Murat Tombuloglu

Telomerase activity in connective tissue diseases: elevated in rheumatoid arthritis, but markedly decreased in systemic sclerosis.

Telomerase is a reverse transcriptase enzyme contributing to the maintenance of the telomeric structure by adding telomere repeat sequences to chromosomal ends, thus compensating for its shortening. Telomerase activity which is common in cancers and human germ line tissue, may also be increased, although to a lesser extent, in systemic autoimmune diseases. We aimed to evaluate telomerase activity in a group of Turkish patients with various connective tissue diseases. In this cross sectional study, 19 patients with systemic sclerosis (SSc), 15 with systemic lupus erythematosus (SLE), 10 with rheumatoid arthritis (RA) and 14 with primary Sjögren’s syndrome (pSjS) were studied. As the control group, 29 healthy subjects were also included. Human telomerase-specific reverse transcriptase (hTERT) was measured in peripheral blood lymphocytes, using online real-time reverse-transcriptase polymerase chain reaction (PCR). We also investigated if hTERT values in each patient group were correlated with clinical parameters and disease activity. Highest hTERT values were observed in RA group (21.24xa0±xa028.54), followed by SLE (13.38xa0±xa026.05) and pSjS (11.73xa0±xa010.59) groups. Only hTERT values in RA group was significantly higher than the healthy control group (7.62xa0±xa04.21) (pxa0<xa00.05). Interestingly, hTERT values in SSc were very low (2.09xa0±xa03.18), even less than the healthy control group. In consistent with previous studies, telomerase activity was increased in SLE and RA. Very low telomerase activity in SSc group was rather surprising. Since existing telomerase data in SSc was limited and telomere shortening was previously reported in SSc, our finding of low telomerase activity in SSc group deserves relevant discussion and further studies.

Dural plasmacytoma mimicking meningioma in a patient with multiple myeloma

Apart from calvarial infiltration, intracranial involvement in multiple myeloma is uncommon. Diffuse leptomeningeal invasion with or without parenchymal involvement is most common. Dural infiltration without involvement of the parenchyma, leptomeninges or skull is rare. The differential diagnosis of a dural plasmacytoma includes meningioma, which has a similar MRI appearance, metastasis, lymphoma and sarcoma of the dura mater. We present a patient with multiple myeloma presenting with an intracerebral mass mimicking a meningioma on MRI. Multiple myeloma had been diagnosed seven years previously. The patient presented with headache and speech disturbance 12 months after autologous peripheral stem cell transplantation for recurrence of multiple myeloma. MRI revealed a left temporal extra-axial mass with a dural tail mimicking meningioma. Histopathological examination of the mass after excision showed multiple myeloma immunopositive for IgG, kappa light chain and CD38. There was no recurrence after postoperative radiotherapy. Plasmacytoma should be considered in the differential diagnosis of a solitary dural mass, particularly in a patient with multiple myeloma.

Cholesterol levels in patients with multiple myeloma

Hypocholesterolemia is seen in solid tumors and some hematological malignancies. We assessed cholesterol levels and the relationship between these levels and types and stages of multiple myeloma (MM) in the patients with MM. One-hundred two patients (60 male and 42 female) of mean age 59u2009±u200911xa0years with MM were enrolled to this study. While 71.6% of the patients were Ig G type, 80.4% of the patients were at stage III. In the control group, there were 71 healthy persons (42 male and 29 female) of mean age 58u2009±u20098xa0years. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in the patients with MM were significantly lower than the controls (pu2009<u20090.001). There was no difference for the levels of very-low-density lipoprotein cholesterol and triglyceride between the two groups (pu2009>u20090.05). Lipid parameters were not different between Ig types (pu2009>u20090.05). The levels of TC and LDL-C in the patients with stage I were higher than those of stages II and III (pu2009<u20090.001 and pu2009<u20090.005, respectively). The levels of TC and LDL-C in the controls were not higher than the patients with stage I (pu2009>u20090.05). HDL-C levels in the patients with stage III were lower than controls (pu2009<u20090.001). Hypocholesterolemia are seen in the patients with MM. Hypocholesterolemia may be due to increased LDL clearance and utilization of cholesterol by myeloma cells.

Risk factors for microbial contamination of peripheral blood stem cell products.

BACKGROUND: Despite the well‐known contamination rates and presence of microbial agents in stem cell products, the risk factors affecting microbial contamination have not been well described.

Budd-Chiari syndrome in an afibrinogenemic patient : A paradoxical complication

Qualitative and quantitative abnormalities of fibrinogen can result in hemostatic disorders (1). Congenital afibrinogenemia is a rare coagulation disorder transmitted as an autosomal recessive trait (2). The incidence of afibrinogenemia is 1–2 cases per million population (3). It is more common in populations with a high rate of consanguinity (3). Symptoms of afibrinogenemia vary from mild hemorrhagic events to severe bleeding episodes, though thrombotic events are very rare. We report an afibrinogenemic patient who presented with hepatic venous thrombosis at 16 years old. Evaluation of all hemostatic parameters and coagulation factors revealed no other pathology except afibrinogenemia. Paradoxically, afibrinogenemia may be a risk factor for vascular thrombotic events like Budd–Chiari Syndrome (BCS).

The plasma levels of activated thrombin activatable fibrinolysis inhibitor and thrombomodulin in Behçet disease and their association with thrombosis.

OBJECTIVEnTo investigate the plasma levels of activated thrombin activatable fibrinolysis inhibitor (aTAFI) and thrombomodulin (TM) in Behçet disease (BD) and their relationship with thrombosis.nnnMETHODSnPlasma aTAFI and TM levels were measured by ELISA in 89 patients with BD (18 having venous thrombosis) and in 86 healthy controls.nnnRESULTSnCompared with healthy controls, the BD group had significantly lower levels of aTAFI (13.49+/-8.88 microg/ml vs. 26.76+/-11.57 microg/ml, p<0.0001) and significantly higher levels of TM (3.26+/-1.85 ng/ml vs. 2.6+/-0.69 ng/ml, p=0.0003). Neither aTAFI, nor TM levels differed significantly between BD patients with and without thrombosis (p>0.05). Despite a tendency to positive correlation (r=0.37, p=0.0004) between plasma levels of aTAFI and TM in healthy controls, there was a tendency for negative correlation (r=-0.51, p<0.0001) between these two parameters in BD patients.nnnCONCLUSIONnThe plasma aTAFI and TM levels do not seem to be related with the presence of thrombosis observed in BD. Increased plasma TM levels in BD may simply reflect endothelial cell activation and dysfunction.

Mitoxantrone and standard dose cytosine arabinoside therapy in refractory or relapsed acute leukemia.

Thirty adult patients with relapsing or refractory acute leukemia were treated with mitoxantrone 10 mg/m2 daily by 20-min intravenous infusion for 5 days and cytosine arabinoside (Ara-C) 200 mg/m2 daily by continuous infusion for 5 days. Complete remission was obtained in 9 of 15 patients (60%) with acute myeloblastic leukemia (AML), with a mean duration of 6 months (range 2-12 months). Among 15 patients with acute lymphoblastic leukemia (ALL), complete remission was obtained in 5 patients (33.3%), with a mean duration of 2 months. Partial remission was achieved in 2 patients with AML and 1 patient with ALL. Myelosuppression developed in all patients following chemotherapy. Nonhematologic side effects consisted of nausea, vomiting, mild alopecia, stomatitis and transient hepatic dysfunction. No cardiopulmonary toxicity or neurotoxicity was observed. Our therapeutic responses are similar to those obtained with high-dose Ara-C and mitoxantrone but with less toxicity.

Risk factors for adverse events during collection of peripheral blood stem cells

We retrospectively reviewed peripheral blood stem cell (PBSCs) collections following 528 mobilization cycles over a 10-year period. A total of 206 (13.1%) AEs occurred in association with the 1572 procedures. One hundred and ninety-one (12.15%) of the AEs were classified as clinical AEs and 15 (0.95%) were classified as apheresis instrument related AEs. The most common clinical AE was numbness of the lips, tongue, or extremities (161 procedures, 10.2%) related to the infusion of acid citrate dextrose-A (ACD). Multivariate analysis revealed high amounts of ACD/weight (odds ratio [OR]=1.11, p=0.009), high numbers of procedures (OR=1.33, p<0.001) and female gender (OR=2.83, p<0.001) as being significantly associated with clinical AEs. Female gender was shown to be the most important risk factor for clinical AEs. Females who have a significantly increased risk of AEs would benefit from prophylactic calcium before and/or during PBSC collection.

Risk factors for a poor hematopoietic stem cell mobilization

Poor mobilization is an important problem in autologous stem cell transplantation. We retrospectively reviewed the data of 165 mobilized patients to identify possible risk factors for a poor stem cell mobilization. 27 patients (16.4%) were categorized as poorly mobilized. The poor mobilization ratio differed according to diagnosis (lymphoma: 25.4%, acute leukemia: 15.4%, amyloidosis: 14.3%, and multiple myeloma: 9.6%). Being diagnosed as lymphoma (odds ratio [OR]=6.02, p=0.001), advanced age (OR=1.05, p=0.007) and increased weight (OR=1.03, p=0.03) were found as possible risk factors. Being diagnosed as lymphoma was shown to be the most important risk factor for a poor mobilization. Leukapheresis staff should be aware of the increased risk of a poor mobilization in lymphoma patients and remobilization methods should be considered from the beginning.

Plerixafor use in patients with previous mobilization failure: A multicenter experience

Plerixafor in conjunction with G-CSF (G-P) is an effective strategy for hematopoietic stem cell mobilization in patients with previously failed mobilization attempt. Here we report our results with G-P among patients with at least one mobilization failure with G-CSF alone (G) or G-CSF plus chemotherapy (G-C). The study included 20 consecutive patients with lymphoma and myeloma from five centers. In 14 (70%) patients, a minimum of 2×10(6)/kg CD34+ stem cells were collected and 16 out of 20 patients (80%) were able to proceed to ASCT. Our study indicates that plerixafor can safely rescue patients with a history of mobilization failure.