Melanie Cermanová

Urinary neopterin in patients with advanced colorectal carcinoma.

In previous studies, mostly in patients with early stage colorectal carcinoma, neopterin, an indicator of systemic immune activation, has been associated with poor prognosis. The aim of the present study was to evaluate urinary neopterin in patients with advanced or metastatic colorectal carcinoma treated with chemotherapy. A retrospective analysis was performed of urinary neopterin, determined by high-performance liquid chromatography, in 88 patients with advanced or metastatic colorectal carcinoma. Peripheral blood cell count and serum carcinoembryonic antigen (CEA) were determined in 72 patients before the start of chemotherapy. Urinary neopterin in colorectal carcinoma patients was significantly increased compared to controls, but lower than in patients with inflammatory bowel disease. Neopterin correlated significantly with serum CEA, age, peripheral blood leukocyte and platelet counts. The median survival of colorectal carcinoma patients with urinary neopterin below 214 mol/mol creatinine was significantly longer compared to that of patients with higher neopterin concentrations (median 18 vs 5 months, log-rank test p=0.003). CEA and hemoglobin were also associated with survival in univariate analysis, but in multivariate analysis only urinary neopterin and serum CEA were independent predictors of survival. High urinary neopterin during follow-up was also predictive of poor prognosis.

Safety and Tolerability of Long Lasting LDL-apheresis in Familial Hyperlipoproteinemia

Abstract:  The aim of this work is to arbitrate the incidence of side effects and tolerability of long lasting LDL‐apheresis in familial hyperlipoproteinemia. 1200 procedures were performed and the last 463 of them were evaluated. An immunoadsorption method of LDL‐apheresis was used (continuous blood cell separator Cobe Spectra; secondary device: automated adsorption‐desorption ADA, Medicap; absorption columns: Lipopak). As a whole, 6.26% adverse events were found and subsequently resolved by standard symptomatic therapy. Vaso‐vagal reactions (symptoms of neurovegetative lability) were the most common adverse effects, presented as malaise, weakness, slight and short‐term drop in blood pressure or other general signs. They were all well controlled by symptomatic therapy. We conclude that LDL‐apheresis in the hands of experienced personnel is a safe procedure. An acceptable procedure duration limit, balancing the possibility to achieve a targeted cholesterol level while still maintaining an acceptable patient tolerance, was confirmed to be 4 hours.

Systemic Immune Activation, Anemia and Thrombocytosis in Breast Cancer Patients Treated by Doxorubicin and Paclitaxel

Abstract Increased urinary concentrations of neopterin, an indicator of systemic immune activation, have been reported only in a minority of patients with breast cancer. We determined urinary neopterin by high-performance liquid chromatography in 78 patients with breast carcinoma, including 51 patients treated by systemic administration of doxorubicin and paclitaxel. Urinary neopterin before the therapy was not statistically different in patients compared to controls. Increased neopterin concentrations were more frequent in patients with advanced disease. A statistically significant increase in urinary neopterin, gradual decrease in hemoglobin and an increase in platelet counts were observed during doxorubicin/paclitaxel chemotherapy. The concentration of urinary neopterin before the second cycle of chemotherapy has shown significant negative correlation with the concentrations of hemoglobin later in the course of chemotherapy and a positive correlation with platelet counts. In conclusion, urinary neopterin is normal in most patients with breast cancer. Increased urinary neopterin concentrations during doxorubicin/ paclitaxel chemotherapy indicate the presence of systemic immune activation that seems to be associated with chemotherapy-induced anemia and thrombocytosis.

Urinary Neopterin and Microalbuminuria in Patients Treated by Low-density Lipoprotein Apheresis

Abstract Low-density lipoprotein (LDL)-apheresis is a method of extracorporeal elimination of LDL-cholesterol in patients with severe primary lipoprotein disorders. LDL-cholesterol activates macrophages, which play an important role in atheromatous plaque formation. In the present study, we have investigated urinary neopterin, a specific marker of macrophage activation and microalbuminuria, an indicator of generalized vascular dysfunction, after a single LDL-apheresis procedure in 10 patients with severe primary lipoprotein disorder. The urinary neopterin/creatinine ratio was increased in patients compared to controls. No significant changes of the neopterin/creatinine and albumin/creatinine ratios were observed after LDL-apheresis, except a significant (p < 0.006) decrease of urinary neopterin/creatinine ratio in the evening after the apheresis. This decrease showed significant negative correlation with the pre-apheretic levels of atherogenic cholesterol fractions (p < 0.05) and with cholesterol decrease during the apheresis (p < 0.05). Urinary albumin/creatinine ratio correlated positively with total and LDL-cholesterol levels before the apheresis and with the evening urinary neopterin/creatinine ratio after the apheresis, but did not correlate with glycemia and triacylglycerides. Elevated urinary neopterin in the patients with severe primary lipoprotein disorders reflects the presence of atherosclerosis. A single LDL-apheresis procedure did not significantly affect microalbuminuria. The decrease of urinary neopterin in the evening after the apheresis corresponds with the diurnal rhythm of neopterin excretion and was less pronounced in patients with more severe hypercholesterolemia. The correlations between microalbuminuria, neopterin and pre-apheretic cholesterol concentrations indicate a possible connection between microvascular dysfunction, macrophage activity and severity of hyperlipidemia, but these results should be interpreted with caution because of small number of subjects evaluated.

Management of severe infusion reactions after cetuximab

To the EditorThe rare instances of severe infusion reactionsaccompanying the initial stages of treatment withcetuximab are considered to be an absolute contra-indication of further treatment with this drug [1].Anecdotal evidence suggests that treatment withanother antibody against the epidermal growth factorreceptor, panitumumab, may be safe following asevere infusion reaction to cetuximab [2]. However,specific information on manifestations and manage-ment of severe infusion reactions associated with theadministration of cetuximab is lacking, as reflected inthe recent review by Patel and Goldberg [1].Although in most clinical trials, severe infusionreactions were rare, a high incidence of severeinfusion reactions after the administration of cetux-imab has been reported in Tennessee and NorthCarolina [3]. Similarly, we have observed an unusualincidence of severe infusion reactions in patientstreated with cetuximab at our institution (4 of 43cases; 9%). We have reported that treatment could beresumedundercarefulmonitoringinanintensivecareunit (ICU) in two patients who experienced severeinfusion reactions after cetuximab [4]. We describehere a similar experience in two additional cases.A 68-year-old man with liver metastases of rectalcarcinoma progressive after two lines of chemother-apy was indicated for intravenous therapy withcetuximab (loading dose 400 mg/m

Prevention of Infection Transmission during Stem Cell Transplantation

Group of 152 patients (investigated before autologous transplantation) and 35 healthy donors for allogeneic transplantation was examined for the risk of infection transmission that can be associated with the infusion of cryopreserved peripheral blood progenitor cells to the patient and/or cross-contamination of stored grafts. No laboratory signs of active infection were found in 22 donors (63 %) and in 91 patients (60%). The most common was active infection by herpes viruses — 50 cases in patients, 21 cases in donors; hepatitis B was found in only two cases. The rate of clinically unsuspected (but dangerous) infections in donors and patients thus remains relatively high in spite of the fact that the system of donor search and the whole transplantation procedure have improved in the last years. The system of safety assurance is extremely important and the whole palette of preventive tests according to EBMT (European Blood and Marrow Transplantation Group) and ISHAGE (International Society for Hemotherapy and Graft Engineering) is fully justified.

Cerebrospinal Fluid Neopterin in Patients with Tumors and other Disorders

Abstract Increased urinary or serum concentrations of neopterin have been reported in cancer patients, but less is known about neopterin concentrations in cerebrospinal fluid (CSF). CSF neopterin was determined with radioimmunoassay in 64 patients. CSF neopterin concentrations in patients with tumors were significantly higher compared to patients with predominantly peripheral infections (Lyme borreliosis and herpes simplex infection) and no infectious, inflammatory or neoplastic disorder, and significantly lower compared to patients with meningitis or encephalitis. Among patients with tumors, CSF neopterin was significantly higher in patients with non- Hodgkin lymphoma (NHL) compared to other tumors. The difference between patients with tumors other than NHL and predominantly peripheral infections was of borderline significance, and a significant difference was observed between patients with tumors other than NHL and no disorder. CSF neopterin was significantly higher in patients with NHL compared to patients with predominantly peripheral infections, multiple sclerosis or polyneuropathy and no disorder, and no difference was evident compared to patients with meningitis or encephalitis. In conclusion, among patients with tumors, high CSF neopterin may suggest the diagnosis of NHL.

Fifteen years of single center experience with stem cell transplantation for multiple myeloma: a retrospective analysis.

INTRODUCTION Autologous stem cell transplantation (ASCT) became standard of care for patients with multiple myeloma (MM) under the age of 65 years. We routinely perform ASCT for newly diagnosed MM since 1996 in our department. PATIENTS AND METHODS We retrospectively analyzed all 285 transplants in 185 patients done for MM from January 1996 till December 2010. We analyzed overall survival (OS) and progression-free survival (PFS) regarding conditioning, stage, complete or very good partial remission (CR, VGPR) achievement, renal impairment, single vs. double transplant. RESULTS Estimated 10-years survival of the whole set of patients is 39% (median survival 95 months). Patients with renal impairment show same OS as those without (p = 0.22). Patients show similar overall survival and event free survival regardless of type of transplant. We observed better outcome in terms of overall survival in patients treated with new drugs (p = 0.0014). Reaching CR or VGPR was not translated into better OS (p = 0.30) and EFS (p = 0.10). Also stage of the disease and whether single or double transplant was used did not make any significant difference in the outcome. CONCLUSION Stem cell transplantation greatly improved outcome of patients with MM. Poor outcome of allogeneic transplantation in our group of patients is related to high transplant related mortality (20% vs. 0%) and unexpected high relapse rate. There is a trend towards better survival, when new drugs are incorporated at any time in the course of the disease. This fact supports hypothesis that use of these drugs with ASCT should translate into better long-term outcome.

Case 2-2012: a 57-year-old woman with post-transplant lymphoproliferative disorder after allogeneic stem cell transplantation for primary myelofibrosis.

allogeneic haematopoietic stem cell transplantation (hsCt) has become a major life sustaining treatment for haematopoietic disorders, and it is the preferred treatment option for selected patients with idiopathic myelofibrosis. Still, it may be accompanied by various complications. here, we present a case of epstein-Barr virus (eBv) – associated post-transplant lymphoproliferative disorder (Ptld), i.e. an infection-induced malignant proliferation following hsCt.