Emin Kaya

Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group.

The combination of melphalan–prednisone–thalidomide (MPT) has been investigated in several clinical studies that differed significantly with regard to patient characteristics and treatment schedules. This prospective trial differs from previous melphalan–prednisone (MP) vs. MPT trials by treatment dosing, duration, routine anticoagulation, and permission for a crossover. Newly diagnosed patients with multiple myeloma (MM) (n = 122) aged greater than 55 yr, not eligible for transplantation were randomized to receive 8 cycles of M (9 mg/m2/d) and P (60 mg/m2/d) for 4 d every 6 wk (n = 62) or MP and thalidomide (100 mg/d) continuously (n = 60). Primary endpoint was treatment response and toxicities following 4 and 8 cycles of therapy. Secondary endpoints were disease‐free (DFS) and overall survival (OS). Overall, MPT‐treated patients were younger (median 69 yr vs. 72 yr; P = 0.016) and had a higher incidence of renal impairment (RI, 19% vs. 7%, respectively; P = 0.057). After 4 cycles of treatment (n = 115), there were more partial responses or better in the MPT arm than in the MP arm (57.9% vs. 37.5%; P = 0.030). However, DFS and OS were not significantly different between the arms after a median of 23 months follow‐up (median OS 26.0 vs. 28.0 months, P = 0.655; DFS 21.0 vs. 14.0 months, P = 0.342, respectively). Crossover to MPT was required in 11 patients, 57% of whom responded to treatment. A higher rate of grade 3–4 infections was observed in the MPT arm compared with the MP arm (22.4% vs. 7.0%; P = 0.033). However, none of these infections were associated with febrile neutropenia. Death within the first 3 months was observed more frequently in the MP arm (n = 8, 14.0%) than in the MPT arm (n = 2, 3.4%; P = 0.053). Long‐term discontinuation and dose reduction rates were also analyzed (MPT: 15.5% vs. MP: 5.3%; P = 0.072). Although patients treated with MPT were relatively younger and had more frequent RI, better responses and less early mortality were observed in all age groups despite more frequent discontinuation. This study is registered at http://www.clinicaltrials.gov as #NCT00934154.

Platelet counts in adults with iron deficiency anemia

In adults with iron deficiency anemia (IDA), abnormal platelet counts were seen in several studies. However we retrospectively examined the clinical records of a larger number of adults with IDA to assess abnormal platelet counts. From November 2006 to April 2008, 615 consecutive adults (73 men and 542 women; age range, 16–88 years) with IDA were included in this study. The mean initial hemoglobin was 9.0 ± 1.8 g/dL (range 2.7–12.8 g/dL), and the mean initial platelet count was 304 × 103/µL ± 92.3 (range, 105–700 × 103/µL). The initial platelet counts were normal in 520 (84.6%) adults with IDA. Thrombocytosis (>400 × 103/µL) and thrombocytopenia (<150 × 103/µL) were detected in 82 (13.3%) and 13 (2.1%) adults with IDA, respectively. In conclusion, thrombocytosis was seen at lower rates in our study. Furthermore, this study shows that mild thrombocytopenia is not so rare in adults with IDA.

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.

Effect of endogen-exogenous melatonin and erythropoietin on dinitrobenzene sulfonic acid–induced colitis

Inflammatory bowel disease has been linked to elevated T cells. Excessive production of reactive oxygen species and apoptosis are known to be accompanied by intestinal inflammation. This study was designed to investigate the effects of melatonin (MEL) and erythropoietin (EPO), which is a known anti‐inflammatory and antiapoptotic agent, in dinitrobenzene sulfonic acid (DNBS)–induced colitis in pinealectomized (Px) rats. In microscopically results, epithelial and goblet cell loss, absence of crypts, and increased colonic caspase‐3 activity were observed in the DNBS group. Also, in flow cytometric analysis, the percentage of CD4+ T cells was highest in the DNBS group. Treatment with MEL or EPO had a curative effect on DNBS‐induced colitis. The MEL + EPO groups showed significantly greater improvement when compared with the other treatment groups. Our results indicate that the combination of EPO and MEL may exert more beneficial effects than either agent used alone.

A life-saving therapy in Class I HELLP syndrome: Therapeutic plasma exchange

HELLP syndrome, which can affect multiple organ systems and cause maternal and fetal mortality, is a serious complication of pregnancy characterized by microangiopathic hemolytic anemia, elevation of liver enzymes, and thrombocytopenia. Delivering the infant usually suffices for the treatment of this syndrome. In cases with Class I HELLP syndrome, however, the clinical picture may rapidly deteriorate despite delivery. In this paper we presented the outcomes with the use of therapeutic plasma exchange in cases with class I HELLP syndrome. This study included 21 patients diagnosed with the Class I HELLP syndrome at Inonu University Faculty of Medicine, Department of Hematology between 2011 and 2014. A central venous catheter was placed and plasma exchange therapy was begun in patients unresponsive to delivery, steroid, and supportive therapy (blood and blood products, antihypertensive therapy, intravenous fluid administration, and antibiotics) within 24 hours after the diagnosis of Class I HELLP syndrome according to the Mississippi Criteria. All patients underwent therapeutic plasma exchange for three sessions each with a 1:1 volume. Hemogram and biochemical parameters of the patients were evaluated before and after the procedure. According to results, there was a statistically significant decrease in total bilirubin, LDH, AST, and ALT levels whereas a significant increase in platelet count was observed. Hemoglobin levels were increased, although this increase was not statistically significant. HELLP syndrome is primarily treated with the delivery of infant; however, some cases may show disease progression despite completion of delivery. As a potential cause of both maternal and fetal mortality, HELLP syndrome condition should be aggressively treated. Therapeutic plasma exchange is one of the available treatment options. Our study has found that postpartum use of plasma exchange therapy within 24 hours is an efficient and lifesaving treatment choice in Class I HELLP syndrome.

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.