Number Of Previous Treatments Research Articles

1512 - Circulating Tumor Cells in Soft Tissue Sarcomas Patients

ABSTRACT Introduction Soft tissue sarcomas (STSs) are an heterogeneous group of highly malignant mesenchymal tumors with only few recognised prognostic and predictive factors. Circulating tumor cells (CTCs) are considered a prognostic marker classically associated with poor prognosis in epithelial solid cancer patients. The purpose of this study was to explore the possibility to detect CTCs in blood samples of STSs metastatic patients. Methods Patients with histologically confirmed STSs and known metastases treated at Campus Bio-Medico Hospital of Rome from June 2011 to February 2012 were included. Blood was collected from patients who progressed on previous chemotherapy (1st, 2nd or 3rd line). All patients signed informed consent before phlebotomy. CTCs were assessed with CellSearchSystem (Veridex, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labelled with anti-Ck8/18/19 and anti-CD45 antibodies to distinguish between epithelial cells and leukocytes. Wilcoxon rank-sum test was used to test for associations between CTC assay results and specific histotype, number of previous treatment, number and localization of metastatic disease sites. Results Twenty-three patients with metastatic STSs were evaluated. CTCs were detectable in 10/23 (43%) patients with CTC counts in the range of 0-4 cells/7.5 mL. The median number of CTCs was significantly lower in patients with only one site of metastasis compared to those with two or more metastatic sites (0 vs 2; P = 0.003). There was no statistically significant difference (P = 0.210) in median CTC counts between patients who received only a first line regimen (0, range 0-4) vs patients who previously received more anticancer therapies (1, range 0-3). Finally, no statistically significant correlation was identified between the number of CTCs and the histological grading evaluated according to the FNCLCC grading system (P = 0.468). Conclusions To our knowledge this is the first detection of circulating Epcam/Ck8/18/19+ cells in STSs patients, even if the identified circulating cells could be epithelial cells due to direct tumour invasion of the blood vessel from the surrounding tissue or tumor cells at the moment of mesenchymal-epithelial transition. Disclosure All authors have declared no conflicts of interest.

Mo1378 Endoscopic Submucosal Dissection(ESD)for Residual or Recurrent Colorectal Adenomas: a Single Center Experience

Endoscopic Submucosal Dissection(ESD)for Residual or Recurrent Colorectal Adenomas: a Single Center Experience Stefania De Lisi*, Giancarla Fiori, Davide Ravizza, Cristina Trovato, Giuseppe De Roberto, Annalisa De Leone, Darina Tamayo, Cristiano Crosta Division of Endoscopy, European Institute of Oncology, Milan, Italy Background and Aims: Endoscopic submucosal dissection (ESD) of refractory colorectal polyps is a challenging procedure carrying higher risk of complication and lower rate of radical resection than “naive” lesions. To date, few western data is available for ESD in this setting. This study aims to evaluate the feasibility, safety and efficacy of ESD for colorectal polyps refractory to previous endoscopic resection. Material and methods: ESD was performed according to Yamamoto’s technique in patients with residual or recurrent polyps with a diameter 10mm, deemed as unsuitable for further endoscopic treatment. Single channel endoscopes were used for ESD: a gastroscope (Pentax EG2990i, Japan) for rectal polyps, a colonscope (Pentax EC3890Fi, Japan) for colonic ones. A standard needle knife, hook knife and Mucosectom (Pentax, Japan) were used for ESD. Results: Eleven consecutive patients (4/7 M/F mean age 70.6 years) with residual or recurrent colorectal polyps (4 colonic, 7 rectal) were treated. Colonic polyps were located in the sigmoid colon (n 1), in descending colon (n 1), at the splenic flexure (n 1) and in transverse colon (n 1). Median number of previous treatment was 2 (range 1-4), 2 patients also had undergone transanal endoscopic microsurgery. Mean polyps diameter was 24mm (range 10-40mm). Mean procedural time standard deviation was 137 75 minutes (range 45-270 minutes). En bloc resection rate was 6/11(54.5%). Three perforation (27.2%), occurred during ESD, were managed conservatively with clips application; no bleeding was observed. Radical resection rate (R0) was 6/11(54.5%), in 2 patients the margins were not evaluable (Rx) because of coagulation artefacts. Histology revealed low grade dysplasia in 5 patients (45.4%) and high grade dysplasia in 6 patients (54.5%). A mean endoscopic follow-up of 5.6 months (range 3-12 months) was available for 8/11patients, six of them (75%) were free of recurrence. During a short follow-up two diminutive, recurrent adenomas ( 5mm) were found and treated endoscopically in two patients with non-radical (R1) or non evaluable resection (Rx). Conclusions: ESD, although technically difficult, is a relatively safe and effective procedure for treatment of refractory colorectal polyps in patients otherwise candidates for surgery.

FDG-PET predicts survival in recurrent high-grade gliomas treated with bevacizumab and irinotecan

Prognosis of recurrent high-grade glioma (HGG) is poor, although bevacizumab has been documented in that context. This study aimed to determine the independent prognostic value of fluorodeoxyglucose (FDG)-PET on progression-free survival (PFS) and overall survival (OS) of recurrent HGG after combined treatment with bevacizumab and irinotecan, compared with other documented prognostic variables. Twenty-five adult patients with histologically proven HGG were included at recurrence. Brain FDG-PET imaging was performed within 6 weeks of starting chemotherapy with bevacizumab and irinotecan. Response based on MRI was assessed every 2 months according to revised assessment in Neuro-Oncology (RANO) criteria. Median PFS and OS were 4 months (range, 0.9-10.4 months) and 7.2 months (range, 1.2-41.7 months), respectively. At 6 months, PFS and OS rate were 16.0% and 72.0%. FDG uptake was the most powerful predictor of both PFS and OS, using either univariate or multivariate analysis, among all variables tested: histological grade, Karnofsky performance status, steroid intake, and number of previous treatments. Moreover, FDG uptake was also prognostic of response to bevacizumab-based therapy. This study provides the first evidence that pretreatment FDG-PET can serve as an imaging biomarker in recurrent HGG for predicting survival following anti-angiogenic therapy with bevacizumab.

Prognostic factors for tumor recurrence after gamma knife radiosurgery of partially resected and recurrent craniopharyngiomas.

A study was conducted to clarify the prognostic factors related to recurrence of craniopharyngioma and to improve the quality of life of patients by the treatment with intentional partial removal and gamma knife radiosurgery. One hundred cases of craniopharyngioma have been treated at Komaki City Hospital since 1991. In a mean follow-up period of 65.5 months, the tumor control rate was 79.5%. The 5- and 10-year actuarial survival rates were 94.1% and 91%, respectively. However, the recurrence-free survival rates were 73.6% at 5 years and 60.2% at 10 years. Nine factors thought to be related to the recurrence were selected from past references and previous studies, including gender, age, pediatric (< or =17 years) or adult patient, partial removal or recurrence, mean tumor diameter, tumor type (solid or cyst), pathological types (squamous cell or adamantinoma), number of previous treatments, and radiation dose. Statistical analysis was performed to determine which factors had a significant prognostic impact. Multivariate analysis showed that mean tumor diameter and radiation dose were independent predictors of outcome. To maximize the prognostic power of these factors, cut-off levels were determined using ROC analysis. These levels were 19 mm for tumor diameter and 13.2 Gy for marginal dose. Significant prognostic factors related to recurrence of craniopharyngioma are tumor diameter and radiation dose. A tumor diameter of <19 mm and a marginal dose of > or =13.2 Gy are favorable prognostic factors for gamma knife radiosurgery.

Clinical experience of bendamustine treatment for non-Hodgkin lymphoma and chronic lymphocytic leukemia in Spain

Bendamustine is a alkylating agent with a purine-like benzamidazole ring currently approved in Europe for indolent non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma. Our aim was to analyze retrospectively the efficacy and toxicity of bendamustine in NHL and CLL in Spain in the bendamustine Compassionate Use Program. Patients with relapsed/refractory NHL or CLL were eligible. Any regimen containing bendamustine was eligible. 109 patients were included from 22 institutions. Forty-nine patients had indolent NHL, 18 aggressive NHL and 42 CLL, being 44 patients (40%) refractory to previous treatment. 63% of patients had adverse events grade 3–4, mainly hematological. Overall response rate (ORR) was 66%, complete responses 30%. ORR observed in refractory patients was 45%. The median progression-free survival (PFS) was 13 months. Outcome was influenced by histology, number of previous treatments, resistance to previous chemotherapy and type of response achieved with bendamustine. Alone or in combination, bendamustine shows a meaningful clinical antitumor activity in patients with relapsed or refractory NHL or CLL, with an acceptable toxicity profile.

Mohs Micrographic Surgery for Re-Excision of Basal Cell Carcinomas on the Head With Positive Margins

BackgroundThere is debate in the literature regarding the management of basal cell carcinoma following excision with positive surgical margins. While in some cases recurrence is not observed even after many years of follow-up, those in which recurrence does occur are at an increased risk of complications.Factors may exist that help to choose the best therapeutic approach for basal cell carcinomas on the head in which positive margins are observed following excision. Material and methodsA total of 46 patients were selected who had been treated by Mohs micrographic surgery as a result of positive surgical margins being present following previous tumor excision. The factors associated with the absence of tumor nests and the occurrence of negative margins following a single Mohs stage were analyzed. ResultsNo associations were observed with sex, tumor size, affected margin (lateral, deep, or both), time since diagnosis, number of previous treatments, histological type, or tumor site. There was a certain trend towards more frequent identification of tumor remnants when both surgical margins were affected and towards a requirement for a single Mohs stage in tumors less than 1.2cm and in which less than 5 years had elapsed since diagnosis. ConclusionsConclusive data are unavailable with which to define cases in which re-excision is necessary or those in which conventional excision could be sufficient. The best option for the treatment of these tumors is Mohs micrographic surgery, although conventional excision could be reasonable in small tumors located at low-risk sites and in which long periods have not elapsed since diagnosis.

Re-exéresis mediante cirugía de Mohs de carcinomas basocelulares de la cabeza previamente extirpados con afectación de márgenes

Background There is debate in the literature regarding the management of basal cell carcinoma following excision with positive surgical margins. While in some cases recurrence is not observed even after many years of follow-up, those in which recurrence does occur are at an increased risk of complications. Factors may exist that help to choose the best therapeutic approach for basal cell carcinomas on the head in which positive margins are observed following excision. Material and methods A total of 46 patients were selected who had been treated by Mohs micrographic surgery as a result of positive surgical margins being present following previous tumor excision. The factors associated with the absence of tumor nests and the occurrence of negative margins following a single Mohs stage were analyzed. Results No associations were observed with sex, tumor size, affected margin (lateral, deep, or both), time since diagnosis, number of previous treatments, histological type, or tumor site. There was a certain trend towards more frequent identification of tumor nests when both surgical margins were affected and towards a requirement for a single Mohs stage in tumors less than 1.2 cm and in which less than 5 years had elapsed since diagnosis. Conclusions Conclusive data are unavailable with which to define cases in which repeat excision is necessary or those in which conventional excision could be sufficient. The best option for the treatment of these tumors is Mohs micrographic surgery, although conventional excision could be reasonable in small tumors located at low-risk sites and in which long periods have not elapsed since diagnosis.

Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors

IntroductionThe long-term treatment of rheumatoid arthritis (RA) most often involves a sequence of different therapies. The response to therapy, disease progression and detailed knowledge of the role of different therapies along treatment pathways are key aspects to help physicians identify the best treatment strategy. Thus, understanding the effectiveness of different therapeutic sequences is of particular importance in the evaluation of long-term RA treatment strategies. The objective of this study was to systematically review and quantitatively evaluate the relationship between the clinical response to biologic treatments and the number of previous treatments with tumor necrosis factor α (TNF-α) inhibitors.MethodsA systematic search was undertaken to identify published, peer-reviewed articles that reported clinical outcomes of biologic treatment among RA patients with an inadequate response to TNF-α inhibitors. Data were systematically abstracted. Efficacy rates were estimated for groups of patients who differed in the number of prior TNF-α inhibitors used. End points included American College of Rheumatology (ACR)-, European League Against Rheumatism (EULAR)- and Disease Activity Score 28 (DAS28)-based response criteria.ResultsThe literature search identified 41 publications, of which 28 reported biologic treatment outcomes for RA patients with prior exposure to TNF-α inhibitors. Seven publications reported outcomes obtained in randomized clinical trials, while the remaining consisted of observational studies. The likelihood of responding to a subsequent biologic treatment decreased as the number of previous treatments with TNF-α inhibitors increased for six of the seven response criteria examined.ConclusionsFor patients with prior exposure to TNF-α inhibitors, the likelihood of response to subsequent treatment with biologic agents declines with the increasing number of previous treatments with TNF-α inhibitors.

Allogeneic Stem Cell Transplantation in Patients with Therapy-Related Acute Myeloid Leukemia and Myelodysplastic Syndromes: Effect of Patient Characteristics and Treatment History.

AbstractAbstract 4577Patients with therapy-related acute myeloid leukemia (tAML) and myelodysplastic syndromes (tMDS) have a bad prognosis. Allogeneic stem cell transplantation (alloSCT) is potentially curative, but the majority of these patients die because of the high incidence of relapse (RI) and non relapse mortality (NRM). Since it is critical to understand which patients should receive alloSCT, we designed this retrospective study to assess which patients' characteristics may predict the alloSCT outcome in tAML/tMDS. All the patients affected by tAML or tMDS and allografted in 4 Italian hematology units between 1998 and 2009 were included. Total patients were 28: 24 (86%) had tAML, 4 (14%) had tMDS. Patients had a median age of 49 years (range 21–65) at transplant; 15 patients were female (54%). Previous neoplasia was lymphoma in 23 patients (82%, 15 Hodgkin and 8 non-Hodgkin), or non-hematologic cancer (5, 18%) like breast carcinoma (2), seminoma (1), testicular embryonal carcinoma (1), and osteosarcoma (1). Previous cancer had been treated with chemotherapy (CT, 7 patients, 25%), radiotherapy (RT, 4 patients, 14%), or both (17, 61%). Fourteen patients (50%) had received >=2 therapy lines, 6 (21%) had received autologous stem cell transplant. tAML/tMDS occurred after a median time of 86 months (range 13–253) after the previous cancer treatment. Cytogenetic analysis was performed in 24 patients (86%): 8 patients (33%) had intermediate risk and 16 (57%) high risk cytogenetics according to Medical Research Council AML10 Trial definitions. Twenty-three patients (82%) received induction CT for tAML/tMDS, 19 (68%) received consolidation; 5 patients (18%) received upfront alloSCT. Induction consisted of idarubicin+cytarabine+/−etoposide (12 patients, 43%) or fludarabine+cytarabine+/−idarubicin (11 patients, 39%); 15 patients (54%) had an infection after induction. Median time from tAML/tMDS diagnosis to alloSCT was 5.7 months (range 0–25). At transplant, 10 patients (36%) had a Karnofsky Performance Status (KPS)<=80% and 13 (46%) a Sorror comorbidity score >1. Donor was identical sibling for 9 patients (32%), and alternative for 19 patients (68%): mismatched related (1, 3%), matched unrelated (15, 54%) or haploidentical (3, 11%). Disease status of patients at transplant was as following: 12 patients (43%) were in CR (11 in CR1), 4 (14%) in PR and 7 (25%) in PD; 5 patients (18%) received alloSCT at diagnosis. Patients underwent reduced intensity (11 RIC, 39%) or myeloablative (17, 61%) alloSCT. Myeloablative conditioning was mainly busulfan-based (15 patients, 54%); the majority of RIC patients received thiotepa+cyclophosphamide-based conditioning (9, 32%). Twelve patients (43%) are alive at last follow-up, 7 patients (25%) died of disease, 9 (32%) died of NRM. The main reason of death by NRM was infection (8 patients, 29%). Median follow-up of surviving patients was 528 days (55-1704). One- and 2-years overall survival (OS) was 50% and 36%, progression free survival (PFS) was 42% and 38%. RI was 28% at both 1 and 2 years, NRM was 18% at 100 days, 30% at 1 year and 35% at 2 years. Nine (32%) patients had acute GVHD of grade >=2, 8 patients had chronic GVHD (cGVHD, 29%), 3 patients (11%) had extensive cGVHD. OS and PFS were reduced in patients with high-risk cytogenetics (p=0.03 and p=0.01, respectively) and KPS<=80% (p=0.008 and p<0.001). RI was higher in patients with KPS<=80% (p=0.02); high-risk cytogenetics increased RI (trend, p=0.08). Patients treated for previous neoplasia with >2 CT lines had a worse NRM (p=0.005) and a reduced OS (p=0.05); treatment type (CT vs RT vs CT+RT) did not have a significant impact on OS, PFS nor NRM. NRM was higher in patients who had infections after induction (p=0.009), or received consolidation (p=0.03). AlloSCT after >180 days from tAML/tMDS diagnosis increased NRM (p=0.05). Conditioning (RIC vs myeloablative), donor type (identical sibling vs alternative) and type of previous neoplasia (hematologic vs non-hematologic) did not affect survival (OS and PFS), NRM and RI. In conclusion, alloSCT is effective in a minority of patients with tAML/tMDS. Survival is reduced by high risk cytogenetics and poor KPS. Number of previous treatments, infections after induction, and consolidation CT increase NRM. Thus, patients' selection for alloSCT in tAML/tMDS setting should be based on cytogenetics, KPS, and treatment history. Prospective trials are awaited in order to confirm these results. Disclosures:Corradini:Novartis Pharmaceuticals, Inc: Consultancy; Genezyme: Consultancy; Roche: Speakers Bureau; Celegene: Speakers Bureau.

Phase II Prospective Multicenter Study of Treosulfan Based Reduced Intensity Conditioning In Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies From 10/10 HLA Identical Unrelated Donor

AbstractAbstract 2353 Background:The key point in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is to find the optimal balance between the graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect particularly in the unrelated HSCT settings, without forgetting the important role of conditioning. Objective:To evaluate the toxicity and efficacy of a new reduced intensity conditioning regimen including Treosulfan, followed by allo-HSCT from a 10/10 HLA identical unrelated donor. Materials and Methods:This prospective study included adult patients presenting a hematological malignancy in need of allo-HSCT using a 10/10 HLA identical unrelated donor. Accepted diagnoses were: CML in 1st chronic phase (CP) resistant to imatinib, in 2nd CP or in complete remission (CR) after blast crisis. Multiple myeloma (MM) or chronic lymphocytic leukemia (CLL) in stage B or C in response after relapse post-auto-HSCT. Acute lymphocytic or myeloid leukemia (ALL, AML) patients in CR1 at high risk or <CR1. Myelodysplasic syndrome (MDS) with poor prognostic factors. The conditioning included:Treosulfan 12g/m2/day intra-venous (day-6 to day-4), fludarabine 30mg/m2/day intra-venous (day-6 to day -2) and ATG 2.5 mg/kg/day (day-2 to day-1). GVHD prophylaxis used cyclosporine A oral (5mg/kg/day) or iv. (3mg/kg/day) from day-1. Peripheral stem cells after mobilization by G-CSF were used as HSC source. Results:Between February 2005 and July 2009, 56 patients were included in 5 different French centers, 30 (54%) males and 26 females with a median age of 57 years (18-65.5). There were 38 (68%) myeloproliferative disorders [29 AML (14 in CR1, 14 CR2 & 1<CR), 8 MDS (1CR1 and 7<CR) and 1 CML in CR1] and 18 (32%) lymphoprolifative disorders [9 MM in PR, 6 CLL (2CR1 & 4PR) and 3 ALL(1CR1 & 2CR2)]. Among 45 explored for cytogenetics, 23 (51%) were normal and 22 with poor prognostic. Before transplantation, two patients did not receive any previous treatment, 21 received 1 line, 22 two lines and 11 > 2 lines. For sex-matching, 49% of patients were sex-mismatched (half of them were F>M). For CMV, 43% were -/-, 25% +/+, 28% +/− and 1% -/+. For ABO matching, 52% were compatible, 24% major incomp. & 24% minor incopm. The median time between diagnosis and allograft was 15 months (4-168). The median number of infused CD34+ cells was 6.5 × 106/Kg(1-17.2)Fifty-four (96%) patients engrafted with a median time to neutrophils (>0.5G/l), and platelets (>50G/l) recovery of 16 days (4-86), 11 (4-82) respectively. Seventeen patients developed aGVHD grade ≥II (8 grade II, 2 grade III & 7 grade IV) with a cumulative incidence at 3 months of 31% (25-38). The cumulative incidence of cGVHD was, at 12 months: 32% (25-39) limited and 6% (2-10) extensive; at 18 months: 34% (27-47) limited and 8% (5-12) extensive. After a median follow-up of 13 months (1-57), the median overall survival (OS) was not reached with a 3 years probability of 52% (38-71). The median time of event free survival (EFS) was 15 months (8 - 57) with a 3-years probability of 47% (35-64). The cumulative incidence of relapse at 3 years was 25% (19-31) and the cumulative incidence of transplant-related mortality (TRM) at 12, 18 and 36 months was 20% (16-27), 23% (16-29) (same at 18 & 36 months) respectively. At the last follow-up, 22 patients died, 7 due to relapse and 15 due to TRM (5 pneumonia, 4 GVHD, 1 secondary malignancy and 6 other causes). We showed in a univariate analysis a higher 3-years OS of patients in CR1 (65%) compared to those <CR1 (44%) at transplantation with a significant better benefit for AML patients (76%). Patients with active cGVHD seem to benefit for the GVL effect on OS with a high significant difference (HR=0.2 (0.1-0.6) p=0.002). The multivariate analysis studying age, sex matching, ABO compatibility, CMV matching, type of disease, CD34+ cells number, cytogenetics, number of previous treatments, disease status and interval diagnosis-allo-HSCT showed: a negative significant impact of both minor ABO incompatibility (p<0.001) and CMV+/− (p=0.01) on OS, a negative significant impact of patients <CR (p=0.03) on relapse. There was no impact of studied factors on TRM. Conclusion:We showed very promising results in terms of OS, relapse and TRM with an impressive GVL effect, in heavily pre-treated patients and transplanted using unrelated donors. Treosulfan appears to be a good choice for conditioning especially with a better outcome in AML patients in CR1. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Pregabalin and gabapentin in matched patients with peripheral neuropathic pain in routine medical practice in a primary care setting: Findings from a cost-consequences analysis in a nested case-control study

Background: Pregabalin and gabapentin are marketed to treat peripheral neuropathic pain, but head-to-head comparison is lacking. Objectives: The aims of this work were to compare the effects of pregabalin and gabapentin on different patient-reported health outcomes and to analyze health care and nonhealth-care resource consumption and their related costs among patients treated for peripheral neuropathic pain in primary medical care. Methods: A cost-consequences comparison in subjects with refractory (suboptimal response to ≥1 previous analgesic treatment for >6 months) chronic peripheral neuropathic pain was carried out using data extracted from two 12-week, observational, prospective studies in primary medical care. Patients were eligible if they were aged ≥18 years, had a score of ≥4 on the Douleur Neuropathique 4 questionnaire, and were able to complete health questionnaires written in Spanish. A nested-paired case-control design was chosen to perform the comparison with 2 controls (pregabalin) per case (gabapentin) matched by age, sex, peripheral neuropathic pain condition, time since diagnosis, number of previous treatments, pain intensity, depressive and anxiety symptom scores, and health state. Adult subjects with refractory chronic pain because of diabetic neuropathy, postherpetic or trigeminal neuralgias, or cervical or lumbosacral radiculopathies were included. Epidemiologic statistical methods were applied for comparing health effects (pain intensity, sleep, anxiety and depressive symptoms, disability, and health state), resources utilization, and related cost variations after 12 weeks. Indirect costs were measured by means of lost-workday equivalent calculations multiplied by the mean national daily salary. Results: Analysis included 44 patients treated with gabapentin (cases) and 88 patients treated with pregabalin (controls) who were matched for age, sex, and other parameters. The mean (SD) gabapentin and pregabalin doses were 1263 (540) and 202 (119) mg/d, respectively. Although there was a greater reduction in last-week mean pain intensity with pregabalin (visual analog scale: 39.1 [22.5] vs 28.0 [22.2] mm; P = 0.008), as well as more patients with a ≥50% reduction in pain rate (60.9% vs 40.5%; P = 0.029), there were no significant differences between groups for sensory, affective, total, or present pain intensity. The significantly higher drug cost associated with pregabalin was offset by a greater reduction in productivity costs compared with gabapentin, yielding similar cost reduction (−€1254 [1479] vs −€1384 [2874], respectively; P = NS). Conclusion: Pregabalin appeared to be associated with greater reduction in mean weekly intensity of pain, but there were no significant differences in cost.

P01-09 - Antidepressant monotherapy and combination of antidepressants in the treatment of resistant depression in current clinical practice. A retrospective study

Introduction and objectivesResistant depression is a long-term, disabling illness. The aim of this study was to compare the efficacy of antidepressant monotherapy (ADM) and combinations of antidepressants (CAD) in the treatment of resistant patient (≥1 unsuccessful antidepressant treatment) in current clinical practice.MethodsWe reviewed chart documents of resistant patients hospitalized at Prague Psychiatric Center for major depressive disorder (DSM IV) and had finished at least 4 - weeks of treatment with ADM or CAD. Clinical status was assessed using MADRS, CGI and BDI-S at baseline, after 2 weeks and in the end of treatment in the framework of regular evaluation during the hospitalization. Response to treatment was defined as a reduction of MADRS score ≥ 50%.Results: We analyzed 78 inpatients (CAD=27, ADM=51). Both groups were equal in baseline characteristics (number of previous treatments, severity of depression etc.) and in the length of index treatment. The CAD group was superior to ADM group in the MADRS score reduction (14.6 vs 10.2 pts, p=0.02) and the proportion of responders (67% vs. 39%, p=0.03) in the end of treatment. The post-hoc effect size of CAD compared to ADM was moderate (Cohen's d=0.54).Conclusion: The results of this study suggest that combinations of antidepressants may be more effective than a monotherapy in patients with resistant depression.This study was supported by a grants from Internal Grant Agency of Ministry of Health of Czech Republic No. NS 10368-3 and a grant from Ministry of Health of Czech Republic MZ0PCP2005.

The risk factors for herpes zoster in bortezomib treatment in patients with multiple myeloma

BackgroundBortezomib has significant activity in treating multiple myeloma (MM). The risk of herpes zoster (HZ) has been reported to increase significantly with bortezomib treatment, but the predisposing factors for HZ are not clear. This study is a retrospective analysis of the relevant risk factors for HZ in Korean MM patients treated with bortezomib.MethodsSixty-six patients with refractory or relapsed MM who underwent chemotherapy with bortezomib were included in the study. Prophylactic antiviral drugs were not used for treatment. The following parameters were reviewed: age, gender, stage and type of MM, extent of previous treatment, history of HZ, duration from the time of diagnosis to the time of bortezomib treatment initiation, and absolute lymphocyte counts (ALC) at the time of bortezomib treatment initiation.ResultsThe incidence of HZ was 16.7%. There were no intergroup differences between the HZ-positive and the HZ-negative groups with regard to a history of HZ, number of previous treatments, and exposure to steroids before bortezomib treatment. The median duration from the time of MM diagnosis to the time of bortezomib treatment initiation in the HZ-positive group was significantly shorter than that in the HZ-negative group. The median ALC at the time of bortezomib initiation in the HZ-positive group was significantly lower than that in the HZ-negative group.ConclusionBortezomib itself might act as a risk factor for HZ by inhibiting cell-mediated immunity, and patients with low ALC at the time of bortezomib treatment initiation were at greater risk of HZ during bortezomib treatment.

Infectious Complications in Asian Patients Treated with Alemtuzumab: Results From a Multicenter Study.

Abstract 5009 IntroductionAlemtuzumab is a monoclonal humanized antibody reactive with CD52 antigen expressed in indolent B-cell non-Hodgkin lymphomas and variably expressed in high grade B- and T-cell lymphomas. Thus, alemtuzumab has been used as a treatment for these lymphomas. Alemtuzumab has also been used for the prevention of graft-versus-host disease. However, alemtuzumab binds to 95% of normal lymphocytes resulting in long-lasting depletion of B- and T-lymphocytes. This prolonged suppression of immunity could influence the occurrences of opportunistic infections. Based on the experiences of infections associated with the use of alemtuzumab, recently the recommendations for prophylaxis against infectious complications were suggested. However, the majority of data used to establish this guideline was from the results of Western countries. Considering the prevalence of infection can be different from Asian countries to Western countries, the effective prophylaxis guideline appropriate for Asian patients should be required. Thus, we performed a multinational retrospective study about the infectious complications among Asian patients who received alemtuzumab. Patients and methodsWe reviewed the medical records of patients who were treated with alemtuzumab. The infectious complications associated with alemtuzumab were defined as any episodes of infections occurred in patients who received alemtuzumab. Results162 patients were assembled from 10 institutes of 5 Asian countries: Korea (5 hospitals), Hong Kong (1 hospital), Thailand (2 hospitals), Indonesia (1 hospital), and Taiwan (1 hospital). The median age was 47 years (range 11-79years), and the Korean (n = 103) and Chinese (n = 43) accounted for 90.1% of the study population. The primary disorders of patients were as follows: T-cell lymphomas (n = 93, 57.4%), B-cell lymphomas (n = 30, 18.5%), Myeloid leukemia/MDS (n = 25, 15.4%), Aplastic anemia (n = 10, 6.2%), and Benign disorder (n = 4, 2.5%). Alemtuzumab was used as frontline and salvage treatments for lymphoid malignancy (n = 120, 74.1%), and as conditioning regimen for allogeneic stem cell transplantation (n = 42). Alemtuzumab was administered as a single agent or combined with other chemotherapeutic agents. The infection prophylaxis was done according to the each institute's policy. The bacterial infections were the most common infectious complications (n = 80, 49.4%), and the median time interval between the start of alemtuzumab and the onset of bacterial infections was 2.20 months (95% confidence interval: 1.14-3.26 months). However, considering the majority of cases received intensive chemotherapy combined with alemtuzumab, this frequency of bacterial infections might be influenced by other chemotherapeutic agents. Thirty-two patients experienced fungal infections including aspergillosis and candidiasis (19.8%, median time interval 2.83 months). Fugal infections were more common when alemtuzumab was used with other chemotherapeutic agents than as a single agent. Cytomegalovirus (CMV) accounted for 40.1% of infectious complications while CMV antigenemia was more frequent than CMV disease (n = 52 versus n = 13). Vanganciclovir as well as valacyclovir prophylaxis did not significantly reduce the occurrence of CMV infections. Herpes zoster was documented in 25 patients (15.4%) and the median time interval was 6.40 months (95% confidence interval: 1.06-11.74 months). The past history of herpes zoster was not related with the occurrence of zoster after alemtuzumab was used. Tuberculosis and hepatitis B were found in 15 and 4 patients, respectively. The past history of tuberculosis and hepatitis B carrier did not affect the occurrence of tuberculosis and hepatitis B. The number of previous treatments before alemtuzumab, and the purpose of alemtuzumab such as salvage treatment and conditioning for transplantation were not significantly associated with the occurrence of infectious complications. ConclusionThe incidence and clinical features of infectious complications associated with alemtuzumab in Asian patients were comparable to the data from Western countries. Considering a substantial number of infectious complications associated with virus, more effective prophylaxis against viral infections should be considered. DisclosuresNo relevant conflicts of interest to declare.

Internet-Based Cognitive-Behavioral Therapy for Bulimia Nervosa: A Controlled Study

The object of this study was to examine the effectiveness of an Internet-based therapy (IBT) for bulimia nervosa (BN) as compared to a waiting list (WL). Sixty-two female BN patients, diagnosed according to DSM-IV criteria, were assigned to either the IBT or a WL. The control participants (WL) were matched to the IBT group in terms of age, duration of the disorder, number of previous treatments, and severity of the disorder. Assessment measures included the EDI, SCL-90-R, BITE, the TCI-R, and other clinical and psychopathological indices, which were administrated before and after the treatment. Considering the IBT, while the mean scores were lower at the end of the treatment for some EDI scales (bulimic, interpersonal distrust, maturity fears, and total score) and the BITE symptomatology subscale, the mean BMI was higher at posttherapy. Predictors of good IBT outcome were higher scores on the EDI perfectionism scale and EAT and a higher minimum BMI. Drop-out (after IBT 35.5% of cases) was related to higher SCL-anxiety scores, a lower hyperactivity, a lower minimum BMI, and lower TCI-reward dependence scores. At the end of the treatment, bingeing and vomiting abstinence rates differed significantly between the two groups. Results suggest that an online self-help approach appears to be a valid treatment option for BN when compared to a WL control group, especially for people who present a lower severity of their eating disorder (ED) symptomatology and some specific personality traits.

Skin testing and drug provocation in the diagnosis of nonimmediate reactions to aminopenicillins in children

Nonimmediate allergic reactions (NIR) to aminopenicillin include several entities, the most common of which are urticaria-like and maculopapular exanthemas. To evaluate a group of children who developed one or more episodes of skin reactions suggestive of NIR after aminopenicillin administration. The inclusion criteria required negative immediate skin tests and absence of specific IgE antibodies to different penicillins. Intradermal and patch tests were carried out with delayed readings and, if negative, a drug-provocation test including a full therapeutic course of the drug was given. Two different groups were compared: A) children with positive skin testing or a positive drug-provocation test and B) children with negative skin testing and good tolerance after a drug-provocation test. Group A was composed of 20 patients. Positive intradermal/patch tests were found in one patient and in the remaining 19, a positive response to a drug-provocation test confirmed the diagnosis. Group B (the control group) consisted of 19 patients with similar symptoms after aminopenicillin intake but good tolerance. No differences in age, dose or number of previous treatments were observed between the groups. The clinical entities were also similar in both groups. Reproducible nonimmediate skin reactions to aminopenicillins may occur in children in spite of negative skin testing. The value of this diagnostic procedure seems to be limited in this type of reaction, with drug-provocation tests (DPT) being a reasonable and safe alternative if the diagnosis has to be confirmed.

Pericranial injection of botulinum toxin type A (Dysport®) for tension‐type headache – A multicentre, double‐blind, randomized, placebo‐controlled study

Increasingly, botulinum type A toxin is used to influence pathologically increased muscle activity in conditions such as dystonia and spasticity. Studies have also assessed its efficacy in tension-type headache, where muscle tenderness may be increased. We undertook a prospective, multicentre, randomized, double-blind, placebo-controlled trial. Patients received injections of Dysport (total dose of 420 or 210 units) or saline placebo in 18 sites on the head and neck. Of 125 patients treated, 118 were included in the intention-to-treat dataset. No significant differences between each verum group and placebo were seen for the primary efficacy parameter - change in the number of headache-free days at 4-8 weeks after injection compared with 4 weeks before injection. The groups receiving 420 or 210 units of Dysport experienced 2.60 and 2.87 more headache-free days respectively, compared with 1.93 more headache-free days for the placebo group (P = 0.66 versus 420 units; P = 0.52 versus 210 units). Treatment with 420 units of Dysport was associated with significant improvements compared with placebo for two secondary efficacy parameters: mean change in headache duration from baseline to weeks 8-12 (P < 0.05) and improved global physician and patient assessment scores (P < 0.05). Further studies should address the possible value of multiple injections with extended observation periods, dose optimization, and whether duration of headache history and number of previous treatments are predictors of patient response.

Incidence of Neutropenia and Hypogammaglobulinemia and Correlation with the Infections Rate in Indolent Non-Hodgkin Lymphoma (NHL) Receiving Rituximab Maintenance.

Rituximab (R) maintenance has demonstrated a significant increase in both median PFS and OS in follicular lymphoma. However, such an effective strategy carries a concern about the long-term effects of rituximab on the immune system and the risk of infectious complications. In fact, neutropenia, and less frequently, hypogammaglobulinemia, occur with rituximab treatment, but this is still a scarcely explored issue. We analyzed our experience with R-maintenance in patients with indolent non-Hodgkin lymphoma (NHL) to evaluate the incidence of neutropenia and hypogammaglobulinemia, the type and incidence of infections and the factors associated with infection.Patients and Methods: Patients (pts) with indolent NHL in CR or PR after induction or salvage treatment (either with or without R), receiving R maintenance (R= 375 mg/m2; 2 schedules: 4 weekly doses every 6 months (4/6) in high-risk patients and 1 dose every 3 months (1/3) in low-risk. Total duration= 2 years) from June 2003 to June 2007. We examined the following variables for correlation with the incidence of infection: number and type of previous treatments (with/without R, with/without fludarabine), previous splenectomy and/or radiotherapy, response to previous treatments before R-maintenance, and R-maintenance schedule used.Results: Forty-seven pts (age (Mean[R]): 57[34–76]; gender F26:M21) with indolent NHL [FL 27 (57.4%), MCL 2 (4.3%), MZL 7 (14.9%), LPL/Waldestrom 5 (10.6%), MALT 6 (12.8%)] were retrospectively evaluated. At diagnosis: ECOG 0–1: 29 (61.7%), 2–3: 6 (12.8%); stage III–IV 43 (91.5%); B-symptoms 23 (48.9%); FLIPI 0–2: 56.4%, 3–5: 43.6%. Marrow involvement 34 (72.3%), splenomegaly 14 (29.8%) and hepatomegaly 5 (10.5%). LDH (Mean[R]): 346 [115–854], b2–microglobulin: 3.17 [1.3–7.9], Neutrophil count (x 109/L): 8.89 [0.14–31.6], IgG: 1044.8 [214–2080], IgA: 186.8 [35–570], IgM: 532.3 [17–6670]. Number of treatments before R-maintenance (M[R]): 1 [1–3]. Thirty-eight (80.9%) pts had received R-containing therapy and 43 (91.5%) fludarabine-containing regimens. Forty (85.1%) had achieved CR and 7 (15.2%) PR. Follow-up from diagnosis (Mean[R]): 35.4 months [8–116]; follow-up from start of R-maintenance: 16.8 months [1–53]. After R-maintenance, 9 pts (19.1%) presented neutropenia grade 3–4. The presence of splenomegaly (p=0.03) and hepatomegaly (p=0.03) at diagnosis significantly correlated with neutropenia 3–4. No relationship was found with the maintenance schedule used (4/6 vs 1/3), previous R or fludarabine, or with the number of previous treatments. Incidence of hypogammaglobulinemia was (*data available from 33 pts): IgG<500: 8 (24.2%), IgA<60: 10 (30.3%), IgM<50: 13 (39.4%). Infections recorded in the 47 pts: recurring gastroenteritis 1 patient, HZV 2 pts, ORL infections 1 patient, and 2 cases of severe pulmonary infections requiring hospitalization. A significant correlation was found between infection and IgG<500 (p=0.04) and with neutropenia 3–4 (p=0.03).Conclusions: Rituximab maintenance is a safe strategy with a low incidence of infectious complications. Although severe neutropenia and hypogammaglobulinemia are not rare side effects of prolongued R treatment, only 2 patients presented severe infectious complications in our cohort. The only factors significantly influencing the incidence of infection were neutropenia 3–4 and low levels of IgG. No differences were observed between both schedules of R-maintenance regarding the infections rate.

Rituximab Therapy for Autoimmune Hemolytic Anemia and Immune Thrombocytopenia: A Belgian Registry.

Background. Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) may respond to the chimeric anti-CD20 monoclonal antibody rituximab, even when refractory to conventional therapy.Aims. To collect data on Belgian patients given rituximab in the setting of ITP or AIHA in order to assess the response rate and the factors predictive for response in a multicenter study.Method. Belgian hematology centers were invited to fill a questionnaire specifying the major characteristics and quality of response of ITP and AIHA patients given rituximab. For ITP, complete response (CR) was defined as a platelet count >150,000/μL, and a partial response (PR) as a platelet count 50–100,000/μL. For AIHA, Response (R) was defined as a 2g increase of the hemoglobin concentration and achievement of transfusion independence.Results. All the patients were given rituximab after relapse or after failing at least one previous line of treatment. Except in 10 cases, rituximab was given at the dose of 375mg/m2 weekly for 4 weeks. In 31 assessable episodes of ITP a CR was achieved in 18 patients (58%) and a PR in 2 patients (6%). In 53 episodes of AIHA, R was achieved 42 times (79%). In both ITP and AIHA patients we could find no significant correlation between response and sex, age, prior splenectomy, platelet count or hemoglobin concentration when rituximab was started, number of previous treatments, response to previous treatments, duration of disease before rituximab was given, presence of an underlying malignant or autoimmune condition. In patients with AIHA, response rates were similar in cold agglutinin disease (8/10) and in warm antibody mediated hemolysis (29/38). Progression-free survival in responding patients is presented graphically. At one year, 83% of ITP patients and 61% of AIHA patients were alive without progression.Conclusion. In this still open registry, we could confirm that rituximab induces responses in a majority of previously treated patients with ITP or AIHA. Responses could not be predicted from pre-treatment patient characteristics. In most patients response duration exceeded one year. [Display omitted]

Restrospective analysis of non-Hodgkin lymphoma (NHL) patients (p) treated with 90Y ibritumomab tiuxetan (90Y- IT): Iberia RIT database

18526 Background: 90Y-IT is approved for the treatment of refractory NHL. The aim of this study was to collect data of NHL p treated with 90Y-IT within the clinical practice setting, to retrospectively analyze treatment effectiveness and tolerability, in order to provide a pragmatic approach to experimental data. Methods: Multicenter, retrospective study. NHL p treated during last year with 90Y-IT, were registered. Effectiveness endpoints retrospectively studied were: objective response rate (ORR), time to progression (TTP) and overall survival (OS). Clinical prognostic factors were collected to asses their possible influence upon treatment effectiveness, by multivariate analyses. Results: 65 p were registered: M/F, 58.5%/41.5%; median age, 59 years (22–83); ECOG 0–1, 73.3%. Median time since lymphoma diagnosis was 3.6 years. At diagnosis, 84.6% had follicular lymphoma (grade 1, 44.9%; grade 2, 40.8%) and 15.4% non- follicular lymphoma. Most of the cases were refractory to previous treatments (78.1%). Median number of previous treatments was 3 (range 1–8) Median administered dose of 90Y-IT was 0.4 mCi/Kg. ORR was 70.8% (95% CI: 59.8, 81.9). With a median follow-up time of 6 months, median TTP was 16.1 months (95% CI: 11.2, 21.1) and median OS has not been achieved. Within the group of follicular lymphoma, ORR was 74.6% (95% CI: 63.1–86.1) and TTP 17.7 months (95% CI: 14.3, 21.1). Bone marrow involvement and high FLIPI score were significantly associated with higher risk of progression disease: hazard ratio 3.71 (95% CI: 1.00, 13.68) and 21.12 (95% CI: 2.37, 187.91), respectively. Median time to G3–4 haematological toxicity ranged between 27–38.5 days, being the most frequent thrombocitopenia (46.2%) and neutropenia (33.8%). 17 p required red blood cell transfusions (median, 4 U) and 19 required platelet transfusions (median, 7 U). The most frequent G3–4 non haematological toxicity was asthenia (10.8%). Updated survival data will be presented at the meeting. Conclusions: These results obtained with 90Y-IT for NHL treatment within the clinical practice setting are concordant with published experimental data, despite the limitations of the retrospective design. [Table: see text]