Auswahl der wissenschaftlichen Literatur zum Thema „HL-1 buňky“

Abstract Background: Bulky disease is considered a major driver of unfavorable prognosis in early stage Hodgkin Lymphoma (HL). Treatment guidelines for bulky early stage HL call for more aggressive initial therapy compared to non-bulky disease. There are limited data on outcomes in bulky disease, particularly in patients treated with chemotherapy alone, or on the utility of interim PET scans. We retrospectively analyzed data on patients with early stage HL to assess the impact of disease bulk, interim PET and treatment modality on outcomes. Methods: We reviewed charts of 151 consecutive patients diagnosed with previously untreated early stage (I & II) HL at the Cleveland Clinic from 1995-2011. Bulky disease was defined as a mediastinal mass >1/3 intra-thoracic diameter on PA chest x-ray or any mass ≥ 10 cm on CT scan at diagnosis. Patients were grouped by intent to treat strategy as chemotherapy alone (C) or combined modality treatment (CMT) with chemo-radiation. Baseline characteristics were compared: categorical variables by the Chi-square or Fisher's exact test; continuous variables by the Wilcoxon rank sum test. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method and compared by the log-rank test. Cox proportional hazards analysis was used to test univariable prognostic factors for OS and PFS. Results: 121 patients (mean age 40±16) with early stage HL had adequate clinical data for inclusion. At the time of review, 106 (87.6%) patients were alive with median follow-up of 47.4 (0-328) months. Characteristics at diagnosis were: 54% female; 80% Caucasian; 77% nodular sclerosis HL; 78% stage II; 31% with B-symptoms; 12% with extranodal disease; 30% (N =36) with bulky disease of whom 89% had bulky mediastinal disease. 96% patients received standard ABVD chemotherapy. The only significant differences in the baseline characteristics of patients with bulky vs. non-bulky disease were age (mean 35 vs. 42 years, P=0.03), hemoglobin (mean 12.4 vs. 13.4 g/dL, P=0.01) and absolute lymphocyte count (mean 1.29 vs. 1.71 k/µL, P=0.02). Although there was no statistically significant difference in the initial treatment strategy chosen, patients with bulky disease tended to receive CMT more often than patients with non-bulky disease (66% vs. 51%, P=0.16). More females were treated with C compared to CMT (70% vs. 43%, P=0.004). Patients with bulky disease received a greater number of chemotherapy cycles (mean 5.6 vs. 4.6, P=0.01). Five years after diagnosis, patients with non-bulky HL had Kaplan-Meier estimates of 83% OS and 69% PFS while patients with bulky HL had 88% OS and 81% PFS. There was no statistical difference in OS [Figure 1] or PFS based on disease bulk. Analysis of the available PET status (65 interim scans) revealed that both the bulky and non-bulky patients had comparable responses on interim PET (negative 82.6% vs. 95.2%, P=0.17). Interim PET scan was highly prognostic for all early stage HL patients for both OS (P < 0.01) and PFS (P < 0.001) as well as specifically for patients with bulky disease (negative vs. positive PET: 5 year OS 90% vs. 75%, P=0.012; 5 year PFS 95% vs. 25%, P<0.01 [Figure 2]). Among the 23 patients with bulky disease managed with initial CMT, 4 required 2nd line treatment including 3 who underwent autologous stem cell transplant (Auto-SCT). Among the 12 patients managed initially with C, 5 required 2nd line treatment and all 5 underwent Auto-SCT. In total, among those with bulky disease, the OS and PFS were similar irrespective of initial treatment strategy chosen. In univariate analysis, extra-nodal disease was the only baseline variable that impacted PFS (HR=2.7, CI 1.01-7.20, P=0.048) but did not affect OS (HR=2.46, CI 0.66-9.19, P=0.18). Conclusions: Patients with bulky early stage HL have comparable survival to patients with non-bulky disease. Among patients with bulky disease, treatment with initial C or CMT resulted in comparable OS and PFS, although a higher proportion of patients treated with C alone required 2nd line treatment. These data support the observation that radiation therapy is not essential to achieve cure in bulky HL. Specifically, omitting radiation in female patients who achieve a negative interim PET scan is a viable treatment strategy which may mitigate the long-term risks of radiation. Figure 1: OS in Early Stage HL Based on Disease Bulk Figure 1:. OS in Early Stage HL Based on Disease Bulk Figure 2: PFS in Bulky Early Stage HL Based on Interim PET Figure 2:. PFS in Bulky Early Stage HL Based on Interim PET Disclosures No relevant conflicts of interest to declare.

e19536 Background: Prognosis of patients with Hodgkin lymphoma (HL) has substantially improved but therapy of HL can however contribute to delayed toxicity. Long term treatment outcomes of HL in our local population were evaluated. Methods: Clinical and treatment data was prospectively collected from all patients with a histological diagnosis of HL. Patients were all fully staged with CT scan and bone marrow biopsy. Results: On the basis of 217 patients seen at the National Cancer Centre Singapore between 1990–2008, we found that there was a peak in young adulthood with 103 patients who were diagnosed before the age of 30 (48%), median age of presentation 32 (range 17–84). Patients who were young (< 30 years) were more likely to present with nodular sclerosis HL (p=0.0001). Treatment outcomes were comparable to other published series, 85% of cases received ABVD based treatment. 5 year OS for early stage HL was 92% and 88% for advanced stage HL. Overall FFTF was 93% at 5 years. Of note, comparing patients with early stage (Stage I/ II) HL (n=114) who had ABVD 4 cycles followed by involved field radiotherapy (IFRT) with those who received 6–8 cycles of ABVD, there was no difference in OS, FFTF (p= 0.99, 0.48 respectively). Bulky early stage HL who received 6 cycles of ABVD and IFRT had better FFTF rates than those who had just 4 cycles of ABVD followed by IFRT (p=0.06). In contrast, patients patients with advanced HL (Stage III/ IV) (n=70) who completed 6–8 cycles of ABVD did not benefit from additional IFRT even in the presence of bulky disease (n=15). Acute toxicities included that of bleomycin induced pneumonitis (BIP) seen in 15% of cases. Neither the omission of bleomycin nor the presence BIP adversely affected treatment outcomes. Hematological malignancies were seen in 1% of survivors appearing after a median of 7.3 years. Hypothyroidism was noted in 3% of cases. Conclusions: 1) Epidemiology of HL in Singapore is increasingly similar to that of developed countries with a peak in young adults. 2)Young age was predictive of a nodular sclerosis subtype 3) Abbreviated chemotherapy using 4 cycles of ABVD followed by IFRT performed similarly to 6 cycles of ABVD in early stage HL, but in patients with bulky disease this may not be sufficient. 4) BIP occurred in 15% of cases. BIP and the omission of bleomycin did not adversely affect treatment outcomes. No significant financial relationships to disclose.

Abstract Abstract 1995 Lymphoma of various types in newly diagnosed patients may exhibit necrotic areas in the tumor mass on imaging. To date, little is known about the clinical significance of this finding and even less is known about the mechanism of cell death in the necrotic tissue - apoptosis, molecular necrosis or autophagy. The objective of this study was to investigate the prognostic significance of tumor necrosis in newly diagnosed Hodgkin's lymphoma (HL) and diffuse large B cell lymphoma (DLBCL) patients and to define the molecular mechanism of cell death responsible for the necrosis. Two hundred and four CT scan or CT-PET studies from newly diagnosed patients with DLBCL (131) and HL (73) were analyzed for the presence of tumor necrosis. Radiographic appearance of necrosis was present in 47% of all patients, 34% HL and 53% DLBCL. A statistically significant correlation was found between necrosis and bulky disease (tumor mass size≥10 cm) (p=0.0002×10-6) and also between necrosis and elevated LDH (p=0.00002) (see Table 1). Radiographic appearance of necrosis Bulky disease tumor mass size ≥10 cm Elevated LDH Yes 41.1% 60.2% No 5.5% 29.9% No statistically significant correlation was found between necrosis and age >60 or more advanced stage of disease. There was also no statistically significant difference in interim response to treatment, disease-free survival and overall survival between patients with necrosis and without it. Our results show that in contrast to solid tumors, tissue necrosis in lymphoma is not a predictor of worse prognosis: though more patients with radiographic appearance of necrosis had also the known bad prognostic signs- elevated LDH and/or bulky disease, this group did not have worse outcome. We suggest that necrosis can lead to a better response to treatment in lymphoma. Among 56 HL and DLBCL patients that underwent an open surgical biopsy of the tumor mass nineteen presented necrotic morphology in the biopsied tissues: 8 HL and 11 DLBCL. Biopsies without evidence of necrotic morphology (10 patients from the above 56) and reactive lymph nodes (4) were included as controls. All sections were stained for ki-67 (proliferation marker), activated caspase-3 (apoptosis marker) and HMGB-1 (necrotic cell death marker). DLBCL cells showed high proliferation rate, with ki-67 index ranging from 40 to 90% and in HL cells the ki-67 index ranged from 5 to 50%. All the samples positive for HMGB-1 were from patients with HL and 10/11 of activated caspase-3 positive samples were from DLBCL. These results show a differential molecular mechanism of cell death in the tumor mass of newly diagnosed HL and DLBCL patients. The constitutive activation of the survival factor Nuclear Factor-kB (NF-κB) was found in Hodgkin and non-Hodgkin lymphoma. We stained the same biopsies for p65/RelA and examined the nuclear localization of NF-κB as an indication for activation of the NF-κB pathway. Four DLBCL and 4 HL samples were positive for NF-κB activity. Nevertheless, we found that activation of caspase-3 and/or HMGB-1 induced cell death in these tissues. In summary, tumor necrosis in HL and DLBCL is correlated with bulky disease and high LDH, yet is not correlated with prognosis. The molecular mechanism of cell death differs between the two types of lymphoma. Disclosures: No relevant conflicts of interest to declare.

Abstract Patients with stage I-II A non bulky Hodgkin’s lymphoma (HL) are successfully treated with 2–4 cycles of ABVD plus IF radiotherapy (RT). Although the negative impact in DFS and OS of B symptoms and bulky disease(X) is widely accepted, other risk factors such as number of lymph node regions involved or extensive spleen involvement have also been reported. What is the best treatment for such patients? Is radiotherapy necessary? We report here our experience with protocol HD 98 in 62 patients, with stage I–II HL. Since January 98 we have included 30 individuals without risk factors and 32 with one of the following risk factors: B symptoms (n:11), X (n:9), extensive spleen involvement (n:1) and involvement of more than two lymph node regions (n:11). Other patient characteristics were: age: x 31yrs (15–69), sex: females 31, males :31. Ann Arbor stage IA :11, IB :1, IIA: 36, IIB :14. Histologic subtypes were: LP: 4, NS: 42, MC: 15, lymphocyte rich :1. Patients with favourable features received 4 cycles of ABVD plus IFRT, those with unfavourable factors received 6–8 cycles of ABVD plus RT in areas of bulky or residual disease. Results: 59/61 evaluable patients obtained CR or CRu. Two patients were considered primary resistant. Three patients relapsed at 7, 13 and 30 months after completion of treatment. Autologus bone marrow transplant was performed in four patients. The two primary resistant patients relapsed after the transplant and died with proggressive disease. Those patients transplanted in a chemosensitive relapse are currently in CR. With a median follow up of 46m (13–84) 96.7% of the patients are alive, in CR. Conclusions: In our experience patients with unfavourable stages I–II HL are succesfully treated with 6–8 cycles of ABVD. In such patients RT might only be necessary in areas of bulky or residual disease.

Abstract Combined modality therapy with radiation and chemotherapy has been the standard treatment for limited-stage HL. Long-term toxicities, including cardiac and disease and secondary cancers, s have been reported in multiple series with long follow-up. Lower doses and smaller fields may be less toxic, but mediastinal/cardiac radiation is unavoidable in most cases. The Dana-Farber Cancer Institute and Massachusetts General Hospital lymphoma teams have now treated 74 patients with localized, non-bulky classical HL with chemotherapy as the only therapy. The median age of the series was 29 years (17–42). The M/F ratio was 33/41. The clinical stages were IA (10), IIA (56), IIB (9). The treatment consisted of ABVD × 6 cycles (70 pts), ABVD × 4 cycles (3 pts), and variants of ABVD (2 pts). The median F/U is 48+ months (4+–174+). One patient had primary refractory disease. Seven patients (median age 30, range 20–38) have relapsed (6, 10, 10, 11, 14, 20 and 63 months) whose original stage was IA (1), IIA (3), IIB (3). The progression-free survival at 4 years is 91%. All patients are alive. Six of seven patients received salvage RT and autologous stem cell transplantation, and only one has relapsed to date. In retrospect, all seven patients who relapsed from CR or CRu were FDG-PET negative at mid-cycle. Thus far, there has been no long-term, chemotherapy-related toxicity in the patients who remain in remission. 94% (62/66) asymptomatic patients remain in remission compared to 6/9 (67%) IIB patients. Conclusion: In young adults with non-bulky, localized HL chemotherapy alone with ABVD can achieve excellent progression-free and overall survival, especially those asymptomatic at diagnosis. These data and previously published results indicate an equivalent long-term outcome when compared to combined modality trials but without the long-term risks of radiation therapy. Avoidance of radiation therapy may be even more important in the pediatric age group.

Abstract Abstract 3153 Hodgkin Lymphoma (HL) is characterized by high cure rates. Approximately 90% early stage and 60–70% advanced stage patients have long term disease free survival. In Brazil it is observed that about 60% of patients present with advanced stage, while in developed countries about 40% belong to this group. The aim of this retrospective study was to analyze data of patients with HL from the Oncohematology Unit of University of São Paulo- Medical School and evaluate the event free survival (EFS) and the overall survival (OS) according to clinical stage. We included all consecutive patients diagnosed with HL between January 1991 and June 2010. The collection of data from medical records was done and the following variables at diagnosis were evaluated: age and sex, staging according to Cotswolds modified Ann-Arbor criteria (CS), histological subtype, presence of B symptoms and bulky disease, International Prognostic Index (IPI) according to International Prognostic Factors Project on Advanced Hodgkin's Disease, laboratorial data, and the protocol used in first line therapy. The complete remission (CR) rate, EFS and OS were analyzed in all patients. The survival analysis was estimated by the Kaplan-Meier method and the survival curves were compared by the log-rank test. Differences in CR rates among staging groups were compared using the chi squared test. Overall, 564 HL patients were identified; thirteen did not have adequate information about clinical staging and were excluded from the analysis. The median age, at diagnosis, of the remaining 551 patients was 28 (12–83) and 54.3% were male. Histological subtypes lymphocyte rich classical HL, nodular sclerosis, mixed cellularity and lymphocyte depletion were found in 3.6%, 51.4%, 24.2% and 5.6% cases, respectively, and 11.8% patients were diagnosed as HL classic not classifiable otherwise. Nodular lymphocyte predominance was observed in 3.3% cases. Stage I, II, III and IV were found in 42 (7.6%), 208 (37.7%), 145 (26.3%) e 156 (28.3%) patients, respectively. B symptoms and bulky disease were present in 65.5%and 58.8% patients, respectively. After staging the patients were divided in three groups: group 1 -CS I/II, without B symptoms nor bulky disease= 62 (11.25%) patients, group 2 -CS I/ II, with B symptoms and/or bulky disease=188 (34.12%) patients and group 3- CS III/ IV= 301 (54.62%) patients. IPI high risk score was recognized in 63.9% patients of group 3. Only 1.5% of patients were treated with exclusive radiotherapy. Of the patients that were treated with chemotherapy, 4.9% were treated with MOPP, 23.1% with MOPPABV, 70.5% with ABVD and 1.5% with other types of chemotherapy. The median follow-up of the entire cohort was 59.6 months (0–258.8 months) and 88.3% (CI 95%: 85.2%-91.1%) were in CR at the end of treatment (CS I: 100%, CS II: 90.6% CS III: 84.6% and CS IV: 85.3%; p=0.03) (group 1: 98.2%, group 2: 90.2% and group 3: 84.9%; p=0.012). The 5-year EFS rate was 69.2% (CS I: 84.8%; CS II: 77.8%; CS III: 64.5%, CS IV: 56%; p=0.0008) (group 1: 88%, group 2: 76% and group 3: 60.3%; p=0.0002) (Figures 1 and 2). The 5-year OS rate was 86.44% (CS I: 90.3%, CS II: 94.6%, CS III: 87.6%, CS IV: 71.4%; p<0.0001) (group 1: 98.3%, group 2: 92.6% and group 3: 79, 6%; p=0.0003).Figure 1Figure 1. Figure 2Figure 2. We found that there were more advanced stage patients (stage III/IV) in comparison to developed countries, however, patients classified as stage I/II without poor prognostic factors, like B symptoms and/or bulky disease, showed high rates of CR, EFS and OS. These data suggest that there is a need to enhance early diagnosis in Brazilian patients, in order to detect less advanced stage patients due to late diagnosis. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: Treatment of Hodgkin lymphoma (HL) requires a careful balance between providing enough therapy to cure the disease and avoiding unnecessary treatment that could result in excessive long-term treatment-related complications. The preferred treatment option for limited stage non-bulky HL currently involves the use of combined chemotherapy and involved-field radiation therapy. Given the unclear overall survival advantage and the long-term side effects associated with consolidative radiation, the use of this modality remains one of the most controversial topics in the treatment of HL. Therefore, alternative consolidation approaches are worthy of exploration for treatment of limited stage non-bulky HL. Brentuximab vedotin has been associated with favorable response rates in patients with relapsed or refractory HL. We hypothesize that brentuximab vedotin may be safe and effective in eradicating residual disease after induction chemotherapy and may potentially replace radiation therapy for consolidation in patients with newly diagnosed limited stage non-bulky HL. Methods: In this phase 2 multicenter study, patients with non-bulky (< 7.5 cm) stage I or II HL are being enrolled to determine the efficacy and safety of brentuximab vedotin when administered for consolidation after a standard chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) (ClinicalTrials.gov #NCT01578967). The primary objective of the study is to estimate the proportion of patients who achieve PET-negative disease (Deauville score of 2 or less) after induction chemotherapy followed by consolidation with brentuximab vedotin. Involved-field radiation is recommended only if the PET scan is positive at the completion of therapy with brentuximab vedotin. Patients received 2 to 6 cycles of ABVD based on their baseline risk factors and the interim PET scan result; patients with favorable disease with negative interim PET received 2 cycles, favorable disease with positive interim PET or unfavorable disease with negative interim PET received 4 cycles, and unfavorable disease with positive interim PET received 6 cycles of ABVD. Approximately 6 to 8 weeks after the induction chemotherapy, 1.8 mg/kg of brentuximab vedotin was given every 3 weeks for 6 cycles for consolidation. Results: Interim analysis was performed per protocol for futility and safety after 15 evaluable patients were enrolled since April 2012. Out of 15 evaluable patients, 8 patients have completed 6 cycles of brentuximab vedotin, and the remaining 7 patients are currently under active treatment. The median age was 28 years (range 19 – 58), and 7 patients (47%) presented with unfavorable disease defined by the presence of B symptoms, ESR > 50, or > 3 sites of disease. All patients had masses measuring less than 7.5 cm in diameter except one patient who requested an exception to the eligibility criteria for a conglomerate mediastinal mass measuring 10 cm. No grade 3 or above adverse events have been observed with brentuximab vedotin therapy. No grade 2 or above peripheral neuropathy or pulmonary toxicity has been reported. Ten out of 12 patients, who completed ABVD, achieved PET-negative disease after 2 cycles of ABVD, and all 7 patients who completed brentuximab vedotin achieved PET-negative disease and remain in remission with a median follow-up of 7.6 months (range 5.6 – 15). Thus far, none of the treated patients on this protocol required consolidative radiation therapy. Conclusion: In this interim analysis of 15 patients with newly diagnosed limited stage non-bulky HL, brentuximab vedotin as consolidation therapy demonstrates promising safety and clinical activity following ABVD. Enrollment is currently open with the target accrual of 40 patients to assess the feasibility of achieving PET-negative disease and thereby avoiding radiation therapy in at least 85% of patients who receive ABVD followed by brentuximab vedotin consolidation. Table: PET results in HL patients who received ABVD followed by BV Consolidation Interim-PET2 (n = 12) Post ABVD (n = 12) Post BV (n = 7) Deauville 1 0 1 4 Deauville 2 10 11 3 Deauville 3 2 0 0 Deauville ≥ 4 0 0 0 PET, positron emission tomography; HL, Hodgkin lymphoma; ABVD, doxorubicin, bleomycin, vinblastine, dacarbazine; BV, brentuximab vedotin; Interim-PET-2, PET scan after 2 cycles of ABVD; Post ABVD, PET scan after 2 to 6 cycles of ABVD; Post BV, PET scan after 6 cycles of brentuximab vedotin Disclosures Park: Seattle Genetics: Research Funding; Teva: Research Funding; Janssen: Travel, Travel Other. Off Label Use: Brentuximab vedotin in previously untreated Hodgkin lymphoma patients.

Abstract Consolidative radiotherapy (RT) is often administered following chemotherapy for advanced stage Hodgkin lymphoma (HL) with bulky disease at diagnosis or for residual abnormalities on post-chemotherapy CT imaging. It is unknown whether RT is necessary for such patients if the residual mass is FDG-PET-negative (PET-neg) following chemotherapy (CHT). Further, it has been previously shown that a post-therapy PET-positive (PET-pos) scan is highly predictive of future relapse; however, it is unclear whether consolidative RT can be used to salvage these cases. Methods Since July 2005, adult (&gt; 16 y) patients in British Columbia (BC) with advanced stage HL (stage III /IV and/or the presence B symptoms and/or bulky disease (&gt; 10cm)) have been treated with 6 cycles with ABVD followed by a PET scan for further treatment planning if residual abnormalities ≥2 cm were observed on CT imaging. Prior to this, post-treatment PET scans were obtained in some individuals by self-pay. If the PET scan was positive, RT was administered if feasible, otherwise, patients were observed. There were 68 eligible patients, including 7 self-pay patients, that were identified in the BC Lymphoid Cancer Database. 16 patients were excluded (PET not performed (5); palliative tx or refusal (3); composite lymphoma (1); progressive disease during CHT or at the time of PET scan (4); HIV + (1); PET mid-therapy (1); death due to unrelated cause prior to PET scan (n=1).), leaving a total of 52 patients who had a PET scan post-chemotherapy for a residual mass and who had adequate follow-up (median 19 m, 10–59 m). Patient characteristics include: M:F 1.1:1, Median age 29 (17–81); 55% stage II, 46% stage III/IV 44%; 49% bulky disease; 69% B symptoms; IPFP Prognostic score 0 8%; 1 39%; 2 26%; &gt;3 26%. Results In total, 40/52 (77%) were PET-neg and 12/52 (23%) were PET-pos (SUV mean 4.4, 2.2–6.8). PET-pos patients had an inferior 2 y PFS compared to PET-neg patients (26% vs 91%, p=.001). In the PET-pos group, 10/12 received the planned RT and 5 have relapsed. In the PET-neg group, there was no difference in the 2 y PFS in patients with bulky (n=17) vs non-bulky disease (n=20) (86% vs 94%, p=.35). Conclusions Advanced stage HL patients who achieve a post-CHT PET-neg status are at a low risk of relapse and do not require additional consolidative RT thus avoiding potential long-term side effects. The majority of patients with bulky disease who have a PET-neg scan following CHT also remain in remission, however, longer follow-up is still needed. Although some patients with a positive PET-scan may be salvaged by consolidative RT, a high proportion ultimately relapse. Figure Figure Figure Figure

8077 Background: Interim 18F-FDG-PET (iPET) is the most important prognosticator in advanced-stage ABVD-treated Hodgkin Lymphoma (HL), but in early stage w/ or w/o bulky lesion a low PPV of iPET was reported. Dual-point PET scan (2P-PET) has been used to discriminate unspecific inflammatory from neoplastic FDG uptake. At the Tx end, with a single FDG-avid mass (SFAM), the specificity of PET in Tx response evaluation was sub-optimal. We report here preliminary results from a cohort of HL patients (p) presenting with bulky lesions, scanned with 2P-PET with the aim to increase specificity and PPV. Methods: From 12.2008 till 01.2012 24 HL bulky p from Italian, French and Polish centers underwent 2P-PET at baseline (2P-PET-0), after 2 ABVD (2P-PET-2) and at Tx end (2P-PET-end). 2P-PET scanning technique consisted in 2 consecutive image acquisitions +60’ (EaS) and +120’(LaS) after single, standard-dose FDG injection. Tx was ABVD (x4 or x6) ± consolidation RxT. No Tx change was done based on iPET results. Scans were reviewed by 2 expert readers in a consensus session. Standardized-Uptake Value (SUV)MAX was calculated both in EaS and LaS using Volume of Interest Regions (VOIs) in sites of residual FDG uptake already recorded in PET-0. ΔSUVMAX and FDG retention index (RI) were calculated from SUVs in the same VOIs of both scans. Results: In 24 p (1 stage I,12 II, 4 III, 7 IV), 34 2P-PET were done.10 p underwent 2P-PET-0: in 10/10 SUVMAX increased from EaS to LaS (ΔSUVMAX 1-4.3). 15 p had a 2P-PET-2: 12 with a mean-follow-up of 18.36 months were evaluable, 3 too short ( +1, +5, +6 months). 7/12 p showed a RI reduction of 55% (200-14): all are in continuous CR (CCR). 5/12 p. showed a 20% (11-26) RI increase: all progressed +1 to +9 months after Tx end. Overall 3/12 cases (1 false +, 2 false- with a Deauville score 4 and 2,3 respectively) were correctly classified after 2P-PET. 9 p with a SFAM had a 2P-PET-end: in the 5/9 with an increased RI of 23% (9-43) a biopsy proved HL relapse. In 4/9 a reduced RI of -29% (9-45) was found: in 2 biopsy disclosed presence of residual thymic along with inflammatory tissue and 2 were in CCR +2 to+8 after Tx end. Conclusions: DSUV Max increased at baseline and in all relapsing patients, and decreased in patients in CCR. The PPV and a PNV of 2P-PET were 100%.

Background: Epstein-Barr virus (EBV) is a ubiquitous virus belonging to γ-Herpesvirus subfamily, infecting B cells, T cells, Natural killer (NK) cells & causes both benign and malignant diseases. It has been detected in large subset of Hodgkin lymphoma (HL) cases around the world, especially in countries with poor socioeconomic conditions and among younger age. Limited studies are available reflecting the Indian scenario of HL and EBV association. EBV positivity in Indian HL varies from 28-97% Majority of these studies employed Immunohistochemistry (IHC) for LMP1, a few performed In Situ Hybridisation (ISH) for EBER. Objective: To study the association of EBV in classical HL by immunohistochemical expression of latent membrane protein 1 (LMP1) antigen in North Indian population and to correlate it with different demographic variables & subtypes of HL. Materials and Methods: Observational study including 26 untreated HL cases diagnosed on lymph node excision biopsy. IHC was performed for EBV LMP1, CD15, CD30, CD45, CD3, CD20. Results: Patients ranged in age from 5-55years (median 18yrs), with M:F ratio of 3.3:1. Palpable lymphadenopathy was found in all cases followed by pallor (64%), B symptoms (50%), nodal pain (30.8%) & bulky disease (19.2%). Maximum number of patients were in Stage I (65.4%) followed by stage II&III (15.4% each) & stage IV (3.8%). Mixed cellularity HL comprised 77%, lymphocyte depleted 11.5%, nodular sclerosis 7.7% & lymphocyte rich 3.8%. IHC for EBV LMP1 was positive in 73.1% cases. Mixed cellularity HL showed an association in 70% cases. Conclusions: HL in India is a disease of young males, with mixed cellularity as the commonest subtype, highly associated with EBV and presentation at an early stage.

Práce se zabývá zarovnáváním excitabilních buněk na multielektrodových polích. Nejprve bylo analyzováno zarovnávání excitabilních buněk. Byly použity embryonální neurony z hippocampusu potkanů a HL-1 buňky, které jsou odvozeny z AT-1 linie nádorových myších atriálních kardiomyocytů. Zarovnávání bylo testováno na drážkovaných površích a na površích s materiály s různou buněčnou afinitou. Bylo prokázáno, že na drážkových površích se ve směru drážek zarovnávají neurony i HL-1 buňky, ale na površích s různou chemickou affinitou se zarovnávají pouze neurony. Dále byly vyrobeny vlastní multielektrodová pole, na těchto multielektrodových polích byly kultivovány HL-1 buňky a byl změřen a analyzován akčních potenciál HL-1 buněk. Cílem bylo prokázat, že je možné měřit akční potenciál na vyrobených multielektrodových polích. Pro zarovnání buněk na multielektrodovém poli bylo vyrobeno speciální multieletrodové pole s uniformním povrchem. Toto multielektrodové pole je nazýváno planární multielektrodové pole. Planární multielektrodové pole bylo vyrobeno speciálním vyrobním procesem. Vrstvy planárního multielektrodového pole byly deponovány na pomocný substrát v opačném pořadí. Pomocný substrátem pro depozici byla křemíková deska, na který byla nadeponována další pomocná vrstva zlata. Horní izolační vrstva planárního multielektrodové pole byla deponována jako první a nejspodnější vrstva substrátu byla nadeponována jako poslední. Planární multielektrodové pole i s pomocnou zlatou vrstvou bylo strhnuto s křemíku díky nízké adhezi zlata ke křemíku a planární multielektrodové pole se otočilo vzhůru nohama. Pomocná zlatá vrstva byla odstraněna mokrým leptadlem a tím bylo planární multielektrodové pole dokončeno. Na planárním multielektrodovém poli byly zarovnány HL-1 buňky do pruhů chemickou metodou pomocí kombinace otisku adhezní látky a následným potažení neotisklých ploch anti-adhezní látkou. Elektrofyziologické vlastnosti zarovnaných HL-1 buněk byly změřeny pomocí planárního multielektrodového pole. Tímto experimentem byla představena výrobní technologie pro výrobu planárních multielektrodových polí a toto planární multielektrodové pole bylo úspěšně testováno pro zarovnání HL-1 buněk na jeho povrchu kombinací otisku adhezní látky a potahování antiadhezivním činidlem.

It has been reported that opioid receptor activation mimics ischemic preconditioning, which may protect the heart from the development of infarction. Toll-like receptor 4 (TLR-4) during infarction stimulates cytokine production leading to inflammation and injury of the heart tissue. Our aim was to study the effect of morphine in vitro on the viability and oxidative state of H9c2 cells (rat cardiomyoblasts) and the role of TLR-4 during oxidative stress. Our experiments showed that pretreatment with morphine before tert-butylhydroperoxide (t-BHP)-, 2,2'-bipyridyl (BP)- and lipopolysaccharide (LPS)-induced oxidative stess had protective effect on the viability of H9c2 cells and markedly reduced the production of reactive oxygen species (ROS). The protective effect of morphine was diminished after naloxone treatment, which confirms the role of opioid receptors in preconditioning. TLR-4 inhibition by TAK-242 pretreatment and silencing TLR-4 by RNA interference resulted in a partial increase in cell viability but significant attenuation of ROS production after t-BHP and BP treatment. The action of LPS was reduced in response to TLR-4 silencing. Interestingly, naloxone pretreatment and suppression of TLR-4 markedly alleviated oxidative stress and resulted in a significant improvement of cell viability. We...