Elif Birtas Atesoglu

Azacitidine has limited activity in ‘real life’ patients with MDS and AML: a single centre experience

Myelodysplastic syndrome (MDS) represents a heterogeneous group of potentially malignant diseases of bone‐marrow stem cells. Acute myelogenous leukaemia (AML) is an inevitable outcome for many patients with MDS. Azacitidine has been reported to result in comparably higher response rates and improved survival than other treatment strategies. In this retrospective study, we report the results on 25 ‘real life’ patients with MDS, CMML or AML treated with azacitidine between 2005 and 2009. All patients fulfilled the World Health Organization criteria for MDS and AML. No eligibility criteria other than diagnosis were considered. Complete response (CR) rate was observed in three of the 25 ‘real life’ patients (12%) with a median duration of CR of 5 months (4–6 months). Seven patients (28%) had mono‐ or bi‐lineage haematologic improvement and 15 patients (60%) showed neither morphologic nor haematologic response. Among 17 non‐AML patients, the median time from onset of Aza‐C treatment to AML transformation was 10 months (4–15 months). Overall death rate was 72%. All of the eight AML patients died. The death rate under Aza‐C among non‐AML patients was 59%. Unlike the results of the clinical trials, our data show that Aza‐C has a limited activity in ‘real‐life’ patients with MDS and AML. It is obvious that Aza‐C can induce complete or partial responses in a considerable number of MDS patients but responses are usually not durable as we observed in our patients. Copyright

Serum hepcidin and growth differentiation factor-15 (GDF-15) levels in polycythemia vera and essential thrombocythemia

Hepcidin plays a regulatory role in systemic iron homeostasis. GDF‐15 has been found to be expressed from matured erythroblasts and very high levels of GDF‐15 suppresses hepcidin secretion. In this study, we evaluated hepcidin and GDF‐15 levels in polycythemia vera (PV) and essential thrombocythemia (ET).

Soluble Programmed Death 1 (PD-1) Is Decreased in Patients With Immune Thrombocytopenia (ITP) Potential Involvement of PD-1 Pathway in ITP Immunopathogenesis

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by dysregulation of T cells. Programmed death (PD) 1 and programmed death 1 ligand 1 (PD-L1) are cosignaling molecules, and the major role of the PD-1 pathway is the inhibition of self-reactive T cells and to protect against autoimmune diseases. We measured levels of serum soluble PD 1 (sPD-1) and serum soluble PD-L1 (sPD-L1) in 67 patients with ITP (24 newly diagnosed ITP [ndITP], 43 chronic ITP [cITP]) and 21 healthy controls (HCs). We determined decreased serum sPD-1 levels both in patients with ndITP and in patients with cITP when compared to HC. Moreover, there was a positive correlation between sPD-1 levels and platelet counts. The sPD-L1 levels were decreased in patients with ndITP when compared to patients with cITP. This is the first study investigating PD-1 signaling pathway in ITP. Decreased sPD-1 levels may have a role in ITP pathogenesis as without the inhibitory regulation of PD-1, sustained activation of T cells may cause inflammatory responses which is the case in ITP.

Serum growth differentiation factor 15 levels in newly diagnosed multiple myeloma patients.

Background/Aims: Multiple myeloma (MM) is a hematological cancer associated with increased clonal malignant plasma cells. Growth differentiation factor 15 (GDF 15) is a protein that is highly expressed in the bone marrow mesenchymal stem cells of patients with MM. This study investigated whether the clinical stage of the disease, treatment response and survival are affected by pretreatment serum GDF 15 levels. Methods: Serum GDF 15 levels were measured in 35 newly diagnosed MM patients and 27 healthy controls. The correlation between serum GDF 15 levels and various clinical and laboratory parameters was analyzed. Results: The study demonstrated significantly higher levels of GDF 15 in MM patients. There was a negative correlation between GDF 15 levels, hemoglobin and albumin levels, and a positive correlation between GDF 15 levels, CRP, creatinine, β-2-microglobulin and stage. GDF 15 levels were lower in patients who could receive autologous stem cell transplantation compared to other groups, representing a statistically significant difference. However, in the survival analyses, GDF 15 level did not have an impact on survival. Conclusion: High serum levels of GDF 15 may indicate a poor treatment response. Our study supports the prognostic value of GDF 15 in MM.

Treatment of patients with multiple myeloma over 65 yr: more tolerability or better response?

Two‐thirds of newly diagnosed patients with multiple myeloma (MM) are over 65 yr and/or physically unfit. Such patients are not eligible for high‐dose chemotherapy or stem cell transplantation. The treatment aims in these patients should be to prolong survival by obtaining the best possible response, while maintaining good tolerability. The aim of our study was to evaluate the response to treatment and treatment‐related toxicities in patients treated with conventional and novel protocols.

The Association Between Gene Polymorphisms and Leukocytosis with Thrombotic Complications in Patients with Essential Thrombocythemia and Polycythemia Vera

Objective: Vascular events are a common complication in patients with polycythemia vera (PV) and essential thrombocythemia (ET). This study aimed to analyze the association between PAI-1 4G/5G and ACE I/D gene polymorphisms, and leukocytosis with thrombosis in patients with PV and ET. Material and Methods: In total, 64 patients with ET and PV were evaluated. Arterial or venous thrombosis, such as cerebral transient ischemic attack, ischemic stroke, myocardial infarction, peripheral arterial thrombosis, deep venous thrombosis, and pulmonary embolism, were defined as a vascular event. DNA samples were screened for mutations via reverse hybridization strip assay. Results: In terms of PAI-1 gene polymorphism, the frequency of the 4G and 5G allele was 48.5% and 51.5%, respectively. The ACE allele frequency was 51.2% and 48.8% for D and I, respectively. There wasn’t an association between occurrence of vascular events and the frequency of any allele. In terms of occurrence of vascular events, there weren’t any significance differences between the patients that were carrying the ACE D/D homozygous allele to ACE I/D and those that carried the I/I allele (P = 0.93). There wasn’t a significant difference in occurrence of vascular events between the PAI-1 5G/5G homozygote allele carriers, and the 4G/5G and 4G/4G allele carriers (P = 0.97). Vascular events were significantly more common in the patients with leukocytosis (leukocyte count >10 × 109 L–1) than in those without leukocytosis (leukocyte count ≤10 × 109 L–1) (P = 0.00). Age >60 years was also a significant risk factor for occurrence of vascular events(P = 0.008). Conclusion: PAI-1 and ACE gene polymorphisms were not considered new risk factors for thrombosis in PV and ET patients. On the other hand, leukocytosis at diagnosis was associated with the occurrence of vascular events in the patients with ET and PV.

Decreased serum heat shock protein 60 levels in newly diagnosed immune thrombocytopenia patients.

Abstract Immune thrombocytopenia (ITP) is an autoimmune disease characterized by peripheral thrombocyte destruction. In some autoimmune disorders, heat-shock proteins (HSP) are suggested to be an important antigenic factor. In this study, we demonstrated the serum free levels of HSP60, HSP70, anti-HSP60, and anti-HSP70 in ITP patients and healthy controls. Twenty-eight newly diagnosed ITP patients, 35 ITP patients in chronic phase, and 25 healthy controls were enrolled to this study. Serum levels of HSP60, HSP70, anti-HSP60, and anti-HSP70 were determined by the ELISA method. Serum HSP60 levels of newly diagnosed ITP patients were significantly decreased when compared with both chronic phase ITP patients and healthy controls. HSP60 levels of ITP patients (both newly diagnosed and chronic phase) with thrombocyte counts more than 30 × 109/L were significantly increased compared with ITP patients with thrombocyte counts less than 30 × 109/L and there was a positive correlation between thrombocyte counts and serum free HSP60 levels in ITP patients. This is the first study demonstrating the extracellular HSP levels in adult ITP patients. HSPs are shown to have a place in the pathogenesis of many autoimmune disorders. Low level of HSP60 may lead to lack of anti-inflammatory response due to less Treg activation, hence, could be a counterpart in the pathogenesis of ITP. Further studies are needed to understand the role of HSPs in the pathogenesis of ITP and whether they can be used for diagnosis, prognosis, and treatment of ITP.

Relationship of P-Selectin Glycoprotein Ligand-1 to Prognosis in Patients With Multiple Myeloma

BACKGROUND Changes occur in adhesion molecules in the disease course of multiple myeloma. P-selectin glycoprotein ligand-1 (PSGL-1, CD162) works as the ligand of selectin-neutrophil adhesion molecules. The aim of the present study was to investigate the relationship between PSGL-1 expression in the bone marrow and the known prognostic factors for multiple myeloma disease, disease stage, and survival. MATERIALS AND METHODS This research included 63 patients with multiple myeloma (26 women [41.3%]; 37 men [58.7%]). The bone marrow biopsy samples obtained at disease diagnosis for each patient were stained immunohistochemically in terms of CD162 expression using standard diagnostic immunohistochemical staining methods. The laboratory results, CD162 expression, overall survival, demographic characteristics of the disease, and the relationship between CD162 expression and the disease stage were evaluated. RESULTS Among the 63 patients included in the present study, the survival rate was 82.3% for 1 year, 73.2% for 2 years, 63.4% for 3 years, 51.7% for 4 years, 40.3% for 5 years, and 33.6% for 6 and 7 years. A statistically significant difference was not detected between the CD162 staining ratio and disease survival (P = .232). A statistically significant difference was not detected between the CD162 staining degree and survival rate (P = .184). However, the overall survival of the patients with no CD162 expression in the bone marrow was lower than that for the patients whose CD162 was stained 1, 2, and 3 degrees (12.33 ± 11.49, 28.65 ± 31.44, 37.25 ± 29.32, and 47.92 ± 45.29 months, respectively; P < .001). CONCLUSION In the present study, CD162 staining and the staining degree, with the other standard immunohistochemical stains, were shown to be beneficial in the diagnosis of multiple myeloma disease. However, the results did not provide information about the disease course. Studies of a larger number of patients to examine P-selectin and interleukin-6 levels are needed to investigate the disease course.

Beta-2 microglobulin predicts the outcome after autologous stem cell transplantation in non-Hodgkin lymphoma

Autologous stem cell transplantation (ASCT) is an established therapeutic modality in the treatment of lymphomas, especially in the relapse setting. In the present study, we aimed to define pretransplantation factors including Beta-2 microglobulin (β2m) that influence outcomes following ASCT in patients with non-Hodgkin lymphoma (NHL). We analyzed retrospectively 78 NHL patients who had undergone ASCT from August 2010 to January 2013. The 2-year overall survival (OS) was 70% and the progression-free survival (PFS) was 60%. While remission status less than complete remission (CR) emerged to be a poor prognostic factor for OS in univariate analysis, high β2m levels and comorbidity indices revealed to be independent poor risk factors for both OS and PFS. The present study demonstrated that even if the patient is in CR before ASCT if he has high β2m, the 2-year OS decreases from 100% to 49%. Moreover, lymphopenia for the first time was demonstrated to predict PFS in ASCT in NHL patients. Our findings suggest that β2m at transplantation predict the outcome after ASCT in NHL and further investigation with larger sample sizes is warranted.

Late-onset Anticonvulsant Hypersensitivity Syndrome Mimicking Lymphoma.

Anticonvulsant hypersensitivity syndrome is a fatal, idiosyncratic drug reaction that is caused by aromatic antiepileptic drugs. This cutaneous drug reaction is also called pseudolymphoma because of its clinical and histological similarities with malignant lymphoma. The primary clinical findings are fever, skin rashes, enlarged lymph nodes, single or multiple internal organ involvement and hematological abnormalities. Typically, anticonvulsant hypersensitivity syndrome occurs 1-8 weeks after drug administration. We herein present the case of a patient who had been on anticonvulsant therapy for five years and died from late-onset anticonvulsant hypersensitivity syndrome.