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Objective: Although inhibition of the complement system at different steps is a promising therapy modality in patients with paroxysmal nocturnal hemoglobinuria (PNH), allogeneic hematopoietic stem cell transplantation (HCT) is still the only curative therapy, especially for patients with intractable hemolysis or bone marrow failure. The aim of this study is to evaluate the outcomes of allogeneic HCT in PNH patients with aplastic anemia (PNH-AA) or without., Materials and Methods: Thirty-five PNH/PNH-AA patients who were treated with allogeneic HCT in 10 transplantation centers in Turkey were retrospectively analyzed., Results: Sixteen (45.7%) and 19 (54.3%) patients were diagnosed with classical PNH and PNH-AA, respectively. The median age of the patients was 32 (18-51) years. The 2-year overall survival (OS) rate and rate of graft-versus-host disease-free, failure-free survival (GFFS) was 81.2% and 78.1%, respectively. The 2-year OS in cases of classical PNH and PNH-AA was 81.3% and 79.9%, respectively (p=0.87), and 2-year GFFS in cases of PNH and PNH-AA was 79% and 76% (p=0.977), without statistical significance. The OS and GFFS rates also did not differ between transplantations with matched sibling donors (MSDs) and matched unrelated donors (MUDs)., Conclusion: Allogeneic HCT with MSDs or MUDs is a good option for selected patients with classical PNH and PNH-AA. In particular, patients with debilitating and refractory hemolysis and patients with bone marrow failure might form an excellent group of candidates for allogeneic HCT.

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, approximately one-third of responders experience disease relapse following first-line therapy. Several studies have shown the efficacy of brentuximab vedotin (BV) in patients with relapsed/refractory HL. We present a retrospective analysis of 58 patients with relapsed/refractory HL treated with BV in a named patient program from 11 centers. The median follow-up duration was 20 (range, 4-84) months. The best overall response rate was 64% (complete response [CR], 31%; partial response [PR], 33%). The 5-year progression-free survival (PFS) and overall survival (OS) rates were 12% (95% confidence interval [CI], 0.05-0.22) and 26% (95% CI, 0.16-0.38), respectively. Among patients who achieved CR, the estimated 5-year PFS and OS rates were 32% (95% CI, 0.13-0.54) and 60% (95% CI, 0.33-0.78), respectively. A total of 26 patients underwent subsequent stem cell transplantation. The 5-year PFS and OS rates for 10 patients who had consolidative stem cell transplantation were 28% and 30%, respectively. Twenty-seven patients required further therapy following BV. At the time of the analysis, 12 patients (21%) were alive. Five patients (9%) had long-term remission after achieving CR with BV monotherapy, with a median PFS of 76 months. Three of them (5%) did not receive any other treatment following BV and their median PFS was 75 months. Our long-term results showed that a small subset of patients with relapsed/refractory cHL may benefit from and even be cured with BV monotherapy.

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.

Transresveratrol (t-resveratrol; 3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic compound found in fresh grapes, grape juice and wine, and has been found to reduce the total cholesterol level in hypercholesterolemic rats. The objective of the present study was to assess the effects of t-resveratrol on platelet-neutrophil complex formation and neutrophil reactive oxygen species (ROS) status in control and hypercholesterolemic rats using a modified flow cytometric method. Rats (n=80) were divided into five groups (control, ethanol, resveratrol, hypercholesterolemic and resveratrol-administered hypercholesterolemic groups), comprising 16 animals per group. Serum levels of lipids and H2O2 were determined using commercially available kits, while platelet-neutrophil complex formation and neutrophil ROS status were determined using a modified flow cytometric method. Serum total cholesterol and low-density lipoprotein cholesterol levels were found to be increased and the high-density lipoprotein cholesterol level was found to be decreased in the HC group compared with the control group (P<0.001). Treatment of HC rats with t-resveratrol significantly lowered total cholesterol and low-density lipoprotein cholesterol levels (P<0.001). In the hypercholesterolemic group, levels of serum H2O2 platelet-neutrophil complex formation and neutrophil ROS status were significantly increased (P<0.001). On the other hand, in the resveratrol-administered hypercholesterolemic group, serum H2O2 levels, platelet-neutrophil complex formation and neutrophil ROS status were decreased compared with the hypercholesterolemic group (P<0.001). Serum H2O2 levels, platelet-neutrophil complex and neutrophil ROS status were positively correlated with one another. The present study is the first to demonstrate the protective effect of t-resveratrol against hypercholesterolemia-induced platelet-neutrophil complex formation and neutrophil ROS burst. Further investigations on its plausible role in antihypercholesterolemic treatment are warranted.

Several age-related alterations occur at the cellular level in the immune system leading to a decrease in the immune response. The present study was designed to determine the effect of L-carnitine on impaired neutrophil functions of aged rats. For this reason, superoxide anion radical production, chemotaxis and phagocytic activity were studied in the neutrophils obtained from the peripheral blood of young and old rats. We orally gavaged L-carnitine (50 mg/kg b.w. per day) or control vehicle into young (2 months) and aged (24 months) rats for 30 consecutive days. The neutrophils of aged rats exhibited an increase in superoxide anion production and decline in phagocytosis and chemotaxis when compared with that in young rat neutrophils. Superoxide anion production in aged rats was significantly decreased by L-carnitine treatment which was accompanied with a significant enhancement of chemotactic and phagocytic activity being restored to control levels. These findings demonstrated that L-carnitine is capable of restoring the age-related changes of neutrophil functions.

Typhlitis (neutropenic enterocolitis) is a potentially life-threatening complication associated with neutropenia and combination chemotherapy. The incidence of this disease is increasing in both patients with hematologic malignancies and solid tumors with the advent of more aggressive chemotherapy. Here, we describe a patient with acute myeloblastic leukemia in whom typhlitis developed during induction chemotherapy and managed successfully with both medical and surgical intervention during neutropenic period. Our experience reinforces prior reports that intense medical treatment, close observation and emergent surgical intervention has been shown to be life saving.

Lymphoproliferative diseases are the most common disorders associated with autoimmune disturbances. We determined the autoimmune phenotype of 64 non Hodgkin's lymphoma patients' and compared their clinicopathologic properties. Serum direct antiglobulin test [(DAT) n=64], indirect antiglobulin test [(IAT) n=61], platelet autoantibodies [(PAA) n=51], anti nuclear antibodies [n=33], anti-native DNA [n=29], anti phospholipid antibodies [n=40] and, lupus anticoagulant [n=33] were used as autoimmune markers. Twenty five patients (39%) displayed one or more autoimmune marker positivity (+). Three patients with (+) DAT and IAT had autoimmune hemolytic anemia and two patients with PAA had autoimmune thrombocytopenia. Male patients were more susceptible to autoimmunity in low grade lymphomas and the statistical difference was significant (p=0.035). Most of the autoimmune markers (+) patients had low grade and disseminated disease but this was not significant. Remission rates were not found to be different between autoimmune marker (+) and (-) patients. Although statistically not significant. median survival was longer in autoimmune marker (-) patients than in the others (50 versus 39 months). The significance of autoimmunity in NHL in a larger series of patients should be investigated in future studies.

The effect of plateletpheresis on endothelium, which has strong effects on blood coagulation, fibrinolysis and platelet function, is not known. Activation of leukocytes and subsequent generation of proinflammatory cytokines during the extracorporeal circulation may activate the endothelium. To test this hypothesis we measured plasma levels of tumor necrosis factor (TNF)-alpha as a prototype of the proinflammatory cytokines, and von Willebrand factor (vWF) and fibronectin as endothelial release/damage markers before and after a single plateletpheresis procedure on an intermittent-flow machine Haemonetics MCS 3p in 17 healthy donors. We found a significant increase in median plasma level of TNF-alpha following plateletpheresis (3.5 vs 26.5 pg/ml, P=0.02). Such increases in vWF and fibronectin were not observed. The increase in plasma TNF-alpha indicates that a single plateletpheresis procedure causes leukocyte activation which does not seemingly impair endothelial cell function. The relation of plateletpheresis-induced proinflammatory cytokine release to some adverse effects observed in both donors and recipients, and the effect of repeated plateletpheresis on endothelium deserve further studies.

Serum soluble CD23 (sCD23) and soluble IL-2 receptor (sIL-2R) levels increase not only in disorders with immune system activation, but also in hematological malignancies. They have been used as markers of disease progression and/or the response to therapy in lymphoproliferative disorders (LPD). In this study, we investigated the serum sCD23 and sIL-2R levels of 21 patients with different hematological malignancies [10 LPD, 6 multiple myeloma (MM), and 5 myelodysplastic syndrome (MDS)] before treatment, and compared them with 19 age- and sex- matched healthy subjects. Median sIL-2R levels were found to be significantly elevated in both the overall patient group and each of the subgroups. Median sCD23 levels were significantly higher in the overall patient group and in patients with LPD and MM. A positive correlation was found between sIL-2R and sCD23 levels in LPD. Our preliminary findings suggest that elevated serum levels of these soluble factors are not only markers of LPD but might be also used for other hematologic malignancies, except for MDS. Further studies should be designed to find out if it might be the result of an overactive immune system or not.

Infectious etiology has been confirmed only in a few lymphoproliferative disorders such as human T-cell lymphotropic virus in adult T-cell leukemia lymphoma, Epstein-Barr virus in African-type Burkitt's lymphoma and Hodgkin's disease, and Helicobacter pylori infection in primary gastric B-cell lymphoma. In recent years, Ferri and colleagues have found hepatitis C virus (HCV) association with non-Hodgkin's lymphoma (NHL) in Italy. The aim of our study was to determine the HCV association in NHL patients in Antalya. Forty-eight patients (22 women and 26 men, with a median age of 52 years) with NHL were included in the study. The control group consisted of 28 patients with various hematological disorders (11 women and 17 men with a median age of 50 years). Anti-HCV antibodies were investigated in 48 patients, and HCV RNA was assessed in 35 of them. Anti-HCV antibodies were found to be negative in the NHL group, but HCV RNA was positive in the serum of three patients (8.6%), who were diagnosed with diffuse small cell lymphoma (19%). Anti-HCV antibodies and HCV RNA were negative in the control group. Since HCV association with NHL has previously been reported in Italy, it is likely that both genetic and environmental factors in the Mediterranean sea-region may be involved in the oncogenesis in HCV RNA-positive patients. Multicenter studies with large patient groups will disclose the true association of HCV with NHL in Turkey.

Activation of platelets during collection and storage has been implicated as a major cause of the platelet storage lesion. In this study, we investigated the effect of an automated plateletpheresis procedure on the in vivo platelet activation in 20 volunteer donors. Peripheral blood samples were collected immediately before and after plateletpheresis on the Haemonetics V50 Blood Cell Separator. Activation of platelets was determined by quantitating the amount of platelet P-selectin (CD62) expression using a whole blood method on flow cytometry. Adenosine diphosphate (ADP), collagen, and ristocetin induced platelet aggregations were also measured on a whole blood impedance aggregometer. Plateletpheresis caused a significant decrease in the CD62-positive platelet percentage and aggregation responses to 3 agonists. We concluded that the plateletpheresis procedure did not cause an increase in platelet activation in donors. Further studies are required to elucidate whether activated platelets are collected during the procedure or removed from the circulation of the donor and replaced by resting platelets, activated platelets bind to leukocytes or endothelial cells, and the plateletpheresis procedure is a powerful stimulus for platelet activation.

A case of Bernard-Soulier syndrome in a five-year-old female is presented. The diagnosis was confirmed by flow cytometric analysis of glycoprotein Ib (CD 42b) in addition to the patient's classic laboratory findings such as prolonged bleeding time, mild thrombocytopenia, large platelets and failure of platelet aggregation with ristocetin. Her parents and sibling had normal coagulation tests and CD 42b levels. It is emphasized that flow cytometric analysis is useful in the confirmation of congenital platelet function defects.

The haemophagocytic syndrome (HS) is an uncommon reactive proliferation of mature histiocytes, and is more frequently but not exclusively associated with infections in individuals with pre-existing immunologic abnormalities. As far as we know, only 13 cases of tuberculosis-associated HS have previously been reported. We present here two cases of disseminated tuberculosis-associated HS. Both of the cases recovered with antituberculosis therapy. High-dose methylprednisolone and intravenous immunoglobulin were added in one case because of the extremely severe clinical presentation. This therapy seemed to contribute to the favourable outcome of the patient. The similarities in HLA phenotypes of this patient and others reported in the literature may provide evidence for an underlying immune dysregulation in some cases of infection-associated HS.

Werner's syndrome is a relatively rare autosomal recessive disorder characterized by several features generally associated with aging. This syndrome is classified in the group of chromosome instability syndromes and there is an increased incidence of neoplasia. Hematologic malignancies associated with this syndrome are, however, unusual. Herein we report a case of Werner's syndrome with myelodysplastic syndrome, a clonal preleukemic disorder of hemopoietic stem cells. Such an association, to the best of our knowledge, has not been reported in the English literature so far.