Methylenetetrahydrofolate reductase C677T polymorphism in adult patients with lymphoproliferative disorders and its effect on chemotherapy.

Methylenetetrahydrofolate reductase (MTHFR) is one of the most critical enzyme in folic acid metabolism, and it converts 5,10-MTHF to 5-MTHF. 5,10-MTHF is required for conversion of uridilate to thymidylate. On the other side, MTHFR enzyme causes methylation of homocysteine into methionine, leading to methylation of DNA. Chemotherapeutic agents have different effects, but DNA is the target for most of them. Because folate is the cornerstone in DNA synthesis, we analysed herein if the polymorphisms in MTHFR gene can alter the susceptibility of lymphoproliferative disease risk and if it has an effect on chemotherapy response. One hundred fifty-six patients with lymphoid malignancies and 82 healthy controls were included into the study. Neither gene frequencies nor allel frequencies were found to increase lymphoproliferative disease risk significantly in both overall group and subgroups. Although it was not statistically significant, we found a 2.7-fold increased risk in acute lymphocytic leukaemia (ALL)/Burkitt lymphoma patients with TT genotype [odds ratio (OR), 2.7; 95% confidence interval (CI), 0.88-8.2] than CC genotype but a 1.7-fold decreased risk with TT genotype in diffuse large B-cell lymphoma (DLBCL; OR, 0.58; 95% CI, 0.17-1.88) and a 1.8-fold decreased risk in Hodgkin's lymphoma with TT genotype (OR, 0.55; 95% CI, 0.10-2.87) than CC genotype. The chemotherapy response was analysed in DLBCL, Hodgkin's lymphoma and ALL/Burkitt's lymphoma because these patients received standard chemotherapy protocols. No significant difference was detected between responder and non-responders according to MTHFR T677C polymorphism, but the patients who had TT genotype respond 1.75-fold worse than CC (OR, 0.57; 95% CI, 0.07-4.64) in ALL patients (p=0.59), and in DLBCL, CT genotype revealed a 1.8-fold worse response than CC genotype (OR, 0.54; 95% CI, 0.17-1.7), but TT genotype revealed 2.6-fold better response rates than patients with CC genotype (OR, 2.6; 95% CI, 0.26-26.8). As a conclusion, MTHFR C677T polymorphism does not increase the risk of lymphoproliferative disease, and it does not have an effect on chemotherapy response significantly; however, the patients with TT genotype have a slightly increased risk for ALL, and they also respond worse than CC genotype. TT genotype slightly decreases the risk of DLBCL, and the patients have much favorable response rates.

Pulmonary involvement in Behçet's disease: evaluation of 123 I-MIBG retention.

Pulmonary involvement in Behçet's disease (BD) is reported to indicate poor prognosis and high mortality. Our aim was to evaluate the pulmonary vascular status in BD. As 123I-meta-iodobenzylguanidine (123I-MIBG) shares the same uptake, storage and release mechanisms as norepinephrine, associated with the functional state of pulmonary endothelium, it may reflect endothelial injury. Twenty-five patients (13 males, 12 females; mean age, 36.44 years) and 12 age-matched controls were included. After intravenous injection of 123I-MIBG, thorax images were taken at 15 min and 4 h. Appropriate regions of interest were drawn, and heart to mediastinum (H/M) ratios and lung retention indices (LRI) were calculated. The difference between the LRI of controls (75.6+/-4%) and patients (87.7+/-10%) was found to be extremely significant (P<0.005). The LRIs of active (92.85+/-12%) and inactive (83.65+/-5%) states of BD were significantly different (P<0.05) from each other. There was no significant difference between the H/M ratios of controls (2.4+/-0.27) and patients (2.39+/-0.31) or between patients in active and inactive disease states. Our study revealed prolonged lung retention of 123I-MIBG in BD, probably reflecting the severity of the disease. In conclusion, 123I-MIBG lung retention is a valuable finding in the evaluation of pulmonary vascular status and may be a potential marker of prognosis in BD.

A case report of multicentric Castleman's disease with simultaneous Epstein-Barr virus infection.

Castleman's disease is a rare B-cell lymphoproliferative disorder of unknown etiology. In this report we describe a 54-year-old woman with a 10-year history of asymptomatic bilateral, multiple cervical lymph node enlargements. She was not evaluated by lymph node biopsy during this period. She had been well until four months previously. The patient presented with multiple enlarged lymph nodes and systemic symptoms including fever, sweats, weight loss, and anorexia. Two lymph nodes were biopsied, yielding a diagnosis of multicentric Castleman's disease (MCCD) of mixed hyaline-vascular and plasma cell type histology. Serologic studies revealed the simultaneous presence of an acute Epstein-Barr virus (EBV) infection. She experienced an aggressive clinical course with a fatal outcome.

Epstein-Barr Virus Latent Membrane Protein 1 (LMP-1) in Hodgkin's Lymphoma Patients in Turkey.

Epstein-Barr virus (EBV) has been implicated as a contributing factor in the development of Hodgkin's lymphoma. The aim of this study was to elucidate the association of Hodgkin's lymphoma with EBV in a Turkish population using immunohistochemical detection of LMP-1. We studied a total of 21 consecutive cases of Hodgkin's lymphoma from Turkey. LMP-1 protein was detected in 9 of 21 (42.8%) cases. LMP-1 was positive in 4 of 7 (57%) mixed cellularity and 5 of 13 (38.4%) nodular sclerosis subtype. The results of the current study suggests a strong association of Epstein-Barr virus with Hodgkin's lymphoma in Turkey and, together with those reported previously showed that Epstein-Barr virus correlated with mixed cellular type, with a slight male predominancy while there was no correlation with age.

Comparison of the hematological effects of a sustained release chitosan formulation of pentoxifylline with a commercial formulation.

In the present study the hematological effects of a sustained release chitosan formulation of pentoxifylline (CAS 6493-05-6) were examined and compared with those of a commercial product. The study was carried out on 12 healthy volunteers. Both formulations were tolerated well clinically. The results demonstrated no antiaggregatory effect of the two different formulations of pentoxifylline in platelet rich plasma. Both drugs resulted in a decrease of plasma fibrinogen levels. A remarkable side effect of the new formulation was mild basophilia, without any clinical problems.

Prophylactic use of fluconazole in neutropenic cancer patients.

This study was carried out on 70 patients with haematological or solid malignancies who were receiving chemotherapy and/or radiotherapy. Forty-one patients were randomly assigned to receive fluconazole, 400 mg/day, while they were neutropenic. Systemic fungal infection developed in four of the 41 patients (9%) receiving prophylaxis in comparison to nine of 29 patients (31%) not receiving prophylaxis. The incidence of systemic fungal infection was significantly different between the groups receiving prophylaxis and those not receiving it (p < 0.05). Fluconazole was found to be effective for preventing systemic fungal infections in neutropenic patients with cancer.