Ismet Aydogdu

Therapeutic plasma exchange in patients with neurologic diseases: Retrospective multicenter study

Therapeutic plasma exchange (TPE) is commonly used in many neurological disorders where an immune etiology was known or suspected. We report our experience with TPE performed for neuroimmunologic disorders at four university hospitals. The study was a retrospective review of the medical records of neurological patients (n=57) consecutively treated with TPE between April 2006 and May 2007. TPE indications in neurological diseases included Guillain-Barrè Syndrome (GBS) (n=41), myasthenia gravis (MG) (n=11), acute disseminated encephalomyelitis (ADEM) (n=3), chronic inflammatory demyelinating polyneuropathy (CIDP) (n=1) and multiple sclerosis (MS) (n=1). Patient median age was 49; there was a predominance of males. Twenty-two patients had a history of other therapy including intravenous immunoglobulin (IVIG), steroid, azothioprin, and pridostigmine prior to TPE. Another 35 patients had not received any treatment prior to TPE. All patients were classified according to the Hughes functional grading scores pre- and first day post-TPE for early clinical evaluation of patients. The TPE was carried out 1-1.5 times at the predicted plasma volume every other day. Two hundred and ninety-four procedures were performed on 57 patients. The median number of TPE sessions per patient was five, and the median processed plasma volume was 3075mL for each cycle. Although the pre-TPE median Hughes score of all patients was 4, it had decreased to grade 1 after TPE. While the pre-TPE median Hughes score for GBS and MG patients was 4, post-TPE scores were decreased to grade 1. Additionally, there was a statistically significant difference between post-TPE Hughes score for GBS patients with TPE as front line therapy and patients receiving IVIG as front line therapy (1 vs. 3.5; p=0.034). Although there was no post-TPE improvement in Hughes scores in patients with ADEM and CIDP, patients with MS had an improved Hughes score from 4 to 1. Mild and manageable complications such as hypotension and hypocalcemia were also observed. TPE may be preferable for controlling symptoms of neuroimmunological disorders in early stage of the disease, especially with GBS.

Serum proinflammatory mediators at different periods of therapy in patients with multiple myeloma.

Multiple myeloma (MM) is a malignant disease characterized by the clonal proliferation of plasma cells within the bone marrow. Several cytokines have been demonstrated to be involved in the control of growth, progression, and dissemination of MM. We determined serum levels of interleukin-1β (IL-1β), soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) in 14 newly diagnosed MM patients. The median age of the patients was 63.4 ± 10.8 years and all of the patients were stage III (classified according to the Durie-Salmon classification). The same parameters were measured in 15 healthy controls. In addition, we also examined the effects of vincristine-adriamycin-dexamethasone (VAD) therapy on the same parameters and mediators as well as the relationship among the parameters in the same patient groups. The serum concentrations of TNF-α, IL-1β, sIL-2R, IL-6, IL-8, and CRP (18.6 ± 3.7 pg/mL, 10.1 ± 2.8 pg/mL, 730 ± 220 U/mL, 11.4 ± 3.3 pg/mL, 23.9 ± 8.3 pg/mL, and 49.9 ± 19.5 mg/dL, resp) were significantly higher in newly diagnosed MM patients than in healthy controls (P < .0001). All of the parameters were found to be significantly reduced after chemotherapy. In conclusion, we found that after the VAD therapy, the level of these cytokines which are thought to play an important role in the pathogenesis of MM was significantly suppressed. This is the first study demonstrating strong impact of VAD treatment on circulating mediators of sIL-2R and IL-8 levels parameters.

Oxidant/antioxidant Parameters and their Relationship with Chemotherapy in Hodgkin's Lymphoma

This study investigated changing levels of serum oxidant/antioxidant with chemotherapy and their relation to treatment in 34 Hodgkins lymphoma patients. The patient population consisted of 19 males and 15 females. Mean age was 30.41 ± 12.08 years. All patients received the adriamycin, bleomycin, vincristine and dexamethasone (ABVD) treatment protocol. Blood samples were taken before treatment, and on days 1 and 7 during treatment for measurement of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA), nitric oxide (NO) and enzyme activities. After ABVD treatment, mean free radical levels were increased and antioxidant levels were significantly decreased in the serum. ABVD treatment results in an increase of free radical levels and a decrease of antioxidant levels in the serum of patients with Hodgkins lymphoma.

Effects of Cyanocobalamin on Immunity in Patients with Pernicious Anemia

Objective: The aim of the study was to evaluate the role of vitamin B12 in patients with pernicious anemia. Materials and Methods: This study was conducted prospectively at the Turgut Özal Medical Center, Department of Hematology, between April and November 2002. Absolute numbers and ratio of the surface antigens of T and B lymphocyte subgroups, CD4/CD8 ratio were calculated in order to evaluate changes in leukocyte and lymphocyte numbers; natural killer (NK) cell count, serum C3, C4, and levels of immunoglobulins G, A, and M were also measured to evaluate vitamin B12 effect on immunity. Values obtained before treatment with cyanocobalamin were compared with those found during peak reticulocyte count. Results: In vitamin B12-deficient patients, absolute numbers of CD4+ and especially CD8+ lymphocytes were found to be decreased; CD4/CD8 ratio increased, and NK cell activity was depressed. After cyanocobalamin treatment, absolute numbers and percentage of lymphocyte subgroups were elevated. Increased CD4/CD8 ratio and depressed NK cell activity were restored and levels of C3, C4, and immunoglobulins were elevated. Conclusion: These findings suggest that vitamin B12 has important immunomodulatory effects on cellular immunity, and abnormalities in the immune system in pernicious anemia are restored by vitamin B12 replacement therapy.

Development of large genital ulcer due to hydroxyurea treatment in a patient with chronic myeloid leukemia and Behcet's disease.

Chronic myeloid leukemia (CML) is a myeloproliferative disease arising from abnormal stem cells and associated with splenomegaly and leukocytosis. Hydroxyurea and interferon alpha are used in treatment very frequently. Behcets disease (BD) is a chronic, repetitive disease of unknown etiology and associated with mucocutaneous, ocular, vascular and central nervous system involvement. Cases with symptoms of BD have been reported during interferon alpha treatment of CML. However, similar symptoms due to hydroxyurea treatment have been reported in only one case until now. A 32-year-old female patient under follow up because of CML and BD, developed a large genital ulcer during hydroxyurea treatment. Ulcers due to hydroxyurea treatment and the co-existence of these two diseases has been reported in only one case in the literature while large genital ulcers have not been reported previously.

Rheumatic diseases and chronic myelogenous leukemia, presentation of four cases and review of the literature

We report four patients with rheumatic disease (RD) and chronic myelogenous leukemia (CML). In two patients with Behcet’s disease (BD) and rheumatoid arthritis (RA), CML developed after RD, in two patients with diffuse cutaneous systemic sclerosis and spondyloarthropathy, RD was diagnosed after CML. A variety of interactions have been described between hematological malignancies and RD. Nevertheless, few cases of RD have been documented associated with CML. It is unclear whether the development of CML in patients with RD and RD development after CML occurs by chance alone, is due to the underlying disease, or is facilitated by drugs. Whatever the cause is, it should be kept in mind that CML may develop in the course of RD and RD may be seen in CML patients.

A Prospective Randomized Study of Alpha-2b Interferon plus Hydroxyurea or Cytarabine for Patients with Early Chronic Phase Chronic Myelogenous Leukemia: The International Oncology Study Group CML1 Study

A prospective randomized international study of 143 patients showed no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy. Combinations of alpha-interferon (INF) and chemotherapeutic agents are currently first-line therapy for the majority of patients with chronic myeloid leukemia (CML). The International Oncology Study Group conducted a prospective randomized study comparing INF combined with hydroxyurea or cytarabine. The primary study aim was to compare the survival durations in these patient cohorts. Patients with early chronic phase CML were randomized to receive INF 5 million units (Mu) given five times per week subcutaneously plus hydroxyurea or cytarabine as required to achieve a complete hematologic response and to maintain a WBC count between 2×109/L and 10×10 /L and a platelet count between 75×109/L and 100×109/L. Therapy continued as tolerated unless progressive or blast phase disease occurred. At 36 months, the actuarial survival rate was equivalent in both groups: HI group (79 patients) survival was 85% (95% CI, 68-100%), as compared to 95% (95% CI, 79-100%) in the CI group (64 patients). In conclusion if seems that there is no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy.

Retrospective Analysis of Patients with Idiopathic Thrombocytopenic Purpura from Eastern Anatolia

Objective: We evaluated the clinical features and the effects of various treatment modalities on the clinical course in patients diagnosed with idiopathic thrombocytopenic purpura (ITP). Materials and Methods: Retrospective investigation of the medical records of 168 patients at our center between 1994 and 2005 was done. Results: Of the 168 patients, 115 (68.4%) were women and 53 (31.6%) men. At initial diagnosis, the median age of the patients was 33 years (range: 15–91) and 139 (82.7%) had signs of bleeding. Follow-up was complete in 130 patients and the median follow-up was 27 months (range: 3–132). Initial treatment with either standard or high-dose steroid as first-line therapy was begun in 123 (73.2%) of the 168 patients. Complete remission (CR) was achieved in 56% of the patients. Sixty-one (61) patients who were followed up regularly received second-line therapies. CR was achieved in 45.8% of the patients who received steroids as second-line therapy. Within a median follow-up of 7 months, 27.2% of these patients relapsed. Splenectomy was performed in 26 patients and CR was obtained in 72% of the 25 patients regularly followed up. CR obtained by splenectomy was significantly higher than that obtained by steroids (p < 0.001). The 10-year disease-free survivals in patients who used steroids and who underwent splenectomy were 15 and 61.6%, respectively. Conclusion: Steroid therapy is effective both in the initial and relapse periods. Splenectomy is the treatment of choice for those ITP patients refractory to steroid therapy and younger than 40 years of age.

Case Report. Rhinocerebral zygomycosis

Summary.  A case of rhinocerebral zygomycosis treated with liposomal amphotericin B is described.

Metastatic bone marrow tumours: a report of six cases and review of the literature.

Bone marrow aspirations and biopsies are now employed in the investigation of many disorders in haematology, oncology, and internal medicine. In this paper, clinical, laboratory, and pathological findings are presented of patients with bone marrow metastases of solid tumours (n = 6). Anemia was detected in four cases (66.6%), thrombocytopenia in five cases (83.3%), leukopenia in three cases (50%), diffuse bone pain in four cases (66.6%), elevated serum alkaline phosphatase levels in four cases (66.6%). and hypercalcaemia in two cases (33.3%). In conclusion, bone marrow aspiration and biopsy examinations are effective, practical, and cheap in detecting solid tumour metastasis to bone marrow in a selected group of patients.