peripheral CD34+ cell count (P < 0.001), bone marrow cellularity (P < 0.001), reticulin fibrosis (P < 0.05) were significantly lower whereas serum ferritin levels (P = 0.06) tended to be higher in patients with MF. CD34+ cell count of the first apheresis product was positively correlated with the white blood cell count (P < 0.05; r = 0.232), platelet count (P = 0.01; r = 0.233), peripheral CD34+ cell count (P < 0.001; r = 0.704) and the grade of bone marrow reticulin fibrosis (P < 0.001; r = 0.366). Serum ferritin levels were negatively correlated with maximum peripheral CD34+ cell count (P = 0.02; r = -0.216) and the CD34+ cell count in the first product (P = 0.05; r = -0.183). Platelet count (P = 0.03; β = 0.262), peripheral CD34+ cell count (P = 0.02; β=0.279) were the two variables which remained to be significant in multivariate analysis. Predicting the poor mobilizers with the platelet count for instance may reduce the risk of MF by using more effective regimens in advance.

ABO incompatibility is not a barrier to allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of an ABO mismatch on the outcome of the HSCT remains controversial. We analyzed whether ABO incompatibility leads to an increased risk of early/late complications, mortality, or increased transfusion requirements. The 147 consecutive allogeneic HSCTs includes 80 ABO-identical and 25 major, 30 minor, and 12 bidirectional ABO-mismatched grafts. The four groups were balanced with respect to disease status at transplantation. Transplantation-related mortality was significantly greater (P < .01) and overall survival significantly shorter (P = 0.2) among HSCT recipients with minor ABO-mismatched grafts. The relapse rate, progression-free survival, and transfusion requirements until discharge were not different between ABO-identical and ABO-mismatched groups. Pure red cell aplasia (PRCA); (P < .0001) and delayed red blood cell (RBC) engraftment (P < .001) were more frequent in HSCT recipients with major mismatched donors. Delayed RBC engraftment was associated with posttransplantation hyperferritininemia and increased mortality risk (P = .05). The greater frequency of sinusoidal obstruction syndrome and graft-versus-host disease (GVHD) in patients with minor mismatched transplants, did not show statistical significance. In contrast severe GVHD was significantly more frequent among minor mismatched patients (P = .04). ABO-mismatched HSCT might have an unfavorable impact on transplant outcomes. Selection of ABO-compatible donors when possible, strategies to prevent and treat PRCA, modifications in transfusion practice, and effective iron chelation are among the measures that can improve transplant outcomes.

Purpose: This study was designed to determine the pretransplantation levels of thrombopoietic cytokines, which have a fundamental role in both megakaryopoiesis and myeloma pathogenesis and P-selectin in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (AHSCT) and to correlate the cytokine levels with time to platelet recovery. The effect of AHSCT on the levels of the cytokines and its correlation with maximum disease response was also investigated., Patients and Methods: The levels of thrombopoietin, interleukin (IL)-6, IL-11, IL-1beta, and P-selectin was measured before and 30 days after AHSCT in 32 patients with a median age of 55 years. The median time to platelet recovery was day +11 (range, 0-14 days) without any significant correlation with pretransplantation cytokine levels., Results: No significant change was observed in thrombopoietic cytokines after AHSCT, whereas serum P-selectin levels showed a significant decrease after AHSCT (P = .001). The decrease in P-selectin was found to be significant in patients who achieved complete remission (P1 = .008) and partial remission (P2 = .018) early after AHSCT. Our data suggest that the level of thrombopoietic cytokines does not have a role in time to platelet recovery., Conclusion: The change in P-selectin levels early after transplantation could be a surrogate marker in determining the maximum posttransplantation response.

We reviewed the outcome in 15 consecutive patients with severe aplastic anemia with a median age of 23 years who received matched sibling peripheral blood stem cell transplantation. Conditioning regimen was cyclophosphamide (Cy)+anti-thymocyte globulin (ATG). Cumulative incidence of transplant related mortality, graft failure, acute and chronic GVHD were 20%, 33%, 25%, and 8.3%, respectively. Conditioning with Cy only, resulted in higher rejection rate compared to Cy plus ATG (75% versus 12.5%, p=0.03). Eighty percent of patients are alive with a median follow-up of 19.5 (4.6-35.6) months. Two of the three patients who were re-transplanted with fludarabine had sustained donor chimerism.

Bortezomib is a potent, selective proteasome inhibitor. It is usually well tolerated, and bortezomib-induced skin lesions are less well known. A 59-year-old man with multiple myeloma underwent autologous hematopoetic stem cell transplantation (AHSCT). Administration of bortezomib was started after AHSCT as his disease progressed despite thalidomide maintenance. He developed a rash afer the third cycle of bortezomib. A biopsy showed superficial and deep perivascular dermatitis. The rash resolved within 4 days; complete response of myeloma was obtained after 8 cycles of bortezomib. The benign clinical course did not require interruption of the treatment, which in turn resulted in complete remission of myeloma.

Objectives: The aim of the present study was to evaluate the possible correlation between bone mass and serum adiponectin levels, and the correlation between adiponectin levels and osteoporotic fracture risk in a prospective clinical trial., Patients and Methods: Postmenopausal non-diabetic 105 women (mean age 63.4+/-8.1; range 52 to 64 years) with hip fracture were evaluated. Of these 105 patients, 46 had trochanteric fractures, 24 had subtrochanteric fractures and 35 had femoral neck fractures. Anthropometric measurements were performed. Serum adiponectin level was measured by means of ELISA. Total bone mineral density and bone mineral content of lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry (DEXA)., Results: Lumbar bone mineral density and proximal femoral bone mineral density were not correlated with serum adiponectin levels. Serum adiponectin level was not found to have any significant effect on bone mass. Serum adiponectin levels were not significantly different between the patients with osteoporotic fractures and those with non-osteoporotic fractures., Conclusion: Our study showed that serum adiponectin level is not associated with bone mass and osteoporotic fracture risk. Investigation of local adiponectin levels in bony tissue is needed to clarify the possible relation between adiponectin and bone mass, and risk of fractures associated with osteoporosis.

Abnormalities in liver function tests are common in hematopoietic SCT (HSCT) recipients. We retrospectively investigated the role of liver biopsy in determining the cause of elevated liver enzymes and its impact on the management of patients in the post-HSCT setting. A total of 24 consecutive liver biopsies were obtained from 20 patients from September 2003 to December 2007. A definite histopathologic diagnosis was obtained in 91.7% of the biopsies. Iron overload (IO) was found in 75% and GVHD in 54.2% of the patients. The initial clinical diagnosis of GVHD was confirmed in 56.5% and refuted in 43.5% of the allogeneic HSCT recipients. The median number of post transplant transfusions, percent transferrin saturation and ferritin levels were found to be higher in patients who had histologically proven hepatic IO (p1=0.007, p2=0.003 and p3=0.009, respectively). Regression analysis showed a significant correlation between serum ferritin levels and histological grade of iron in the hepatocytes. Our data suggest that hepatic IO is a frequent finding in the post-HSCT setting, which contributes to hepatic dysfunction and it should be considered in the differential diagnosis, particularly in patients with high serum ferritin levels.

To evaluate the relationship between the adiponectin levels and left ventricular mass index (LVMI) in uncomplicated obese subjects. Fifty-nine subjects were assigned to the obese (BMI> or =30 kg/m(2)) and 58 to the lean (BMI<30 kg/m (2) ) group. Plasma glucose, insulin, serum total cholesterol and high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides and adiponectin were measured. Insulin resistance was determined by the Homeostasis Assessment Model (HOMA-IR). The left ventricular functions of all subjects were determined by 2D and pulse wave Doppler echocardiography. LVMI was calculated as left ventricular mass (LVM) normalized for height in m (2.7) . The obese group displayed significantly higher LVMI and late mitral inflow velocity. Thirty-three obese subjects met the criteria for left ventricular hypertrophy (LVH) and had lower serum adiponectin levels compared with obese subjects without LVH and lean subjects (p<0.05). Adiponectin was negatively correlated with LVMI (R: -0.277, p: 0.002). Furthermore, during the partial correlation analysis where HOMA-IR was controlled, the negative correlation between adiponectin and LVMI progressed (r: -0.283, p: 0.002). The linear regression analysis showed an independent relationship between LVMI and adiponectin. (beta: -0.214, p: 0.01) Obesity is associated with LVH. This study showed direct influence of adiponectin on LVMI.

One hundred eleven patients who received 125 hematopoetic stem cell transplantations (HSCT) with myeloablative conditioning regimens were retrospectively evaluated for the development of cardiac toxicity (CT). The aims of this study were to assess the frequency of cardiac complications in patients receiving HSCT and to investigate the value of pretransplantation variables to predict posttransplantation CT. Severe grade III-IV CT was not observed in this cohort, in whom pretransplantation eligibility criteria excluded the patients with a left ventricular ejection fraction (LVEF) of 50% or less. Grade I-II CT was seen in 13.4% patients. Patients with a history of previous mediastinal radiotherapy, high doses of anthracycyclines, and a longer interval between diagnosis and treatment were found to have higher risk of developing CT. Pretransplantation ferritin levels and the type of HSCT did not seem to have an effect on posttransplantation cardiac complications. Our results indicated that CT was managable in patients with a LVEF of at least 50%.

Sinusoidal obstruction syndrome (SOS) is a frequent, troubling, and potentially fatal complication of hematopoietic stem cell transplantation. Despite promising results with defibrotide (DF), no treatment has been established as standard. DF is a single-stranded polydeoxyribonucleotide, obtained from controlled depolymerization of porcine intestinal mucosal cells. It has antithrombotic, antiischemic, antiinflammatory, and thrombolytic properties without significant side effects. We retrospectively evaluated the charts of 80 consecutive patients, with 89 hematopoietic stem cell transplants for hematologic malignancies. The results of early initiation of DF treatment in 14 patients with SOS are presented in this study. Fourteen patients, 8 males and 6 females % median age 40.5 years (range, 16-46 years) were diagnosed to have SOS. Disease severity was classified as severe in 6 (42.85%), moderate in 4 (28.57%), and mild in 4 (28.57%) patients. We treated 14 patients with DF for a median of 21.5 days (range, 4-39 days). All 14 patients received DF after the diagnosis of SOS. Three patients with severe and all of the patients with mild to moderate SOS responded to treatment with complete resolution of SOS-related signs and symptoms. All patients responding to DF were alive at 100 days posttransplantation. There was no significant drug-related side effect among patients treated with DF. With an overall response rate of 78.56% and a 50% complete response rate in severe SOS cases and minimal side effects, we suggest that DF is the best available agent to treat SOS.

Infection with Helicobacter pylori (H. pylori) strains secreting cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) proteins is associated with more severe gastroduodenal pathologies. However, this association varies among geographical regions and ethnic groups. We investigated the frequencies of antibodies to CagA and VacA proteins in 131 H. pylori-infected dyspeptic patients [40 duodenal ulcer (DU), 19 gastric ulcer (GU), 28 gastric cancer (GC), and 44 non-ulcer dyspepsia (NUD)] across 30 H. pylori-infected and endoscopically normal asymptomatic subjects (AS). Anti-CagA and anti-VacA antibodies were detected by Western blotting. The positivity rates of anti-CagA and anti-VacA antibodies were higher in patients with DU (92.5 and 75%), GU (89.5 and 84.2%) and GC (96.4 and 85.7%) than patients with NUD (70.5 and 50%) and AS (50 and 23.3%) (p < 0.05). CagA+ VacA+ phenotype was more frequent in patients with DU, GU and GC than patients with NUD and AS (75, 84.2, 85.7 vs. 47.7 and 20%, respectively) (p < 0.01). Our results showed that there is a significantly positive association between the presence of anti-CagA and anti-VacA antibodies and DU, GU and GC in our region.

Objective: The objective of this study was to investigate the contribution of insulin resistance, hyperinsulinaemia and obesity, independently of other major factors, to changes in left ventricular mass a cardiovascular risk indicator, in a healthy population without co-morbid states such as diabetes or hypertension., Methods and Results: This cross-sectional relational study was perfomed in 153 healthy subjects, comprising 76 men and 77 women with ages ranging from 23 to 67 years. All of them were normotensive and had a normal oral glucose tolerance test, none had cardiovascular disease and none were taking any medication. Weight, height and waist circumference were measured and BMI was calculated. A blood sample was drawn in the fasting state: plasma glucose, insulin, serum total and high density lipoprotein (HDL), low density lipoprotein cholesterol and triglycerides were measured. Insulin resistance was determined by the 'Homeostasis Assessment Model' (HOMA-IR). Subjects were studied by echocardiography. The left ventricular mass was calculated by using the anatomically validated formula of Devereux et al., Results: Left ventricular mass significantly and positively correlated with BMI, age, systolic and diastolic blood pressure and fasting blood glucose. The correlation of left ventricular mass with fasting blood glucose was not maintained after controlling for BMI. BMI, fasting blood glucose, HOMA-IR, systolic and diastolic blood pressure showed significant differences with higher values for people with left ventricular hypertrophy. The logistic regression analysis showed a strong association between left ventricular hypertrophy and BMI (p < 0.05)., Conclusion: Insulin resistance and fasting insulin is not associated with left ventricular hypertrophy in healthy people, independent of obesity. Obesity appears to be an independent risk factor for left ventricular hypertrophy.

Background/aims: To determine H. pylori eradication rate with lansoprazole-amoxicillin-clarithromycin treatment regimen, which is the most frequently used as first-line therapy, in the Kirikkale region., Methods: One hundred and five patients (44 male, 61 female) with H. pylori infection were included in the study. Patients were divided into two groups based on the endoscopic findings: non-ulcer dyspepsia (n=84, 31 male, 53 female) and acute gastric or duodenal ulcer (n=21, 13 male, 8 female) groups. The diagnosis of H. pylori infection was confirmed if both the urease test and histological examination, which were performed on endoscopic biopsies, were positive. Lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg were given twice daily for 14 days to all patients. Endoscopic biopsies were repeated for the evaluation of eradication three months after the treatment., Results: Ninety-six patients completed the study. Eradication rates were found to be 45.8% (44 of 96) in all patients, 42.1% (32 of 76 patients) in the non-ulcer dyspepsia group and 60% (12 of 20 patients) in the gastric or duodenal ulcer group for per protocol analysis, and the difference between non-ulcer dyspepsia and gastric or duodenal ulcer groups was not statistically significant (p=0.208)., Conclusions: Lansoprazole-amoxicillin-clarithromycin treatment regimen, the most frequently preferred regimen in H. pylori eradication, is ineffective in our region. The low eradication rates observed with lansoprazole-amoxicillin-clarithromycin, at least in our region, bring into question its use as a first-line therapy. The use of alternative treatment protocols or antibiotic susceptibility test before the treatment may be helpful in achieving successful eradication with first-line therapy.

Atherosclerosis is a disease of the arterial wall, with increasing wall thickness representing an early event in the progression of the disease. It has been suggested that iron overload, as assessed by increased serum ferritin concentration, may be a risk factor for atherosclerosis. The aim of this study was to investigate the relationship between the influence of intravenous (IV) iron therapy and ferritin levels and carotid intima media thickness (C-IMT) in dialysis patients. Sixty patients (51 +/- 14) years were divided into two groups according to their IMT obtained by ultrasound; group I (high risk) and group II (low risk). The parameters assessed were serum creatinine, urea, calcium, phosphorus, hemoglobin, albumin, uric acid, iron, ferritin, and lipid levels. Thirty-eight patients (88%) in group I and 5 patients (12%) in group II received IV iron therapy while 5 patients (29%) in group I and 12 patients (71%) in group II (P < 0.001) did not receive IV iron therapy. Ferritin levels were higher in group I than in group II (581 +/- 303 and 306 +/- 224) (P < 0.001). C-IMT measurements correlated with serum ferritin and with the intravenous iron dose received during the 24 months preceding the study (r = 0.315, P = 0.015; r = 0.471, P = 0.001). The findings indicate that IV iron therapy and elevated serum ferritin levels may cause an increase in the incidence of atherosclerosis.