Eren Gündüz

Abnormality of regulatory T-cells in remission and non-remission idiopathic thrombocytopaenic purpura patients

Primer immunologic defect in patients with idiopathic thrombocytopaenic purpura (ITP) result from autoreactive B-lymphocytes secreting antiplatelet antibodies. Dysfunctional cellular immunity has also great importance in ITP pathogenesis. CD4+CD25+ regulatory T-cells have immunoregulatory features and it is able to inhibit CD4+CD25− and CD8+ responses. ITP is also an autoimmune disease; the CD4+CD25+ T-cell levels of the patients decrease during the active state. According to our findings, immunosuppressive treatments increase the CD4+CD25+ Treg cell levels in the non-remission ITP patients. However, this level is not enough to overcome the resistance. CD4+CD25−Foxp3+ and CD4+Foxp3+ Treg cells are responsible for the pathogenesis of the non-remission ITP patients and other factors exist, which are responsible for the resistance of ITP treatment.

Can thrombelastography be a new tool to assess bleeding risk in patients with idiopathic thrombocytopenic purpura

Thrombelastography (TEG) analyses the status of blood coagulation including abnormalities associated with low platelet count. The aim of this study was to investigate the changes in TEG parameters in idiopathic thrombocytopenic purpura (ITP) patients. Thirty nine patients with ITP (platelet count < 100 × 103  µl−1) were included in the study. Age-matched 17 patients with thrombocytopenia due to chemotherapy were selected as a control group. Platelet count was positively correlated with maximum clot formation (MCF) in INTEM (r = 0.716, p < 0.001) and MCF in EXTEM (r = 0.679, p < 0.001); negatively correlated with clot formation time (CFT) in INTEM (r = −0.755, p < 0.001) and CFT in EXTEM (r = −0.585, p < 0.001) in ITP patients. Platelet count was positively correlated with MCF in INTEM (r = 0.776, p < 0.001) and MCF in EXTEM (r = 0.878, p < 0.001); negatively correlated with CFT in INTEM (r = −0.627, p < 0.001) in control group. Receiver operating characteristic curves to describe the critical platelet count and fibrinogen level that affect MCF revealed 31 × 103 µl−1 and 375 mg dl−1 as cut-off values, respectively. In conclusion, ROTEM determines the contribution of fibrinogen and platelets to clot strength in patients with ITP. MCF appears to be the most important TEG parameter in predicting bleeding in ITP patients that makes TEG superior to other hemostatic tests.

The effect of clinical characteristics on the performance of galactomannan and PCR for the diagnosis of invasive aspergillosis in febrile neutropenic patients

Rapid diagnosis and early treatment of invasive aspergillosis is crucial for the management of the patients with haematological malignancy. We evaluated 358 sera from 78 febrile neutropenic episodes in patient with invasive aspergillosis (IA) (one proven, 17 probable, and 60 possible) and 83 episodes in patients with no IA according to the EORTC/MSG criteria. Patients specimens were tested by Mycassay Aspergillus PCR (first commercial real‐time PCR test) and in house real‐time PCR to investigate the presence of Aspergillus DNA, and by ELISA for detect the galactomannan (GM) antigen. We systematically investigated the medical background that can be effective on the test results. The hospitalisation period was longer in proven/probable episodes when compared with no IA (P = 0.001) and possible episodes. With regard to duration of neutropenia, the differences between both proven/probable with no IA (P = 0.023) and possible with no IA (P = 0.002) were highly significant. Similarly, the rates of T cell suppressant therapy in group proven/probable and possible episodes were significantly higher than in no IA (P = 0.005). There are significant differences in the performance of GM and PCR‐based tests among studies, and standardisation is required. Therefore, it can be useful to determine the effective factors on these tests. The use of larger volume of sera improved the performance of real‐time PCR for detection of Aspergillus DNA in high‐risk adult patients in the present study. Some host factors such as duration of neutropenia and administration of T cell suppressants related to the development of IA.

Evaluation of mobilized peripheral stem cells according to CD34 and aldehyde dehydrogenase expression and effect of SSClo ALDHbr cells on hematopoietic recovery

BACKGROUND AIMS We evaluated hematopoietic stem cells according to CD34 expression and aldehyde dehydrogenase (ALDH) activity in peripheral blood and apheresis product samples from patients after mobilization with granulocyte-colony-stimulating factor (G-CSF) alone or G-CSF after high-dose cyclophosphamide (4 g/m²) once daily, intravenously on day 1). We also investigated the relationship between the number of SSC(lo) CD45(dim) CD34(hi) cells, SSC(lo) ALDH(br) cells and engraftment. METHODS Thirty patients (20 males and 10 females), who were candidates for autologous peripheral blood stem cell transplantation, were included in the study. Cyclophosphamide + G-CSF was used for 17 and G-CSF alone for 24 mobilizations. Primary diagnoses were multiple myeloma (n = 14), Hodgkins lymphoma (n = 7), non-Hodgkins lymphoma (n = 2), acute myloid leukemia (n = 2), chronic lymphocytic leukemia (n = 1) and germ cell testis tumor (n = 1). RESULTS Numbers of SSC(lo) CD45(dim) CD34(hi) cells and SSC(lo) ALDH(br) cells were highly correlated in both peripheral blood and apheresis products (P < 0.001). We could not find a relationship between the transplanted SSC(lo) CD45(dim) CD34(hi) cell dose or SSC(lo) ALDH(br) cell dose and platelet or neutrophil recovery. The optimal thresholds for SSC(lo) CD45(dim) CD34(hi) cells were 5.40 × 10⁶/kg for neutrophil recovery and 7.22 x 10⁶/kg for platelet recovery. The optimal thresholds for SSC(lo) ALDH(br) cells were 6.53 x 10⁶/kg for neutrophil recovery and 8.72 x 10⁶/kg platelet recovery. CONCLUSIONS According to our data, numbers of SSC(lo) ALDH(br) cells are in very good agreement with numbers of SSC(lo) CD45(dim) CD34(hi) cells and can be a predictor of stem cell mobilization.

Are the high serum interleukin-6 and vascular endothelial growth factor levels useful prognostic markers in aggressive non-hodgkin lymphoma patients?

Objective: Pro-inflammatory and pro-angiogenic cytokines play an important role in the pathogenesis of lymphoma, and recent studies have shown that cytokines can be used as prognostic markers. Non-Hodgkin lymphoma (NHL) patients with high levels of serum interleukin-6 (s-IL6) and serum vascular endothelial growth factor (s-VEGF) have poor prognosis and shorter survival time. We aimed to determine pre-treatment levels of s-IL6 and s-VEGF and their relation with known prognostic markers, especially International Prognostic Index (IPI) scores, and to examine their effects on overall survival in newly diagnosed, untreated aggressive NHL patients. Materials and Methods: The study included 51 newly diagnosed NHL patients and 17 healthy controls. Blood samples were obtained to study s-IL6 and s-VEGF cytokine levels. Results: Patients with aggressive NHL diagnosis had higher s-VEGF and s-IL6 levels than the healthy population. If the s-IL6 levels of patients were above the cut-off levels, the overall survival time was shorter. There was no relation between s-VEGF and overall survival time. Conclusion: s-IL6 is an independent prognostic factor that may be included in IPI risk classification. In addition to the s-IL6 level, age, erythrocyte sedimentation rate, beta-2 microglobulin, WHO performance status, and IPI score are independent prognostic factors that are effective, especially for overall survival, in the clinical follow-up of NHL patients.

Isolated Granulocytic Sarcoma of the Breast after Allogeneic Stem Cell Transplantation: A Rare Involvement Also Detected by 18FDG-PET/CT.

Granulocytic sarcoma is a tumor consisting of myeloid blasts with or without maturation that occurs at an anatomical site other than bone marrow. Most frequently affected sites are skin, lymph nodes, gastrointestinal tract, bone, soft tissue and testes. AML may manifest as granulocytic sarcoma at diagnosis or relapse. Although it has been considered to be rare relapse as granulocytic sarcoma after stem cell transplantation is being increasingly reported. However it is rare without bone marrow involvement and in AML M6 subtype. Breast is also a rare involvement. We report a 30-year-old woman with AML M6 relapsed 16 months after allogeneic stem cell transplantation as a granulocytic sarcoma in right breast without bone marrow involvement. She was treated with systemic chemotherapy but died of sepsis. 18FDG-PET/CT images were also obtained and detected lesions other than detected by breast ultrasound. The incidence of granulocytic sarcoma may increase if suspected or new diagnostic modalities are performed.

Incidence of red-cell alloimmunization due to non-anti-D antibodies during pregnancy: An experience from Turkey

Antigen D incompatibility between mother and fetus is the most frequent cause of red-cell alloimmunization. However there are surface antigens capable of producing hemolytic disease other than antigen D. Populational antigen frequencies may be country specific. The aim of this retrospective study was to evaluate the incidence of red-cell alloimmunization due to non-anti-D antibodies during pregnancy. We evaluated the indirect antiglobulin test results of 535 pregnant women performed between March 2003 and 2009. The incidence of non-anti-D antibodies was found 1.21%, similar with reported in literature, but the spectrum of non-anti-D antibodies was different from other countries.

Cardiac and pulmonary thrombosis during multidrug treatment in an idiopathic thrombocytopenic purpura patient

Glucocorticosteroids, intravenous immunoglobulins, vincristine, danazol, and eltrombopag are used in refractory chronic idiopathic thrombocytopenic purpura (ITP). All those treatment modalities are susceptible for thrombosis generation. There is an increased risk of thrombosis in the diseases’ natural course. The case we present is a resistant chronic ITP patient who developed pulmonary and intracardiac thrombosis during multidrug treatment. Risk of concomitant usage of drugs and rapid increase in platelet count are discussed.

Blastic Plasmacytoid Dendritic Cell Leukemia Successfully Treated by Autologous Hematopoietic Stem Cell Transplantation to a Remission of 48-Month Duration

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare subtype of AML characterized by the clonal proliferation of precursors of plasmacytoid dendritic cells. It presents with an aggressive behavior. The clinical findings include cytopenia, particularly thrombocytopenia. Although it responds well to chemotherapy initially, the relapse is a rule and prognosis is very poor. There is limited data published in the literature, making it very problematic to define the biological and clinical features, hence, the appropriate therapeutic approach. There are various treatment methods such as multiagent chemotherapy based on ALL or AML and/or hematopoietic stem cell transplantation. However, none of them is approved as a standard therapy. From this point of view, we herein report a 20-year-old case at onset of a leukemic form of BPDCN who survived 48 months after autologous hematopoietic stem cell transplantation.

Peripheral blood regulatory T cell levels are correlated with some poor prognostic markers in newly diagnosed lymphoma patients.

Regulatory T cells (Tregs) are a specialized subpopulation of CD4+ T cells which maintain the immune system homeostasis. They may increase during cancer progression and have been correlated with a worse prognosis in many malignancies. However, the role of Treg cells in lymphoma is debated.