Clinical value of ALK and CD30 expression in mature systemic T cell lymphomas: analysis from the Czech Lymphoma Study Group database (NIHIL).

Mature T cell lymphomas (MTCLs) have worse prognosis, and in contrast to B cell lymphomas, there is no universal marker like CD20 with exception of ALK and CD30, which are present in proportion of MTCL only. Up to now, ALK is traditionally associated with good prognosis in ALCLs, and there are some evidences that CD30-positive T cell or B cell lymphomas have better prognosis. In our retrospective, population-based analysis, we analyzed the real clinical value of ALK and CD30 in the most frequent MTCL subtypes. Between 2000 and 2017, we identified 732 patients with newly diagnosed ALCL, AITL, or PTCL-NOS. Among them, 207 ALCL patients were with known ALK, whereas 61 AITL and 238 PTCL-NOS with known CD30 expression. There were 69/207 (33.3%) ALK + ALCLs, who displayed better 5-year PFS (65.6% vs. 36.2%) (p .001) and 5-year OS (71.5% vs. 45.9%) (p .002) compared to ALK - ; ALK + patients were significantly younger (median 48 vs. 60 years; p < 0.001). For patients ≥ 60 years, 5-year PFS (38.5% vs. 31.2%) and 5-year OS (38.5% vs. 39.6%) were similar between ALK + vs. ALK - patients. For AITL and PTCL-NOS, there were 44/61 (72.1%) and 120/238 (50.4%) CD30 + samples, and difference in CD30 expression was significant (p .02). AITL patients had 5-year OS of 43.8% vs. 55.7% (p 0.848) and 5-year PFS of 36.7% vs. 29.4% (p .624) for CD30 + vs. CD30 - patients, whereas PTCL-NOS had 5-year OS of 35.7% vs. 34.3% (p .318) and 5-year PFS of 29.3% vs. 22.5% (p.114) for CD30 + vs. CD30 - cases. We conclude that ALK in ALCLs (≥ 60 years) and CD30 expression in PCTL-NOS and AITL have only limited prognostic value.

Advanced stages of classical Hodgkin lymphoma - first-line treatment options.

BACKGROUND: Advanced stages of classical Hodgkin lymphoma can be cured by the first-line treatment in 80% of patients. Conventional treatment options include ABVD chemotherapy (doxorubicin bleomycin, vinblastine, dacarbazine) or escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) are commonly used in advanced stages. The result of interim positron emission tomography allows adjustment of the treatment intensity during chemotherapy and this approach can affect the treatment results and toxicity. PURPOSE: This review summarizes current options of conventional chemotherapy and implementation of brentuximab vedotin and PD-1 inhibitors in combination with chemotherapy into the first-line treatment.

Outcome of elderly patients with classical Hodgkin's lymphoma.

INTRODUCTION: The optimal management of elderly patients (pts) with Hodgkin's lymphoma is not yet defined. The aims of the present study were: 1) to evaluate clinical and laboratory characteristics of elderly pts; 2) to indentify risk factors for unfavorable outcome. PATIENTS AND METHODS: The outcome of 182 pts ≥ 60 years (y) was retrospectively analyzed (median age, 67y). Mixed cellularity histology was diagnosed in 49.5 %, advanced stage of disease was in 68.7 % pts, CIRS > 3 in 35.7 %, ECOG PS ≥ 2 in 22.9 % (60-69y) of pts. Chemotherapy (CMT) alone was used in 69.2 % and combination of CMT and radiotherapy in 26.9 % of pts. Anthracycline-based CMT received 83.5 % of pts. The median follow-up was 4.5y. RESULTS: The overall response/complete remission rate was 85.6/70.7 %. The median progression free survival (PFS) and overall survival (OS) were 10y and 11.3y, respectively. Estimated 5-y PFS and 5-y OS were 65.7 % (in contrast to 98.2 % in pts < 60y; p < 0.001) and 70.5 % (99.4 % in pts < 60y; p < 0.001). Overall 70 (38.5 %) elderly pts died. The independent risk factors for a shorter OS included CIRS > 3, lymphopenia < 8 % and anthracycline-free CMT, for a shorter PFS anthracycline-free CMT and lymphopenia < 8 %. CONCLUSION: CIRS > 3, lymphopenia < 8 % and anthracycline-free chemotherapy appear to be significant for unfavorable outcome.

[The Importance of MicroRNA Deregulation in the Molecular Pathogenesis and Histological Transformation of Follicular Lymphoma]. / Význam deregulace mikroRNA v molekulární patogenezi a histologické transformaci folikulárního lymfomu.

BACKGROUND: Molecular pathogenesis of follicular lymphoma (FL) is characterized by substantial dysregulation of epigenetic regulators. Many cases of FL are associated with the aberrant expression of non-coding regulatory RNAs, namely microRNAs (miRNA). Here we studied changes in miRNA expression and their association with histological transformation of FL to diffuse large B-cell lymphoma (DLBCL). MATERIAL AND METHODS: To identify changes in miRNA levels during FL transformation we performed a global expression analysis of 377 miRNAs in 16 samples (8 pairs) from FL patients vs. transformed FL (tFL) (TLDA miRNA cards; Thermo Fisher Scientific). The association of miRNA expression with clinical-biological characteristics and target proteins were further analyzed in a cohort of 89 FL patients. RESULTS: The miRNA expression profiling of paired FL-tFL samples revealed statistically significant changes in the expression of five miRNAs (p < 0.05). Four of them were down-regulated and one was up-regulated in tFL compared to FL. Lower levels of one of these miRNA were also associated with higher proliferation rate of FL cells (Ki-67 > 20%), higher FLIPI score ( 3) and shorter overall survival of FL patients. Furthermore, we found that this miRNA regulates the levels of FOXP1 protein in FL. The patients with high-level FOXP1 expression (> 70% positive cells) had significantly shorter overall survival in comparison to those with low-level FOXP1 expression (< 30% positive cells). Moreover, FOXP1 protein levels were higher in most tFL samples compared to FL before transformation. CONCLUSION: We found miRNAs associated with the transformation of FL to a more aggressive DLBCL, and described that one of them could serve as a prognostic marker. We found that reduced expression of this tFL-associated miRNA results in increased levels of FOXP1 protein and we assume that the increased activity of FOXP1 proto-oncogene contributes to the histological transformation of FL.Key words: follicular lymphoma - microRNA - histological transformation This work was supported by Czech Ministry of Health registration No. 16-29622A. All rights reserved. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 5. 3. 2017Accepted: 26. 3. 2017.

[Chemotherapy-related Cognitive Impairment in Patients with Hodgkin Lymphoma - Pathophysiology and Risk Factors]. / Poskození kognitivních funkcí po chemoterapii u pacientu s Hodgkinovým lymfomem - patofyziologie a rizikové faktory.

BACKGROUND: Cognitive impairment (impairment of memory, attention, or concentration) is documented in 17-75% of patients with various malignancies treated with chemotherapeutic agents that worsen quality of life. CRCI affects patients of all ages. The impairment of cognitive function in connection with chemotherapy is usually mild, but an event. relationship with dementia remains to be confirmed. Chemotherapy in combination with radiotherapy in Hodgkin lymphoma can cure 80-90% of patients. AIM: This review summarizes the most frequently observed changes in cognitive function in patients suffering from CRCI. The article further describes the possible pathophysiological mechanisms behind these changes and the risk factors that can increase the likelihood of cognitive functional impairment after chemotherapy of malignant tumors. Special attention is given to how this relates to Hodgkins lymphoma. We also discuss the neuroprotective factors involved in chemotherapy-related cognitive impairment and its treatment options. CONCLUSION: Changes occur mainly in the ability to learn and remember, in the speed of reactions, and in attention and executive functions. Although CRCI pathophysiological mechanisms are complex and not yet fully understood, the involvement of neurotoxicity, such as that induced by treatment, anemia, higher levels of oxidative stress and inflammatory responses, genetic factors, and reduced brain connectivity is discussed. CRCI is further modified by comorbidities and patient age. Pharmacological and nonpharmacological treatment options for CRCI are outlined.Key words: Hodgkin lymphoma - chemotherapy - cognitive impairment - risk factors The project was supported by the grant of the Agency for the Czech Republic Health Research of the Ministry of Health of the Czech Republic 16-29857A and by the project Sustainability for the National Institute of Mental Health No. LO1611 with a financial support of the Ministry of Education, Youth and Sports of the Czech Republic in the frame of the National Sustainability Programme I. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 29. 9. 2016Accepted: 12. 2. 2017.

[Treatment of Relapsed and Refractory Hodgkin Lymphoma - Recommendations of the Czech Hodgkin Lymphoma Study Group]. / Lécba relabovaného a refrakterního Hodgkinova lymfomu - doporucení ceské studijní skupiny Hodgkinuv lymfom.

High-dose chemotherapy with autologous stem cell transplantation remains the current standard of treatment for young patients with Hodgkin lymphoma in first relapse or in those who are refractory to first-line treatment. The most important prognostic factors in relapses are clinical stage IV, poor performance status, bulky mass, and less than partial remission after salvage chemotherapy. Standard salvage chemotherapy in relapse before autologous transplantation has not been defined; however, DHAP and ICE are most frequently used in this setting. A standard conditioning regimen before autologous transplantation is BEAM. Tandem autologous transplantation has been investigated in high-risk patients. Brentuximab vedotin is recommended as a consolidation treatment in patients with a high risk of relapse after autologous transplantation. Brentuximab vedotin is the standard of treatment for relapse after autologous transplantation, and subsequent allogeneic stem cell transplantation should be considered in young patients. Bretuximab vedotin in combination with bendamustine, nivolumab, and pembrolizumab, and combinations thereof with other drugs, were investigated in clinical trials in relapsed or refractory patients with Hodgkin lymphoma.Key words: Hodgkin lymphoma - autologous stem cell transplantation - brentuximab vedotin - nivolumabThis work was supported by grant awarded by AZV 16-29857, Ministry of Health in Czech Republic, Research project P 27/2012 awarded by Charles University in Prague, 3rd Faculty of Medicine, Prague.The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 7. 6. 2016Accepted: 24. 8. 2016.

[Staging and Treatment Response Evaluation in Malignant Lymphomas - Czech Lymphoma Study Group Recommendations According to Criteria Revised in 2014 (Lugano Classification)]. / Hodnocení klinického stadia a lécebné odpovedi u maligních lymfomu - doporucení Kooperativní lymfomové skupiny na základe revidovaných kritérií z roku 2014 (Luganská klasifikace).

BACKGROUND: Recent advances in the use of the imaging modalities, especially PET/CT, and their utilization for determining clinical stage (CS) and assessment treatment response (TR) in malignant lymphomas, along with development of prognostic tools and new treatment modalities, formed the basis for the revised criteria for evaluating CS and TR (published as the Lugano classification, 2014). MATERIALS AND METHODS: The authors summarize the new Lugano recommendations (published in 2014) and the changes from the criteria published in 2007. Moreover, discussion of the changes places emphasis on practical use. The practicality of the Lugano classification, 2014 was the subject of consensus meeting at the annual meeting of the Cooperative Lymphoma Study Group (CLSG) in March 2015. This study reports the final consensus. The CLSG recommends use of the Lugano classification, 2014, but recommends some modifications. CONCLUSIONS: Standardization of the criteria used to determine CS and TR in malignant lymphomas has led to improvements in initial staging and assessment of TR. The criteria are helpful for unifying response assessment in clinical trials and simplify the work of regulatory agencies (e.g., the EMA and the Czech State Institute for Drug Control) when registering new drugs. It also allows evaluation of treatment outcomes outside clinical trials, for example within the CLSG prospective registry of patients with newly diagnosed lymphoma. KEY WORDS: malignant lymphoma - computed tomography - positron emission tomography - staging - treatment responseThis work was supported by the grant Prvouk P27/2012 of the Third Faculty of Medicine, Charles University in Prague and by the grant of the Czech Lymphoma Study Group No. NT12193-5/2011.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 24. 1. 2016Accepted: 16. 2. 2016.

[Treatment and prognosis of relapsed or refractory Hodgkin lymphoma patients ineligible for stem cell transplantation]. / Lécba a prognóza pacientu s relabovaným nebo refrakterním Hodgkinovým lymfomem nevhodných k transplantaci kmenových bunek.

BACKGROUND: Relapses occur in 20-30% of patients with Hodgkin lymphoma (HL). Currently, there is no widely accepted standard treatment strategy in relapsed/refractory HL patients ineligible for autologous stem cell transplantation (ASCT). This article retrospectively evaluates survival and prognosis of patients with relapsed/refractory HL who were not suitable for high-dose chemotherapy and ASCT. New drugs and their efficacy in this indication are also disscussed. PATIENTS AND METHODS: A total of 17 patients treated with at least three lines of standard chemotherapy ± radiotherapy were analysed. High-dose chemotherapy and ASCT was not indicated due to advanced age (seven patients), chemorefractory disease (seven patients), cardiotoxicity (two patients) and insufficient stem cell collection of CD34+ cells (one patient). RESULTS: Median follow-up of the whole group after establishing the diagnosis was 3.48 years. Overall response to the second-line treatment was achieved in eight patients (47.0%). Four patients (23,5%) were classified as primary refractory after the first-line treatment and three more chemorefractory patients (17,6%) were detected after the second-line treatment. Out of 17 patients four are still alive (23,5%) in remission and 13 have died (eight due to HL progressions, four due to toxicity of the treatment and one patient with unknown cause of death). The estimated 5-year overall survival from the time of initial diagnosis was 46.3% and 30.8% when counted from the diagnosis of the first relapse. The estimated 5-year overall survival of four primary chemorefractory patients was significantly worse when compared to the group of 13 relapsed patients: 0 vs. 60.6%, p < 0,001. CONCLUSION: Prognosis of relapsed/refractory HL patients ineligible for ASCT and treated with several lines of standard chemotherapy ± radiotherapy is poor. Brentuximab vedotin is indicated in primary refractory patients in the second-line settings and in other relapsed patients in the third-line treatment. This strategy would help to increase the number of remissions, hence achieving a higher survival rate.

[The role of radiotherapy in the treatment of malignant lymphomas - recommendations of the Czech Lymphoma Study Group]. / Postavení radioterapie v lécbe maligních lymfomu - doporucení Kooperativní lymfomové skupiny.

BACKGROUND: Indication of radiotherapy in lymphoma treatment is an important strategic decision requiring comprehensive expertise. It also calls for a better definition of the position of radiotherapy in clinical practice. DESIGN: This position paper represents a consensus between hematooncologists and radiation oncologists on the role of RT in treatment of different histological types and stages of malignant lymphomas. The discussion was underway within professional societies of both specializations (Czech Lymphoma Study Group for the hematooncologists and the Society of Radiation Oncology, Biology and Physics for the radiation oncologists). RESULTS: The consensus presented here was reached in early 2012 and draws on evidence-based medicine and clinical practice. Besides defining the role of radiotherapy in lymphoma treatment, this paper also gives specific recommendations on total doses of radiotherapy in lymphoma treatment. CONCLUSION: These recommendations will supplement 7th edition of "Diagnostic and treatment guidelines in patients with malignant lymphoma" scheduled for publication in 2013.

Central nervous system involvement in mantle cell lymphoma: clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network.

BACKGROUND: Central nervous system (CNS) involvement in mantle cell lymphoma (MCL) is uncommon, and the manifestations and natural history are not well described. PATIENTS AND METHODS: We present the data on 57 patients with MCL who developed CNS involvement, from a database of 1396 consecutively treated patients at 14 institutions. RESULTS: The crude incidence of CNS involvement was 4.1%, with 0.9% having CNS involvement at diagnosis. Blastoid histology, B-symptoms, elevated lactate dehydrogenase, Eastern Cooperative Group performance status ≥2 and a high Mantle Cell Lymphoma International Prognostic Index score were enriched in the cohort with CNS involvement, and the presence of ≥1 of these features defined a high-risk subset (an actuarial risk of CNS involvement 15% at 5 years) in a single-institution subset. The median time to CNS relapse was 15.2 months, and the median survival from time of CNS diagnosis was 3.7 months. The white blood cell count at diagnosis <10.9 × 109/l, treatment of CNS involvement with high-dose anti-metabolites, consolidation with stem cell transplant and achievement of complete response were all associated with improved survival. CONCLUSIONS: In MCL, CNS involvement is uncommon, although some features may predict risk. Once manifest outlook is poor; however, some patients who receive intensive therapy survive longer than 12 months.

Alterations of CHEK2 forkhead-associated domain increase the risk of Hodgkin lymphoma.

Checkpoint kinase 2 gene (CHEK2) codes for an important mediator of DNA damage response pathway. Mutations in the CHEK2 gene increase the risk of several cancer types, however, their role in Hodgkin lymphoma (HL) has not been studied so far. The most frequent CHEK2 alterations (including c.470T>C; p.I157T) cluster into the forkhead-associated (FHA) domain-coding region of the CHEK2 gene. We performed mutation analysis of the CHEK2 gene segment coding for FHA domain using denaturing high-performance liquid chromatography in 298 HL patients and analyzed the impact of characterized CHEK2 gene variants on the risk of HL development and progression-free survival (PFS). The overall frequency of CHEK2 alterations was significantly higher in HL patients (17/298; 5.7%) compared to the previously analyzed non-cancer controls (19/683; 2.8%; p= 0.04). Presence of any alteration within the analyzed region of the CHEK2 gene was associated with increased risk of HL development (OR = 2.11; 95% CI = 1.08 - 4.13; p= 0.04). The most frequent I157T mutation was found in 4.0% of HL patients and 2.5% of controls (p = 0.22), however, the frequency of 5 other alterations (excluding I157T) was significantly higher in HL cases and associated with increased risk of HL development (OR = 5.81; 95% CI = 1.12 - 30.12; p= 0.03). PFS in HL patients did not differ between CHEK2 mutation carriers and non-carriers. The predominant I157T mutation together with other alterations in its proximity represent moderate genetic predisposition factor increasing the risk of HL development.

[Treatment of patients with relapsed/refractory Hodgkin lymphoma]. / Lécba pacientu s relabovaným/refraktérním Hodgkinovým lymfomem.

BACKGROUNDS: This retrospective study evaluated treatment outcomes in patients undergoing autologous stem cell transplantation (ASCT) for relapsed/refractory Hodgkin lymphoma (HL). PATIENTS AND METHODS: Overall, 194 HL patients treated with ASCT between 2000 and 2009 were analyzed. Survival was calculated using Kaplan-Meier method and differences in survival between subgroups with log-rank test. RESULTS: Best responses observed after ASCT: 124 complete and 35 partial remissions, 2 patients with stable disease and 33 relapses/progressions. During a median follow-up of 44 months, seventy patients after ASCT progressed/relapsed. Thirty-seven patients received salvage chemotherapy only with or without radiotherapy, 25 underwent allogeneic stem cell transplantation (SCT), 4 the second ASCT and 4 refused treatment. 5-year overall survival after ASCT was 71% and progression-free survival 54%. Median survival of the 70 patients relapsing after ASCT was 16.9 months. Median survival in patients after allogeneic SCT was 31.8 months and 12.4 months in patients treated with other modalities (p = 0.21). Overall mortality was 26.3% (51/194 patients): 13.4% progressions/relapses of HL and 12.9% non-relapse mortality. CONCLUSION: Efficacy of ASCT was confirmed in 54% progression-free survivors. Median survival after ASCT failure is relatively short. There is a slightly longer overall survival after allogeneic SCT, although not statistically significant when compared to other approaches.

[Staging of non-Hodgkin's lymphoma--recommendations of the Czech Lymphoma Study Group]. / Urcování rozsahu onemocnení u non-Hodgkinových lymfomu--doporucení Kooperativní lymfomové skupiny.

BACKGROUNDS: The Ann Arbor system is typically used for the staging of Non-Hodgkin's lymphomas. This classification was nevertheless originally developed in the 1970s for Hodgkin's lymphoma, a disease usually confined to the lymph nodes with less frequent dissemination to extralymphatic organs/tissues and extremely rare primary extranodal involvement. Non-Hodgkin's lymphomas, however, are more often associated with extralymphatic involvement and primary extranodal lymphomas are relatively common (approximately 1/3 of cases). Therefore, the value of the Ann Arbor staging system appears to be limited in these cases. An analysis of data from centres participating within the Czech Lymphoma Study Group showed that staging of Non-Hodgkin's lymphomas with extranodal involvement is not uniform. DESIGN: At the end of 2009, a draft for a Non-Hodgkin's lymphomas staging system was put forward for use by the lymphoma register of the Czech Lymphoma Study Group with special regard paid to the involvement of extralymphatic organs/tissues. This draft was further refined following comments from members of the Czech Lymphoma Study Group committee and the final form was accepted at the meeting of the Czech Lymphoma Study Group committee in January 2010. RESULTS: A consensus was reached at the meeting of the Czech Lymphoma Study Group committee regarding the staging of various combinations of nodal and extranodal involvement. For the purpose of suitable staging and appropriate treatment intensity, extranodal organs were divided into "major"--liver, lungs, bones, mesothelium (pleura, peritoneum, pericardium) and soft tissues. All other organs were defined as "minor". CONCLUSION: The Ann Arbor staging system is suitable for the staging of Non-Hodgkin's lymphomas with lymph node/lymphatic tissue involvement. As regards the extralymphatic spread of the disease or primary extranodal lymphomas, this classification should rather be adapted to practical needs. The validity of the updated classification system will be assessed in both prospective and retrospective Czech Lymphoma Study Group studies.

Prognostic significance of absolute lymphocyte count and lymphocyte subsets in lymphomas.

Lymphocytopenia is a poor prognostic marker in initial staging of non- Hodgkin lymphomas (below 1.0 x 10(9)/l) and Hodgkin lymphoma (below 0.6 x 10(9)/l) and in relapsed diffuse large B cell lymphoma. Early lymphocyte recovery > or =0.5 x 10(9)/l after autologous and allogeneic stem cell transplantation is a significant predictor of tumor control and survival in lymphomas. Natural killer cells are involved in tumor cell killing and are the only subset of lymphocytes associated with disease outcome in initial staging and after autologous stem cell transplantation in lymphomas. The antitumor effect of various NK cell subsets should be defined.

Positron emission tomography at the end of first-line therapy and during follow-up in patients with Hodgkin lymphoma: a retrospective study.

BACKGROUND: Routine positron emission tomography (PET) in follow-up of Hodgkin lymphoma (HL) after treatment is still controversial. The aim of this retrospective study was to analyze the clinical impact of routine PET examination during the follow-up for relapse detection in PET-negative HL patients at the end of therapy. PATIENTS AND METHODS: PET scans were carried out in 113 HL patients at the end of therapy and during the follow-up either in regular intervals or in a suspected relapse. Median follow-up of the group was 34 months. RESULTS: Overall 327 PET scans were evaluated in 113 patients (median three PET scans per patient). At the end of therapy, 94 (83.2%) patients were PET negative and 19 (16.8%) PET positive. Regular follow-up PET scans in 67 of 94 PET-negative patients correctly identified tumor in 6 of 155 PET scans (3.9%). In 27 of 94 patients with clinically suspected relapse, 5 of 27 PET scans (18.5%) confirmed tumor. CONCLUSIONS: Our analysis showed that there is no need for regular follow-up with PET scans in PET-negative patients at the end of therapy: the ratio of true-positive PET scans during the follow-up is low (3.9%). Positive PET at the end of therapy and during follow-up should be evaluated with caution.

[Serious cutaneous toxicity following ifosfamide, gemcitabine and vinorelbine therapy in a patient with relapsed Hodgkin lymphoma and ichthyosis]. / Závazná kozní toxicita po lécbe ifosfamidem, gemcitabinem a vinorelbinem u pacienta s relapsem Hodgkinova lymfomu a ichtyózou.

Nodular sclerosis classical Hodgkin lymphoma, clinical stage IIB with cervical and axillar lymph node involvement was histologically proven in a 47-year-old male patient with a long-lasting history of ichthyosis. Skin histology revealed only nonspecific lichenoid inflammatory changes. Patient was treated with six cycles of combined chemotherapy: doxorubicin, bleomycin, vinblastine and dacarbazine. 15 months after initial treatment the first relapse of Hodgkin lymphoma was histologically confirmed and involvement of lymph nodes was identical with initial staging. Patient was successfully treated with six cycles of chemotherapy: ifosfamide, carboplatinum and etoposide followed by radiotherapy. The above mentioned chemotherapies did not cause serious cutaneous toxicity. 4 years after previous therapy the second relapse of Hodgkin lymphoma occurred with axillar and inguinal lymph node involvement. Skin histology confirmed nonspecific lichenoid inflammatory changes. Patient was treated with three cycles of combined chemotherapy: ifosfamide, gemcitabine, vinorelbine and prednisone. This chemotherapy caused neutropenia WHO grade 4 after each cycle and a serious diffuse toxoallergic cutaneous reaction with bullous erythema developed. Several skin lesions fulfilled criteria for cutaneous WHO grade 3 and 4 toxicity. We assumed that combined toxic effect of gemcitabine and vinorelbine resulted in serious cutaneous toxicity under pre-existing condition of diffuse ichthyosis. The cutaneous toxicity subsequently resolved and residual lymph nodes were irradiated.

The biological environment of Hodgkin's lymphoma and the role of the chemokine CCL17/TARC.

Hodgkin's lymphoma is a lymphoproliferative disease, which differs in its morphology and therapeutic response from other lymphomas. Neoplastic cells represent only a minor cell population of the tumour, while the major part of the tumour is formed by inflammatory cells. It results from the production of cytokines and chemokines both by neoplastic cells and by inflammatory cells. An important prognostic marker in Hodgkin's lymphoma appears to be the chemokine (C-C motif) ligand 17 (CCL17), also known as thymus and activation-related chemokine (TARC). This chemokine is expressed by many cell types and tissues, and in the case of Hodgkin lymphoma, also by Reed-Sternberg cells. CCL17/TARC binds to chemokine receptors CCR4 and CCR8 and displays chemotactic activity for T lymphocytes and some other leukocytes. The understanding of biological pathways in Hodgkin's lymphoma could be important for monitoring of disease activity and for the development of future targeted therapy.

Prognostic impact of bone involvement in Hodgkin lymphoma.

The purpose of the study is to determine incidence and prognostic impact of osseous Hodgkin lymphoma (HL). Between 1997 and 2004, 198 patients with HL were treated at our institution. Advanced stages and nodular sclerosis histology prevailed. All patients were treated according to protocols of the German Hodgkin Study Group (GHSG). After minimum follow-up of 24 months, we retrospectively analyzed the incidence of osseous HL, treatment response and parameters of survival. We recorded 14 cases of osseous HL (7 %), always with concurrent nodal disease. Axial skeleton was most frequently involved. Eleven patients (78,5 %) achieved complete remission and three (21,5 %) progressed primarily. The patients with osseous HL had significantly lower 2-year freedom from treatment failure than the patients without bone involvement (71,4 and 92,7 %, respectively, p=0,004), with no significant difference in 2-year overall survival (85,7 and 95 %, respectively, p=0,14). On multivariate analysis, advanced stage was the only independent adverse prognostic factor. In conclusion, bone involvement is a relatively common finding in HL and is not an independent adverse prognostic factor.

Inhalation trauma in burns, cytology and biochemical findings.

We have followed in a pilot study a group of patients for cytological and biochemical changes of lavage in the upper and lower respiratory system. Into the study patients with respiratory burns confirmed by bronchoscopy and skiagraphy were included. We divided patients according to the Lung Injury Scores (LIS). We obtained the values in our sample group between intubation and last swab (before extubation). Listed are the risk factors, probability of survival, and lung histology results are listed for patients who died.

[Comparison between conventional imaging methods and positron emission tomography in the treatment of Hodgkin's lymphoma]. / Srovnání konvencních zobrazovacích metod a pozitronové emisní tomografie v lécbe Hodgkinova lymfomu.

BACKGROUND: Positron emission tomography with fluorodeoxyglucose offers the possibility to differentiate between lymphoma and nonmalignant tissue. The aim of this retrospective study was a comparison between PET and conventional imaging methods before and after therapy--during the follow-up of Hodgkin's lymphoma. METHODS AND RESULTS: The group of 94 patients with HL underwent 180 PET examinations. PET was performed in 53 patients during initial staging of lymphoma. 119 PET studies were undertaken after therapy during the follow-up. Eight patients underwent PET examination for suspected relapse or progression of HL. Findings were verified by a follow-up in all patients and by histology in selected cases. PET and conventional imaging methods were positive in 42 of 53 (79%) patients in initial stages. The stage of the disease was changed in 7 patients (13.2%) according to PET. False negative findings were recorded in three cases and false positive in one case. Sensitivity of PET was higher compared to conventional imaging methods (92% vs 87%) in initial staging. PET and conventional imaging methods were identical in 94.9% of cases during the follow-up (77.3% negative and 17.6% positive findings). Sensitivity of PET during the follow-up after therapy was higher compared to conventional imaging methods (99.1% vs 95.7%). PET was positive in all eight cases in relapse/progression of HL and conventional imaging methods were positive in only seven of eight cases. CONCLUSIONS: PET is a more sensitive method in initial staging, during follow-up and in suspected progression/relapse of HL than conventional imaging methods and it should be included into routine examination methods of HL.