INTRODUCTION: Driver mutations in Philadelphia chromosome-negative myeloproliferative neoplasms are well known. In the past, whole-genome sequencing identified nondriver mutations in other genes, potentially contributing to evolution of malignant clones. METHODS: Next-generation sequencing was used to assess the presence of any mutations in 14 candidate genes at the point of diagnosis and the resultant impact on the clinical course of the disease. RESULTS: The study analysed 63 patients with myelofibrosis (MF). Nondriver mutations were detected in 44% of them. The most frequently affected genes were ASXL1 (27%), TET2 (11%) and SF3B1 (6%). The frequency of such mutations was highest in primary MF (59%) and lowest in the prefibrotic phase of primary MF (21%). Patients with prognostically unfavourable sequence variants in genes had significantly worse overall survival (53 vs 71 months; HR = 2.77; 95% CI 1.17-6.56; P = .017). CONCLUSION: In our study, multivariate analysis proved DIPSS to be the only significant factor to predict patient survival. DIPSS contains all of the important clinical and laboratory factors except genetic changes. Stratification of patients according to DIPSS is still beneficial although there are newer and improved scoring systems like GIPSS or MIPSS70. Assessing subclonal mutations in candidate genes during diagnosis may aid in the identification of high-risk MF patients and is therefore relevant for making a prediction for overall survival more accurate.

• Klíčová slova
• myelofibrosis, next-generation sequencing, prognostic stratification,
• MeSH
• dioxygenasy genetika   MeSH
• DNA vazebné proteiny genetika   MeSH
• dospělí MeSH
• fosfoproteiny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• primární myelofibróza genetika   MeSH
• represorové proteiny genetika   MeSH
• senioři MeSH
• sestřihové faktory genetika   MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ASXL1 protein, human MeSH Prohlížeč
• dioxygenasy MeSH
• DNA vazebné proteiny MeSH
• fosfoproteiny MeSH
• represorové proteiny MeSH
• sestřihové faktory MeSH
• SF3B1 protein, human MeSH Prohlížeč
• TET2 protein, human MeSH Prohlížeč

Pneumatic tube transport systems (PTS) for delivery of patient samples to a hemostasis laboratory are often used to reduce turnaround time for vital analyses. PTS in our hospital has the ability to regulate the transport speed in the range of 3-6 m/s with acceleration control technology. We evaluated the effects of PTS transport for routine coagulation tests, platelet function tests and special global coagulation tests. Duplicate samples were collected from 29 patients and 40 healthy individuals. One sample was sent using PTS and the other was carried by personnel to the lab for determination of protrombin time, activated partial thromboplastin time, trombin time, fibrinogen, antitrombin and thrombin generation test. Platelet function was measured by means of a Apact 4004® analyzer using the inductors (ADP, Arachidonic acid and Epinephrine). Samples transported using PTS with normal transport speed 6 m/s does not affect basic coagulation tests (PT, aPTT, FIB, TT and AT), but TGT has significantly altered. The use of PTS with controlled acceleration regulated the increase in thrombin generation from 10% to 3%, which is not statistically signifiant. The use of PTS with controlled acceleration did not show a significant difference even with the highly sensitive method of platelet aggregation. We conclude that PTS with acceleration control with transport speed from 3 to 6 m/s does not affect to platelet activity as measured by LTA and also global coagulation test - TGT. The advantage of PTS transport is very rapid assessment laboratory testing. From the above validation study, it is clear that PTS should always be validated for specialized laboratory methods and appropriately adapted to specific transport conditions.

• Klíčová slova
• Controlled acceleration, Platelet, Pneumatic tube system,
• MeSH
• agregace trombocytů * MeSH
• lidé MeSH
• trombocyty * MeSH
• vyšetření krevní srážlivosti MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

One out of ten patients with Philadelphia-negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of MPN-specific therapies. Data were therefore extracted from an international nested case-control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person-years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1-6.9) deaths for every 100 PYs. A "poor prognosis" SC (stomach, esophagus, liver, pancreas, lung, ovary, head-and-neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the cause of death in 65% of them (MR 11.0/100 PYs). In contrast, patients with a "non-poor prognosis" SC (NPPSC) incurred a MR of 4.6/100 PYs: 31% of the deaths were attributed to SC and 15% to MPN evolution. At multivariable analysis, death after SC diagnosis was independently predicted (HR and 95% CI) by patient age greater than 70 years (2.68; 1.88-3.81), the SC prognostic group (2.57; 1.86-3.55), SC relapse (1.53; 10.6-2.21), MPN evolution (2.72; 1.84-4.02), anemia at SC diagnosis (2.32; 1.49-3.59), exposure to hydroxyurea (1.89; 1.26-2.85) and to ruxolitinib (3.63; 1.97-6.71). Aspirin was protective for patients with a NPPSC (0.60; 0.38-0.95). In conclusion, SC is a relevant cause of death competing with MPN evolution. Prospective data are awaited to confirm the role of cytoreductive and anti-platelet drugs in modulating patient survival after the occurrence of a SC.

• MeSH
• hematologické nádory mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• myeloproliferativní poruchy mortalita   MeSH
• následné studie MeSH
• přežití po terapii bez příznaků nemoci MeSH
• sekundární malignity mortalita   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• věkové faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

Patients with Philadelphia-negative myeloproliferative neoplasm (MPN) are prone to the development of second cancers, but the factors associated with these events have been poorly explored. In an international nested case-control study, we recruited 647 patients with carcinoma, nonmelanoma skin cancer, hematological second cancer, and melanoma diagnosed concurrently or after MPN diagnosis. Up to 3 control patients without a history of cancer and matched with each case for center, sex, age at MPN diagnosis, date of diagnosis, and MPN disease duration were included (n = 1234). Cases were comparable to controls for MPN type, driver mutations and cardiovascular risk factors. The frequency of thrombosis preceding MPN was similar for cases and controls (P = .462). Thrombotic events after MPN and before second cancer were higher in cases than in controls (11.6% vs 8.1%; P = .013), because of a higher proportion of arterial thromboses (6.2% vs 3.7%; P = .015). After adjustment for confounders, the occurrence of arterial thrombosis remained independently associated with the risk of carcinoma (odds ratio, 1.97; 95% confidence interval, 1.14-3.41), suggesting that MPN patients experiencing arterial events after MPN diagnosis deserve careful clinical surveillance for early detection of carcinoma. This study was registered at www.clinicaltrials.gov as NCT03745378.

• MeSH
• arterie patologie   MeSH
• filadelfský chromozom * MeSH
• Kaplanův-Meierův odhad MeSH
• lidé MeSH
• multivariační analýza MeSH
• myeloproliferativní poruchy patologie   MeSH
• následné studie MeSH
• sekundární malignity patologie   MeSH
• studie případů a kontrol MeSH
• trombóza patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

We conducted a large international nested case-control study including 1881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n = 647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer, and melanoma) and controls (n = 1234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis, and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR = 1.06, 95% CI 0.82-1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had two-fold higher risk of non-melanoma (NM) skin cancer (OR = 2.28, 95% CI 1.15-4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR = 3.74, 95% CI 1.00-14.01), ruxolitinib (OR = 3.87, 95% CI 1.18-12.75), and for drug combination (OR = 3.47, 95% CI 1.55-7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan, and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.

• MeSH
• antitumorózní látky škodlivé účinky   MeSH
• esenciální trombocytemie farmakoterapie   genetika   MeSH
• filadelfský chromozom * MeSH
• hydroxymočovina škodlivé účinky   MeSH
• lidé MeSH
• nitrily MeSH
• pipobroman škodlivé účinky   MeSH
• polycythaemia vera farmakoterapie   genetika   MeSH
• primární myelofibróza farmakoterapie   MeSH
• pyrazoly škodlivé účinky   MeSH
• pyrimidiny MeSH
• sekundární malignity chemicky indukované   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky MeSH
• hydroxymočovina MeSH
• nitrily MeSH
• pipobroman MeSH
• pyrazoly MeSH
• pyrimidiny MeSH
• ruxolitinib MeSH Prohlížeč

OBJECTIVES: Positron emission tomography using 2-[fluorine-18]-fluoro-2-deoxy-D-glucose ((18) F-FDG) is considered to be the most beneficial imaging method for staging patients with non-Hodgkin's lymphoma (NHL). The intensity of (18) F-FDG accumulation may be determined by calculating the so-called standardised uptake value (SUV). The study aimed at assessing the benefit of SUV(max) determination in staging (18) F-FDG PET/CT in untreated patients with NHL. METHODS: One hundred and forty-nine initial staging (18) F-FDG PET/CT scans performed in patients with NHL between January 2007 and August 2009 were assessed, and the SUV(max) was determined. RESULTS: The highest mean and median values of SUV(max) were observed in patients with diffuse large B-cell lymphoma (DLBCL), the lowest mean and median values were found in small lymphocytic lymphoma. The overlap in SUV(max) < 10 between DLBCL and the other subgroups of NHL was very significant. Statistically, no correlation was found between the lactate dehydrogenase and SUV(max) values. On the other hand, a correlation of the Ki-67 proliferative index of tumour cells and SUV(max) was revealed (r = 0.409, P < 0.001). The geometric mean of SUV(max) in patients with Ki-67 ≤ 60 and those with Ki-67 > 60 was 8.8 and 14.3, respectively (P < 0.001). CONCLUSIONS: The results confirm that SUV(max) is not beneficial for making a more precise diagnosis in most patients with NHL. Correlation of SUV(max) with the Ki-67 values suggests that SUV(max) might have a prognostic values in NHL.

• MeSH
• antigen Ki-67 analýza   MeSH
• dospělí MeSH
• fluorodeoxyglukosa F18 farmakokinetika   MeSH
• L-laktátdehydrogenasa analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nehodgkinský lymfom diagnóza   diagnostické zobrazování   MeSH
• pozitronová emisní tomografie metody   normy   MeSH
• prognóza MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• staging nádorů metody   normy   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• antigen Ki-67 MeSH
• fluorodeoxyglukosa F18 MeSH
• L-laktátdehydrogenasa MeSH