AIMS: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a vital treatment for various paediatric malignant and nonmalignant diseases. The conditioning treatment before allo-HSCT is crucial for successful engraftment. Treosulfan, a cytotoxic prodrug, has gained popularity due to its lower toxicity compared to traditional alkylating agents used for conditioning treatment. METHODS: We investigated the relationship between pharmacokinetics and pharmacodynamics of treosulfan in paediatric patients, in a substudy pooling from 2 multicentre phase 2 clinical trials. A total of 83 children with malignant and nonmalignant diseases received treosulfan-based conditioning. Treosulfan exposure and its relationship with clinical outcomes, including survival, graft failure and graft-vs.-host disease, were investigated. RESULTS: Our findings reveal no significant association between treosulfan exposure and the key clinical outcomes or toxicity (P-values between .22 and .99), if the dosing is based on the approved product information. CONCLUSION: These findings suggest that treosulfan exposure after standardized body surface area-based dosing is appropriate in paediatric allo-HSCT.

• Klíčová slova
• paediatrics, stem cell transplantation, treosulfan,
• MeSH
• alkylační protinádorové látky * farmakokinetika   aplikace a dávkování   škodlivé účinky   MeSH
• busulfan * analogy a deriváty   farmakokinetika   aplikace a dávkování   škodlivé účinky   MeSH
• dítě MeSH
• homologní transplantace MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• nemoc štěpu proti hostiteli epidemiologie   prevence a kontrola   etiologie   MeSH
• předškolní dítě MeSH
• příprava pacienta k transplantaci * metody   škodlivé účinky   MeSH
• transplantace hematopoetických kmenových buněk * metody   škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• Názvy látek
• alkylační protinádorové látky * MeSH
• busulfan * MeSH
• treosulfan MeSH Prohlížeč

PURPOSE: This phase 1/2 study aimed to evaluate the safety and preliminary efficacy of combining disulfiram and copper (DSF/Cu) with radiation therapy (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM). METHODS AND MATERIALS: Patients received standard RT and TMZ with DSF (250-375 mg/d) and Cu, followed by adjuvant TMZ plus DSF (500 mg/d) and Cu. Pharmacokinetic analyses determined drug concentrations in plasma and tumors using high-performance liquid chromatography-mass spectrometry. RESULTS: Thirty-three patients, with a median follow-up of 26.0 months, were treated, including 12 IDH-mutant, 9 NF1-mutant, 3 BRAF-mutant, and 9 other IDH-wild-type cases. In the phase 1 arm, 18 patients were treated; dose-limiting toxicity probabilities were 10% (95% CI, 3%-29%) at 250 mg/d and 21% (95% CI, 7%-42%) at 375 mg/d. The phase 2 arm treated 15 additional patients at 250 mg/d. No significant difference in overall survival or progression-free survival was noted between IDH- and NF1-mutant cohorts compared with institutional counterparts treated without DSF/Cu. However, extended remission occurred in 3 BRAF-mutant patients. Diethyl-dithiocarbamate-copper, the proposed active metabolite of DSF/Cu, was detected in plasma but not in tumors. CONCLUSIONS: The maximum tolerated dose of DSF with RT and TMZ is 375 mg/d. DSF/Cu showed limited clinical efficacy for most patients. However, promising efficacy was observed in BRAF-mutant GBM, warranting further investigation.

• MeSH
• alkylační protinádorové látky terapeutické užití   farmakokinetika   MeSH
• chemoradioterapie * metody   MeSH
• disulfiram * terapeutické užití   farmakokinetika   aplikace a dávkování   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• glioblastom * radioterapie   genetika   mortalita   terapie   farmakoterapie   MeSH
• isocitrátdehydrogenasa genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• měď * krev   terapeutické užití   MeSH
• nádory mozku * radioterapie   mortalita   genetika   terapie   MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• senioři MeSH
• temozolomid * terapeutické užití   farmakokinetika   aplikace a dávkování   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, fáze I MeSH
• klinické zkoušky, fáze II MeSH
• Názvy látek
• alkylační protinádorové látky MeSH
• disulfiram * MeSH
• isocitrátdehydrogenasa MeSH
• měď * MeSH
• protoonkogenní proteiny B-Raf MeSH
• temozolomid * MeSH

OBJECTIVE: To discover new variants associated with low ovarian reserve after gonadotoxic treatment among adult female childhood cancer survivors using a genome-wide association study approach. DESIGN: Genome-wide association study. SETTING: Not applicable. PATIENTS: A discovery cohort of adult female childhood cancer survivors from the pan-European PanCareLIFE cohort (n = 743; median age: 25.8 years), excluding those who received bilateral ovarian irradiation, bilateral oophorectomy, central nervous system or total body irradiation, or stem cell transplantation. Replication was attempted in the US-based St. Jude Lifetime Cohort (n = 391; median age: 31.3 years). EXPOSURE: Female childhood cancer survivors are at risk of therapy-related gonadal impairment. Alkylating agents are well-established risk factors, and the interindividual variability in gonadotoxicity may be explained by genetic polymorphisms. Data were collected in real-life conditions, and cyclophosphamide equivalent doses were used to quantify alkylation agent exposure. MAIN OUTCOME MEASURE: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function, and the findings were combined in a meta-analysis. RESULTS: Three genome-wide significant (<5.0 × 10-8) and 16 genome-wide suggestive (<5.0 × 10-6) loci were associated with log-transformed AMH levels, adjusted for cyclophosphamide equivalent dose of alkylating agents, age at diagnosis, and age at study in the PanCareLIFE cohort. On the basis of the effect allele frequency (EAF) (>0.01 if not genome-wide significant), and biologic relevance, 15 single nucleotide polymorphisms were selected for replication. None of the single nucleotide polymorphisms were statistically significantly associated with AMH levels. A meta-analysis indicated that rs78861946 was associated with borderline genome-wide statistical significance (reference/effect allele: C/T; effect allele frequency: 0.04, beta (SE): -0.484 (0.091). CONCLUSION: This study found no genetic variants associated with a lower ovarian reserve after gonadotoxic treatment because the findings of this genome-wide association study were not statistically significant replicated in the replication cohort. Suggestive evidence for the potential importance of 1 variant is briefly discussed, but the lack of statistical significance calls for larger cohort sizes. Because the population of childhood cancer survivors is increasing, large-scale and systematic research is needed to identify genetic variants that could aid predictive risk models of gonadotoxicity as well as fertility preservation options for childhood cancer survivors.

• Klíčová slova
• GWAS, Ovarian reserve, childhood cancer, gonadotoxicity, survivorship,
• MeSH
• alkylační protinádorové látky škodlivé účinky   MeSH
• antimülleriánský hormon * krev   genetika   MeSH
• celogenomová asociační studie * MeSH
• dítě MeSH
• dospělí MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory genetika   farmakoterapie   MeSH
• ovariální rezerva * genetika   účinky léků   účinky záření   MeSH
• přežívající onkologičtí pacienti * MeSH
• rizikové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• Názvy látek
• alkylační protinádorové látky MeSH
• antimülleriánský hormon * MeSH

Retinoblastoma is the most common primary malignant intraocular tumor in children. Seeding, specifically the dispersion of the tumor into the adjacent compartments, represents a major parameter determining the degree of retinoblastoma according to the International Classification of Retinoblastoma. In this article we focused on vitreous seeding, one of the main limiting factors in the successful "eye preservation treatment" of retinoblastoma. This article presents an overview of the history of vitreous seeding of retinoblastoma, established treatment procedures and new-research modalities. The introduction of systemic chemotherapy in the treatment of retinoblastoma at the end of the 1990s represented a significant breakthrough, which enabled the progressive abandonment of radiotherapy with its attendant side effects. However, the attained concentrations of chemotherapeutics in the vitreous space during systemic chemotherapy are not sufficient for the treatment of vitreous seeding, and the toxic effects of systemic chemotherapy are not negligible. A significant change came with the advent of chemotherapy in situ, with the targeted administration of chemotherapeutic drugs, namely intra-arterial and intravitreal injections, contributing to the definitive eradication of external radiotherapy and a reduction of systemic chemotherapy. Although vitreous seeding remains the most common reason for the failure of intra-arterial chemotherapy, this technique has significantly influenced the original treatment regimen of children with retinoblastoma. However, intravitreal chemotherapy has made the greatest contribution to increasing the probability of preservation of the eyeball and visual functions in patients with advanced findings. Novel local drug delivery modalities, gene therapy, oncolytic viruses and immunotherapy from several ongoing preclinical and clinical trials may represent promising approaches in the treatment of vitreous retinoblastoma seeding, though no clinical trials have yet been completed for routine use.

• Klíčová slova
• eye preservation treatment, intravitreal chemotherapy, retinoblastoma, vitreous seeding,
• MeSH
• alkylační protinádorové látky farmakologie   terapeutické užití   MeSH
• dítě MeSH
• injekce intravitreální MeSH
• lidé MeSH
• melfalan škodlivé účinky   MeSH
• nádory sítnice * chemicky indukované   farmakoterapie   MeSH
• retinoblastom * chemicky indukované   farmakoterapie   MeSH
• retrospektivní studie MeSH
• sklivec patologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• alkylační protinádorové látky MeSH
• melfalan MeSH

BACKGROUND: Chemotherapy with lomustine is widely considered as standard treatment option for progressive glioblastoma. The value of adding radiotherapy to second-line chemotherapy is not known. METHODS: EORTC-2227-BTG (LEGATO, NCT05904119) is an investigator-initiated, pragmatic (PRECIS-2 score: 34 out of 45), randomized, multicenter phase III trial in patients with first progression of glioblastoma. A total of 411 patients will be randomized in a 1:1 ratio to lomustine (110 mg/m2 every 6 weeks) or lomustine (110 mg/m2 every 6weeks) plus radiotherapy (35 Gy in 10 fractions). Main eligibility criteria include histologic confirmation of glioblastoma, isocitrate dehydrogenase gene (IDH) wild-type per WHO 2021 classification, first progression at least 6 months after the end of prior radiotherapy, radiologically measurable disease according to RANO criteria with a maximum tumor diameter of 5 cm, and WHO performance status of 0-2. The primary efficacy endpoint is overall survival (OS) and secondary endpoints include progression-free survival, response rate, neurocognitive function, health-related quality of life, and health economic parameters. LEGATO is funded by the European Union's Horizon Europe Research program, was activated in March 2024 and will enroll patients in 43 sites in 11 countries across Europe with study completion projected in 2028. DISCUSSION: EORTC-2227-BTG (LEGATO) is a publicly funded pragmatic phase III trial designed to clarify the efficacy of adding reirradiation to chemotherapy with lomustine for the treatment of patients with first progression of glioblastoma. TRIAL REGISTRATION: ClinicalTrials.gov NCT05904119. Registered before start of inclusion, 23 May 2023.

• Klíčová slova
• Glioblastoma, LEGATO, Lomustine, Progression, Randomized controlled trial, Reirradiation,
• MeSH
• alkylační protinádorové látky * terapeutické užití   MeSH
• časové faktory MeSH
• chemoradioterapie metody   MeSH
• doba přežití bez progrese choroby * MeSH
• glioblastom * patologie   farmakoterapie   mortalita   radioterapie   terapie   MeSH
• klinické zkoušky, fáze III jako téma MeSH
• kvalita života MeSH
• lidé MeSH
• lomustin * aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• multicentrické studie jako téma * MeSH
• nádory mozku * radioterapie   patologie   mortalita   terapie   MeSH
• pragmatické klinické studie jako téma MeSH
• progrese nemoci * MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Názvy látek
• alkylační protinádorové látky * MeSH
• lomustin * MeSH

PURPOSE: We aimed to find metabolic, functional or morphological characteristics of the tumor predicting failure to achieve complete metabolic remission (CMR) by the midtreatment PET/MRI (positron emission tomography/magnetic resonance imaging) in cervical cancer patients. METHODS: We evaluated 66 patients treated between August 2015 and November 2019 who underwent pretreatment staging, subsequent midtreatment evaluation, and definitive restaging 3 months after completing the whole treatment, all using PET/MRI. The pretreatment parameters (pre-SUVmax, pre-SUVmean, pre-MTV, pre-MTV‑S, pre-TLG, pre-TLG‑S [SUV: standard uptake value, MTV: metabolic tumor volume, TLG: total lesion glycolysis]), and the midtreatment parameters at week 5 during chemoradiotherapy (mid-SUVmax, mid-SUVmean, mid-MTV, mid-MTV‑S, mid-TLG and mid-TLG-S) were recorded. The value of ADC (apparent diffusion coefficient) was also measured. Furthermore, we recorded absolute and relative changes in all parameters-∆ and ∆%. We divided the whole group of patients into "responders" (CMR) and "non-responders" (non-CMR), and compared them on the basis of the parameters from pre-PET/MRI and mid-PET/MRI. RESULTS: A statistically significant difference in the evaluated parameters between responders and non-responders was found for the following parameters: mid-MTV, mid-TLG, mid-TLG‑S, mid-MTV‑S, mid-tumor size, and ∆%SUVmax. According to the ROC (receiver operating characteristic) analysis, mid-MTV‑S showed the best albeit moderate discrimination ability for the prediction of non-CMR. Significant mutual correlations of all variables, in particular between mid-MTV‑S and mid-TLG‑S and between mid-MTV and mid-TLG, were found (all p < 0.05). CONCLUSION: Our study confirmed that when using the midtreatment PET/MRI we are able to identify metabolic parameters having the discrimination ability for the prediction of non-CMR. In particular mid-MTV‑S, mid-MTV, mid-tumor size, mid-TLG‑S, mid-TLG and ∆%SUVmax.

• Klíčová slova
• Cervical cancer, Magnetic resonance imaging, Positron emission tomography, Treatment response, Uterovaginal brachytherapy,
• MeSH
• alkylační protinádorové látky terapeutické užití   MeSH
• brachyterapie MeSH
• chemoradioterapie * MeSH
• cisplatina terapeutické užití   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• magnetická rezonanční tomografie * MeSH
• multimodální zobrazování * MeSH
• nádory děložního čípku diagnostické zobrazování   metabolismus   patologie   terapie   MeSH
• ozařování lymfatického systému MeSH
• plocha pod křivkou MeSH
• počítačové zpracování obrazu MeSH
• pozitronová emisní tomografie * MeSH
• prognóza MeSH
• radioterapie s modulovanou intenzitou MeSH
• ROC křivka MeSH
• senioři MeSH
• spinocelulární karcinom diagnostické zobrazování   metabolismus   patologie   terapie   MeSH
• staging nádorů metody   MeSH
• tumor burden MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• alkylační protinádorové látky MeSH
• cisplatina MeSH

Limited information is available on the efficacy of front-line bendamustine and rituximab (BR) in chronic lymphocytic leukemia (CLL) with reduced renal function or coexisting conditions. We therefore analyzed a cohort of real-world patients and performed a matched adjusted indirect comparison with a cohort of patients treated with ibrutinib. One hundred and fifty-seven patients with creatinine clearance (CrCl) <70 mL/min and/or CIRS score >6 were treated with BR. The median age was 72 years; 69% of patients had ≥2 comorbidities and the median CrCl was 59.8 mL/min. 17.6% of patients carried TP53 disruption. The median progression-free survival (PFS) was 45 months; TP53 disruption was associated with a shorter PFS (P = 0.05). The overall survival (OS) at 12, 24, and 36 months was 96.2%, 90.1%, and 79.5%, respectively. TP53 disruption was associated with an increased risk of death (P = 0.01). Data on 162 patients ≥65 years treated with ibrutinib were analyzed and compared with 165 patients ≥65 years treated with BR. Factors predicting for a longer PFS at multivariable analysis in the total patient population treated with BR and ibrutinib were age (HR 1.06, 95% CI 1.02-1.10, P < 0.01) and treatment with ibrutinib (HR 0.55, 95% CI 0.33-0.93, P = 0.03). In a post hoc analysis of patients in advanced stage, a significant PFS advantage was observed in patient who had received ibrutinib (P = 0.03), who showed a trend for OS advantage (P = 0.08). We arrived at the following conclusions: (a) BR is a relatively effective first-line regimen in a real-world population of unfit patients without TP53 disruption, (b) ibrutinib provided longer disease control than BR in patients with advanced disease stage.

• Klíčová slova
• bendamustine, chronic lymphocytic leukemia, ibrutinib, real-world analysis, unfit patients,
• MeSH
• adenin škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• alkylační protinádorové látky škodlivé účinky   terapeutické užití   MeSH
• bendamustin hydrochlorid škodlivé účinky   terapeutické užití   MeSH
• časové faktory MeSH
• chronická lymfatická leukemie diagnóza   farmakoterapie   mortalita   MeSH
• doba přežití bez progrese choroby MeSH
• inhibitory proteinkinas škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• piperidiny škodlivé účinky   terapeutické užití   MeSH
• progrese nemoci MeSH
• protinádorové látky imunologicky aktivní škodlivé účinky   terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• retrospektivní studie MeSH
• rituximab škodlivé účinky   terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH
• Názvy látek
• adenin MeSH
• alkylační protinádorové látky MeSH
• bendamustin hydrochlorid MeSH
• ibrutinib MeSH Prohlížeč
• inhibitory proteinkinas MeSH
• piperidiny MeSH
• protinádorové látky imunologicky aktivní MeSH
• rituximab MeSH

INTRODUCTION: The overall survival of patients with multiple myeloma has improved with the advent of novel agents; however, multiple myeloma remains incurable. Combinations of standard-of-care agents such as immunomodulators, proteasome inhibitors, and anti-CD38 monoclonal antibodies are increasingly used in earlier lines of therapy. Patients with disease that is refractory to multiple novel agents represent a population with high unmet medical need and for whom therapies with new mechanisms of action could be beneficial. Melphalan flufenamide (melflufen) has demonstrated encouraging activity in patients with relapsed and refractory multiple myeloma. AREAS COVERED: This review provides an overview of the mechanism of action of melflufen, a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly delivers alkylating agents into tumor cells. It reviews key Phase I and II clinical trial data for melflufen in combination with dexamethasone as well as in triplet combinations with daratumumab or bortezomib. The safety profile of melflufen, which is characterized primarily by clinically manageable hematologic adverse events, is described. EXPERT OPINION: Melflufen has potential to fill a gap in the myeloma treatment landscape by providing a new mechanism of action with clinically meaningful efficacy and a favorable safety profile in patients refractory to multiple novel agents.

• Klíčová slova
• Melflufen, melphalan flufenamide, relapsed/refractory multiple myeloma,
• MeSH
• alkylační protinádorové látky aplikace a dávkování   škodlivé účinky   farmakologie   MeSH
• fenylalanin aplikace a dávkování   škodlivé účinky   analogy a deriváty   farmakologie   MeSH
• lidé MeSH
• melfalan aplikace a dávkování   škodlivé účinky   analogy a deriváty   farmakologie   MeSH
• míra přežití MeSH
• mnohočetný myelom farmakoterapie   patologie   MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   škodlivé účinky   farmakologie   MeSH
• recidiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• alkylační protinádorové látky MeSH
• fenylalanin MeSH
• melfalan MeSH
• melflufen MeSH Prohlížeč

INTRODUCTION: Glioblastoma (GBM) is the most common malignant primary brain tumor, and methods to improve the early detection of disease progression and evaluate treatment response are highly desirable. We therefore explored changes in whole-brain apparent diffusion coefficient (ADC) values with respect to survival (progression-free [PFS], overall [OS]) in a cohort of GBM patients followed at regular intervals until disease progression. METHODS: A total of 43 subjects met inclusion criteria and were analyzed retrospectively. Histogram data were extracted from standardized whole-brain ADC maps including skewness, kurtosis, entropy, median, mode, 15th percentile (p15) and 85th percentile (p85) values, and linear regression slopes (metrics versus time) were fitted. Regression slope directionality (positive/negative) was subjected to univariate Cox regression. The final model was determined by aLASSO on metrics above threshold. RESULTS: Skewness, kurtosis, median, p15 and p85 were all below threshold for both PFS and OS and were analyzed further. Median regression slope directionality best modeled PFS (p = 0.001; HR 3.3; 95% CI 1.6-6.7), while p85 was selected for OS (p = 0.002; HR 0.29; 95% CI 0.13-0.64). CONCLUSIONS: Our data show tantalizing potential in the use of whole-brain ADC measurements in the follow up of GBM patients, specifically serial median ADC values which correlated with PFS, and serial p85 values which correlated with OS. Whole-brain ADC measurements are fast and easy to perform, and free of ROI-placement bias.

• Klíčová slova
• Apparent diffusion coefficient, Diffusion-weighted imaging, Glioblastoma, Histogram analyses, Magnetic resonance imaging,
• MeSH
• alkylační protinádorové látky terapeutické užití   MeSH
• chemoradioterapie mortalita   MeSH
• difuzní magnetická rezonance metody   MeSH
• glioblastom mortalita   patologie   terapie   MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• míra přežití MeSH
• nádory mozku mortalita   patologie   terapie   MeSH
• následné studie MeSH
• počítačové zpracování obrazu metody   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• retrospektivní studie MeSH
• temozolomid terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkylační protinádorové látky MeSH
• temozolomid MeSH

BACKGROUND: Evolution of indolent to aggressive lymphoma has been described in dogs but is difficult to distinguish from the de novo development of a second, clonally distinct lymphoma. Differentiation of these scenarios can be aided by next generation sequencing (NGS)-based assessment of clonality of lymphocyte antigen receptor genes. CASE PRESENTATION: An 8-year-old male intact Mastiff presented with generalized lymphadenomegaly was diagnosed with nodal T zone lymphoma (TZL) based on cytology, histopathology, immunohistochemistry and flow cytometry. Thirteen months later, the dog re-presented with progressive lymphadenomegaly, and based on cytology and flow cytometry, a large B cell lymphoma (LBCL) was diagnosed. Sequencing-based clonality testing confirmed the de novo development of a LBCL and the persistence of a TZL. CONCLUSIONS: The occurrence of two distinct lymphoid neoplasms should be considered if patient features and tumor cytomorphology or immunophenotype differ among sequential samples. Sequencing-based clonality testing may provide conclusive evidence of two concurrent and distinct clonal lymphocyte populations, termed most appropriately "composite lymphoma".

• Klíčová slova
• Antigen receptor gene rearrangement, Canine, Clonality, Composite lymphoma, Dog, Lymphoma, Lymphosarcoma, PARR,
• MeSH
• alkylační protinádorové látky aplikace a dávkování   terapeutické užití   MeSH
• chlorambucil aplikace a dávkování   terapeutické užití   MeSH
• difúzní velkobuněčný B-lymfom komplikace   patologie   veterinární   MeSH
• hormonální protinádorové látky aplikace a dávkování   terapeutické užití   MeSH
• lymfom T-buněčný komplikace   patologie   veterinární   MeSH
• nemoci psů patologie   MeSH
• prednison aplikace a dávkování   terapeutické užití   MeSH
• psi MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• alkylační protinádorové látky MeSH
• chlorambucil MeSH
• hormonální protinádorové látky MeSH
• prednison MeSH