Multicenter retrospective analysis regarding the clinical manifestations and treatment results in patients with hairy cell leukemia: twenty-four year Turkish experience in cladribine therapy.

In this multicenter retrospective analysis, we aimed to present clinical, laboratory and treatment results of 94 patients with Hairy cell leukemia diagnosed in 13 centers between 1990 and 2014. Sixty-six of the patients were males and 28 were females, with a median age of 55. Splenomegaly was present in 93.5% of cases at diagnosis. The laboratory findings that came into prominence were pancytopenia with grade 3 bone marrow fibrosis. Most of the patients with an indication for treatment were treated with cladribine as first-line treatment. Total and complete response of cladribine was 97.3% and 80.7%. The relapse rate after cladribine was 16.6%, and treatment related mortality was 2.5%. Most preferred therapy (95%) was again cladribine at second-line, and third line with CR rate of 68.4% and 66.6%, respectively. The 28-month median OS was 91.7% in all patients and 25-month median OS 96% for patients who were given cladribine as first-line therapy. In conclusion, the first multicenter retrospective Turkish study where patients with HCL were followed up for a long period has revealed demographic characteristics of patients with HCL, and confirmed that cladribine treatment might be safe and effective in a relatively large series of the Turkish study population.

Elevated serum angiotensin converting enzyme levels as a reflection of bone marrow renin-angiotensin system activation in multiple myeloma.

INTRODUCTION: Angiotensin converting enzyme (ACE) is a circulating enzyme that participates in the body's renin-angiotensin system (RAS) and is localized on the endothelial cell surface in the lung and other vascular beds. It catalyses the conversion of decapeptide angiotensin I to octapeptide angiotensin II. In the present study, we aimed to analyse the possible relationship between the levels of ACE in the context of RAS in multiple myeloma (MM) pathogenesis. MATERIALS AND METHODS: The study was conducted on 25 MM patients (13 males, 12 females; median age 66 years, range 47-88) and 20 healthy controls. The clinical features of MM patients including demographics and laboratory findings were summarized. Serum ACE levels were measured by using commercially available kits. RESULTS: The serum ACE levels of MM patients and controls were 32.60±20.26 and 15.35±6.47 respectively. Serum ACE levels were significantly higher in MM patients compared with control groups (p<0.001). CONCLUSIONS: Being an important component of RAS, circulating ACE might be associated with clonal proliferation of malignant plasma cells in the bone marrow microenvironment. Identification of the pathobiological activity of the local RAS in MM would enlighten the biologic basis and clinical management of haematologic disorders.

Serious skin reaction associated with imatinib in a patient with chronic myeloid leukemia.

Imatinib mesylate (STI 571) is one of the fundamental chemotherapeutic agents used in the treatment of the chronic, accelerated and blastic phases of chronic myelocytic leukemia (CML), gastrointestinal stromal tumors and Philadelphia chromosome-positive acute lymphoblastic leukemia. It selectively inhibits receptor tyrosine kinases. Its effects limit the use of this drug. We present a case with a serious skin reaction requiring the discontinuation of the drug and that developed in relation to imatinib therapy. Six months prior, a 61-year-old male patient presenting to the hematology polyclinic with complaints of weight loss and sweating was hospitalized due to high leukocyte value. As a result of the hemogram, biochemistry analyses, peripheral blood smear examination, bone marrow aspiration evaluation, cytogenetic examination using FISH and PCR that were performed, CML was diagnosed. Additionally, to exclude myelofibrosis, we examined a bone marrow biopsy. Imatinib mesylate was started at 400 mg/day orally. In the fourth month of treatment, the patient complained of itching and a skin rash. Although the drug dose was reduced (300 mg/day), his complaints gradually increased. The skin biopsy result was superficial perivascular dermatitis. Imatinib was discontinued, and the patient was started on corticosteroid. The lesions disappeared completely. A month later, the patient was restarted on imatinib mesylate. However, the lesions recurred more prominently. His itching increased. The patient was considered intolerant to imatinib mesylate, and a second-generation tyrosine kinase inhibitor, dasatinib 100 mg/day, was started orally. The follow-up and treatment continues for the patient, who has been taking dasatinib 100 mg/day for the last two months without any skin finding or complaints. Imatinib mesylate-induced skin reactions are associated with the pharmacologic effect of the drug rather than hypersensitivity to the drug. Skin reactions are frequently observed, and this side effect is dose dependent. However, the interesting aspect of our case was that despite dose reduction, skin findings gradually increased, and eventually the drug had to be discontinued.

Is lipid lowering treatment aiming for very low LDL levels safe in terms of the synthesis of steroid hormones?

Today atherosclerotic diseases are among the most important causes of death in the world. Epidemiological, clinical, genetic, experimental and pathological studies have clearly shown the role of lipoproteins in atherosclerosis. LDL is the major atherogenic lipoprotein and has been defined as the primary target of lipid lowering treatment by NCEP. Although the level of LDL, the primary target in the treatment of dyslipidemia, has been set as below 100 mg/dl in coronary heart diseases (CHD) and CHD risk equivalents, this level has been pulled down to below 70 mg/dl for the group defined as very high risk group by the ATP (Adult Treatment Panel) guide that has been updated following the new clinical studies. As we already know, cholesterol is the precursor of glucocorticoids, mineralocorticoids and sex steroids, besides being a structural component of the cell membrane. Both adrenal and non-adrenal (ovarian+testicular) all steroid hormones are primarily synthesized using the LDL-cholesterol in the circulation. In addition to this, there is 'de novo' cholesterol synthesis in both the adrenals and gonads controlled by the HMG-CoA reductase enzyme. A third pathway, which under normal circumstances has little contribution as compared to the first two, is the use of circulatory HDL-cholesterol by the adrenal and gonadal tissues for the synthesis of steroids. Our knowledge on extremely lowered LDL levels is quite limited. However, since statins both decrease circulatory LDL and inhibit de novo cholesterol synthesis, they are likely to affect the synthesis of steroid hormones.

The prevalence of neuropathy and relationship with risk factors in diabetic patients: a single-center experience.

OBJECTIVE: To determine the rate of distal symmetrical polyneuropathy (DSP) in patients with type 2 diabetes mellitus, to evaluate the role of history, neurological examination and the electrodiagnostic methods in the diagnosis of DSP, and to determine the association between electromyography-supported neuropathy (ESN), neuropathic complaints (NCs) and risk factors. SUBJECTS AND METHODS: A total of 191 type 2 DM patients (109 female, 82 male; mean age 58.7 +/- 10 years) were recruited. The NCs were recorded. All patients had electromyographic (EMG) examinations. The relationship between ESN, NCs and risk factors were evaluated. RESULTS: Of the 191 patients, 83 (43.5%) had DSP on EMG examinations and 92 (48.2%) patients suffered from NCs. Among the ESN patients, a significant relationship existed with HbA1(c) level, illness duration, smoking, male gender or insulin usage (p < 0.05) but not with age, hypertension, hypercholesterolemia or hypertriglyceridemia. The frequency of NCs was higher in patients with ESN. There was also a significant association between NCs and ESN (p < 0.05). The presence of NCs was not related to age, gender, smoking, hypertension, hypercholesterolemia and hypertriglyceridemia (p > 0.05) but NCs were correlated to HbA1(c) level, illness duration and insulin usage (p < 0.05). CONCLUSION: Our data show that a strong association exists between the presence of DSP and illness duration, HbA1(c), smoking, thereby indicating that cessation of smoking and near normal glycemic control would be additional precautions to delay the beginning or progression of polyneuropathy.

Evaluation of right ventricular function in patients with thyroid dysfunction.

BACKGROUND: Thyroid gland dysfunction affects the structure and function of the heart. Tissue Doppler echocardiography is a new technique, and it has been used frequently in the evaluation of ventricular function. In the present study, right ventricular function was assessed in patients with overt or subclinical hypothyroidism and hyperthyroidism and in healthy subjects using the tissue Doppler method, and results were compared. PATIENTS AND METHODS: 20 healthy subjects and 63 patients diagnosed with overt and subclinical hypothyroidism and hyperthyroidism were included in the study. Annular and myocardial systolic peak velocities, early and late diastolic peak velocities, precontraction, total contraction and relaxation times of the right ventricle were recorded by tissue Doppler echocardiography. The results of the patients were compared to those of the controls. RESULTS: Myocardial systolic velocity was significantly higher in patients with hyperthyroidism. Annular and myocardial late diastolic velocities were found to be significantly lower in patients with overt hypothyroidism. Annular precontraction time was increased in patients with overt and subclinical hypothyroidism. Myocardial precontraction time was decreased in patients with hyperthyroidism, and increased in patients with overt hypothyroidism patients. Annular relaxation time was increased in patients with overt hypothyroidism. CONCLUSIONS: Right ventricular function is affected in patients with thyroid diseases. The tissue Doppler technique is a suitable tool to detect impairments in right ventricular function. There is a significant correlation between serum thyroid hormone levels and right ventricular velocities and time intervals.

Cytomegalovirus antigenemia is observed more frequently following allogeneic peripheral blood stem cell transplantation compared to bone marrow transplantation.

One of the major complications following hematopoietic stem cell transplantation (HSCT) is cytomegalovirus (CMV) infection. In our institution, three methods have been applied routinely for the diagnosis of CMV antigenemia (CMV-Ag): 1. Direct immunofluorescence microscopic (IFM) examination; 2. Flow cytometric (FC) analysis; and 3. Serological investigation. We were able to detect CMV-Ag by FC in 18 out of 75 transplanted cases. In 14 of these, positivity was confirmed by IFM as well. CMV-Ag was detected as positive by FC in samples from peripheral blood (14 cases) and/or bronchoalveolar lavage (BAL) fluid (4 cases). Eighteen patients had been transplanted [peripheral blood stem cell transplantation (PBSCT)/bone marrow transplantation (BMT): 16/2]. CMV-Ag was detected in 34% of PBSCTs and 7% of BMTs (p<0.008). Antigenemia was observed at a median of 4.5 months. In most of the patients, graft-versus-host disease (GVHD) was accompained by CMV-Ag. The ratio of acute GVHD/chronic GVHD was 6/10. Out of 18 CMV-Ag positive patients, 16 also had signs of infection. They were all positive by IFM as well. The two methods of CMV-Ag detection were correlated (r=0.619, p<0.0001). An important finding is the higher frequency of CMV-Ag and GVHD in patients who had received PBSCT.

Does chronic hepatitis B increase Staphylococcus nasal carriage?

OBJECTIVES: To determine the prevalence of Staphylococcus aureus nasal carriage in patients with chronic hepatitis B virus infection. PATIENTS AND METHODS: The prevalence of S. aureus nasal carriage was determined in patients with chronic hepatitis B virus infection and compared with the prevalence of S. aureus nasal carriage among control patients. RESULTS: Between February 2003 and November 2004, 70 chronic hepatitis B patients and 70 control patients were enrolled in the study. S. aureus nasal carriage was shown in 15 (12%) of the patients with chronic hepatitis B and 13 (19%) of the control group (P > 0.05). There was no difference in nasal colonization between the cases and controls when analysed by age, sex, frequency of skin infection, prior use of antibiotics and hospital admission in the preceding six months. CONCLUSION: The results of our study show that chronic hepatitis B virus infection is not associated with S. aureus nasal carriage.

Impaired immunity against tetanus in type 2 diabetes.

BACKGROUND: The aim of this study was to compare serum levels of tetanus antibody in diabetic patients over 50 years of age with those of age- and sex-matched non-diabetic controls. MATERIAL/METHODS: The study population consisted of 115 type 2 diabetic patients and 115 age- and sex-matched non-diabetic patients. Serum levels of tetanus IgG were measured by a commercial ELISA kit, and levels over 0.1 IU/ml were considered protective. RESULTS: Mean serum levels of tetanus antibody in the diabetic and control groups were 0.164+/-0.140 IU/ml vs. 0.374+/-0.534 IU/ml, respectively (p<0.001). Mean serum levels of tetanus antibody in the diabetics vs. controls aged 50-64 years were 0.172+/-0.141 IU/ml vs. 0.568+/-0.653 IU/ml and in those p<0.001, p=1.000). Among patients aged 50-64 years, 38 (55.9%) cases in the diabetic and 45 (73.8%) in the control group demonstrated protective levels of tetanus antibodies (p=0.034). Of patients p=0.298). CONCLUSIONS: Serum levels of tetanus antibody decreased in diabetic patients older than 50 years of age, whereas this period of time is prolonged to 65 years in healthy individuals. All individuals over 65 years should be vaccinated against tetanus; however, vaccination over 50 years of age might be considered for diabetic patients.

Effectiveness of lamivudine and interferon-alpha combination therapy versus interferon-alpha monotherapy for the treatment of HBeAg-negative chronic hepatitis B patients: a randomized clinical trial.

Results comparing the effectiveness of lamivudine used as monotherapy or in combination with interferon-alpha (IFN-alpha) in the treatment of chronic hepatitis B are not conclusive. This study compared the effects of IFN-alpha alone or in combination with lamivudine for the treatment of hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B. Participation of patients in the IFN-alpha monotherapy and combination groups was randomized to a 1:1 ratio. Twenty seven HBeAg-negative patients with chronic hepatitis B received IFN-alpha (13 patients) at 9 million units 3 times weekly for 24 weeks or IFN-alpha at 9 million units 3 times weekly for 24 weeks plus lamivudine 100 mg/day (14 patients) daily for 1 year. Hepatitis B virus (HBV) DNA was measured quantitatively by real-time polymerase chain reaction at 0, 6, 12 and 18 months after the start of treatment. Sustained virologic response was defined as non-detectable serum HBV DNA 72 weeks after starting treatment. Sustained biochemical response was defined as normalization of alanine aminotransferase (ALT) values 72 weeks after starting treatment. The baseline characteristics of the 2 treatment groups were similar with respect to age, gender, ALT, HBV DNA levels and histologic diagnosis. Sustained biochemical responses were found at week 72 in 7 patients in each group (54% with IFN-alpha monotherapy and 50% with combination therapy) [p>0.05]. Sustained virologic responses were found at week 72 in 5 patients (38%) in the monotherapy and 7 patients (50%) in the combination therapy group (p>0.05). Combination therapy was not superior to IFN-alpha alone for the treatment of chronic hepatitis B. Combination treatment was associated with some disadvantages, such as additional cost. Lamivudine, on the other hand, may be more suitable for patients with cirrhosis, non-responders to IFN-alpha or in cases with contraindication for IFN-alpha.

Bone marrow microvessel density (MVD) in adult acute myeloid leukemia (AML): therapy induced changes and effects on survival.

Based on the strong evidence in favor of an increase in microvessel density (MVD) in hematological malignancies, we evaluated VEGF immunoreactivity and MVD measurement in bone marrow biopsies of 36 AML patients at diagnosis and following therapy. MVD assessment was based on CD31, CD34 expressing vessels. The values were calculated for only one marker if the other vascular marker was positive on blasts, otherwise both markers were used. VEGF immunoreactivity was also scored. Comparison of MVD values of 36 AML patients with 18 non-malignant controls showed a significantly higher MVD in AML (CD31: P = 0.004, CD34: P < 0.001), which is independent of other variables such as cellularity or blast percentage. Following induction chemotherapy, the responders showed a significant decrease in blast counts (P < 0.001), cellularity (P = 0.001) and MVD (P = 0.050) quantification with CD31. Higher baseline MVD (CD34) values were associated with shorter overall survival (P = 0.0027). These results are encouraging for inclusion of MVD enumeration in bone marrow examinations of AML patients at diagnosis as an additional prognostic factor.

Albendazole versus metronidazole treatment of adult giardiasis: An open randomized clinical study.

AIM: To investigate the efficacy and tolerability of albendazole and metranidazole treatment in giardiasis. METHODS: The open comparative randomized trial was carried out prospectively from December 1999 to July 2001 in Duzce City of Turkey. The diagnosis was based on the presence of signs and symptoms compatible with giardiasis including a positive stool examination of giardia cysts or trophozoite. Metranidazole group consisted of 29 patients and was given metranidazole 500 mg, three times a day for 5 d and albendazole group was consisted of 28 patients and was given albendazole 400 mg/d for 5 d. RESULTS: There were no significant differences in demographical and therapeutical effects and patient's compliance between both groups. But side effects were seen more in metranidazole group than in albendazole group. CONCLUSION: Albendazole is as effective as metranidazole in adults' giardiasis. Albendazole has less side effect potentials than metranidazole in the treatment of giardiasis.

Nephrotic syndrome after allogeneic peripheral blood stem cell transplantation.

Nephrotic syndrome has been rarely reported after hematopoietic stem cell transplantation. We report a patient who developed nephrotic syndrome after allogeneic peripheral blood stem cell transplantation for acute myelogenous leukemia. Renal biopsy was performed and immunofluorescence and light microscopy were compatible with minimal change disease. The patient was treated with cyclophosphamide and prednisolone. Complete remission was achieved after three months. Previous reported cases are discussed.

The Role of ABO Incompatibility in Allogeneic Peripheral Blood Stem Cell Transplant.

ABO incompatibility is not a contraindication for allogeneic bone marrow transplantation, but this procedure requires an extra effort for erythrocyte or plasma depletion in certain well established conditions. Some acute or delayed immunohematological complications such as acute or chronic hemolysis and pure red cell aplasia may be encountered. In this study the outcome and transplant related complications of ABO incompatible and identical cases, who have received allogeneic peripheral blood stem cells from their HLA identical siblings were compared with each other. Ninety-one patients (CML 36, AML 37, other 18) were analyzed retrospectively including 51 (60.4%) ABO identical patients and 36 (39.6%) ABO mismatched (MM) patients, who have a bi-directional MM (n= 5), major MM (n= 16), minor MM (n= 9) and Rh MM (n= 6). Median follow up was 13 (0.5-43.0) months. We did not observed any significant differences between two groups (identical vs non-identical) in terms of acute hemolysis preceding stem cell infusion, peritransplant transfusion demand, acute- and chronic graft versus host disease. There was no change in estimated disease free survival and overall survival durations. We did not observed any influence of ABO/Rh incompatibility on short term outcome in allogeneic peripheral blood stem cell transplantation in our series and did not recommend further manipulation of the infused stem cells.