Sequencing-based analysis of clonal evolution of 25 mantle cell lymphoma patients at diagnosis and after failure of standard immunochemotherapy.

Our knowledge of genetic aberrations, that is, variants and copy number variations (CNVs), associated with mantle cell lymphoma (MCL) relapse remains limited. A cohort of 25 patients with MCL at diagnosis and the first relapse after the failure of standard immunochemotherapy was analyzed using whole-exome sequencing. The most frequent variants at diagnosis and at relapse comprised six genes: TP53, ATM, KMT2D, CCND1, SP140, and LRP1B. The most frequent CNVs at diagnosis and at relapse included TP53 and CDKN2A/B deletions, and PIK3CA amplifications. The mean count of mutations per patient significantly increased at relapse (n = 34) compared to diagnosis (n = 27). The most frequent newly detected variants at relapse, LRP1B gene mutations, correlated with a higher mutational burden. Variant allele frequencies of TP53 variants increased from 0.35 to 0.76 at relapse. The frequency and length of predicted CNVs significantly increased at relapse with CDKN2A/B deletions being the most frequent. Our data suggest, that the resistant MCL clones detected at relapse were already present at diagnosis and were selected by therapy. We observed enrichment of genetic aberrations of DNA damage response pathway (TP53 and CDKN2A/B), and a significant increase in MCL heterogeneity. We identified LRP1B inactivation as a new potential driver of MCL relapse.

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.

[Further development of regional early care-Many roads lead to Rome : Developmental stages of four established rheumatological early care concepts in different regions of Germany]. / Regionale Frühversorgung weiterentwickeln ­ Viele Wege führen nach Rom : Entwicklungsetappen von 4 etablierten rheumatologischen Frühversorgungskonzepten in verschiedenen Regionen Deutschlands.

In order to shorten the prognostically relevant waiting time until diagnosis and initiation of appropriate treatment in inflammatory rheumatic diseases, rheumatological centers in many regions across Germany have established and continuously developed specific early care concepts. Evaluated models from Altötting·Burghausen, Berlin Buch, Düsseldorf and Heidelberg and their developmental stages as a response to internal and external challenges are presented in this overview. The transparent publication of the developmental steps and the exchange of experiences aim at promoting new early care concepts in other regions and continuing the joint dialogue for improvement of the early detection and quality of care of inflammatory rheumatic diseases in Germany.

[Clinical management of rheumatic immune-related adverse events : Recognize and treat rheumatological side effects of checkpoint inhibition]. / Diagnostik und Management rheumatischer "immune-related adverse events" : Rheumatologische Nebenwirkungen der Checkpoint-Inhibition erkennen und behandeln.

Immune checkpoint inhibitors (ICPi) represent a major breakthrough in the treatment and prognosis of many cancers, particularly of malignant melanoma and non-small cell lung cancer; however, the high tumor response rates with ICPi are also frequently associated with autoimmune side effects, so-called immune-related adverse events (irAEs), which can involve virtually any organ system and mirror classical autoimmune diseases. Recent studies revealed that around 5-20% of patients treated with ICPi experience rheumatic irAEs covering the full spectrum of inflammatory rheumatic diseases. This article summarizes the state of the art of knowledge with respect to diagnostics and management of this newly recognized disease entity in rheumatology.

The role of the NOD2/CARD15 gene in surgical treatment prediction in patients with Crohn's disease.

PURPOSE: Crohn's disease (CD) belongs to chronic disorders with unpredictable disease course. The aim of this study was to identify how genetic testing (NOD2/CARD15) can be used in patients with CD to predict the need for surgical treatment (to define an aggressive type of disease where the patient can profit from early surgery). METHODS: The patients who were tested genetically had undergone a surgery due to CD at the Department of Surgery University Hospital Brno Bohunice between 2010 and 2016. The control group consisted of patients with CD who had been diagnosed with CD at least 5 years prior to the testing and had not required any surgical intervention. The second control group was healthy subjects. RESULTS: In total, there were 117 operated patients for CD, 77 patients with CD that had not undergone surgery for CD and 30 healthy subjects. For patients with at least one genetic mutation, the risk of the necessity of surgical treatment of CD is 1.96 times higher than for patients with no mutation. Patients with two or more mutations were generally operated on at a younger age, in a shorter time after being diagnosed and each patient had a partial resection of the ileum. CONCLUSION: The group of operated patients with CD had a significantly higher distribution of at least one genetic mutation as opposed to the non-operated group. In patients with two or more mutations, the disease course was more aggressive. This group of patients might profit from the conservative top-down or early surgical therapy.

[Early recognition and screening consultation: a necessary way to improve early detection and treatment in rheumatology? : Overview of the early recognition and screening consultation models for rheumatic and musculoskeletal diseases in Germany]. / Früh- und Screeningsprechstunden: Ein notwendiger Weg zur besseren Frühversorgung in der internistischen Rheumatologie? : Rheumatologische Früh- und Screeningsprechstundenmodelle in Deutschland.

In order to reduce the prognostically relevant time interval between the initial manifestation of a rheumatic and musculoskeletal disease and diagnosis as well as the consecutive initiation of an appropriate treatment, several rheumatological centers in Germany have improved the access to initial rheumatologic evaluation by establishing early recognition/screening clinics at their respective sites. Corresponding models located at Altoetting·Burghausen, Bad Pyrmont, Berlin Buch, Duesseldorf, Heidelberg, Herne, Mannheim as well as supraregional/multicenter initiatives Rheuma Rapid, RhePort and Rheuma-VOR are presented in this overview along with the respective characteristics, potential advantages and disadvantages, but also first evaluation results of several models. The aim of this publication is to promote early detection of rheumatic and musculoskeletal diseases as one of the most important challenges in current rheumatology by encouraging further rheumatologic centers and practices to launch their own early recognition/screening consultation model on the basis of aspects presented herein.

The quality of life following allogeneic hematopoietic stem cell transplantation - a multicenter retrospective study.

UNLABELLED: Although allogeneic haematopoietic stem cell transplantation (allo-HSCT) offers a unique curative potential, it may be connected with high treatment-related morbidity and mortality. Besides many organ complications, allo-HSCT may significantly affect quality of life (QOL). PATIENTS AND METHODS: Between January 2011 and December 2012, five hundred and ninety patients (pts) from 6 transplant centers in the Czech Republic filled in the questionnaire for the quantitative measurement of QOL using Functional Assessment of Cancer Therapy-General (FACT-G) version 4. Study cohort characteristics were as follows: 325 males, 340 pts received myeloablative conditioning, 383 pts received PBPC, representation of diagnoses; acute leukemia (n=270), bone marrow failure (n=36), chronic myeloid leukemia (n=74), myelodysplastic/myeloproliferative syndrom (n=110), lymphoproliferative disease (n=93). The median age at allo-HSCT was 43 years (range: 1.7 - 71.0), the median time from allo-HSCT to questionnaire completing was 3.8 years (range: - 0.2 - 21.6). The earliest allo-HSCT was performed in November 1989, the last in September 2012. In this retrospective study, we investigated the impact of various factors on the QOL after allo-HSCT: age, gender, diagnosis, type of conditioning, time from diagnosis to allo-HSCT, disease stage, graft type, donor type, time from allo-HSCT to questionnaire completing, GVHD, relapse. Only data from patients who were more than 3 months after allo-HSCT were used for the multivariate analysis. The overall results of the total FACT-G score (median=85.0; range: 29-108) as well as the results of each specific dimension - PWB (median=23.0; range: 5-28), SWB (median=24.0; range: 7-28), EWB (median= 19.0; range: 4-24), FWB (mean=21.0; range: 2-28) showed a value in the highest quartile of the possible evaluation. In multivariate analysis, an inferior QOL score was reported for patients with aGVHD (p=0.002), cGVHD (p<0.001), QOL decreased with increasing age (p=0.048) and increased with time elapsed since allo-HSCT (p<0.001).Allogeneic HSCT represents an important intervention into the overall integrity of the organism. In particular, the development of GVHD can cause very serious organ, but also mental problems which can significantly reduce the QOL. The QOL is steadily increasing with increasing interval from allo-HSCT but improvement and disappearance of these complications may take many years, and sometimes these effects may probably persist permanently.

Screening of Psychological Distress 4.5 Years after Diagnosis in Breast Cancer Patients Compared to Healthy Population.

BACKGROUND: Survival rate of breast cancer patients has improved significantly in recent years. Cancer diagnosis represents a great psychological distress for patients which may not stem solely from the disease itself. Patients may experience higher distress even several years after treatment. PATIENTS AND METHODS: The study was carried out at the Department of Obstetrics and Gynecology and Department of Internal Medicine, Haematology and Oncology, Faculty Hospital Brno. Results of 85 patients at 4.5 years after diagnosis of breast cancer compared to 72 healthy controls are presented in this paper. The data were collected in the form of semi-structured interviews, from the patients medical records and by Symp-tom Check List-90. RESULTS: The overall rate of psychological distress (GSI) 4.5 years after breast cancer dia-gnosis does not differ significantly (p = 0.703) from the healthy population. Also, we did not find any statistically significant relationship between the observed factors and the level of psychological distress in breast cancer patients. CONCLUSION: Screening investigation showed no difference in the psychological distress in breast cancer patients 4.5 years following diagnosis, compared with the healthy population.

Change in Quality of Life Measured over Time in Czech Women with Breast Cancer.

BACKGROUND: This study examined the impact of breast cancer on quality of life (QOL) of Czech women by comparing the QOL of breast cancer patients with that of age-matched healthy controls. METHODS: The sample consisted of 74 breast cancer patients who filled in self-assessment questionnaires retrospectively before treatment and at the time of the study. In addition, 73 healthy controls completed the same battery of questionnaires. QOL was assessed using the Rand 36-Item Health Survey, the Life Satisfaction Questionnaire, and the Czech research version of Functional Assessment of Breast Cancer Therapy. The Wilcoxon paired test and Mann-Whitney U test were used for data analysis. RESULTS: A statistically significant decline in QOL in breast cancer patients was found for the following components: Physical Functioning (p = 0.021), Role Functioning-Physical (p < 0.001), Bodily Pain (p = 0.001), General Health (p = 0.031), Role Functioning-Emotional (p = 0.023), and Physical Well-being (p = 0.001). The only significant increase over time was observed in Social/Family Well-being (p = 0.024). For most of the components, patients showed a statistically significant lower QOL than that of healthy controls. A recent diagnosis, advanced disease stage, more comorbidities, a higher BMI, and other sociodemographic characteristics were associated with a higher incidence of a lower QOL over time. CONCLUSION: Perceived QOL decreased over time in breast cancer patients mainly in components such as physical and emotional functioning, bodily pain, and general health, with several risk factors strongly influencing this change. The QOL of patients was lower than that of the non-cancer population, indicating that subsequent care should be improved to minimize the adverse effects that breast cancer has on QOL.

Predicting Vitality Change in Older Breast Cancer Survivors after Primary Treatment--an Approach Based on Using Time-related Difference of Pro-inflammatory Marker C-reactive Protein.

BACKROUND: We aimed to determine prognosis of vitality change and functional status of breast cancer survivors after primary oncological treatment using time-related differences of elevated levels of highly sensitive proinflammatory C-reactive protein (CRP). PATIENTS AND METHODS: The test group consisted of 46 elderly breast cancer survivors (median age was 65 years) who completed Vitality Scale of Short Form 36 (SF-36) after completing treatment and another retrospectively at diagnosis. Data on tumor-related factors, treatment, and outcomes were obtained retrospectively from medical records, and linear regression analysis was performed. CRP was followed at diagnosis and one year after primary treatment. Within the scope of this study, clinically important difference in the Vitality Scale was set at five points of change. RESULTS: Results showed a statistically significant relationship between CRP change and vitality component of SF-36 change (rs = - 0.350, p = 0.023) in which a decrease in CRP inversely correlated with the quality of life component. The overall change was 1.078 of the vitality scale score (approximately 1 point) for each 1 unit decrease of CRP (1 mg/ L). Association of CRP levels (before and after treatment, its difference between these time points) with age, number of comorbidities and stage of the disease was analyzed and no statistically significant relationship was found in our study. CONCLUSION: Preliminary results suggested time-related differences in elevated CRP levels as a potentially suitable predictor for change in vitality status for long term, chronic condition for older breast cancer survivors. We suggest the interpretation schema including an understanding that CRP change of 5 mg/ L and more should be considered a potential risk factor for subsequent negative clinical outcomes.

[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.

[Follicular Lymphoma]. / Folikulární lymfom.

Follicular lymphomas represent the second most frequent lymphoma subtype. Translocation t(14;18)(q32;q21) is a characteristic biologic hallmark. It is not sufficient to drive follicular lymphomas development and subsequent molecular defect appears which lead to follicular lymphomas development and progression. The microenvironment plays an important role. The disease is usually diagnosed in an advanced clinical stage. The course is mostly indolent, but there is a subgroup characterized by rapid progression. The outcome has been improved with median of progression free survival between 6-7 years and overall survival between 10 and 15 years. The outcome improvement was caused by introduction of immunotherapy - rituximab, both in induction as well as in maintenance therapy. Despite this improvement, subsequent relapses occur, they can be managed by a variety of approaches based on many factors. The most adverse event is histological transformation. The present review briefly summarizes understanding of biology, clinical course and management.

The Hans algorithm failed to predict outcome in patients with diffuse large B-cell lymphoma treated with rituximab.

Diffuse large B-cell lymphoma (DLBCL) consists of at least two biologically and pathogenetically different subtypes, the germinal centre B-cell (GCB) and the activated B cell type (ABC). It has been suggested that immunohistochemistry can discriminate these subtypes as well. The aim of this study was to verify the validity of the most commonly used Hans algorithm in patients with DLBCL treated with anthracycline- based chemotherapy with rituximab. Immunohistochemical staining using standard protocols was performed on formalin fixed paraffin-embedded tissues. CD20, CD5, CD23, BCL2, CD10, BCL6, MUM1 and Ki67 antibodies were applied. Out of 120 examined cases 52 patients were evaluated as GCB type and 68 patients as having non-GCB, out of a set of 99 patients treated with immunochemotherapy 45 patients with GCB and 54 patients with non-GCB DLBCL were identified. In this set of patients, there was no statistically significant difference neither in overall survival (OS) (HR 1.47 95% CI 0.51-2.63; p=0.45) nor in progression free survival (PFS) (HR 1.57, 95 % CI 0.76-3.22; p=0.731) between both groups.

[Visceral leishmaniasis (two case reports)]. / Viscerální leishmanióza (dve kazuistiky).

Two cases of imported visceral leishmaniasis are described. The first patient was a 32-year-old Czech man who developed leishmaniasis 5 months after a holiday in Italy (Bibione). The second patient was a 62-year-old Czech man who developed leishmaniasis 18 months after visiting Croatia (Makarska); the disease began after a course of chemotherapy due to metastasizing testicular tumor. Both patients were successfully treated with amphotericin B lipid complex (Abelcet). Difficulties in establishing the correct diagnosis of visceral leishmaniasis are discussed.

The effect of allogeneic stem cell transplantation on high risk chronic lymphocytic leukaemia: a single centre retrospective analysis.

In recent years, many studies have confirmed that allogeneic stem cell transplantation (allo-SCT) can provide long-term disease control and possible cure in selected patients with chronic lymphocytic leukaemia (CLL), including those with a biologically highly unfavourable risk profile. A retrospective analysis of allo-SCT in 30 patients with CLL whose risk profile was unfavourable and who were treated in the years 2000-2009 was performed. The aim was to compare the results of allo-SCT by prognostic factors and conditioning type and evaluate the results of unrelated transplantation. The median age was 54 years. Donors were 8 HLA-matched siblings and 22 unrelated volunteers, 11 of whom were mismatched. Eighteen patients were treated with reduced intensity conditioning. Twelve patients received myeloablative conditioning. Estimated overall survival (OS) at 3 years was 78%, progression-free survival (PFS) 71%, relapse incidence 10% and non-relapse mortality (NRM) 16%, respectively, with a median follow-up of 35 months. According to molecular/cytogenetic characteristics, OS and PFS for the high risk group (17p- or 11q-) were 89 and 77%, respectively, not significantly different from those with standard risk. Graft-versus-host disease (GVHD) was associated with greater toxicity; significantly higher NRM for patients with aGVHD (p = 0.04) and worse PFS for patients with cGVHD (p = 0.04). Our results for the refractory disease group (77% responses) indicate that chemoresistance may be overcome by the GVL effect. Transplants from unrelated donors may be considered comparable to those from related donors.

How we identify and treat neuromuscular toxicity induced by immune checkpoint inhibitors.

Immune-related neuromuscular adverse events are rare, but potentially life-threatening side-effects of immune checkpoint inhibitors (ICIs). They usually arise within the first 3 months after initiation of ICIs. Subacute symptom onset with more rapid progression than in idiopathic autoimmune neuromuscular diseases is typical. Prompt clinical diagnosis and treatment is essential for a favourable outcome. The importance of careful medical history and a well-established clinical diagnosis is emphasised rather than antibody detection or radiologic visualisation. Muscle weakness as a leading symptom can give rise to the suspicion of either neuropathy or myositis-myasthenia complex and differentiation may be complicated by their overlap. It is of utmost importance to recognise immune-related myositis and monitor for myocardial as well as bulbar involvement that may rapidly lead to cardiac or respiratory failure, persisting disability or even a fatal outcome. Symptoms typically improve with ICI discontinuation and early administration of glucocorticoids (prednisolone 1-2 mg/kg/day) in patients markedly affected. Severe and persisting symptoms including myocardial or bulbar affection can require therapy escalation to steroid-sparing agents. In patients with mild symptoms, not influencing functional abilities, careful clinical monitoring while staying on ICI therapy may be sufficient. Re-challenging with ICIs may be considered in selected cases, based on the initial severity of immune-related adverse events (irAEs) and clinical disease course. Depending on the individual irAE characteristics, the decision should be preferably discussed in an interdisciplinary irAE expert team with an experienced neurologist, rheumatologist and/or cardiologist and take the patient's preferences into account. The yet unmet need of systematic data on treatment, follow-up results and options of re-challenge of ICI treatment in neuromuscular toxicity has to be particularly considered in the shared decision-making process.

Circulating endothelial precursor cells (EPC) in patients undergoing allogeneic haematopoietic progenitor cell transplantation.

We have studied the number of endothelial precursor cells in eighteen patients undergoing allogeneic haematopoietic stem cell transplantation. Endothelial precursor cells were evaluated by colony-forming assay and compared to healthy controls. Patients undergoing allogeneic haematopoietic stem cell transplantation had significantly lower numbers of endothelial precursor cells before the procedure than healthy controls. The numbers of endothelial precursor cells were even lower in the first year after the treatment and seemed to recover partially after twelve months, but even then, they were lower than in healthy volunteers. On the other hand, the number of circulating CD146+CD31+ mature endothelial cells were higher than in healthy controls after more than a one-year follow-up. We hypothesize that lower numbers of endothelial precursor cells and higher numbers of endothelial cells in patients undergoing allogeneic haematopoietic stem cell transplantation reflect ongoing endothelial damage, probably caused by immunological mechanisms, and that this longterm damage may explain the higher risk of cardiovascular events in allogeneic haematopoietic stem cell transplant survivors.

[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.

[Side effects of novel cancer immunotherapies]. / Nebenwirkungen neuer onkologischer Immuntherapien.

Systemic treatment with immune checkpoint inhibitors (ICI) has revolutionized the treatment of hematological and oncological diseases in recent years. The mechanism of action hinges on enhancing the natural ability of the immune system to eliminate malignant cells. The most important substances in this arena include inhibitors of PD­1, PD-L1 and CTLA­4. As a consequence, the spectrum of treatment-associated adverse reactions is shifting away from classical cytotoxic effects (e.g. pancytopenia and polyneuropathy) towards novel entities of immune-mediated complex diseases. These so-called immune-related adverse events (irAEs) can involve any organ system and mimic known classical autoimmune conditions. Timely recognition of irAEs is the key for rapid initiation of a suitable treatment and is especially challenging in the clinical routine as it requires an intensive interdisciplinary management. Nephrologists are particularly confronted with this kind of problem due to the highly interdisciplinary nature of their work. This article summarizes the broad spectrum of currently known renal and more frequently occuring non-renal forms of irAEs and aims to prime the reader on diagnostic and therapeutic options.

The results of allogeneic transplants in patients with malignant lymphoma-a retrospective analysis of data from the Czech National Registry.

We processed data of 79 patients (pts) with malignant lymphoma from the National Registry of haematopoietic stem cell transplants conducted between 1997 and 2006. The haematopoietic stem cell donor in 48 pts was an HLA matched relative, and in 30 pts an unrelated volunteer. Sixty (77%) pts were transplanted with reduced intensity conditioning (RIC), eleven (23%) pts with myeloablative conditioning (MC). Acute graft-versus-host disease (aGVHD) was recorded in 26 (33%) pts. Chronic GVHD was diagnosed in 19 (36%) of the 53 assessable pts. Transplant-related mortality (TRM) in the first 100 days, 1 year and 3 years for the whole group was 26%, 33% and 33%. Twenty (26%) of the pts relapsed. During the median follow-up of 26 months the overall survival (OS) was 44%, the progression free survival (PFS) was 54% and cumulative incidence of relapse was 45%. Pts with chemoresistant disease had significantly worse results (OS at 3 years 22% vs. 56%, p=0.002). We did not find any correlation between the incidence of GVHD and the frequency of relapse. Similarly, we did not observe any difference in survival between patients following MC vs. RIC. Survival of pts transplanted from related donors did not differ statistically from unrelated donors. Key words: Lymphoma, allogeneic, transplantation, GVHD.